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2. Candidate genes without a plausible mechanism of action related to ADHD

2. Candidate genes without a plausible mechanism of action related to ADHD

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In this post, we are compiling a list of genes with mechanisms whose role in ADHD we do not yet understand.
This article is currently being revised. Genes with a “1” as their first digit have not yet been studied for their mechanisms of action in relation to ADHD.

2.68. FHIT, FRAGILE HISTIDINE TRIAD GENE (Chromosome 3p14.2)

Other names: Fragile Histidine Triad Diadenosine Triphosphatase; AP3Aase; Bis(5’-adenosyl)-triphosphatase; FRA3B; Diadenosine 5’,5’’’-P1,P3-triphosphate hydrolase; Adenylylsulfate-Ammonia Adenylyltransferase; Adenosine 5’-Monophosphoramidase FHIT; Dinucleoside Triphosphatase; Adenylylsulfatase; AP3A Hydrolase; Fragile Histidine Triad Protein; Fragile Histidine Triad Gene; Fragile Histidine Triad; EC 3.6.1.29; EC 2.7.7.51; EC 3.9.1.-; EC 3.6.2.1

The FHIT protein is a P1-P3-bis(5’-adenosyl)triphosphate hydrolase involved in purine metabolism.
Abnormal transcripts of this gene were found in about half of all esophageal, gastric, and colorectal cancers. FHIT acts as a tumor suppressor, including synergistically with the tumor suppressor VHL, and protects against chemically induced lung cancer as well as HER2/neu-induced breast cancer. This gene encompasses the common fragile site FRA3B on chromosome 3, where damage caused by carcinogens can lead to translocations and aberrant transcripts. In fact, aberrant transcripts of this gene have been found in about half of all esophageal, gastric, and colorectal cancers. FHIT possesses dinucleoside triphosphate hydrolase activity. FHIT cleaves P(1)-P(3)-bis(5’-adenosyl)triphosphate (Ap3A) into AMP and ADP. FHIT can hydrolyze P(1)-P(4)-bis(5’-adenosyl)tetraphosphate (Ap4A), but exhibits extremely low activity with ATP. FHIT exhibits adenylyl sulfatease activity and hydrolyzes adenosine-5’-phosphosulfate to yield AMP and sulfate. FHIT exhibits adenosine-5’-monophosphoramidase activity, hydrolyzes purine nucleotide phosphoramidates with a single phosphate group, such as adenosine-5’-monophosphoramidate (AMP-NH₂), to yield AMP and NH₂. FHIT exhibits adenylyl sulfate-ammonia-adenylyltransferase activity, which catalyzes the ammonolysis of adenosine-5’-phosphosulfate, leading to the formation of adenosine-5’-phosphoramidate. FHIT catalyzes the ammonolysis of adenosine-5’-phosphofluoridate and diadenosine triphosphate. FHIT modulates transcription activation by CTNNB1 and thereby contributes to the regulation of the expression of genes important for cell proliferation and survival, such as CCND1 and BIRC5. FHIT plays a role in the induction of apoptosis via SRC and AKT1 signaling pathways. FHIT inhibits MDM2-mediated proteasomal degradation of p53/TP53 and thereby plays a role in p53/TP53-mediated apoptosis. The induction of apoptosis depends on FHIT’s ability to bind P(1)-P(3)-bis(5’-adenosyl)triphosphate or related compounds, but does not require its catalytic activity. It may be partly attributable to the mitochondrial form, which sensitizes low-affinity Ca(2+) transporters and promotes mitochondrial calcium uptake. FHIT acts as a tumor suppressor.1
FHIT is affiliated with

  • Non-papillary renal cell carcinoma
  • sporadic breast cancer

Related signal paths:

  • Endometrial cancer
  • small-cell lung cancer
  • identical protein-binding hydrolase activity

Paralog: HINT1

OMIM: FRAGILE HISTIDINE TRIAD GENE; FHIT

ADHD correlates with SNP rs6791644 60746148, located in the intron of FHIT2, as well as rs37724753.

2.80. TMEM161B; TRANSMEMBRANE PROTEIN 161B

Other names: MGC33214; FLB3342; PRO1313

The TMEM161B protein appears to

  • To enable nucleic acid-binding activity
  • to be involved in DNA integration
  • to be an integral part of the cell membrane

The TMEM161B protein is essential for maintaining a normal heart rhythm in the developing heart and for the survival of newborns. It inhibits potassium and calcium currents in cardiomyocytes, which contributes to the timely repolarization of the action potential and thereby maintains a normal heart rhythm.4

TMEM161B is associated with:

  • Brachial plexus neuritis
  • Bruxism
    Related metabolic pathways: Nucleic acid binding.

Paralog: TMEM161A

TMEM161B is considered a candidate gene for depression and for personality traits.5
TMEM161B is a candidate gene for ADHD.6

2.88. B4GALT2, UDP-GAL:BETA-GlcNAc BETA-1,4-GALACTOSYLTRANSFERASE, POLYPEPTIDE 2

The B4GALT2 protein is one of seven beta-1,4-galactosyltransferases (beta4GalT). These are type II membrane-bound glycoproteins that appear to be specific exclusively for the donor substrate UDP-galactose. All transfer galactose via a beta1,4 bond to similar acceptor sugars: GlcNAc, Glc, and Xyl.
B4GalT2 is used to

  • Metabolism and transport to the Golgi apparatus, followed by modification.
  • Galactosyltransferase activity
  • Synthesis of complex N-linked oligosaccharides in many glycoproteins, as well as the carbohydrate components of glycolipids
  • N-acetyl-lactosamine synthase activity
    Its substrate specificity is influenced by alpha-lactalbumin, but it is not expressed in lactating breast tissue.

Three transcript variants were identified for this gene, which encode two different isoforms.
B4GALT2 is associated with

  • Ehlers-Danlos syndrome
    • We observed Ehlers-Danlos syndrome at a higher-than-average rate among patients with ADHD

OMIM: B4GALT2, UDP-GAL:BETA-GlcNAc BETA-1,4-GALACTOSYLTRANSFERASE, POLYPEPTIDE 2

A study found a change in the expression of B4GALT2 in ADHD.7
This gene was identified as a candidate for ADHD in a large-scale GWAS.8

2.92. TRIO, Trio Rho Guanine Nucleotide Exchange Factor

Other names: ARHGEF23; Triple Functional Domain (PTPRF-Interacting); Triple Functional Domain Protein; PTPRF-Interacting Protein; EC 2.7.11.1; MEBAS; RD44; MRD63; Tgat; TRIPLE FUNCTIONAL DOMAIN

Some isoforms of kalirin and trio are colocalized with immature secretory granules in neuroendocrine cells of mice and rats and modulate their secretion of charges.
Overexpression of their N-terminal GEF domains enhanced secretion from the immature granules, causing the cells to lose their secretory content in the absence of the secretagogue (the agent that triggered their secretion). This response required GEF activity and was mimicked by the Kalirin/Trio substrates Rac1 and RhoG. Selective pharmacological inhibition of endogenous GEF activity reduced secretagog-independent release of hormone precursors and led to an accumulation of the product peptide in mature secretory granules. The modulation of cargo secretion from immature granules by kalirin/TRIO provides secretory cells with additional control over the amounts of peptides released and broadens the range of physiological responses that can be triggered.
TRIO (amino acids 1227–1407) catalyzes nucleotide exchange for Rac1. This all-alpha-helical protein has a structure that differs significantly from that of other exchange factors. Using site-directed mutagenesis, the authors identified functionally important residues in the DH domain. These residues are all highly conserved and are located in close proximity on two alpha-helices. Furthermore, Liu et al. (1998) discovered a unique ability of the pleckstrin homology (PH) domain to enhance nucleotide exchange in proteins containing the DH domain.9
TRIO is affiliated with

  • intellectual disability
    • TRIO-associated intellectual disability is characterized by:10
      • delayed development of motor and language skills
      • mild to borderline intellectual disability
      • neurological behavioral problems, including:
        • autistic traits or autism spectrum disorder
          - ADHD
        • Aggression)
    • The following symptoms often continue to occur:
      • Feeding difficulties in newborns or infants
        • e.g., poor sucking, difficulty with bottle-feeding, and failure to thrive
      • Microcephaly
      • Hand and dental anomalies
      • have striking facial features

OMIM: TRIO, TRIPLE FUNCTIONAL DOMAIN

A study conducted at TRIO found a change in gene expression associated with ADHD.7

2.94. SYNE1, SPECTRIN REPEAT-CONTAINING NUCLEAR ENVELOPE PROTEIN 1

Other names: Nesprin-1; Enaptin; MYNE1; Myocyte Nuclear Envelope Protein 1; KIAA0796; DJ45H2; C6orf98; SCAR8; ARCA1; Nesp1; CPG2; 8B; Spectrin Repeat-Containing Nuclear Envelope Protein 1; Synaptic Nuclear Envelope Protein 1; KASH Domain-Containing Protein 1; SYNE-1B; KASH1; Nuclear Envelope Spectrin Repeat Protein 1; Nuclear Envelope Spectrin Repeat-1; Chromosome 6 Open Reading Frame 98; Synaptic Nuclei Expressed Gene 1; CPG2 Full Length; EC 4.2.1.49; EC 4.3.1.3; Nesprin 1; KIAA1262; KIAA1756; Myne-1; Syne-1; EDMD4; AMC3; AMCM

SYNE1 is one of the largest genes in the human genome and is therefore particularly susceptible to mutations or genetic defects. Its longest isoform comprises 146 exons that encode the synaptic nuclear envelope protein 1, consisting of 8,797 amino acids. Synaptic nuclear envelope protein 1 (Nesprin 1, nuclear envelope spectrin 1) belongs to the spectrin family of structural proteins, whose common function is to link the plasma membrane to the actin cytoskeleton. SYNE1 encodes a protein that is important for the maintenance of the cerebellum—the part of the brain that coordinates complex body movements. Truncating recessive mutations in SYNE1 result in a slowly progressive, relatively pure cerebellar ataxia with only a few extracerebellar symptoms (spinocerebellar ataxia, autosomal recessive 8; SCAR8/autosomal recessive cerebellar ataxia type 1, ARCA1)11

SYNE1 is a spectrin-repeat-containing protein that is expressed in skeletal and smooth muscle as well as in peripheral blood lymphocytes and is localized to the nuclear membrane. SYNE1 forms a network connecting organelles to the actin cytoskeleton to maintain subcellular spatial organization. As a component of the LINC complex (LInker of Nucleoskeleton and Cytoskeleton), SYNE1 is involved in the connection between the nuclear lamina and the cytoskeleton. The nucleocytoplasmic interactions established by the LINC complex play an important role in the transmission of mechanical forces to the nuclear envelope and in the movement and positioning of the nucleus. SYNE1 may be involved in nuclear-centrosome attachment and nuclear migration in neural progenitor cells, implying an association of the LINC complex with SUN1/2 and, likely, an association with cytoplasmic dynein-dynactin motor complexes. SYNE1 and SYNE2 may function redundantly. SYNE1 is required for centrosome migration to the apical cell surface during early ciliogenesis. SYNE1 may be involved in nuclear reorganization during sperm head formation in spermatogenesis.12
SYNE1 is associated with

  • Spinocerebellar ataxia, autosomal recessive 8
    • also known as autosomal recessive cerebellar ataxia type 1 or recessive ataxia of Beauce
  • Arthrogryposis Multiplex Congenita Type 3, Myogenic Type

Symptoms of SYNE1 ataxia:

  • Gait and limb ataxia
  • cerebellar dysarthria
  • Changes in the antisaccade paradigm
    • These could be related to working memory problems13

Related signal paths:

  • Cell cycle
  • Mitosis
  • Meiosis
  • RNA binding
  • Nucleotide bond

Paralog: DMD

OMIM: SYNE1, SPECTRIN REPEAT-CONTAINING NUCLEAR ENVELOPE PROTEIN 1

A study found altered expression of SYNE1 in ADHD.7 One study identified this gene as one of the 51 most likely candidate genes for ADHD.14

2.96. BMPR1B; Bone morphogenetic protein receptor type 1B

Other names: CDw293; ALK6; Bone Morphogenetic Protein Receptor, Type IB; Bone Morphogenetic Protein Receptor Type-1B; BMP Type-1B Receptor; EC 2.7.11.30; BMPR-1B; Serine/Threonine Receptor Kinase; Activin Receptor-Like Kinase 6; CDw293 Antigen; EC 2.7.11; ALK-6; BDA1D; AMD3; AMDD; BDA2; CDw293, Cluster of differentiation w293

BMPR1B is a member of the family of transmembrane serine/threonine kinases that belong to the bone morphogenetic protein (BMP) receptor family. The ligands for this receptor are BMPs of the TGF-beta superfamily. BMPs are involved in endochondral bone formation and embryogenesis. These proteins transmit their signals by forming heteromeric complexes consisting of two different types of serine (threonine) kinase receptors: Type I receptors, with a molecular weight of approximately 50–55 kD, and Type II receptors, with a molecular weight of approximately 70–80 kD. Type II receptors bind ligands in the absence of type I receptors but require their respective type I receptors for signal transduction, whereas type I receptors require their respective type II receptors for ligand binding.
The BMPR1B receptor plays a role in the formation of the middle and proximal phalanges.15
BMPR1B is found in prepartilaginal condensations (in the chick embryo). BMPR1B is the most important signaling molecule in these condensations. BMPR1B transmits GDF5 more effectively than BMPR1A. While BMPR1A-KO mice die at an early embryonic stage, BMPR1B-KO mice are viable.16
BMP signaling is involved in the formation of the pre-bellary moss fiber nuclei, from which the cerebellar moss fibers originate.17
BMPR1B is associated with

  • primary pulmonary hypertension
  • Brachydactyly181920
  • Breast cancer21
  • Pan-acromesomeric dysplasia and Grebe dysplasia2223

A study identified this gene as one of the 51 most likely candidate genes for ADHD.14

2.285. HAS3, Hyaluronan Synthase 3

Other names: Hyaluronic Acid Synthase 3; Hyaluronate Synthase 3; HA Synthase 3; EC 2.4.1.212

The enzyme HAS3 is involved in the synthesis of the unbranched glycosaminoglycan hyaluronan, or hyaluronic acid, which is a major component of the extracellular matrix. HAS3 is one of three isoenzymes responsible for cellular hyaluronan synthesis. HAS3 catalyzes the addition of GlcNAc or GlcUA monosaccharides to the nascent hyaluronan polymer. Hyaluronan is a major component of most extracellular matrices, plays a structural role in tissue architecture, and regulates cell adhesion, migration, and differentiation.24
Related signal paths:

  • Glycosaminoglycan metabolism
  • Glycosaminoglycan metabolism
  • Hyaluronan synthase activity

Paralog: HAS2

Hyaluronan, like dopamine and serotonin, is elevated in the blood during neonatal hyperoxia; dopamine is also elevated in the urine. Hyperoxia increased mRNA expression in the dorsal brainstem of the HAS3 serotonin 1A receptor, dopamine D1 receptor, and dopamine D2 receptor.2526
Extracellular hyaluronate pressure, generated by cellular linkages, drives tissue morphogenesis.27
Extracellular and intracellular hyaluronan binds to hyaluronan-binding proteins such as CD44, RHAMM, CDC37, and USP17, thereby influencing cell behavior. Intracellular hyaluronan appears to play important regulatory roles during the cell cycle, cell motility, RNA translation and splicing, and autophagy.28
Oxidative stress caused by tobacco smoke leads to inflammation and the depolymerization of hyaluronan.29

A study identified HAS3 as one of the 51 most likely genetic candidates for ADHD.14

2.103. ITIH3, Inter-Alpha-Trypsin Inhibitor Heavy Chain 3

Other names: Inter-alpha-trypsin inhibitor heavy chain H3, H3P, Inter-alpha (globulin) inhibitor, H3 polypeptide, Pre-alpha (globulin) inhibitor, H3 polypeptide

The ITIH3 protein is a subunit of the heavy chain of the pre-alpha-trypsin inhibitor complex. By binding to hyaluronic acid, this complex can stabilize the extracellular matrix. It appears to respond to elevated cytosolic Ca2+ in platelets and to form cell-matrix glycoconjugates_. It is associated with serine-type endopeptidase inhibitor activity and endopeptidase inhibitor activity.30

ITIH3 is associated with

  • Schizophrenia
    • rs2535629 showed a better response to clozapine31
  • Depression
    • ITIH3 rs2535629 significantly influences the expression of ITIH4 and GLT8D1. The expression of GLT8D1 was significantly elevated in patients with depression.32
  • Autism Spectrum Disorder33
  • Cancer29
  • Myocardial infarction34

Related signal paths:

  • oxidative stress29

Reduced levels of the ITIH3 protein were found in the plasma of cigarette smokers.29

A study identified this gene as one of the 51 most likely candidate genes for ADHD.14 Another study found no evidence of an association between the ITIH3 polymorphism rs52535629 and ADHD.35

2.113. ATP2C2, ATPase Secretory Pathway Ca2+ Transporter 2

Other names: SPCA2, KIAA0703, Secretory Pathway Ca(2+)-Transporting ATPase Type 2, ATPase, Ca++ Transporting, Type 2C, Member 2, Calcium-Transporting ATPase Type 2C Member 2

The ATP2C2 protein enables the activity of the P-type calcium transporter and the P-type manganese transporter and is thus involved in the transmembrane transport of calcium ions, cellular calcium ion homeostasis, and manganeseion transport. ATP2C2 is an ATP-driven pump that supplies the Golgi apparatus with Ca(2+) and Mn(2+) ions, both of which are essential cofactors for the processing and transport of newly synthesized proteins in the secretory pathway. During a single catalytic cycle, ATP2C2 takes up Ca²⁺ or Mn²⁺ ions on the cytoplasmic side of the membrane and releases them to the luminal side. The transfer of ions across the membrane is coupled to ATP hydrolysis and is accompanied by transient phosphorylation, which shifts the pump’s conformation from an inward-facing state to an outward-facing state ATP2C2 induces the Ca(2+) influx independently of its ATP-driven pumping function. ATP2C2 interacts with the Ca(2+) channel ORAI1 on the basolateral membrane of mammary epithelial cells and mediates Ca(2+) influx independently of the Ca(2+) content of the endoplasmic reticulum or Golgi reservoirs. ATP2C2 can facilitate the transepithelial transport of large amounts of Ca(2+) for milk secretion by activating Ca(2+) influx channels on the plasma membrane and promoting active Ca(2+) transport at the Golgi apparatus.36

ATP2C2 is associated with

  • specific language disorders
    • A rare missense variant (chr16:84405221, GRCh38.p12) in the ATP2C2 gene is more common in individuals with speech disorders. This rare variant appears to affect the ATPase activity of SPCA2.37 Another study identifies c.2465C>T as the variant responsible.38
  • Dyslexia39
    • ATP2C2 rs11860694 modulates phonological short-term memory in speech disorders40

One study identified ATP2C2 as one of the 51 most likely candidate genes for ADHD.14 Another study identified it among 96 candidate genes.41 A review considers ATP2C2 to be part of a neurological network involved in the directed growth of neurites, which appears to play a significant role in ADHD.42

2.118. MPP6, MAGUK p55 subfamily member 6

Other names: VAM-1; P55T; MPP6; Membrane Protein, Palmitoylated 6 (MAGUK P55 Subfamily Member 6); Protein Associated With LIN7 2, MAGUK Family Member; Membrane Palmitoylated Protein 6; MAGUK P55 Subfamily Member 6; Protein PALS2; VAM1; Membrane Protein, Palmitoylated 6; Protein Associated With Lin7; VELI-Associated MAGUK 1; Veli-Associated MAGUK 1; MAGUK Protein P55T

The MPP6 protein is a member of the family of peripheral membrane-associated guanylate kinases (MAGUK, membrane-associated guanylate kinase homologs). These proteins are involved in tumor suppression and receptor cluster formation by forming multiprotein complexes that contain various groups of transmembrane, cytoskeletal, and cytoplasmic signaling proteins.43
MPP6 appears to be involved in myelination.44
A GWAS identified a link between MPP6 and sleep disorders.45

A study identified this gene as one of the 51 most likely candidate genes for ADHD.14

2.123. PALB2, a partner and localizer of BRCA2

Other names: PALB2, FANCN

The PALB2 gene encodes a protein responsible for maintaining the genome (repairing double-strand breaks). PALB2 binds to and colocalizes with the Breast Cancer 2 Early Onset Protein (BRCA2) in nuclear foci and likely facilitates the stable intranuclear localization and accumulation of BRCA2.46

The PALB2 gene is associated with

  • an increased risk of breast cancer
  • hereditary pancreatic cancer
  • Ovarian cancer
  • Fanconi anemia
  • reduced fertility (observed in mice)

A study identified this gene as one of the 51 most likely candidate genes for ADHD.14

2.124. ZNF385D, Zinc Finger Protein 385D

Other names: Zinc Finger Protein 659, ZNF659, FLJ22419

The ZNF385D protein mediates sequence-specific double-stranded DNA binding. ZNF385D is thought to be active in the cell nucleus47 and is found primarily in the cerebellum and the retina.
ZNF385D is associated with

  • Reading difficulty48
    • ZNF385D was found to be a predictor of the total volume of fiber tracts in both hemispheres as well as of global brain volume
  • Dyscalculia
  • ADHD
  • Schizophrenia; negative symptoms49
    • rs2060531
    • rs9869330

A study identified ZNF385D as one of the 51 most likely candidate genes for ADHD.14 ZNF385D rs11719664 was identified as a candidate gene for ADHD in another study from 2008. .50

2.126. CHMP7, Charged Multivesicular Body Protein 7

Other names: Chromatin-Modifying Protein 7, CHMP Family, Member 7, MGC29816

The CHMP7 protein is involved in the late transport of endosomes to vacuoles, in the abscission of the centriole, and in mitotic nuclear division. CHMP7 is found in the cytosol, the nuclear envelope, and the nucleoplasm. CHMP7 is part of the ESCRT III complex. CHMP7 colocalizes with chromatin. CHMP7 is required for the recruitment of the ESCRT III complex to the nuclear envelope during late anaphase. Together with SPAST, the ESCRT III complex promotes nuclear envelope sealing and the disassembly of the mitotic spindle during late anaphase. CHMP7 is recruited to the newly forming nuclear envelope by LEMD2 during anaphase. CHMP7 plays a role in the endosomal sorting pathway.51
CHMP7 is associated with

  • Type 48 cerebellar ataxia
  • ADHD
  • spinal and bulbar muscular atrophy52

A study identified CHMP7 as one of the 51 most likely gene candidates for ADHD.14 Another study identified CHMP7 rs2294123, G→T, as one of 65 candidate genetic variants for ADHD.53
CHMP7-KO zebrafish exhibited significant hyperactivity over a 24-hour period 6 days after fertilization compared to chmp7+/+, although this effect did not persist into adolescence and adulthood and was significantly reduced by methylphenidate. CHMP7+/- fish exhibited a significantly reduced total brain volume.54

2.128. MUCL3, DPCR1, Human Diffuse Panbronchiolitis Critical Region 1, Real-Time PCR Primer Set

Other names: Mucin-Like 3, C6orf37, PBLT, DPCR1, Diffuse Panbronchiolitis Critical Region Protein 1, Diffuse Panbronchiolitis Critical Region 1, Mucin-Like Protein 3, BCX105N19.6

The MUCL3 protein is thought to be localized in the cytoplasm and the plasma membrane. It appears to be an integral component of the membrane. MUCL3 may modulate NF-kappaB signaling and play a role in cell growth.55
MUCL3 is associated with

  • Panbronchiolitis, diffuse
  • spinocerebellar ataxia, autosomal recessive 8

A study identified this gene as one of the 51 most likely candidate genes for ADHD.14

2.129. PIWIL4, Piwi-Like RNA-Mediated Gene Silencing 4

Other names: HIWI2, Piwi-like protein 4, FLJ36156, Miwi2

The PIWIL4 protein belongs to the Argonaute protein family, which plays a role in the development and maintenance of germline stem cells. PIWIL4 plays a central role during spermatogenesis by suppressing transposable elements and preventing their mobilization, which is essential for germline integrity. PIWIL4 acts through the piRNA metabolic process, which mediates the suppression of transposable elements during meiosis by forming complexes of piRNAs and Piwi proteins and controls the methylation and subsequent suppression of transposons. PIWIL4 directly binds piRNAs, a class of RNAs consisting of 24 to 30 nucleotides that are generated by a Dicer-independent mechanism and primarily originate from transposons and other repetitive sequence elements. PIWIL4 is associated with antisense secondary piRNAs. PIWIL2/MILI is required for this association. The piRNA process acts upstream of known mediators of DNA methylation. PIWIL4 plays a key role in the piRNA amplification loop—also known as the ping-pong amplification cycle—by acting as a “slicer-incompetent” component that loads cleaved piRNAs from the “slicer-competent” component PIWIL2 and directs them to genomic transposon loci in the cell nucleus. PIWIL4 may be involved in the chromatin-modifying pathway by inducing “Lys-9” methylation of histone H3 at certain loci. PIWIL4 also plays a role in regulating somatic cell activities, as well as in pancreatic beta-cell function and insulin secretion. PIWIL4 is involved in maintaining the cell morphology and functional integrity of the retinal epithelium through the Akt/GSK3alpha/beta signaling pathway. When overexpressed, PIWIL4 acts as an oncogene by inhibiting apoptosis and promoting cell proliferation in tumors.56
PIWIL4 is associated with

  • Spermatogenic Failure (Male Infertility)
  • Cervical cancer.

A study identified PIWIL4 as one of the 51 most likely genetic candidates for ADHD.14

2.130. AK8, Adenylate Kinase 8

Other names: C9orf98, ATP-AMP transphosphorylase 8, FLJ32704, AK 8

The AK8 protein mediates AMP-binding activity and kinase activity for nucleobase-containing compounds. AK8 is involved in nucleoside diphosphate phosphorylation and the nucleoside triphosphate biosynthesis process.
AK8 is found in the 9+2 motile cilium. AK8 is a nucleoside monophosphate (NMP) kinase that catalyzes the reversible transfer of the terminal phosphate group between nucleoside triphosphates and monophosphates. AK8 exhibits the highest activity toward AMP and weaker activity toward dAMP, CMP, and dCMP. AK8 also displays broad nucleoside diphosphate kinase activity.57

AK8 is associated with reticular dysgenesis.

A study identified AK8 as one of the 51 most likely genetic candidates for ADHD.14

2.131. CFAP221, Cilia and Flagella-Associated Protein 221

Other names: PCDP1, FAP221, Cilia- and Flagella-Associated Protein 221

The protein CFAP221 is thought to activate calmodulin-binding activity and appears to be involved in ciliogenesis. It is believed to function upstream of or within the cerebrospinal fluid circulation, the assembly of the motile cilium, and mucociliary clearance.CFAP221 is likely found in the axon, in the extracellular region, and in the flagellum of sperm.58 CFAP221 could play an important role in the calcium-mediated regulation of dynein activity.59
CFAP221 is associated with

  • ciliary dyskinesia
  • cerebral degeneration

A study identified this gene as one of the 51 most likely candidate genes for ADHD.14

2.329. FEZF2, FEZ Family Zinc Finger 2

Other names: FEZL, Zinc Finger Protein 312, FKSG36, Zfp312, ZNF312, TOF, Forebrain Embryonic Zinc Finger-Like Protein, Fez Family Zinc Finger Protein 2, FLJ10142, Too Few, Forebrain Embryonic Zinc Finger-Like Protein, Testis Tissue Sperm-Binding Protein Li 80P, Zinc Finger Protein Fez-Like, FEZ

FEZF2 encodes a protein. It mediates binding to cis-regulatory regions of transcription and is involved in the positive regulation of DNA-templated transcription. FEZF2 is involved in the negative regulation of transcription by RNA polymerase II, in the development of the nervous system, and in the regulation of the differentiation of corticospinal motor neurons and other subcortical projection neurons. FEZF2 may be involved in the layer- and neuron-subtype-specific patterning of subcortical projections and axonal fasciculation. FEZF2 controls the development of dendritic branching and spines in the large pyramidal neurons of layer V. FEZF2 may be involved in innate immunity. FEZF2 is thought to be active in the cell nucleus.60

FEZF2 is associated with:

  • Uterine inversion
  • Congenital myopathy 7A, myosin storage disorder, autosomal dominant.

FEZF1 is involved in the development of the diencephalon and is a candidate gene for AS.61

Paralog: FEZF1

Rare variants of the FEZF2 gene may cause ADHD.62
FEZF1 was identified as a candidate gene specifically for ADHD in children. The most common variant was rs55686778.61

Genes whose role in ADHD we have not yet investigated

1.132. CEP112, Centrosomal Protein 112

Other names: CCDC46, Coiled-Coil Domain-Containing Protein 46, 112 kDa Centrosomal Protein, 112 kDa Centrosomal Protein

CEP112 is a protein containing a coiled-coil domain and belongs to the cell cycle regulatory effector protein family 42. In neurons, it is localized in the cytoplasm of dendrites and is also enriched in the nucleus, where it interacts with the RNA polymerase IIItranscription repressor Maf1 to regulate the surface expression of the gamma-aminobutyric acid A receptor. Furthermore, the protein has been identified as a component of the human centrosome.63CEP112 is involved in the localization of receptors at the synapse.((
CEP112 is associated with

  • Spermatogenic Failure 44 (male infertility)
  • Spermatogenic Failure 16. (Male Infertility)

A study identified this gene as one of the 51 most likely candidate genes for ADHD.14

1.133. KIF6, Kinesin Family Member 6

Other names: DJ1043E3.1, DJ137F1.4, DJ188D3.1

The KIF6 protein is a member of a family of molecular motors involved in the intracellular transport of protein complexes, membrane organelles, and ribonucleic acid messengers along microtubules. Kinesins function as homodimers with two N-terminal head domains that move along the microtubules and two C-terminal tail domains that interact with the transported cargo either directly or indirectly via adapter molecules. This gene is ubiquitously expressed in coronary arteries and other vascular tissues.
KIF6 is associated with coronary heart disease.

A study identified this gene as one of the 51 most likely candidate genes for ADHD.14

1.135. NCKAP5, NCK-Associated Protein 5

Other names: NAP5, ERIH1, ERIH2

The NCKAP5 protein is thought to be involved in the formation of microtubule bundles and the depolymerization of microtubules, and to be active at the microtubule plus end.64
NCKAP5 is associated with

  • ADHD
  • drug-induced lupus erythematosus

A study identified this gene as one of the 51 most likely candidate genes for ADHD.14

1.136. SPATA33, Spermatogenesis-Associated 33

Other names: C16orf55, Spermatogenesis-Associated Protein 33, FLJ31606, Chromosome 16 Open Reading Frame 55

The SPATA33 protein is thought to play a role upstream of or within the processes of cellular protein localization, fertilization, and sperm flagellar motility. SPATA33 appears to be localized in the mitochondrial envelope of sperm and to be active in the cytoplasm and nucleus.6566
SPATA33 is associated with Fanconi anemia, complementation group A.

A study identified this gene as one of the 51 most likely candidate genes for ADHD.14

1.137. CDK10, Cyclin-Dependent Kinase 10

Other names: PISSLRE, Cyclin-Dependent Kinase (CDC2-Like) 10, Cell Division Protein Kinase 10, Cyclin-Dependent Kinase 10, EC 2.7.11.22

The CDK10 protein belongs to the CDK subfamily of the Ser/Thr protein kinase family. The members of the CDK subfamily are very similar to the gene products of S. cerevisiae cdc28 and S. pombe cdc2 and are essential for cell cycle progression. This kinase has been shown to play a role in cell proliferation, and its function is limited to the G2-M phase of the cell cycle. CDK10 is a cyclin-dependent kinase that phosphorylates the transcription factor ETS2 (in vitro) and promotes its proteasomal degradation (in cells). CDK10 is involved in regulating the organization of the actin cytoskeleton by phosphorylating regulators of actin dynamics such as PKN2. CDK10 acts as a negative regulator of ciliogenesis by phosphorylating PKN2 and promoting RhoA signaling.67
CDK10 is associated with

  • Al-Kaissi syndrome
  • syndactyly of the toes
  • Telecanthus
  • anogenital and renal malformations

A study identified this gene as one of the 51 most likely candidate genes for ADHD.14

1.138. PPP1R11, PROTEIN PHOSPHATASE 1, REGULATORY SUBUNIT 11

Other names: HCGV, CFAP255, HCG-V, TCTE5, Protein Phosphatase 1 Regulatory Subunit 11, Hemochromatosis Candidate Gene V Protein, E3 Ubiquitin-Protein Ligase PPP1R11, TCTEX5

The PPP1R11 protein is a specific inhibitor of protein phosphatase-1 (PP1) with varying sensitivity to the metal-independent and metal-dependent forms of PP1. PPP1R11 is an atypical E3 ubiquitin ligase that ubiquitinates TLR2 at ‘Lys-754,’ leading to its degradation by the proteasome. PPP1R11 plays a role in regulating the release of inflammatory cytokines and the elimination of Gram-positive bacteria, in part by ubiquitinating and degrading TLR2.68

OMIM: PPP1R11, PROTEIN PHOSPHATASE 1, REGULATORY SUBUNIT 11

A study identified this gene as one of the 51 most likely candidate genes for ADHD.14

1.140. NME5, NME/NM23 FAMILY, MEMBER 5

Other names: Nm23-H5, RSPH23, Non-Metastatic Cells 5, Protein Expressed In (Nucleoside Diphosphate Kinase), Nucleoside Diphosphate Kinase Homolog 5, Inhibitor of P53-Induced Apoptosis-Beta, Testis-Specific Nm23 Homolog, NDP Kinase Homolog 5, IPIA-Beta, NDK-H 5, Non-Metastatic Cells 5 Protein Expressed In, Radial Spoke 23 Homolog (Chlamydomonas), Radial Spoke 23 Homolog, NM23-H5, NM23H5

The NME5 protein is thought to mediate nucleoside diphosphate kinase activity. NME5 is believed to be involved in the negative regulation of the intrinsic apoptotic signaling pathway induced by oxidative stress and in spermatid development. NME5 is likely to function upstream of or within ciliary organization, epithelial ciliary movement—which is involved in the movement of extracellular fluid—and the development of the ventricular system. NME5 is thought to be located in the cilia. NME5 appears to lack NDK kinase activity. NME5 protects against Bax-mediated cell death and alters the cellular levels of various antioxidant enzymes, including Gpx5. NME5 may play a role in spermatogenesis by enhancing the ability of late-stage spermatids to eliminate reactive oxygen species.69
NME5 is associated with

  • Nemalin myopathy type 5
  • primary ciliary dyskinesia

OMIM: NME5, NME/NM23 FAMILY, MEMBER 5

NME5 is a candidate for ADHD.70

1.141. ABHD5, ABHYDROLASE DOMAIN-CONTAINING 5

Other names: CGI-58, CGI58, 1-Acylglycerol-3-phosphate O-acyltransferase, Lysophosphatidic acid acyltransferase, NCIE2, 1-Acylglycerol-3-Phosphate O-Acyltransferase ABHD5, Abhydrolase Domain-Containing Protein 5, Lipid Droplet-Binding Protein CGI-58, EC 2.3.1.51, Truncated Abhydrolase Domain-Containing Protein 5, Abhydrolase Domain-Containing 5, IECN2, External IDs for the ABHD5 Gene

The ABHD5 protein is characterized, among other things, by an alpha/beta-hydrolase fold. ABHD5 contains three sequence motifs that correspond to a catalytic triad found in the esterase/lipase/thioesterase subfamily. ABHD5 plays a role in phosphatidic acid biosynthesis; it may regulate cellular triacylglycerol storage by activating the phospholipase PNPLA2 and is involved in the differentiation of keratinocytes. ABHD5 regulates lipid droplet fusion.
ABHD5 is a coenzyme A-dependent lysophosphatidic acid acyltransferase that catalyzes the transfer of an acyl group to lysophosphatidic acid. ABHD5 preferentially functions with:71

  • as a lipid acceptor
    • 1-oleyl-lysophosphatidic acid, followed by
    • 1-Palmitoyl-lysophosphatidic acid
    • 1-Stearoyl-lysophosphatidic acid
    • 1-Arachidonoyl-lysophosphatidic acid
  • as acyl group donors
    • Arachidonoyl-CoA, followed by
    • Oleoyl-CoA

The enzyme ABHD5 plays a regulatory role in fat metabolism. Among other things, it stimulates lipolysis.
ABHD5 is expressed in, among other tissues, adipose tissue, the liver, neurons, and the epidermis.

In adipose tissue, ABHD5 is bound to perilipin-1. β-adrenergic stimulation activates protein kinase A, which phosphorylates perilipin-1. This causes ABHD5 to dissociate from perilipin-1. The unbound ABHD5 then activates adipocyte triglyceride lipase (ATGL). This enzyme catalyzes the first step of lipolysis, the breakdown of triacylglycerol into diacylglycerol. G0S2 acts as an antagonist. Outside of adipocytes: ABHD5 interacts with, among others, adipophilin (perilipin-2) and perilipin-5. ABHD5 converts lysophosphatidic acid to phosphatidic acid via acyl-CoA-dependent lysophosphatidic acid acyltransferase (LPAAT) activity.72
ABHD5 is associated with

  • Chanarin-Dorfman syndrome, a triglyceride storage disorder characterized by impaired oxidation of long-chain fatty acids
  • lipid storage disease.

OMIM: ABHD5, ABHYDROLASE DOMAIN-CONTAINING 5

ABHD5 is a candidate gene for ADHD.70

1.142. GMPR2, GUANOSINE MONOPHOSPHATE REDUCTASE 2

Other names: Guanosine 5’-monophosphate oxidoreductase 2, GMP reductase 2, EC 1.7.1.7, GMPR 2, Guanosine monophosphate reductase isolog 3

The enzyme GMPR2 catalyzes the irreversible, NADPH-dependent reductive deamination of guanosine monophosphate (GMP) to inosine monophosphate (IMP). GMPR2 is involved in the recycling of free intracellular bases and purine nucleosides. GMPR2 is involved in the conversion of nucleobase, nucleoside, and nucleotide derivatives of G to A nucleotides and in maintaining the intracellular balance of A and G nucleotides. GMPR2 plays a role in the modulation of cellular differentiation.73
GMPR2 is associated with urethral cancer.

OMIM: GMPR2, GUANOSINE MONOPHOSPHATE REDUCTASE 2

GMPR2 is a candidate gene for ADHD.70

1.144. BLOC1S2, Biogenesis of Lysosome-Related Organelles Complex 1, Subunit 2

Other names: BLOS2, BLOC-1 subunit 2, BORCS2, Biogenesis of Lysosome-Related Organelles Complex 1 subunit 2, Centrosome Protein Oncogene, MGC10120, FLJ30135, CEAP, Biogenesis of Lysosome-Related Organelles Complex-1 Subunit 2, 11 kDa Centrosome-Associated Protein, Centrosome-Associated Protein, Centrosomal 10 kDa Protein, CEAP11

OMIM: BLOC1S2, Biogenesis of Lysosome-Related Organelles Complex 1, Subunit 2

The BLOC1S2 protein has several functions:74

  • was found in association with the centrosome
  • colocalizes with gamma-tubulin
  • is a protein in the BLOC-1 complex
    • plays a role in the formation of lysosomal organelles (e.g., dense granules in platelets and melanosomes)
  • BLOC-1 complex
    • (together with the AP-3 complex) channels membrane protein cargo into vesicles formed in cell bodies to transport them to neurites and nerve endings.
    • is also thought to be involved (in conjunction with SNARE proteins) in neurite outgrowth
    • is part of the BORC complex; may be involved in the movement and localization of lysosomes at the cell periphery
    • may play a role in cell proliferation
  • BLOC1S2 is associated with
    • Hermansky-Pudlak syndrome
    • primary autosomal recessive microcephaly (small skull)

Microcephaly is often associated with ADHD.
BLOC1S2 is a candidate drug for ADHD.70

1.145. KIAA0319L, KIAA0319-LIKE

Other names: KIAA0319-like, AAVR, KIAA1837, Dyslexia-Associated Protein KIAA0319-Like Protein, Adeno-Associated Virus Receptor, Polycystic Kidney Disease 1-Related, AAV Receptor-Like, KIAA0319-Like, AAV Receptor, AAVRL

OMIM: KIAA0319L, KIAA0319-LIKE

The KIAA0319L protein may be involved in axon guidance through its interaction with RTN4R.
KIAA0319L acts as a receptor for adeno-associated viruses and is involved in infection with adeno-associated viruses via the endocytosis system.75
KIAA0319L is associated with

  • Dyslexia
  • limited scleroderma

KIAA0319L is a candidate gene for ADHD.70

1.146. FMNL3, Formin-Like 3

Other names: WBP3, Formin Homology 2 Domain-Containing Protein 3, Formin-Like Protein 3, DKFZp762B245, MGC45819, FHOD3, WBP-3, FRL2, WW Domain Binding Protein 3, WW Domain-Binding Protein 3, Formin-Like 3, KIAA2014

The FMNL3 protein contains a formin homology 2 domain and exhibits high sequence identity with the mouse Wbp3 protein. FMNL3 is involved in the regulation of cell morphology and cytoskeletal organization. FMNL3 is required for the control of cell shape and migration, as well as for development-related angiogenesis. In quiescent endothelial cells, FMNL3 triggers a reorganization of the actin cytoskeleton without altering the alignment of the microtubules.76
FMNL3 is associated with

  • malignant breast melanoma
  • cerebral amyloid angiopathy, Itm2b-related, 2.

FMNL3 is a candidate gene for ADHD.70

1.147. CCDC138, Coiled-Coil Domain Containing 138

Other names: FLJ32745

CCDC138 is expressed in small amounts in nearly all human tissues, including peripheral blood lymphocytes, fetal thymus, thymus, testes, ovaries, wild-type brain, colon, mammary gland, and bone marrow. Elevated concentrations are found in some cancer tissues. CCDC138 is a soluble protein that accumulates in the cell nucleus. CCDC138 is involved in the initiation of labor contractions in the myometrium.
The CCDC138 protein is associated with77

  • Chromosome 3q13.31 deletion syndrome
  • Fundus dystrophy

CCDC138 is a candidate gene for ADHD.70

1.148. TMBIM6, Transmembrane BAX Inhibitor Motif Containing 6

Other names: BI-1, BAXI1, TEGT, Transmembrane BAX Inhibitor Motif-Containing Protein 6, Testis-Enhanced Gene Transcript Protein, Testis Enhanced Gene Transcript, Bax Inhibitor 1, BAX Inhibitor 1, BI1

The TMBIM6 protein mediates endoribonuclease inhibitor activity and ubiquitin-protein ligase binding activity. TMBIM6 is involved in:78

  • inhibits RNA metabolism
  • inhibits the intrinsic apoptotic signaling pathway
  • inhibits the response to L-glutamate
  • modulates the signaling of the unfolded protein response
  • inhibits autophagy and autophagosome formation, particularly in the absence of nutrients
    • reduces cell survival during starvation
  • acts upstream of or within the negative regulation of calcium ion transport into the cytosol
  • Located in the endoplasmic reticulum membrane and the mitochondrial membrane
    • modulates calcium homeostasis in the endoplasmic reticulum by acting as a calcium leak channel
  • Biomarkers for squamous cell carcinoma of the cervix and prostate cancer

TMBIM6 is associated with

  • chronic congestive splenomegaly (an enlarged spleen)
  • Inclusion conjunctivitis (a type of conjunctivitis)

TMBIM6 is a candidate gene for ADHD.70

1.149. SV2A, Synaptic Vesicle Glycoprotein 2A

Other names: KIAA0736, SV2

SV2A is one of three related synaptic vesicle proteins. SV2A can interact with synaptotagmin to enhance low-frequency neurotransmission in resting neurons.
SV2A positively regulates vesicle fusion by maintaining the readily releasable pool of secretory vesicles.79
SV2A is a receptor for

  • Clostridium botulinum neurotoxin type A2 (BoNT/A, botA)
  • Clostridium botulinum neurotoxin type A1 (probably)

SV2A is associated with:

  • food-related
  • Carbamazepine allergy

SV2A is a candidate gene for ADHD.70

1.150. TARBP1, TAR (HIV-1) RNA-Binding Protein 1

Other names: TRP-185, TRM3, TRMT3, TAR RNA-Binding Protein of 185 kDa, Probable Methyltransferase TARBP1, TAR RNA-Binding Protein 1, TRP185, TRNA Methyltransferase 3 Homolog (S. cerevisiae), Tar (HIV-1) RNA-Binding Protein 1, tRNA Methyltransferase 3 Homolog 3, TAR (HIV) RNA-Binding Protein 1, TAR RNA Loop-Binding Protein, EC 2.1.1.-
External IDs for the TARBP1 Gene

TARBP1 is a methyltransferase that is thought to be S-adenosyl-L-methionine-dependent and that methylates RNA molecules such as tRNAs. During HIV-1 infection, it binds to the loop region of TAR RNA, a region that is also bound by RNA polymerase II. The binding of TARBP1 and RNA polymerase II to HIV-1 TAR-RNA is mutually exclusive, suggesting that TARBP1, either alone or in conjunction with HIV-1 Tat, can displace RNA polymerase II from HIV-1 TAR-RNA.80
TARBP1 is associated with immunodeficiency disorders.

TARBP1 is a candidate gene for ADHD.70

1.151. TATDN3

Other names: TatD DNase Domain Containing 3, Putative Deoxyribonuclease TATDN3, EC 3.1.21.-, EC 3.1.21

The protein TATDN3 is thought to activate metal ion-binding activity and nuclease activity. TATDN3 is thought to be involved in the hydrolysis of nucleic acid phosphodiester bonds and is likely localized in the nucleus.81

TATDN3 is a candidate gene for ADHD.70

1.153. ST3GAL3

Other names: ST3 Beta-Galactoside Alpha-2,3-Sialyltransferase 3; ST3Gal III; SIAT6; CMP-N-Acetylneuraminate-Beta-1,4-Galactoside Alpha-2,3-Sialyltransferase 3; Sialyltransferase 6 (N-Acetyl-lactosaminide Alpha 2,3-Sialyltransferase); N-Acetyl-lactosaminide Alpha-2,3-Sialyltransferase; Alpha 2,3-ST 3; ST3GalIII; MRT12; ST3N; Sialyltransferase 6 (N-Acetyl-lactosaminide alpha 2,3-sialyltransferase); Mental Retardation, Non-Syndromic, Autosomal Recessive, 12; Gal Beta-1,3(4)GlcNAc Alpha-2,3 Sialyltransferase; Gal Beta-1,3(4)GlcNAc Alpha-2,3 Sialyltransferase 3; Beta-Galactoside Alpha-2,3-Sialyltransferase 3; Alpha 2,3-Sialyltransferase III; Alpha-2,3-Sialyltransferase II; Sialyltransferase 6; EC 2.4.99.6; ST3GALII; EIEE15; DEE15

ST3GAL3 is a type II membrane protein that catalyzes the transfer of sialic acid from CMP-sialic acid to galactose-containing substrates. ST3GAL3 is normally located in the Golgi apparatus but can be cleaved proteolytically into a soluble form. ST3GAL3 belongs to glycosyltransferase family 29. ST3GAL3 catalyzes the formation of NeuAc-alpha-2,3-Gal-beta-1,4-GlcNAc, NeuAc-alpha-2,3-Gal-beta-1,3-GlcNAc, and NeuAc-alpha-2,3-Gal-beta-1,3-GalNAc sequences, which occur in the terminal carbohydrate moieties of glycoproteins and glycolipids. The highest activity is observed toward Gal-beta-1,3-GlcNAc, and the lowest toward Gal-beta-1,3-GalNAc.82
ST3GAL3 is associated with

  • autosomal recessive, non-syndromic intellectual disability
  • childhood epileptic encephalopathy / epileptic encephalopathy
  • Developmental disorders

ST3GAL5 gene variants can cause GM3 synthase deficiency. This rare, autosomal recessive disorder is associated with:83

  • severe intellectual disability
  • Developmental disorder
  • Childhood epilepsy

Three siblings with a homozygous pathogenic ST3GAL5 variant showed:83

  • a normal labor and delivery history
  • subsequent stagnation in development
  • severe intellectual disability
  • Choreoathetosis (chorea + athetosis; hyperkinesis of the arms and legs, as well as the facial muscles)
  • Developmental, visual, and hearing impairments/deafness
  • Ichthyosis (severe dry skin with scaling)
  • self-harming behavior

ST3GAL3 has been identified as a candidate gene for ADHD in numerous studies and GWAS8470 85 86 87 8 , including for ADHD that persists into adulthood61. Correlations were also found with ASD and schizophrenia.

1.154. ELAVL4

Other names: ELAV-like RNA-binding protein 4; PNEM; HUD; ELAV (Embryonic Lethal, Abnormal Vision, Drosophila)-like 4 (Hu Antigen D); ELAV-Like Neuron-Specific RNA-Binding Protein 4; Paraneoplastic Encephalomyelitis Antigen HuD; ELAV-Like Protein 4; Hu Antigen D; ELAV (Embryonic Lethal, Abnormal Vision, Drosophila)-Like 4; Hu Antigen D; HuD

The ELAVL4 protein mediates mRNA 3’-UTR AU-rich binding activity, poly(A) binding activity, and pre-mRNA intronic pyrimidine-rich binding activity. ELAVL4 is involved in 3’-UTR-mediated mRNA stabilization, RNA processing, and the positive regulation of 3’-UTR-mediated mRNA stabilization. ELAVL4 is thought to be located in the axon, cytoplasm, and dendrites. It appears to be part of the polysomal ribosome and to be active in the glutamatergic synapse.88
ELAVL4

  • is involved in the post-transcriptional regulation of mRNA
  • is involved in the regulation of mRNA stability, alternative splicing, and translation
  • binds to AU-rich element (ARE) sequences in the 3’ untranslated region (UTR) of target mRNAs, including GAP43, VEGF, FOS, CDKN1A, and ACHE mRNA
  • contributes to the differentiation of neural progenitor cells, the development of the nervous system, and learning and memory mechanisms
  • promotes the neural differentiation of neural stem/progenitor cells in the adult subventricular zone of the hippocampus by binding to and stabilizing SATB1 mRNA
  • binds to and stabilizes MSI1 mRNA in neural stem cells
  • binds more strongly to ACHE mRNA during neuronal differentiation, thereby stabilizing ACHE mRNA and increasing its expression
  • protects CDKN1A mRNA from degradation by binding to its 3’-UTR
  • can bind to APP and BACE1 mRNAs and the BACE1AS lncRNA and enhance their stabilization
  • plays a role in the growth of neurites and in the formation and maturation of dendritic branches, thereby contributing to the function of neocortical and hippocampal circuits
  • stabilizes GAP43 mRNA and protects it from degradation during postembryonic development in the brain
  • promotes the stabilization of GAP43 mRNA and plays a role in NGF-mediated neurite growth
  • binds to the long 3’UTR of BDNF mRNA, thereby stabilizing it and increasing its translation in dendrites following PKC activation
  • increases BDNF translation following nerve injury and may thereby contribute to nerve regeneration
  • acts as a stabilizing factor by binding to the 3’UTR of the NOVA1 mRNA, thereby increasing its translation and enhancing its functional activity in neuron-specific splicing
  • stimulates mRNA translation in a poly(A)- and cap-dependent manner, possibly through association with the EIF4F cap-binding complex
  • can negatively regulate translation by binding to the 5’UTR of the Ins2 mRNA and thereby suppressing its translation
  • releases Ins2 mRNA in response to glucose stimulation, which lifts the inhibition of translation
  • plays a role in regulating alternative splicing
  • may regulate the alternative splicing of CALCA pre-mRNA into calcitonin and calcitonin gene-related peptide 1 (CGRP) by competing with the splicing regulator TIAR for binding to U-rich intronic sequences of the CALCA pre-mRNA

ELAVL4 is associated with

  • Lambert-Eaton myasthenic syndrome
  • sensory peripheral neuropathy.

Paralog: ELAVL2.

ELAVL4 is a candidate gene for ADHD.70

1.155. NBEAL1

Other names: GeneCards symbol: NBEAL1; Neurobeachin-like 1; ALS2CR16; ALS2CR17; Amyotrophic Lateral Sclerosis 2 Chromosomal Region Candidate Gene 16 Protein; Amyotrophic Lateral Sclerosis 2 Chromosomal Region Candidate Gene 17 Protein; Amyotrophic Lateral Sclerosis 2 (Juvenile) Chromosome Region, Candidate 17; Amyotrophic Lateral Sclerosis 2 (Juvenile) Chromosome Region, Candidate 16; Neurobeachin-Like Protein 1; MGC164581; Neurobeachin-Like 1; A530083I02Rik; Beach

The protein NBEAL1 is thought to activate protein kinase binding activity and appears to be involved in protein localization. NBEAL1 is thought to be active in the cytosol and in the membrane.
NBEAL1 is associated with

  • Amyotrophic Lateral Sclerosis 2, juvenile
  • Serous adenocarcinoma of the ovaries

Paralog: NBEAL2

NBEAL1 is a candidate gene for ADHD.70

1.156. FGFR3

Other names: GeneCards symbol: FGFR3; Fibroblast Growth Factor Receptor 3; JTK4; CD333; CEK2; EC 2.7.10.1; FGFR-3; ACH; Achondroplasia, Thanatophoric Dwarfism; Fibroblast Growth Factor Receptor 3-S; Hydroxyaryl Protein Kinase; Tyrosine Kinase JTK4; CD333 Antigen; HSFGFR3EX; EC 2.7.10

FGFR3 is a member of the fibroblast growth factor receptor (FGFR) family. A representative full-length protein consists of an extracellular region composed of three immunoglobulin-like domains, a single hydrophobic transmembrane segment, and a cytoplasmic tyrosine kinase domain. The extracellular portion of the protein interacts with fibroblast growth factors and triggers a cascade of downstream signaling events that ultimately influence mitogenesis and differentiation.
Fibroblast growth factors (FGFs) are mitogenic signaling molecules that play a role in angiogenesis, wound healing, cell migration, nerve cell growth, and embryonic development. FGF receptors (FGFRs) are transmembrane catalytic receptors with intracellular tyrosine kinase activity.
FGFR3 binds both acidic and basic fibroblast growth hormone and plays a role in bone development and maintenance.
FGFR3 is a tyrosine protein kinase that functions as a cell surface receptor for fibroblast growth factors and plays an essential role in regulating cell proliferation, differentiation, and apoptosis. Plays an essential role in regulating the differentiation, proliferation, and apoptosis of chondrocytes and is required for normal skeletal development. Regulates both osteogenesis and postnatal bone mineralization by osteoblasts. Required for the normal development of the inner ear. Phosphorylates PLCG1, CBL, and FRS2. Ligand binding leads to the activation of several signaling cascades. The activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol-1,4,5-trisphosphate. The phosphorylation of FRS2 triggers the recruitment of GRB2, GAB1, PIK3R1, and SOS1 and mediates the activation of RAS, MAPK1/ERK2, MAPK3/ERK1, and the MAP kinase signaling pathway as well as the AKT1 signaling pathway.
Plays a role in regulating vitamin D metabolism.
Mutations that lead to constitutive kinase activation or that impair the normal maturation, internalization, and degradation of FGFR3 result in disrupted signal transduction. Overexpressed or constitutively activated FGFR3 promotes the activation of PTPN11/SHP2, STAT1, STAT5A, and STAT5B. The secreted isoform 3 retains its ability to bind FGF1 and FGF2 and can therefore disrupt FGF signaling.89
FGFR3 is associated with

  • Craniosynostosis
  • various types of skeletal dysplasias.
    • Achondroplasia
    • Hypochondroplasia

FGFR3 is a candidate gene for ADHD.70

Paralog: FGFR2

Knocking out FGFR2 in mice in embryonic pluripotent precursors or in early postnatal astrocytes caused the mice to become hyperactive and resulted in (minor) changes in working memory, sociability, and anxiety-like behavior.90

1.157. ACAD11, Acyl-CoA Dehydrogenase Family Member 11

Other names: Acyl-Coenzyme A Dehydrogenase Family, Member 11; FLJ12592; ACAD-11; Acyl-CoA Dehydrogenase Family, Member 11; EC 1.3.8.-

The ACAD11 protein is an acyl-CoA dehydrogenase enzyme with a preference for carbon chain lengths between 20 and 26. Naturally occurring read-through transcription occurs between the upstream gene NPHP3 (nephronophthisis 3 (adolescent)) and this gene. ACAD11 exhibits maximum activity with saturated C22-CoA. ACAD11 is likely involved in beta-oxidation and energy production, but may also play a role in the metabolism of specific fatty acids to regulate the fatty acid composition of cellular lipids in the brain.91
ACAD11 is associated with

  • Developmental disorders
  • Epileptic encephalopathy 44
  • benign secondary hypertension

Paralog: ACAD10

ACAD11 is a candidate gene for ADHD.70

1.158. CNPY2

Other names: Canopy FGF Signaling Regulator 2; ZSIG9; Transmembrane Protein 4; HP10390; TMEM4; MIR-Interacting Saposin-Like Protein; Putative Secreted Protein Zsig9; Protein Canopy Homolog 2; MSAP; Canopy 2 Homolog (Zebrafish)

The CNPY2 protein is thought to be active in the endoplasmic reticulum. CNPY2 is a positive regulator of neurite growth by stabilizing the myosin-regulatory light chain (MRLC). It prevents MIR-mediated ubiquitination of MRLC and its subsequent proteasomal degradation.92
CNPY2 is associated with

  • Fanconi anemia, complementation group C
  • Craniosynostosis

Paralog: ENSG00000144785.

CNPY2 is a candidate gene for ADHD.70

1.159. PACC1, TMEM206

Other names: PACC1; Proton-Activated Chloride Channel; PAC; Transmembrane Protein 206; C1orf75; TMEM206; PAORAC; ASOR; Proton-Activated Outwardly Rectifying Anion Channel; Acid-Sensitive Outwardly-Rectifying Anion Channel; Acid-Sensitive Outwardly Rectifying Channel; Proton-Activated Chloride Channel; FLJ10874; HTMEM206; HPAC; Chromosome 1 Open Reading Frame 75

The PACC1 protein enables the activity of the pH-gated chloride channel. PACC1 is involved in chloride transport. PACC1 is an integral component of the plasma membrane. PACC1 is a proton-activated chloride channel that mediates the import of chloride ions in response to an acidic extracellular pH. PACC1 is involved in acidosis-induced cell death by mediating chloride influx and subsequent cell swelling.

PACC1, also known as TMEM206, is a candidate gene for ADHD.70

1.160. BST1, Bone Marrow Stromal Cell Antigen 1

Other names: ADP-ribosyl cyclase 2; CD157; BST-1; ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 2; bone marrow stromal antigen 1; Cyclic ADP-Ribose Hydrolase 2; NAD(+) Nucleosidase 2; CADPr Hydrolase 2; CD157 Antigen; EC 3.2.2.6

The BST1 protein is a stromal cell-derived glycosylphosphatidylinositol-anchored molecule that promotes the growth of pre-B cells. Its deduced amino acid sequence shows 33% similarity to CD38. BST1 expression is elevated in stromal cell lines derived from the bone marrow of patients with rheumatoid arthritis. The polyclonal B-cell abnormalities observed in rheumatoid arthritis can be attributed, at least in part, to the overexpression of BST1 in the stromal cell population.93
BST1 is associated with

  • Paroxysmal nocturnal hemoglobinuria
  • Hemoglobinuria

Paralog: CD38.

UniProtKB/Swiss-Prot Summary for the BST1 Gene
Synthesizes the signaling molecules cyclic ADP-ribose and nicotinamide adenine dinucleotide phosphate, the former of which is a signaling molecule that triggers the release of calcium from intracellular stores. May be involved in the growth of pre-B cells. BST1_HUMAN,Q10588

BST1 is a candidate gene for ADHD.70

1.161. RASSF4, Ras Association Domain Family Member 4

Other names: AD037; Ras Association (RalGDS/AF-6) Domain Family Member 4; Ras Association Domain-Containing Protein 4; MGC44914; Ras Association (RalGDS/AF-6) Domain Family 4; Ras Association Domain Family 4; Tumor Suppressor RASSF4

However, the RASSF4 protein may play a role in tumor suppression. Its associated pathways include malignant pleural mesothelioma. RASSF4 can act as a KRAS effector protein and promote apoptosis and cell cycle arrest.94

Paralog: RASSF2

RASSF4 is a candidate gene for ADHD.70

1.163. RAPGEF5, Rap Guanine Nucleotide Exchange Factor 5

Other names: MR-GEF; GFR; KIAA0277; Rap Guanine Nucleotide Exchange Factor (GEF) 5; Guanine Nucleotide Exchange Factor for Rap1; M-Ras-Regulated Rap GEF; M-Ras-Regulated GEF; Related to Epac; MRGEF; REPAC; Repac

Members of the RAS (see HRAS; MIM 190020) subfamily of GTPases function in signal transduction as GTP/GDP-regulated switches that alternate between inactive GDP-bound and active GTP-bound states. Guanine nucleotide exchange factors (GEFs), such as the protein RAPGEF5, act as RAS activators by promoting GTP acquisition to maintain the active GTP-bound state, and are the central link between cell surface receptors and RAS activation. The protein RAPGEF5 is a guanine nucleotide exchange factor (GEF) for RAP1A, RAP2A, and MRAS/M-Ras-GTP. Its association with MRAS inhibits the activation of Rap1.95
RAPGEF5 is associated with

  • Familial isolated hypoparathyroidism

Paralog: RAPGEF4

RAPGEF5 is a candidate gene for ADHD.70

1.164. MVP, Major Vault Protein

Other names: LRP; Lung Resistance-Related Protein; VAULT1; Testicular Secretory Protein Li 30

The MVP protein is the main component of the Vault complex. Vaults are ribonucleoprotein structures composed of multiple subunits that may be involved in nucleocytoplasmic transport. Vaults are structures composed of multiple subunits that can serve as a scaffold for proteins involved in signal transduction. Vaults may also play a role in nucleocytoplasmic transport. MVP may play a role in several cellular processes by regulating the MAP kinase, JAK/STAT, and phosphoinositide-3-kinase/Akt signaling pathways. MVP reduces IFNG-mediated STAT1 signaling and the subsequent activation of JAK. MVP downregulates SRC activity and signal transduction via MAP kinases. MVP also plays a role in multidrug resistance. The expression of this gene may serve as a prognostic marker for various types of cancer.96
MVP is associated with

  • Familial infantile convulsions with paroxysmal choreoathetosis
  • treatment-induced acute myeloid leukemia
  • myelodysplastic syndrome

MVP is a candidate for ADHD.70

1.165. RPS20, Ribosomal Protein S20

Other names: US10; S20; Small Ribosomal Subunit Protein US10; 40S Ribosomal Protein S20

Ribosomes, the organelles that catalyze protein synthesis, consist of a small 40S subunit and a large 60S subunit. Together, these subunits are composed of 4 types of RNA and about 80 structurally distinct proteins.
The ribosomal protein RPS20 is a component of the 40S subunit. RPS20 belongs to the S10P family of ribosomal proteins. It is located in the cytoplasm. This gene is transcribed together with the gene for the small nucleolar RNA U54, which is located within its second intron. As is typical for genes encoding ribosomal proteins, there are several processed pseudogenes of this gene scattered throughout the genome.97
RPS20 is associated with:

  • Diamond-Blackfan anemia
  • Hereditary colorectal cancer, Type X

RPS20 is a candidate for ADHD.70

1.166. RASGRP4, RAS Guanylate-Releasing Protein 4

Other names: RAS Guanyl-Releasing Protein 4; Guanyl Nucleotide Releasing Protein 4

The RASGRP4 protein belongs to the Ras guanine nucleotide exchange factor family, the Ras guanyl nucleotide-releasing protein (RasGRP). It contains a Ras exchange motif, a diacylglycerol-binding domain, and two calcium-binding EF-hands. RASGRP4 activates H-Ras in vitro in a cation-dependent manner. RASGRP4 functions as a cation- and diacylglycerol (DAG)-regulated nucleotide exchange factor that activates Ras by exchanging bound GDP for GTP. RASGRP4 may play a role in mast cell differentiation. It has been found that the expression of this protein in myeloid cell lines correlates with an increased concentration of the activated RAS protein and that RAS activation can be greatly enhanced by phorbol estertreatment, suggesting a role for this protein in diacylglycerol-regulated cellular signaling pathways. Studies of a mast cell leukemia cell line that expresses significant amounts of abnormal transcripts of this gene suggest that this gene may play an important role in the final stages of mast cell development. Several transcript variants of this gene have been identified that encode different isoforms.98
RASGRP4 is associated with

  • Mast cell leukemia
  • Mastocytosis

Paralog: RASGRP1

RASGRP4 is a candidate gene for ADHD.70

1.167. MAP1A, Microtubule-associated protein 1A

Other names: MAP1L; Microtubule-Associated Protein 1A; Proliferation-Related Protein P80; MAP-1A; EC 2.7.2.8; EC 6.3.4.5; MTAP1A

The MAP1A protein belongs to the family of microtubule-associated proteins. MAP1A is a structural protein involved in the filamentous cross-linking between microtubules and other cytoskeletal elements. MAP1A is a precursor polypeptide that is thought to undergo proteolytic processing to form the final heavy chain of MAP1A and the light chain of LC2. This gene is expressed almost exclusively in the brain. Studies of the rat microtubule-associated protein 1A gene suggest a role in early events of spinal cord development.99
MAP1A is associated with

  • Granulomatous disease, chronic, autosomal recessive, 3
  • Woodhouse-Sakati syndrome

Paralog: MAP1B.

MAP1A is a candidate gene for ADHD.100

1.168. FBXO25, F-BOX ONLY PROTEIN 25

Other names: FBX25; F-Box Only Protein 25; F-Box Protein Fbx25

OMIM: FBXO25, F-BOX ONLY PROTEIN 25

FBXO25 is a member of the F-box protein family, which is characterized by a motif consisting of approximately 40 amino acids, known as the F-box. F-Box proteins form one of the four subunits of the ubiquitin-protein ligase complex known as SCF (SKP1-Cullin-F-Box), which mediates phosphorylation-dependent ubiquitination. F-Box proteins are divided into three classes: Fbws, which contain WD-40 domains; Fbls, which contain leucine-rich repeats; and Fbxs, which contain either various protein-protein interaction modules or no recognizable motifs. The protein encoded by this gene belongs to the Fbxs class. FBXO25 is a substrate recognition component of the SCF (SKP1-CUL1-F-Box protein) type E3 ubiquitin ligase complex. FBXO25 may play a role in the accumulation of the expanded polyglutamine (polyQ) protein huntingtin (HTT).101

Paralog: FBXO32

Overexpression of FBXO25 could potentially be correlated with hyperactivity.102

1.169. TRAPPC9, TRAFFICKING PROTEIN PARTICLE COMPLEX, SUBUNIT 9

Other names: NIBP; KIAA1882; IKBKBBP; TRS120; MRT13; T1; Trafficking Protein Particle Complex 9; NIK- and IKK-beta-Binding Protein; Tularik Gene 1 Protein; TRAPP 120 kDa Subunit; NIK- and IKK-beta-Binding Protein; IKK2-Binding Protein; Tularik Gene; IBP

OMIM: TRAPPC9, TRAFFICKING PROTEIN PARTICLE COMPLEX, SUBUNIT 9

The TRAPPC9 protein likely plays a role in NF-kappa-B signaling. Mutations in this gene have been associated with autosomal-recessive intellectual disability. TRAPPC9 acts as an activator of NF-kappa-B by increasing phosphorylation of the IKK complex. TRAPPC9 may play a role in the differentiation of neuronal cells. TRAPPC9 may play a role in vesicular transport from the endoplasmic reticulum to the Golgi apparatus.103
TRAPPC9 is associated with

  • Intellectual developmental disorder, autosomal recessive 13
  • Intellectual Disability-Obesity-Brain Malformations-Facial Dysmorphism Syndrome

TRAPPC9 is a candidate gene for ADHD.85

1.170. MEF2C, MADS BOX TRANSCRIPTION ENHANCER FACTOR 2, POLYPEPTIDE C

Other names: Myocyte Enhancer Factor 2C; Myocyte-Specific Enhancer Factor 2C; MADS Box Transcription Enhancer Factor 2, Polypeptide C; C5DELq14.3; DEL5q14.3; NEDHSIL

OMIM: MEF2C, MADS BOX TRANSCRIPTION ENHANCER FACTOR 2, POLYPEPTIDE C

This locus encodes a member of the MADS-box transcription enhancer factor 2 (MEF2) family, which plays a role in myogenesis. The MEF2C protein has both trans-activating and DNA-binding activities. MEF2C may play a role in maintaining the differentiated state of muscle cells. Mutations and deletions at this locus have been associated with severe cognitive impairments, stereotyped movements, epilepsy, and cerebral malformations. MEF2C is a transcription activator that specifically binds to the MEF2 element in the regulatory regions of many muscle-specific genes. MEF2C controls cardiac morphogenesis and myogenesis and is involved in vascular development. MEF2C enhances SOX18-mediated transcriptional activation. MEF2C plays an essential role in hippocampus-dependent learning and memory by suppressing the number of excitatory synapses, thereby regulating basal and evoked synaptic transmission. MEF2C is critical for normal neuronal development, distribution, and electrical activity in the neocortex. MEF2C is required for the proper development of megakaryocytes and platelets, as well as for B-cell differentiation in the bone marrow. MEF2C is required for the survival and proliferation of B cells in response to BCR stimulation, for efficient IgG1 antibody responses to T-cell-dependent antigens, and for the normal induction of B cells in the germinal center. MEF2C may also be involved in neurogenesis and the development of cortical architecture.104
MEF2C is associated with

  • Neurodevelopmental disorder characterized by hypotonia, stereotyped hand movements, and impaired speech
  • Autism Spectrum Disorder

Paralog: MEF2A

MEF2C is a candidate gene for ADHD.85

1.171. TNRC6B, TRINUCLEOTIDE REPEAT-CONTAINING GENE 6B

Other names: KIAA1093; Trinucleotide Repeat-Containing Gene 6B Protein; Trinucleotide Repeat Containing 6B; GDSBA

OMIM: TNRC6B, TRINUCLEOTIDE REPEAT-CONTAINING GENE 6B

The TNRC6B protein mediates RNA-binding activity. TNRC6B is involved in the regulation of gene expression and is thought to be present in the cytosol and active in the P-body and nucleoplasm. TNRC6B plays a role in RNA-mediated gene silencing via both microRNAs (miRNAs) and short interfering RNAs (siRNAs). TNRC6B is required for miRNA-dependent translational repression and siRNA-dependent endonucleolytic cleavage of complementary mRNAs by proteins of the Argonaute family. As a scaffold protein, it associates with Argonaute proteins bound to partially complementary mRNAs and can simultaneously recruit CCR4-NOT and PAN deadenylase complexes.105
TNRC6B is associated with

  • Global developmental delay with speech and behavioral abnormalities
  • Non-specific syndromic intellectual disability
  • subserosal uterine fibroid
  • Uterine fibroid

Paralog: TNRC6A

TNRC6B is a candidate gene for ADHD.106

1.173. EPHA5, EPH Receptor A5

Other names: TYRO4; EHK1; CEK7; HEK7; Ephrin Type-A Receptor 5; EPH Homology Kinase 1; Brain-Specific Kinase; EPH-Like Kinase 7; EC 2.7.10.1; EHK-1; Hek7; EK7; Epididymal Secretory Sperm-Binding Protein; Tyrosine-Protein Kinase Receptor EHK-1; Receptor Protein-Tyrosine Kinase HEK7; EC 2.7.10; EphA5; BSK

EPHA5 belongs to the ephrin receptor subfamily of the protein tyrosine kinase family. EPH and EPH-related receptors are involved in mediating developmental events, particularly in the nervous system. Receptors in the EPH subfamily typically have a single kinase domain and an extracellular region containing a cysteine-rich domain and two fibronectin type III repeats. Ephrin receptors are divided into two groups based on the similarity of their extracellular domain sequences and their affinities for binding ephrin-A and ephrin-B ligands. EPHA5 is a receptor tyrosine kinase that promiscuously binds GPI-anchored ligands of the Ephrin-A family located on neighboring cells, leading to contact-dependent bidirectional signal transduction to neighboring cells. The signaling pathway downstream of the receptor is referred to as forward signaling, while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling. Among the GPI-anchored Ephrin-A ligands, EFNA5 is most likely the cognate ligand for EPHA5. It acts as an axon-guiding molecule during development and may be involved in the development of the retinotectal, entorhino-hippocampal, and hippocamposeptal pathways. Together with EFNA5, it also plays a role in synaptic plasticity in the adult brain by regulating synaptogenesis. In addition to its function in the nervous system, the interaction between EPHA5 and EFNA5 mediates communication between pancreatic islet cells to regulate glucose-stimulated insulin secretion.107
EPHA5 is associated with

  • Leber Congenital Amaurosis 17
  • Lung Cancer Susceptibility 3

Paralog: EPHA3

A study identified EPHA5 (variant rs4860671) as one of 96 candidate genes for ADHD.41

1.174. RIMS1, Regulating Synaptic Membrane Exocytosis 1

Other names: RIM1; KIAA0340; RAB3IP2; RIM; Regulating Synaptic Membrane Exocytosis Protein 1; Rab-3-Interacting Protein 2; CORD7; Rab-3-Interacting Molecule 1; Rab3-Interacting Molecule 1; RAB3 Interacting Protein 2; RAB3-Interacting Protein 2; Rab3-Interacting Molecule 2; RIM 1

The RIMS1 protein is a member of the RAS gene superfamily that regulates synaptic vesicle exocytosis. RIMS1 also acts as a scaffolding protein in the active zone, regulating voltage-gated calcium channels during the release of neurotransmitters and insulin. Mutations suggest a role in cognitive function. RIMS1 is essential for maintaining the normal probability of neurotransmitter release and for regulating release during short-term synaptic plasticity. RIMS1 plays a role in dendrite formation by melanocytes.108
RIMS1 is associated with

  • Cone-Rod Dystrophy 7
  • Gyrate Atrophy of the Choroid and Retina

Paralog: RIMS2.

A study identified RIMS1 (variant rs4707940) as one of 96 ADHD candidate genes.41

1.175. NRG3, Neuregulin 3

Other names: Pro-Neuregulin-3, Membrane-Bound Isoform 3; Pro-NRG3; Neuregulin-3-Like Polypeptide; HRG3

NRG3 is a member of the neuregulin gene family. This gene family encodes ligands for the transmembrane tyrosine kinase receptors ERBB3 and ERBB4—members of the epidermal growth factor receptor family. Ligand binding activates intracellular signaling cascades and induces cellular responses such as proliferation, migration, differentiation, and survival or apoptosis. NRG3 activates the tyrosine phosphorylation of its cognate receptor ERBB4 and is thought to influence the proliferation, migration, and differentiation of neuroblasts by mediating signals via ERBB4. Does not bind to the EGF receptor, the ERBB2 receptor, or the ERBB3 receptor. May be a survival factor for oligodendrocytes. NRG3 promotes mammary gland differentiation during embryogenesis. Linkage studies have shown that this gene is a susceptibility locus for schizophrenia and schizoaffective disorders.109
NRG3 is associated with

  • Hirschsprung’s disease 1
  • schizoaffective disorder
  • Schizophrenia

Paralog: NRG1

A study identified NRG3 (variant rs12244269) as one of 96 ADHD candidate genes.41

1.176. TENM4, Teneurin Transmembrane Protein 4

Other names: Ten-M4; KIAA1302; TEN4; ODZ4; Odd Oz/Ten-M homolog 4 protein; Tenascin-M4; Teneurin-4; Ten-4; TNM4; Odz, Odd Oz/Ten-M homolog 4 (Drosophila); Odz, Odd Oz/Ten-M Homolog 4; Doc4; ETM5

The TENM4 protein plays a role in establishing proper neuronal connectivity during development. TENM4 plays a role in the formation of the anterior-posterior axis during gastrulation. TENM4 regulates the differentiation and cellular process formation of oligodendrocytes and the myelination of small-diameter axons in the CNS. TENM4 promotes the activation of focal adhesion kinase and can act as a cellular signaling molecule.110
TENM4 is associated with:

  • Tremor, Hereditary Essential, 5
  • Tremor

Paralog: TENM3

A study identified TENM4 (variant rs1944959) as one of 96 candidate genes for ADHD.41

1.178. MDGA2, MAM Domain-Containing Glycosylphosphatidylinositol Anchor 2

Other names: MAMDC1; MAM Domain-Containing Glycosylphosphatidylinositol Anchor Protein 2; MAM Domain Containing 1; MAM Domain-Containing Protein 1; C14_5286

The MDGA2 protein is thought to be involved in cell-cell interactions: it plays a role in regulating presynaptic formation, synaptic membrane adhesion, and the differentiation of spinal cord motor neurons. MDGA2 is thought to act upstream of or within the neuronal migration and pattern specification process and is likely localized in the extracellular region and the plasma membrane. MDGA2 is likely active in GABAergic and glutamatergic synapses.111
MDGA2 is associated with:

  • Dependent Personality Disorder
  • Benign epilepsy with centrotemporal spikes

Paralog: MDGA1

A study identified MDGA2 (variant rs12232114) as one of 96 ADHD candidate genes.41

1.179. RBFOX1, RNA-Binding Fox-1 Homolog 1

Other names: HRNBP1; A2BP1; FOX-1; RNA-Binding Protein, Fox-1 Homolog 1; Hexaribonucleotide-Binding Protein 1; RNA-Binding Protein Fox-1 Homolog 1; Ataxin 2-Binding Protein 1; Fox-1 Homolog A; FOX1; RNA-Binding Protein, Fox-1 Homolog (C. elegans) 1; Hexaribonucleotide-Binding Protein 1; Fox-1-Like RNA-Binding Protein 1; Ataxin-2-Binding Protein 1; 2BP1; A2BP

The Fox-1 family of RNA-binding proteins is evolutionarily conserved and regulates tissue-specific alternative splicing in metazoans of tissue-specific exons and differentially spliced exons during erythropoiesis. Fox-1 recognizes a (U)GCAUG sequence in regulated exons or in flanking introns. The protein binds to the C-terminus of Ataxin-2. Ataxin-2 is the product of the SCA2 gene, which causes familial neurodegenerative diseases. Fox-1 and Ataxin-2 are both localized in the trans-Golgi network.112
RBFOX1 is associated with:

  • Benign epilepsy with centrotemporal spikes
  • Colorectal cancer
  • Spinocerebellar ataxia type 2 (SCA2)

Paralog: RBFOX2

A study identified RBFOX1 (variant rs9935453) as one of 96 candidate genes for ADHD.41

1.180. LIG4, DNA ligase 4

Other names: Polydeoxyribonucleotide Synthase [ATP] 4; DNA Ligase IV; Ligase IV, DNA, ATP-Dependent; Polynucleotide Ligase; DNA Repair Enzyme; DNA Joinase; EC 6.5.1.1; Sealase; LIG4S

The LIG4 protein is a DNA ligase that joins single-strand breaks in a double-stranded polydeoxynucleotide in an ATP-dependent reaction. LIG4 is essential for V(D)J recombination and the repair of DNA double-strand breaks (DSBs) via non-homologous end-joining (NHEJ). This protein forms a complex with X-ray repair cross-complementing protein 4 (XRCC4) and interacts with DNA-dependent protein kinase (DNA-PK). Both XRCC4 and DNA-PK are required for NHEJ.113
LIG4 is associated with

  • Lig4 syndrome
  • Multiple myeloma

Paralog: LIG3

A study identified LIG4 (variant rs9514807) as one of 96 candidate genes for ADHD.41

1.181. NEDD4L, NEDD4-like E3 ubiquitin protein ligase

Other names: KIAA0439; NEDD4-2; RSP5; Neural Precursor Cell Expressed, Developmentally Down-Regulated 4-Like, E3 Ubiquitin Protein Ligase; HECT-Type E3 Ubiquitin Transferase NED4L; E3 Ubiquitin Protein Ligase NEDD4-Like; NEDD4.2; Neural Precursor Cell Expressed, Developmentally Down-Regulated 4-Like; Ubiquitin Protein Ligase Rsp5; EC 2.3.2.26; EC 2.3.2.36; HNEDD4-2; EC 6.3.2; Nedd4-2; PVNH7; NEDL3

The NEDD4L protein is a member of the Nedd4 family of HECT-domain E3 ubiquitin ligases. E3 ubiquitin ligases with a HECT domain transfer ubiquitin from E2 ubiquitin-conjugating enzymes to protein substrates, thereby directing specific proteins toward lysosomal degradation. The encoded protein mediates the ubiquitination of several target substrates and plays a crucial role in epithelial sodium transport by regulating the cell surface expression of the epithelial sodium channel (ENaC). NEDD4L is involved in the regulation of various signaling pathways, such as autophagy, innate immunity, and DNA repair. NEDD4L inhibits TGF-beta signaling by inducing the ubiquitination of SMAD2 and TGFBR1 and their proteasome-dependent degradation. NEDD4L reduces autophagy and cell growth by ubiquitinating and decreasing cellular levels of ULK1 or ASCT2. NEDD4L plays a role in the formation of melanocyte dendrites and in the regulation of TOR signaling.114
NEDD4L is associated with

  • Periventricular Nodular Heterotopia 7
  • Periventricular nodular heterotopia
  • essential hypertension

Paralog: NEDD4

A study identified NEDD4L (variant rs1620068) as one of 96 ADHD candidate genes.41

1.182. BMP2, Bone Morphogenetic Protein 2

Other names: BMP2A; Bone Morphogenetic Protein 2A; SSFSC1; BMP-2A; SSFSC; BMP-2; BDA2

The BMP2 protein is a growth factor and a secreted ligand of the TGF-beta (Transforming Growth Factor-beta) superfamily of proteins. Ligands in this family bind to various TGF-beta receptors, leading to the recruitment and activation of SMAD family transcription factors, which regulate gene expression. The encoded preprotein undergoes proteolytic processing to form the individual subunits of the disulfide-linked homodimer, which plays a role in bone and cartilage development. The growth factor BMP2 plays an essential role in many developmental processes, including cardiogenesis, neurogenesis, and osteogenesis. BMP2 induces cartilage and bone formation. BMP2 initiates the canonical BMP signaling cascade by binding to the type I receptor BMPR1A and the type II receptor BMPR2. BMP2 can also act via non-canonical signaling pathways, such as the ERK/MAP kinase signaling cascade, which regulates osteoblast differentiation. BMP2 stimulates the differentiation of myoblasts into osteoblasts via the EIF2AK3-EIF2A-ATF4 signaling pathway by stimulating EIF2A phosphorylation, which leads to increased expression of ATF4, a key player in osteoblast differentiation.115
BMP2 is associated with

  • Short stature
  • Facial dysmorphism
  • Skeletal anomalies with or without cardiac anomalies 1
  • Brachydactyly, Type A2

Paralog: BMP4

A study identified BMP2 (rs952793 variant) as one of 96 candidate genes for ADHD.41

1.182. FAM19A4, TAFA4, TAFA Chemokine-Like Family Member 4

Other names: TAFA-4; Family With Sequence Similarity 19, Member A4, C-C Motif Chemokine-Like; Chemokine-Like Protein TAFA-4; Family With Sequence Similarity 19 (Chemokine (C-C Motif)-Like), Member A4

The TAFA4 protein belongs to the TAFA family. These proteins contain conserved cysteine residues at fixed positions and are distantly related to MIP-1alpha, a member of the CC chemokine family. TAFA proteins are primarily expressed in specific regions of the brain and are thought to function as brain-specific chemokines or neurokinins that act as regulators of immune and nerve cells. TAFA4 modulates injury-induced and chemical pain hypersensitivity. TAFA4 can attract macrophages, promote phagocytosis, and increase ROS release.116
TAFA4 is associated with

  • Inflammatory bowel diseases 9

Paralog: TAFA2

A study identified FAM19A4 (variant rs9871910) as one of 96 candidate genes for ADHD.41

1.183. ATXN8OS, ATXN8 Opposite Strand LncRNA

Other names: NCRNA00003; KLHL1AS; SCA8; ATXN8 Opposite Strand (Non-Protein Coding); Non-Protein Coding RNA 3; Spinocerebellar Ataxia 8; Kelch-Like 1 Antisense; Kelch-Like 1 Antisense (Drosophila); Ataxin 8 Opposite Strand; Putative Protein ATXN8OS; ATXN8 Opposite Strand; NONHSAG013730.2; HSALNG0097806; HSALNG0097807; ATXN8OS

ATXN8OS is an antisense transcript of the KLHL1 gene (homologous to the Drosophila KELCH gene); it does not appear to encode a protein itself. A TAC/TGC trinucleotide repeat expansion, which is incorporated into this gene transcript but not into the KLHL1 transcript, causes spinocerebellar ataxia type 8. It is presumed that the expansion disrupts the normal antisense function of this transcript.117
ATXN8OS is associated with

  • spinocerebellar ataxia

A study identified ATXN8OS (variant rs2498502) as one of 96 ADHD candidate genes.41

1.184. PPP1R26-AS1

Other names: PPP1R26 antisense RNA 1; NONHSAG053763.2; HSALNG0075163; HSALNG0075157; PPP1R26-AS1

PPP1R26-AS1 is an RNA gene that belongs to the lncRNA class.118

A study identified PPP1R26-AS1 (variant rs895192) as one of 96 ADHD candidate genes.41

1.185. BCR, BCR Activator of RhoGEF and GTPase

Other names: D22S662; D22S11; BCR1; CML; PHL; ALL; BCR, RhoGEF and GTPase-activating protein; Breakpoint cluster region protein; Renal carcinoma antigen NY-REN-26; Breakpoint Cluster Region; EC 2.7.11.1; BCR/FGFR1 Chimera Protein; FGFR1/BCR Chimera Protein

The BCR protein has a unique structure with two opposing regulatory activities toward small GTP-binding proteins:

  • The C-terminus is a GTPase-activating protein (GAP) domain that stimulates GTP hydrolysis by RAC1, RAC2, and CDC42. It accelerates the intrinsic rate of GTP hydrolysis of RAC1 or CDC42, leading to downregulation of the active GTP-bound form. The central Dbl homology (DH) domain functions as a guanine nucleotide exchange factor (GEF) that modulates the GTPases CDC42, RHOA, and RAC1. BCR promotes the conversion of CDC42, RHOA, and RAC1 from the GDP-bound to the GTP-bound form.
  • The N-terminus possesses intrinsic kinase activity. BCR functions as an important negative regulator of neuronal RAC1 activity, regulates macrophage functions such as CSF1-driven motility and phagocytosis by modulating RAC1 activity; it plays an important role as a RHOA GEF in keratinocytes and is involved in the formation of focal adhesions and keratinocyte differentiation.

A reciprocal translocation between chromosomes 22 and 9 results in the Philadelphia chromosome, which is frequently found in patients with chronic myeloid leukemia. The breakpoint on chromosome 22 for this translocation is located within the BCR gene. The translocation leads to the formation of a fusion protein encoded by sequences from both BCR and ABL, the gene at the breakpoint on chromosome 9. The unregulated tyrosine kinase activity of BCR-ABL1 contributes to the immortality of leukemic cells. The BCR protein has serine/threonine kinase activity and acts as a GTPase-activating protein for p21rac and other kinases.119
BCR is affiliated with

  • Chronic Myeloid Leukemia
  • Chromosome 8p11 Myeloproliferative Syndrome

Paralog: ABR

A study identified BCR (variant rs140502) as one of 96 ADHD candidate genes.41

1.186. ZBTB7C, Zinc Finger and BTB Domain-Containing 7C

Other names: ZNF857C; ZBTB36; Protein 1 Affected by Papillomavirus DNA Integration in ME180 Cells; Zinc Finger and BTB Domain-Containing Protein 7C; Zinc Finger and BTB Domain-Containing Protein 36; Zinc Finger and BTB Domain-Containing 36; Zinc Finger Protein 857C; APM-1; APM1; B230208J24Rik

The ZBTB7C protein is believed to mediate DNA-binding transcription factor activity, as well as RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA-binding activity. ZBTB7C is involved in the negative regulation of cell population proliferation and is thought to be localized in the cell nucleus. ZBTB7C may be a tumor suppressor gene.120
ZBTB7C is associated with

  • L-2-hydroxyglutaric acid disorder

Paralog: ZBTB16

A study identified ZBTB7C (variant rs11662736) as one of 96 ADHD candidate genes.121

1.187. TSPAN11, Tetraspanin 11

Other names: Tetraspanin-11; Tspan-11; VSSW1971

The protein TSPAN11 is likely involved in cell migration . It is thought to be an integral component of the membrane and an integral component of the plasma membrane.122

Paralog: CD151

A study identified TSPAN11 (variant rs11051194) as one of 96 ADHD candidate genes.41

1.188. GRIP1, Glutamate Receptor Interacting Protein 1

Other names: Glutamate Receptor-Interacting Protein 1; FRASRS3; GRIP-1; GRIP

GRIP1 is a member of the glutamate receptor-interacting protein family. GRIP1 is a scaffolding protein that binds to a number of transmembrane proteins. GRIP1 mediates their trafficking and membrane organization. GRIP1 may play a role as a localized scaffold for the assembly of a multiprotein signaling complex and as a mediator of the trafficking of its binding partners to specific subcellular locations in neurons. By forming complexes with NSG1, GRIA2, and STX12, it controls the intracellular fate of AMPAR and the endosomal sorting of the GRIA2 subunit toward recycling and membrane targeting.123
GRIP1 is associated with

  • Fraser Syndrome 3
  • Fraser syndrome 1

Paralog: GRIP2

A study identified GRIP1 (variant rs4913506) as one of 96 ADHD candidate genes.41

1.189. PRDM2, PR/SET Domain 2

Other names: MTB-ZF; KMT8; RIZ; Retinoblastoma Protein-Interacting Zinc Finger Protein; MTE-Binding Protein; HUMHOXY1; KMT8A; RIZ1; RIZ2; Retinoblastoma Protein-Binding Zinc Finger Protein; PR Domain Containing 2, With ZNF Domain 2; Zinc-Finger DNA-Binding Protein; PR Domain Zinc Finger Protein 2; PR Domain-Containing Protein 2; Lysine N-Methyltransferase 8; GATA-3 Binding Protein G3B; Zinc Finger Protein RIZ; PR Domain 2; GATA-3-Binding Protein G3B; EC 2.1.1.355

PRDM2 is a tumor suppressor gene and belongs to the superfamily of nuclear histone/protein methyltransferases. PRDM2 encodes a zinc-finger protein that can bind to the retinoblastoma protein, the estrogen receptor, and the TPA-responsive element (MTE) of the heme oxygenase-1 gene. PRDM2 may play a role in transcriptional regulation during neuronal differentiation and in the pathogenesis of retinoblastoma. PRDM2 may function as a transcriptional activator of the heme oxygenase-1 gene. PRDM2 may be a specific effector of estrogen action. PRDM2 is an S-adenosyl-L-methionine-dependent histone methyltransferase that specifically methylates ‘Lys-9’ of histone H3. PRDM2 can act as a DNA-binding transcription factor. PRDM2 binds to the macrophage-specific TPA-responsive element (MTE) of the HMOX1 gene (heme oxygenase 1) and may act as a transcriptional activator of this gene.124
PRDM2 is associated with

  • Retinoblastoma
  • Dyskeratosis Congenita, Autosomal Dominant 2

Paralog: ZNF287

A study identified PRDM2 (variant rs7519796) as one of 96 ADHD candidate genes.41

1.190. LINC00609, Long Intergenic Non-Protein-Coding RNA 609

Other names: NONHSAG014722.2; NONHSAG014716.2; HSALNG0100629; LINC00609

LINC00609 is an RNA gene that belongs to the lncRNA class.125

A study identified LINC00609 (variant rs1537424) as one of 96 candidate genes for ADHD.41

1.191. NAV1, Neuron Navigator 1

Other names: POMFIL3; Steerin-1; KIAA1151; Pore Membrane and/or Filament Interacting-Like Protein 3; Unc-53 Homolog 1; DKFZp781D0314; FLJ12560; FLJ14203; MGC14961; STEERIN1; Pore Membrane and/or Filament-Interacting-Like Protein; Neuron Navigator-1; KIAA1213; UNC53H1; Unc53H1

The NAV1 protein belongs to the family of neuronal navigators and is expressed primarily in the nervous system. The encoded protein contains coiled-coil domains and a conserved AAA domain, which is characteristic of ATPases associated with a variety of cellular activities. NAV1 is similar to unc-53, a gene from Caenorhabditis elegans that is involved in axon guidance. It is believed that NAV1 plays a role in neuronal development and regeneration.126
NAV1 is associated with

  • Congenital Paramyotonia of Von Eulenburg
  • Paroxysmal Extreme Pain Disorder

Paralog: NAV2

A study identified NAV1 (variant rs2078097) as one of 96 ADHD candidate genes.41

1.195. GIMAP6, GTPase, IMAP Family Member 6

Other names: IAN6; Immune-Associated Nucleotide-Binding Protein 6; GTPase IMAP Family Member 6; FLJ22690; IAN-2; IAN-6; IAN2; Immunity-Associated Nucleotide 2 Protein; Immunity-Associated Nucleotide 6 Protein; Immune-Associated Nucleotide 2; Immune-Associated Nucleotide 6; HIAN2; HIAN6

The GIMAP6 protein is a member of the GTPase family of immunity-associated proteins (GIMAP). GIMAP proteins contain GTP-binding and coiled-coil motifs and may play a role in regulating cell survival.127
GIMAP6 is associated with

  • Lymphopenia
  • Lung cancer

Paralog: GIMAP1

A study identified GIMAP6 (variant rs1403220) as one of 96 ADHD candidate genes.41

1.196. LIG4, DNA Ligase 4

Other names: Polydeoxyribonucleotide Synthase [ATP] 4; DNA Ligase IV; Ligase IV, DNA, ATP-Dependent; Polynucleotide Ligase; DNA Repair Enzyme; DNA Joinase; EC 6.5.1.1 4; Sealase; LIG4S

The LIG4 protein is a DNA ligase that joins single-strand breaks in a double-stranded polydeoxynucleotide in an ATP-dependent reaction. LIG4 is essential for V(D)J recombination and the repair of DNA double-strand breaks (DSBs) via non-homologous end-joining (NHEJ). LIG4 forms a complex with the X-ray repair cross-complementing protein 4 (XRCC4) and also interacts with DNA-dependent protein kinase (DNA-PK). Both XRCC4 and DNA-PK are required for NHEJ.113
LIG4 is associated with

  • Lig4 syndrome
  • Multiple myeloma

Paralog: LIG3

A study identified LIG4 (variant rs9514807) as one of 96 ADHD candidate genes.41

1.202. MDGA2, MAM Domain-Containing Glycosylphosphatidylinositol Anchor 2

Other names: MAMDC1; MAM Domain-Containing Glycosylphosphatidylinositol Anchor Protein 2; MAM Domain Containing 1; MAM Domain-Containing Protein 1; 14_5286

The MDGA2 protein is likely involved in the

  • Regulation of presynaptic assembly
  • Regulation of synaptic membrane adhesion
  • Differentiation of motor neurons in the spinal cord.111
    MDGA2 is likely active in both GABAergic and glutamatergic synapses.
    MDGA2 is associated with
  • Dependent Personality Disorder
  • Benign epilepsy with centrotemporal spikes

Paralog: MDGA1

A study identified MDGA2 (variant rs12232114) as one of 96 ADHD candidate genes.41

1.203. TBX3, T-Box Transcription Factor 3

Other names: TBX3-ISO; XHL; T-Box Transcription Factor TBX3; T-Box Protein 3; T-Box 3; UMS; Bladder Cancer-Related Protein XHL; Ulnar Mammary Syndrome

The TBX3 protein belongs to a phylogenetically conserved family of genes that share a common DNA-binding domain, the T-box. T-box genes encode transcription factors involved in the regulation of developmental processes. TBX3 is a transcription repressor and is thought to play a role in the anterior-posterior axis of the forelimbs of tetrapods. TBX3 is required, together with TBX2, to maintain cell proliferation in the embryonic lung mesenchyme.128
TBX3 is associated with

  • Ulnar-Mammary Syndrome
    • impaired development of limbs, apocrine glands, teeth, hair, and genitals
  • Holt-Oram syndrome

Paralog: TBX2

A study identified TBX3 (variant rs4534630) as one of 96 ADHD candidate genes.41

1.206. FSCB, Fibrous Sheath CABYR Binding Protein

Other names: C14orf155; Fibrous Sheath CABYR-Binding Protein; DKFZP434F1017; Chromosome 14 Open Reading Frame 155

The FSCB protein activates calcium ion binding and is likely involved in the negative regulation of protein sumoylation. FSCB may be involved in the later stages of fibrous sheath biogenesis and sperm capacitation. FSCB inhibits the SUMOylation of ROPN1 and ROPN1L.129
FSCB is affiliated with

  • Transient Tic Disorder
  • Cataract 8, Multiple Types

A study identified FSCB (rs1957260 variant) as one of 96 candidate genes for ADHD.41

1.207. GAN, Gigaxonin

Other names: KLHL16; GAN1; GIG; Kelch-Like Family Member 16; Kelch-Like Protein 16; Epididymal Secretory Sperm-Binding Protein; Giant Axonal Neuropathy (Gigaxonin)

The GAN protein is a member of the cytoskeletal BTB/kelch (Broad Complex, Tramtrack, and Bric-a-brac) repeat family. GAN plays a role in neurofilament architecture and is involved in mediating the ubiquitination and degradation of certain proteins. GAN regulates the degradation of TBCB, MAP1B, and MAP1S and is essential for the maintenance and survival of neurons.130
GAN is associated with

  • Giant Axonal Neuropathy 1, Autosomal Recessive
  • Axonal Neuropathy

Paralog: KLHL2

A study identified GAN (variants rs3809632 and rs9926795) as one of 96 candidate genes for ADHD.41

1.208. FSIP2, Fibrous Sheath Interacting Protein 2

Other names: Fibrous Sheath-Interacting Protein 2; FLJ34780; SPGF34

The FSIP2 protein is associated with the fibrous sheath of sperm and plays a role in spermatogenesis. Genes encoding most of the proteins associated with the fibrous sheath are transcribed only during the postmeiotic period of spermatogenesis. FSIP2 is specific to spermatogenic cells.131
FSIP2 is associated with

  • Germ cell tumors in the testicles
  • Spermatogenic Failure 34
  • Non-syndromic male infertility due to impaired sperm motility.

A study identified FSIP2 (variant rs12998684) as one of 96 ADHD candidate genes.41

1.209. LPAR1, Lysophosphatidic Acid Receptor 1

Other names: LPA1; Rec.1.3; Mrec1.3; Gpcr26; Edg-2; Vzg-1; EDG2; Endothelial Differentiation, Lysophosphatidic Acid G-Protein-Coupled Receptor, 2; Lysophosphatidic Acid Receptor Edg-2; LPA Receptor 1; LPA-1; Ventricular Zone Gene 1; VZG1

LPAR1 is an integral membrane protein. LPAR1 is essential for normal brain development. LPAR1 is essential for the normal proliferation, survival, and maturation of newly formed neurons in the dentate gyrus in adults. LPAR1 plays a role in pain perception and in the onset of neuropathic pain.
LPAR1 is a lysophosphatidic acid (LPA) receptor belonging to a group known as EDG receptors. These receptors are members of the G-protein-coupled receptor superfamily. EDG receptors are utilized by LPA for cell signaling and mediate various biological functions, including proliferation, platelet aggregation, smooth muscle contraction, inhibition of neuroblastoma cell differentiation, chemotaxis, and tumor cell invasion. LPAR1 activates RALA; this leads to the activation of phospholipase C (PLC) and the formation of inositol 1,4,5-trisphosphate. LPAR1 promotes Rho-dependent reorganization of the actin cytoskeleton in neuronal cells and neurite retraction. Through its interaction with CD14, LPAR1 plays a role in triggering inflammation in response to bacterial lipopolysaccharide (LPS).132
LPAR1 is associated with

  • Pulmonary fibrosis
  • Whooping cough (pertussis)

Paralog: LPAR2

A study identified LPAR1 (variant rs9919025) as one of 96 ADHD candidate genes.41

1.211. NXPE2, Neurexophilin and PC-Esterase Domain Family Member 2

Other names: FAM55B; Family With Sequence Similarity 55, Member B; NXPE Family Member 2; Protein FAM55B; FLJ25224; Neurexophilin and PC-Esterase Domain Family, Member 2

The NXPE2 protein is likely an integral component of the membrane.133

Paralog: NXPE1

A study identified NXPE2 (variant rs4938140) as one of 96 ADHD candidate genes.41

1.214. WNK1, WNK Lysine-Deficient Protein Kinase 1

Other names: PPP1R167; PRKWNK1; HSAN2; HSN2; Protein Phosphatase 1, Regulatory Subunit 167; Serine/Threonine Protein Kinase WNK1; Protein Kinase With No Lysine 1; Erythrocyte 65 kDa Protein; EC 2.7.11.1; KDP; P65; Prostate-Derived Sterile 20-Like Kinase; Hereditary Sensory Neuropathy, Type II; Serine/Threonine Protein Kinase WNK1 1; Serine/Threonine Protein Kinase WNK1 2; Protein Kinase, Lysine-Deficient 1; Protein Kinase Lysine-Deficient 1; Kinase-Deficient Protein; EC 2.7.11; KIAA0344; HWNK1; PSK

The WNK1 protein is a member of the WNK subfamily of serine/threonine protein kinases. WNK1 may be an important regulator of blood pressure by controlling the transport of sodium and chloride ions. WNK1 plays a key role in regulating electrolyte homeostasis, cell signaling, survival, and proliferation. WNK1 acts as an activator and inhibitor of sodium-coupled chloride cotransporters and potassium-coupled chloride cotransporters, respectively. WNK1 activates SCNN1A, SCNN1B, SCNN1D, and SGK1. WNK1 controls sodium and chloride ion transport by inhibiting the activity of WNK4, either through phosphorylation of the kinase or via an interaction between WNK4 and the autoinhibitory domain of WNK1. WNK4 regulates the activity of the thiazide-sensitive Na-Cl cotransporter SLC12A3 through phosphorylation. WNK1 may also play a role in the reorganization of the actin cytoskeleton. WNK1 phosphorylates NEDD4L. WNK1 acts as a scaffold to inhibit the activity and surface expression of SLC4A4, SLC26A6, and CFTR. WNK1 recruits STK39, which mediates this inhibition.
Isoform 3 is a dominant-negative regulator of the longer isoform 1. Isoform 3 has no kinase activity, does not directly inhibit WNK4, and has no direct effect on sodium and chloride ion transport. Isoform 3 indirectly regulates the activity of the sodium-chloride cotransporter by inhibiting isoform 1, associating with isoform 1, and attenuating its kinase activity. In the kidney, isoform 3 may play an important role in regulating sodium and potassium balance.134
WNK1 is associated with

  • Neuropathy, Hereditary Sensory and Autonomic, Type Iia
  • Pseudohypoaldosteronism, Type Iic

Paralog: WNK2

A study identified WNK1 (variant rs7295704) as one of 96 candidate genes for ADHD.41

1.197. LOC101927967, Uncharacterized LOC101927967

Other names: AITD3; TGN; Tg

The protein thyroglobulin (Tg) is a glycoprotein homodimer produced primarily by the thyroid gland. It serves as a substrate for the synthesis of thyroxine and triiodothyronine, as well as for the storage of the inactive forms of thyroid hormone and iodine. Thyroglobulin is secreted from the endoplasmic reticulum to the site of iodination and subsequent thyroxine biosynthesis in the follicular lumen. TG acts as a substrate for the production of the iodinated thyroid hormones thyroxine (T4) and triiodothyronine (T3). The synthesis of T3 and T4 involves the iodination of selected tyrosine residues of TG/thyroglobulin, followed by their oxidative coupling in the lumen of the thyroid follicle. Following the re-internalization of TG and lysosomal-mediated proteolysis, T3 and T4 are released from the polypeptide backbone, leading to their secretion into the bloodstream. One dimer produces 7 thyroid hormone molecules.135
TG is affiliated with

  • Thyroid Dyshormonogenesis 3
  • autoimmune thyroid disease 3
  • Susceptibility to autoimmune thyroid diseases (AITD) such as Graves’ disease and Hashimoto’s thyroiditis

Paralog: BCHE

A study identified TG (rs61744749 variant) as one of 96 ADHD candidate genes.41

The BCHE gene, which encodes butyrylcholinesterase—an enzyme that metabolizes acetylcholine—was identified as a candidate CNV in a de novo deletion on chromosome 3q26.1 in a study of 99 children and adolescents with severe ADHD. The study used genome-wide screening for copy number variations (CNVs) to identify microdeletions and microduplications that might play a role in the pathogenesis of ADHD.136

1.219. MEP1A, Meprin A Subunit Alpha

Other names: PABA Peptide Hydrolase; PPHA; N-Benzoyl-L-Tyrosyl-P-Amino-Benzoic Acid Hydrolase Subunit Alpha; Meprin A, Alpha (PABA Peptide Hydrolase); Endopeptidase-2; EC 3.4.24.18; PPH Alpha; BA268F1.1 (Meprin A Alpha (PABA Peptide Hydrolase)); EC 3.4.24

The MEP1A protein likely mediates metallopeptidase activity. MEP1A is likely involved in proteolysis. MEP1A is located in the extracellular exosome and is part of the meprin A complex.
MEP1A is associated with

  • Colorado tick fever
  • Anisakiasis

Paralog: MEP1B

A study identified MEP1A (variant rs7760667) as one of 96 ADHD candidate genes.41

1.220. ZMYM4, Zinc Finger MYM-Type Containing 4

Other names: Zinc Finger Protein 262; KIAA0425; ZNF198L3; ZNF262; MYM; Zinc Finger MYM-Type Protein 4; Cell Death Inhibiting RNA; Zinc Finger, MYM-Type 4; CDIR

The ZMYM4 protein likely mediates DNA-binding activity. ZMYM4 is involved in the organization of the cytoskeleton and the regulation of cell morphogenesis.137

Paralog: ZMYM6.

A study identified ZMYM4 (variant rs3768336) as one of 96 ADHD candidate genes.41

1.221. DIAPH3, Diaphanous-Related Formin 3

Other names: DRF3; NSDAN; AN; Diaphanous Homolog 3; FLJ34705; AUNA1; MDia2; Auditory Neuropathy, Autosomal Dominant; Diaphanous (Drosophila, Homolog) 3; Diaphanous Homolog 3 (Drosophila); Diaphanous-Related Formin-3; Diaphanous Homolog 3; Diap3; DIAP3; DIA2

The DIAPH3 protein is a member of the diaphan subfamily of the formin family. Members of this family are involved in actin remodeling and regulate cell movement and adhesion. DIAPH3 is an actin nucleation and elongation factor that is required for the assembly of F-actin structures, such as actin cables and stress fibers. DIAPH3 is required for cytokinesis, the formation of stress fibers, and the transcriptional activation of the serum response factor. DIAPH3 binds to the GTP-bound form of Rho and to profilin. DIAPH3 acts in a Rho-dependent manner to recruit profilin to the membrane, where it promotes actin polymerization. DFR proteins couple Rho and Src tyrosine kinase during signal transduction and the regulation of actin dynamics. DIAPH3 also acts as an actin nucleation and elongation factor in the nucleus by promoting nuclear actin polymerization to drive serum-dependent SRF-MRTFA activity.138
DIAPH3 is associated with

  • Auditory Neuropathy, Autosomal Dominant 1
  • Autosomal Dominant Non-Syndromic Sensorineural Deafness, Type Dfna

Paralog: DIAPH2

A study identified DIAPH3 (variant rs2321867) as one of 96 ADHD candidate genes.41

1.222. SP140L, SP140 Nuclear Body Protein-Like

Other names: Nuclear Body Protein SP140-Like Protein; SP140 Nuclear Body Protein-Like; SP140L-1 Protein; SP140L-2 Protein; SP140L-3 Protein

The SP140L protein likely mediates a DNA-binding transcription factor activity that is specific to RNA polymerase II. SP140L is thought to be involved in the regulation of transcription by RNA polymerase II. SP140L is likely located in the nucleus and is expected to be active there.

Paralog: SP140

A study identified SP140L (variants rs11688362 and rs6732684) as one of 96 ADHD candidate genes.41

1.223. FAM120A, Family with Sequence Similarity 120A

Other names: OSSA; KIAA0183; C9orf10; Constitutive Coactivator of PPAR-Gamma-Like Protein 1; Oxidative Stress-Associated Src Activator; Oxidative Stress-Associated Src Activator; Chromosome 9 Open Reading Frame 10; Protein FAM120A; HBVPTPAP

The FAM120A protein mediates RNA-binding activity. FAM120A is found in the cytosol. FAM120A appears to be involved in mRNA transport within the cytoplasm. FAM120A is a critical component of oxidative stress-induced survival signaling. FAM120A activates src family kinases and acts as a scaffold protein that enables src family kinases to phosphorylate and activate PI3 kinase. FAM120A binds to RNA and promotes the secretion of IGF-II.139
FAM120A is associated with stomach cancer by promoting the survival of cancer cells in environments with varying levels of oxidative stress.
Paralog; FAM120C

A study identified FAM120A (variant rs1556416) as one of 96 candidate genes for ADHD.41

1.227. CTNNA3, Catenin Alpha 3

Other names: VR22; Catenin (Cadherin-Associated Protein), Alpha 3; Alpha-T-Catenin; Catenin Alpha-3; MGC26194; Cadherin-Associated Protein; Alpha-Catenin-Like Protein; Alpha T-Catenin; ARVD13

This gene encodes a protein that belongs to the vinculin/alpha-catenin family. CTNNA3 plays a role in cell-cell adhesion in muscle cells. It may be involved in the formation of stretch-resistant cell-cell adhesion complexes.140
CTNNA3 is associated with

  • arrhythmogenic right ventricular dysplasia, familial 13
  • Familial isolated arrhythmogenic ventricular dysplasia, biventricular form

Paralog: CTNNA1

UniProtKB/Swiss-Prot Summary for the CTNNA3 Gene
May be involved in the formation of stretch-resistant cell-cell adhesion complexes. (CTNA3_HUMAN,Q9UI47)

A study identified CTNNA3 (variant rs7094454) as one of 96 ADHD candidate genes.41

1.228. SULT6B1, Sulfotransferase Family 6B Member 1

Other names: Sulfotransferase Family, Cytosolic, 6B, Member 1; Thyroxine Sulfotransferase; Sulfotransferase 6B1; ST6B1; Sulfotransferase SULT6B1; EC 2.8.2.N2

The SULT6B1 protein likely mediates sulfotransferase activity. SULT6B1 is thought to be involved in sulfation and is likely localized in the cytosol and
be active in the cytoplasm. The sulfotransferase SULT6B1 uses 3’-phospho-5’-adenylyl sulfate (PAPS) as a sulfonate donor to catalyze the sulfation of thyroxine. It is involved in thyroxine metabolism.
SULT6B1 is associated with

  • partial motor epilepsy

Paralog: SULT1C2

A study identified SULT6B1 (variant rs4670667) as one of 96 ADHD candidate genes.41

Sulfotransferases are also involved in the breakdown of dopamine. See the article on Dopamine Degradation: Sulfation by Sulfotransferases
We do not know to what extent SULT6B1 is involved in dopamine degradation.

1.235. IPO8, Importin 8

Other names: RANBP8; RAN-binding protein 8; Ran-binding protein 8; Importin-8; IMP8; Imp8; RanBP8; VISS

IPO8 is a protein. The importin-alpha/beta complex and the GTPase Ran mediate the nuclear import of proteins with a classical nuclear localization signal. IPO8 belongs to a class of about 20 potential Ran targets that share a sequence motif with the Ran-binding site of importin-beta. IPO8 binds to the nuclear pore complex and, together with RanGTP and RANBP1, inhibits the GAP-mediated inactivation of the Ran GTPase. IPO8 is involved in nuclear protein import, either as an autonomous nuclear transport receptor or as an adapter-like protein in conjunction with the importin-beta subunit KPNB1. IPO8 acts autonomously, can serve as a receptor for nuclear localization signals (NLS), and promotes the translocation of import substrates through the nuclear pore complex (NPC) via an energy-intensive, Ran-dependent mechanism. On the nucleoplasmic side of the NPC, Ran binds to importin; the importin/substrate complex dissociates, and importin is reexported from the nucleus into the cytoplasm, where GTP hydrolysis releases Ran.141
IPO8 is associated with

  • Viss syndrome
  • Aortic aneurysm

Paralog: IPO7
A study identified IPO8 (variant rs16906369) as one of 96 candidate genes for ADHD.41

1.236. TBC1D13, TBC1 Domain Family Member 13 2 3 4 5

Other names: FLJ10743; Epididymal Secretory Sperm-Binding Protein; TBC1 Domain Family, Member 13

The TBC1D13 protein likely activates the GTPase activity of RAB35. WTBC1D13 is thought to be involved in the activation of GTPase activity and in intracellular protein transport, and is likely to be found in the cytosol and in the membrane. TBC1D13 may, together with RAB35, be involved in regulating the insulin-induced translocation of the glucose transporter SLC2A4/GLUT4 to the plasma membrane in adipocytes.142
TBC1D13 is associated with

  • Apocrine breast carcinoma

Paralog: TBC1D16
A study identified TBC1D13 (variant rs12235388) as one of 96 ADHD candidate genes.41

1.240. PCSK6, Proprotein Convertase Subtilisin/Kexin Type 6

Other names: SPC4; Subtilisin-Like Proprotein Convertase 4; Subtilisin/Kexin-Like Protease PACE4; PACE4; Paired Basic Amino Acid Cleaving System 4; Paired Basic Amino Acid Cleaving Enzyme 4; Subtilisin-Like Protease; EC 3.4.21.75’); EC 3.4.21.75; EC 3.4.21.61; EC 3.4.21.-; EC 3.4.21

The PCSK6 protein is a member of the subtilisin-like proprotein convertase family, which includes proteases that process protein and peptide precursors transported via regulated or constitutive branches of the secretory pathway. PCSK6 undergoes an initial autocatalytic processing in the ER to form a heterodimer, which leaves the ER and localizes to the trans-Golgi network, where a second autocatalytic event occurs and catalytic activity is acquired. The encoded protease is constitutively secreted into the extracellular matrix and is expressed in many tissues, including neuroendocrine organs, the liver, the intestine, and the brain. PCSK6 is one of seven basic amino acid-specific members that cleave their substrates at single or paired basic residues. Some of its substrates include transforming growth factor beta-related proteins, proalbumin, and von Willebrand factor. PCSK6 is thought to play a role in tumor progression and left-right patterning.
PCSK6 is associated with

  • Anthrax
  • Melon allergy

Paralog: PCSK5

A study identified PCSK6 (variant rs2020951) as one of 96 candidate genes for ADHD.41

1.241. DSC3, Desmocollin 3

Other names: CDHF3; DSC1; DSC2; DSC4; DSC; Cadherin Family Member 3; Desmocollin-3; Desmocollin-4; HT-CP

DSC3 is a calcium-dependent glycoprotein that belongs to the desmocollin subfamily of the cadherin superfamily. These members of the desmosome family, along with the desmogleins, are found primarily in epithelial cells, where they form the adhesive proteins of the desmosomal cell-cell junction and are essential for cell adhesion and desmosome formation. The members of the desmosome family are arranged in two clusters on chromosome 18, which together occupy less than 650 kb.143
DSC3 is associated with

  • Hypotrichosis
  • recurrent skin blisters
  • Pemphigus
  • Biomarkers for certain types of cancer

Paralog: DSC2

UniProtKB/Swiss-Prot Summary for the DSC3 Gene
A component of intercellular desmosomal junctions. It participates in the interaction between plaque proteins and intermediate filaments, which mediate cell-cell adhesion. May contribute to epidermal cell positioning (stratification) by mediating the differing levels of adhesion between cells that express different isoforms. (DSC3_HUMAN,Q14574)

Gene Wiki entry for the DSC3 gene

A study identified DSC3 (variant rs2729396) as one of 96 ADHD candidate genes.41

1.243. EPHA6, EPH Receptor A6

Other names: Ephrin Type-A Receptor 6; EPH Homology Kinase 2; EPH-Like Kinase 12; EC 2.7.10.1; FLJ35246; EHK-2; HEK12; EHK2; EK12; Ephrin Receptor EphA6; EC 2.7.10; PRO57066; EPA6

The EPHA6 protein likely mediates transmembrane ephrin receptor activity. EPHA6 is thought to be involved in axon guidance, the positive regulation of kinase activity, and the transmembrane receptor protein tyrosine kinase signaling pathway. EPHA6 is located in the nucleoplasm. EPHA6 is a receptor tyrosine kinase that promiscuously binds GPI-anchored ligands of the ephrin-A family located on neighboring cells, leading to contact-dependent bidirectional signal transduction to neighboring cells. The signaling pathway downstream of the receptor is referred to as forward signaling, while the signaling pathway downstream of the ephrin ligand is referred to as backward signaling. Eph receptors constitute the largest family of receptor tyrosine kinases (RTKs) and are divided into two subclasses, EphA and EphB. Eph receptors were originally identified as mediators of axon guidance and are involved in many processes, particularly in cancer development and progression.144
EPHA6 is associated with

  • oculoauricular syndrome

Paralog: EPHA3

A study identified EPHA6 (variant rs2053246) as one of 96 ADHD candidate genes.41

1.244. PLXNC1, Plexin C1

Other names: VESPR; CD232; Virus-Encoded Semaphorin Protein Receptor; Plexin-C1; Receptor for Virally-Encoded Semaphorin; Receptor for Viral Semaphorin Protein; Plexin (Semaphorin Receptor); CD232 Antigen; PLXN-C1

The PLXNC1 protein is a member of the plexin family. Plexins are transmembrane receptors for semaphorins, a large family of proteins that regulate axon guidance, cell motility and migration, and the immune response. PLXNC1 is a receptor for SEMA7A, smallpox semaphorin A39R, vaccinia virus semaphorin A39R, and herpesvirus Sema protein. The binding of semaphorins triggers cellular responses that lead to cytoskeletal reorganization and the secretion of IL-6 and IL-8. PLXNC1 and its ligand regulate melanocyte adhesion, and viral semaphorins can modulate the immune response by binding to this receptor. PLXNC1 may be a tumor suppressor protein for melanoma.145
PLXNC1 is associated with:

  • Polycystic kidney disease type 4, with or without polycystic liver disease
  • Smallpox

Paralog: PLXND1

A study identified PLXNC1 (variant rs10859690) as one of 96 ADHD candidate genes.41

1.245. FSTL5, Follistatin-Like 5

Other names: KIAA1263; Follistatin-Related Protein 5; Follistatin-Like Protein 5; DKFZp566D234; Follistatin-Like 5

The FSTL5 protein is thought to facilitate the binding of calcium ions. FSTL5 is likely involved in cell differentiation and is located in the extracellular region.146
FSTL5 is associated with

  • Clubfoot
  • Medulloblastoma

Paralog: FSTL4

A study identified FSTL5 (variant rs17504151) as one of 96 ADHD candidate genes.41

1.246. CYFIP1, Cytoplasmic FMR1 Interacting Protein 1

Other names: P140SRA-1; KIAA0068; SHYC; Cytoplasmic FMRP-Interacting Protein 1; Cytoplasmic FMR1-Interacting Protein 1; Specifically Rac1-Associated Protein 1; Selective Hybridizing Clone; P140sra-1; SRA-1; Sra-1; SRA1

The CYFIP1 protein regulates cytoskeletal dynamics and protein translation. CYFIP1 is a component of the WAVE regulatory complex (WRC), which promotes actin polymerization. CYFIP1 also interacts with the synaptic function regulator FMR1 protein and the translation initiation factor 4E to inhibit protein translation. CYFIP1 is part of the CYFIP1-EIF4E-FMR1 complex, which binds to the mRNA cap and mediates translation repression. Within the CYFIP1-EIF4E-FMR1 complex, this subunit acts as an adapter between EIF4E and FMR1. CYFIP1 promotes the translational repression activity of FMR1 in the brain, likely by mediating its association with EIF4E and mRNA. CYFIP1 regulates the formation of membrane ruffles and lamellipodia. CYFIP1 plays a role in axon outgrowth. CYFIP1 binds to F-actin but not to RNA. CYFIP1 is part of the WAVE complex, which regulates actin filament reorganization through its interaction with the Arp2/3 complex. Actin remodeling activity is regulated by RAC1. CYFIP1 regulates epithelial morphogenesis. As a component of the WAVE1 complex, CYFIP1 is required for endocytic BDNF-NTRK2 transport and signal transduction from early endosomes. CYFIP1 may act as an invasion suppressor in cancer.147
CYFIP1 is associated with

  • Fragile X syndrome
  • Angelman syndrome
  • A large chromosomal deletion that includes this gene is associated with an increased risk of schizophrenia and epilepsy in humans
  • Reduced expression has been observed in various types of human cancer
  • CYFIP1 may inhibit tumor invasion

Paralog: CYFIP2

A study identified CYFIP1 (variant rs11632784) as one of 96 candidate genes.41

1.247. TUSC1, Tumor Suppressor Candidate 1

Other names: TSG-9; CCDC89B; Tumor Suppressor Candidate Gene 1 Protein; TSG9

The TUSC1 gene is located in the 9p region of chromosome 9, which contains tumor suppressor genes that play a role in cancer development. It is an intronless gene.148
TUSC1 is associated with

  • Duodenal obstruction
  • Lung cancer
    • TUSC1 is downregulated in non-small-cell lung cancer and small-cell lung cancer cell lines

A study identified TUSC1 (variant rs2498716) as one of 96 ADHD candidate genes.41

1.248. NOTCH2, Notch Receptor 2

Other names: Notch 2; Neurogenic Locus Notch Homolog Protein 2; HN2; Notch (Drosophila) Homolog 2; Notch Homolog 2 (Drosophila); Notch Homolog 2; HJCYS; AGS2

The NOTCH2 protein is a member of the Notch family. This family of type-1 transmembrane proteins shares common structural features, such as an extracellular domain consisting of multiple EGF-like repeats and an intracellular domain consisting of several different types of domains. Members of the Notch family play a role in a wide range of developmental processes by controlling decisions regarding cell fate. The Notch signaling network is an evolutionarily conserved intercellular signaling pathway that regulates interactions between physically adjacent cells. In Drosophila, the interaction of Notch with its cell-bound ligands (Delta, Serrat) establishes an intercellular signaling pathway that plays a key role in development. Homologs of the Notch ligands have also been identified in humans. NOTCH2 is cleaved in the trans-Golgi network and presented as a heterodimer on the cell surface. NOTCH2 functions as a receptor for membrane-bound ligands and may play a role in vascular, renal, and hepatic development. NOTCH2 functions as a receptor for the membrane-bound ligands Jagged-1 (JAG1), Jagged-2 (JAG2), and Delta-1 (DLL1) and regulates cell fate determination. Following ligand activation by the released intracellular Notch domain (NICD), NOTCH2 forms a transcription activator complex with RBPJ/RBPSUH and activates genes of the Enhancer of Split locus. NOTCH2 influences the execution of differentiation, proliferation, and apoptosis programs. NOTCH2 is involved in bone remodeling and homeostasis. NOTCH2, in collaboration with RELA/p65, enhances NFATc1 promoter activity and positively regulates RANKL-induced osteoclast differentiation. NOTCH2 positively regulates the self-renewal of liver cancer cells.149
NOTCH2 is associated with

  • Alagille syndrome type 2
  • Hajdu-Cheney syndrome

Paralog: NOTCH1

A study identified NOTCH2 (variant rs2453044) as one of 96 ADHD candidate genes.41

1.249. OPRK1, Opioid Receptor Kappa 1

Other names: OPRK; KOR; Kappa-type opioid receptor; K-OR-1; KOR-1; Opioid receptor, kappa 1; Opiate receptor, kappa-1; Kappa opioid receptor; KOR1; KOP

The OPRK1 protein is a G-protein-coupled opioid receptor for endogenous alpha-neoendorphins, dynorphins, various synthetic opioids, and the psychoactive diterpene salvinorin A. OPRK1 has a low affinity for beta-endorphins. OPRK1 plays a role in pain perception and in mediating the hypolocomotor, analgesic, and aversive effects of synthetic opioids.
Ligand binding leads to inhibition of adenylate cyclase activity and inhibition of neurotransmitter release. OPRK1 inhibits neurotransmitter release by reducing calcium ion currents and increasing potassium ion conductance. Plays a role in pain perception. OPRK1 plays a role in mediating reduced physical activity during treatment with synthetic opioids, as well as in regulating salivary flow in response to synthetic opioids. OPRK1 may be involved in the excitation and regulation of autonomic and neuroendocrine functions.150
OPRK1 is associated with

  • Morphine addiction
  • Alcohol dependence

Paralog: OPRM1

A study identified OPRK1 (variant rs7461467) as one of 96 ADHD candidate genes.41

1.250. ACAA2, Acetyl-CoA Acyltransferase 2

Other names: DSAEC; Mitochondrial 3-Oxoacyl-Coenzyme A Thiolase; 3-Ketoacyl-CoA Thiolase, Mitochondrial; Mitochondrial 3-Oxoacyl-CoA Thiolase; Acetyl-Coenzyme A Acyltransferase 2; Acyl-CoA Hydrolase, Mitochondrial; Acetyl-CoA Acetyltransferase; EC 2.3.1.16; T1; Acetyl-CoA Acyltransferase; Beta-Ketothiolase; Beta-Ketothiolase; EC 2.3.1.9; EC 3.1.2.-; EC 3.1.2.1; EC 3.1.2.2; EC 2.3.1

The ACAA2 protein catalyzes the final step of the mitochondrial fatty acid beta-oxidation cycle, an aerobic process in which fatty acids are broken down into acetyl-CoA. ACAA2 is thought to catalyze, using free coenzyme A/CoA, the thiolytic cleavage of medium- to long-chain unbranched 3-oxoacyl-CoAs into acetyl-CoA and a fatty acyl-CoA that is two carbon atoms shorter. ACAA2 is also thought to catalyze the condensation of two acetyl-CoA molecules to form acetoacetyl-CoA and may be involved in the production of ketone bodies. ACAA2 exhibits hydrolase activity on various fatty acyl-CoAs and may therefore be responsible for the production of acetate in a side reaction to beta-oxidation. ACAA2 inhibits BNIP3-mediated apoptosis and mitochondrial damage. Unlike most mitochondrial matrix proteins, ACAA2 contains a non-cleavable N-terminal target signal.151
ACAA2 is associated with

  • Alpha-methylacetoacetic aciduria
  • Ureteral transitional cell carcinoma

Paralog: ACAT2

A study identified ACAA2 (variant rs617619) as one of 96 ADHD candidate genes.41

1.251. DPH2, Diphthamide Biosynthesis 2

Other names: 2-(3-Amino-3-Carboxypropyl)Histidine Synthase Subunit 2; DPH2L2; S-Adenosyl-L-Methionine:L-Histidine 3-Amino-3-Carboxypropyltransferase 2; Diphtheria Toxin Resistance Protein 2; DPH2 Homolog; Diphtheria Toxin Resistance Protein Required for Diphthamide Biosynthesis-Like 2 (S. cerevisiae); Diphtheria Toxin Resistance Protein Required for Diphthamide Biosynthesis-Like 2; Diphthamide Biosynthesis Protein 2 Homolog-Like 2; Diphthamide Biosynthesis-Like Protein 2; Diphthamide Biosynthesis Protein 2; DPH2 Homolog (S. cerevisiae); DPH2-Like 2 (S. cerevisiae); DPH2-Like 2

The DPH2 gene is one of two human genes that resemble the yeast gene dph2. The yeast gene was identified based on its ability to complement a diphthamide mutant strain and thus likely plays a role in diphthamide biosynthesis. Diphthamide is a posttranslationally modified histidine residue in elongation factor 2 (EF2) that is the target of ADP-ribosylation by diphtheria toxin. DPH2 is required for the first step of diphthamide biosynthesis, a posttranslational modification of histidine that occurs in elongation factor 2. DPH1 and DPH2 transfer a 3-amino-3-carboxypropyl (ACP) group from S-adenosyl-L-methionine (SAM) to a histidine residue. The reaction is supported by a reduction system comprising DPH3 and an NADH-dependent reductase. DPH2 facilitates the reduction of the catalytic iron-sulfur cluster in the DPH1 subunit.152
DPH2 is associated with

  • Diphtheria
  • Immunodeficiency 24

Related metabolic pathways:

  • Protein metabolism
  • Gamma-carboxylation
  • Hypus formation
  • Arylsulfatase activation
  • 2-(3-Amino-3-carboxypropyl)-histidine synthase activity

Paralog: DPH1

DPH2 was identified as an ADHD candidate gene in a large-scale GWAS.8

1.252. OCT, Ornithine Transcarbamylase

Other names: Ornithine Transcarbamylase; OTCase; OTCD; Ornithine Carbamoyltransferase, Mitochondrial; Ornithine Transcarbamylase, Mitochondrial; EC 2.1.3.3; OTC1; Ornithine Transcarbamylase Deficiency; Ornithine Carbamoyltransferase; EC 2.1.3; OCTD

The OTC protein is a mitochondrial matrix enzyme. OTC catalyzes the second step of the urea cycle, the condensation of carbamoyl phosphate with L-ornithine to form L-citrulline. The urea cycle detoxifies ammonia by converting it into urea for excretion.153
OTC is associated with

  • Ornithine transcarbamylase deficiency
  • Hyperammonemia
  • Disorder of ornithine metabolism

Related metabolic pathways:

  • Key pathway in L-citrulline metabolism
  • Pyrimidine metabolism
  • Phospholipid binding
  • Phosphate ion binding

Paralog: CAD

Ornithine transcarbamylase deficiency154 occurs in approximately 1 in 30,000 people and is caused by a genetic defect in the OTC gene. There are also gene mutations that result in residual enzyme activity, so these may not be diagnosed immediately. People with ADHD develop typical neuropsychological complications such as155

  • Developmental delay
  • Learning disability
  • intellectual disability
  • Attention-Deficit/Hyperactivity Disorder
  • Deficits in executive functions

1.253. KC6, Keratoconus Gene 6

Other names: NONHSAG023745.2; HSALNG0121143; Lnc-RIT2-2

KC6 is an RNA gene and belongs to the lncRNA class.156
KC6 is associated with

  • Keratoconus
  • Inhalation anthrax

A study identified KC6 (variant rs16974432) as one of 96 ADHD candidate genes.41

1.255. LINC00970, Long Intergenic Non-Protein-Coding RNA 970

Other names: NONHSAG003406.2; HSALNG0008302; LINC00970

LINC00970 is an RNA gene that belongs to the lncRNA class.157
LINC00970 is associated with

  • Corneal dystrophy
  • sensorineural hearing loss
  • Fuchs’ endothelial dystrophy

A study identified LINC00970 (variant rs16861817) as one of 96 candidate genes for ADHD.41

1.257. MTRR, 5-Methyltetrahydrofolate-Homocysteine Methyltransferase Reductase

Other names: Methionine Synthase Reductase; CblE; Aquacobalamin Reductase; AqCbl Reductase; MSR; [Methionine Synthase]-Cobalamin Methyltransferase (Cob(II)Alamin Reducing); Methionine Synthase Reductase, Mitochondrial; EC 1.16.1.8

The MTRR protein is a member of the ferredoxin-NADP(+)-reductase (FNR) family of electron transferases. MTRR is a key enzyme in methionine and folate homeostasis, responsible for reactivating methionine synthase (MTR/MS) activity by catalyzing the reductive methylation of MTR-bound cob(II)alamin. Since methionine synthesis requires methyl group transfer via a folate donor, the activity of the encoded enzyme is important for folate metabolism and cellular methylation. Cobalamin (vitamin B12) forms a complex with MTR and serves as an intermediate in methyl transfer reactions that occur cyclically between MTR-bound methylcob(III)alamin and MTR-bound cob(I)alamin forms. Occasional oxidative loss of the cob(I)alamin intermediate during the catalytic cycle presumably leads to the formation of the inactive cob(II)alamin species. The processing of cobalamin in the cytosol occurs within a multiprotein complex consisting of at least MMACHC, MMADHC, MTRR, and MTR, which may contribute to the safe and efficient transport of cobalamin to MTR for the production of methionine. MTRR is necessary for the utilization of methyl groups from the folate cycle, thereby influencing transgenerational epigenetic inheritance. MTRR acts as a molecular chaperone for methionine synthase by stabilizing apoMTR and incorporating methylcob(III)alamin into apoMTR to form the holoenzyme. MTRR functions as aquacob(III)alamin reductase by reducing aquacob(III)alamin to cob(II)alamin; this reduction stimulates the conversion of apoMTR and aquacob(III)alamin to the MTR holoenzyme.158
Mutations in this gene can cause homocystinuria-megaloblastic anemia, type cbl E. Alternative splicing of this gene results in several transcript variants.
MTRR is associated with

  • Homocystinuria - megaloblastic anemia, Cble complementation type
  • Homocystinuria without methylmalonic aciduria

Related metabolic pathways include cobalamin (Cbl, vitamin B12) transport, metabolism, and disease

Paralog: POR

A study identified MTRR (rs924977 variant) as one of 96 candidate genes for ADHD.41

1.258. ADAMDEC1, ADAM-like Decysin 1

Other names: M12.219; A Disintegrin and Metalloproteinase Domain-Like Protein Decysin-1; ADAM-Like Protein Decysin-1; ADAM DEC1; Disintegrin Protease; EC 3.4.24.-; Decysin

ADAMDEC1 is believed to be a secreted protein belonging to the disintegrin metalloproteinase family. Its expression is upregulated during the maturation of dendritic cells. This protein may play an important role in the function of dendritic cells and their interaction with germinal center T cells. ADAMDEC1 may play an important role in regulating the immune response and during pregnancy.159
ADAMDEC1 is associated with

  • Rosacea

Paralog: ADAM28

A study identified ADAMDEC1 (variants rs4872233 and rs7012077) as one of 96 ADHD candidate genes.41

1.259. CLIC4, Chloride Intracellular Channel 4

Other names: P64H1; CLIC4L; HuH1; H1; Intracellular Chloride Ion Channel Protein P64H1; Chloride Intracellular Channel Protein 4; DKFZP566G223; Epididymal Secretory Sperm-Binding Protein; Chloride Intracellular Channel 4-Like; MTCLIC

The protein is a chloride channel. Chloride channels are a diverse group of proteins that regulate fundamental cellular processes, including the stabilization of the cell membrane potential, transepithelial transport, the maintenance of intracellular pH, and the regulation of cell volume. CLIC4 belongs to the p64 family. CLIC4 can insert into membranes and form poorly selective ion channels that can also transport chloride ions. Channel activity depends on pH. Membrane insertion appears to be redox-regulated and can only occur under oxidizing conditions. CLIC4 promotes the expression of HRH3 on the cell surface. CLIC4 has alternative cellular functions, such as a possible role in angiogenesis or in maintaining apical-basolateral membrane polarity during mitosis and cytokinesis. CLIC4 may also promote the proliferation of endothelial cells and regulate endothelial morphogenesis (tubulogenesis).CLIC4 is expressed in many tissues and exhibits an intracellular vesicular pattern in Panc-1 cells (pancreatic cancer cells).160
CLIC4 is associated with pancreatic cancer.
Related metabolic pathways are

  • Glucose/Energy Metabolism
  • Activation of cAMP-dependent PKA
    Paralog: CLIC6

A study identified CLIC4 (variant rs2223365) as one of 96 candidate genes for ADHD.41

1.260. SLC13A5, Solute Carrier Family 13, Member 5

Other names: NACT; INDY; Solute Carrier Family 13 (Sodium-Dependent Citrate Transporter), Member 5; Na(+)/Citrate Cotransporter; Sodium-Dependent Dicarboxylate Transporter; Na+-Coupled Citrate Transporter Protein; Sodium-Dependent Citrate Transporter; Sodium-Coupled Citrate Transporter; EIEE25; DEE25; MIndy; NaCT

The SLC13A5 protein belongs to the Solute Carrier Family 13 (SLC13A) group and is a sodium-dependent citrate cotransporter that mediates the entry of citrate into cells. Other intermediates of the citric acid cycle, such as succinate, fumarate, malate, oxaloacetate, and alpha-ketoglutarate, also serve as substrates for SLC13A5, albeit with significantly lower affinity. The substrate sensitivity of SLC13A5 is citrate > malate ~ alpha-ketoglutarate > succinate ~ fumarate > oxaloacetate ~ isocitrate.161
SLC13A5 is associated with

  • Developmental and Epileptic Encephalopathy 25 with Amelogenesis Imperfecta
  • Developmental and Epileptic Encephalopathy 25

Related signaling pathways involve the transport of inorganic cations/anions and amino acids/oligopeptides.
Paralog: SLC13A2.

A study identified SLC13A5 (variant rs41463346) as one of 96 ADHD candidate genes.41

1.262. ACSL3, Acyl-CoA Synthetase Long Chain Family Member 3

Other names: ACS3; PRO2194; FACL3; Fatty Acid Coenzyme A Ligase, Long-Chain 3; Long-Chain Fatty Acid CoA Ligase 3; Medium-Chain Acyl-CoA Ligase Acsl3; Long-Chain Acyl-CoA Synthetase 3; Fatty Acid CoA Ligase Acsl3; Arachidonate-CoA Ligase; EC 6.2.1.3 4; LACS 3; LACS3; Lignoceroyl-CoA Synthase; EC 6.2.1.15; EC 6.2.1.2

The ACSL3 protein is an isozyme of the long-chain fatty acid coenzyme A ligase family. Although all isozymes in this family differ in terms of substrate specificity, subcellular localization, and tissue distribution, they convert free long-chain fatty acids into fatty acyl-CoA esters, which are used both for the synthesis of cellular lipids and for their breakdown via beta-oxidation. Fatty acid coenzyme A ligases thus play a key role in lipid biosynthesis and fatty acid catabolism. ACSL3 is required for the incorporation of fatty acids into phosphatidylcholine, the most important phospholipid on the surface of VLDL (very low-density lipoproteins). ACSL3 primarily plays an anabolic role in energy metabolism. ACSL3 mediates hepatic lipogenesis.
ACSL3 is highly expressed in the brain and preferentially uses myristate, arachidonic acid, and eicosapentaenoic acid as substrates.162
ACSL3 is associated with

  • Intellectual Developmental Disorder, Autosomal Dominant 38
  • Saethre-Chotzen syndrome

Related signaling pathways:

  • Integration of energy metabolism
  • Arachidonic acid biosynthesis III (6-desaturase, mammals)
  • Protein kinase binding
  • long-chain fatty acid CoA ligase activity

Paralog: ACSL4

A study identified ACSL3 (variant rs10498143) as one of 96 ADHD candidate genes.41

1.264. METTL8, Methyltransferase 8, Methylcytidines

Other names: TIP; tRNA N(3)-methylcytidine methyltransferase METTL8, mitochondrial; mRNA N(3)-methylcytidine methyltransferase METTL8; Tension-Induced/Inhibited Protein; Methyltransferase-Like Protein 8; Methyltransferase-Like 8; FLJ13984; EC 2.1.1.-

The METTL8 protein mediates mRNA methyltransferase activity. METTL8 is involved in mRNA methylation and is thought to be located in the cytoplasm and the nucleus. METTL8 is a mitochondrial S-adenosyl-L-methionine-dependent methyltransferase that mediates the N(3)-methylcytidine modification of residue 32 of the tRNA anticodon loop of mitochondrial tRNA(Ser)(UCN) and tRNA(Thr). The N(3)-methylcytidine methylation modification regulates mitochondrial translation efficiency and is required for respiratory chain activity. N(3)-methylcytidine methylation of mitochondrial tRNA(Ser)(UCN) requires the formation of N(6)-dimethylallyladenosine(37) (i6A37) by TRIT1 as a prerequisite. METTL8 can mediate the N(3)-methylcytidine modification of mRNAs.163
METTL8 is associated with

  • Woodhouse-Sakati syndrome
  • hepatocellular carcinoma in adults

Related metabolic pathways:

  • Methyltransferase activity
  • Histone acetyltransferase activity

Paralog: METTL2A

A study identified METTL8 (variant rs17218608) as one of 96 candidate genes for ADHD.41

1.265. ZNF777, Zinc Finger Protein 777

Other names: KIAA1285

The ZNF777 protein likely mediates DNA-binding transcription factor activity, an RNA polymerase II-specific region, and an RNA polymerase II cis-regulatory region with sequence-specific DNA-binding activity. ZNF777 is thought to be involved in the regulation of transcription by RNA polymerase II and is active in the cell nucleus. ZNF777 may be involved in transcriptional repression and inhibits cell proliferation by inducing CDKN1A/p21 through downregulation of NIBAN1/FAM129A at low cell density.164
Related metabolic pathway:

  • Gene expression (transcription)
  • Nucleic acid binding

Paralog: ZNF398

A study identified ZNF777 (variant rs17852167) as one of 96 candidate genes.41

1.266. TFAP2D, Transcription Factor AP-2 Delta

Other names: AP-2delta; TFAP2BL1; Transcription Factor AP-2 Beta (Activating Enhancer-Binding Protein 2 Beta)-Like 1; Transcription Factor AP-2 Delta (Activating Enhancer-Binding Protein 2 Delta); Activating Enhancer-Binding Protein 2-Delta; Transcription Factor AP-2-Beta-Like 1; Transcription Factor AP-2-Delta; AP2-Delta; Activating Enhancer Binding Protein 2 Beta-Like 1; AP-2-Like

The TFAP2D protein is thought to activate

  • DNA-binding transcription factor activity
  • an RNA polymerase II-specific DNA-binding activity
  • RNA polymerase II transcription regulatory region sequence-specific DNA-binding activity

TFAP2D is thought to be involved in

  • Development of anatomical structures
  • Regulation of the proliferation of cell populations
  • Regulation of transcription by RNA polymerase II
  • downregulation of the apoptotic process in neurons
  • positive regulation of transcription by RNA polymerase II

TFAP2D interacts with inducible viral and cellular enhancer elements to regulate the transcription of selected genes. AP-2 factors bind to the consensus sequence 5’-GCCNNNNGGC-3’ and activate genes involved in a wide range of important biological functions, including the proper development of the eyes, face, body wall, limbs, and neural tube. They also suppress a number of genes, including MCAM/MUC18, C/EBP alpha, and MYC.165

TFAP2D is associated with

  • Char syndrome
  • Branchio-oculo-facial syndrome

Related metabolic pathways:

  • Transcription regulation by the AP-2 (TFAP2) family of transcription factors
  • Gene expression (transcription)

A study identified TFAP2D (variant rs78648104) as one of 96 ADHD candidate genes.41

1.267. OTOR, Otoraplin

Other names: FDP; Fibrocyte-Derived Protein; MIAL1; MIAL; Melanoma Inhibitory Activity-Like Protein

The OTOR protein belongs to the melanoma-inhibiting activity family. OTOR is secreted via the Golgi apparatus and may play a role in the development and maintenance of cartilage.
OTOR is affiliated with

  • Melanomas
  • Reversal of the translation
  • Numbness

Paralog: MIA

A study identified OTOR (variant rs6105651) as one of 96 candidate genes for ADHD.41

1.269. EEPD1, Endonuclease/Exonuclease/Phosphatase Family Domain-Containing 1

Other names: KIAA1706; Endonuclease/Exonuclease/Phosphatase Family Domain-Containing Protein 1; HSPC107

The EEPD1 protein is thought to possess DNA-binding activity and to be involved in the positive regulation of cholesterol efflux.
EEPD1 is anchored in the plasma membrane.166
EEPD1 is associated with

  • Meningitis carcinoma

Related signaling pathways:

  • Signal transduction
  • NR1H2- and NR1H3-mediated signal transduction

A study identified EEPD1 (variant rs2726059) as one of 96 ADHD candidate genes.41

1.270. MAD2L1, Mitotic Arrest Deficient 2-Like 1

Other names: MAD2; HSMAD2; MAD2 (Mitotic Arrest Deficient, Yeast, Homolog)-Like 1; Mitotic Spindle Assembly Checkpoint Protein MAD2A; Mitotic Arrest Deficient 2-Like Protein 1; MAD2-Like Protein 1; Mitotic Arrest Deficient, Yeast, Homolog-Like 1; MAD2 Mitotic Arrest Deficient-Like 1; HsMAD2

The MAD2L1 protein is a component of the mitotic spindle assembly checkpoint, which prevents the onset of anaphase until all chromosomes are properly aligned at the metaphase plate.167
MAD2L1 is associated with

  • Mosaic Variegated Aneuploidy Syndrome 1
  • Embryoma

Related signaling pathways:

  • APC-Cdc20-mediated degradation of Nek2A
  • Cell cycle, mitotic
  • Protein homodimerization activity
  • identical protein binding

Paralog: MAD2L2

A study identified MAD2L1 (variant rs1553692) as one of 96 ADHD candidate genes.41

1.271. FLRT2, Fibronectin Leucine-Rich Transmembrane Protein 2

Other names: Fibronectin-Like Domain-Containing Leucine-Rich Transmembrane Protein 2; Leucine-Rich Repeat Transmembrane Protein FLRT2; KIAA0405

The FLRT2 protein is a member of the fibronectin-leucine-rich transmembrane (FLRT) family of cell adhesion molecules that regulate early embryonic vascular and neural development. FLRT2 functions both as a homophilic cell adhesion molecule and as a heterophilic chemorepellent through its interaction with members of the uncoordinated-5 receptor family. The proteolytic removal of the extracellular region controls the migration of neurons in the developing cerebral cortex.168

FLRT2 is involved in

  • Cell-cell adhesion
    • through its interactions with ADGRL3 and, likely, other latrophilins expressed on the surface of neighboring cells
  • Cell migration
    • on its interaction with UNC5D in the migration of cortical neurons during brain development
  • Axon guidance.
    • mediates the collapse of the axonal growth cone
    • Plays a inhibitory role in neuron guidance through its interaction with UNC5D and possibly other members of the UNC-5 family. Plays a role in fibroblast growth factor-mediated signaling cascades
  • Organization of the cardiac basement membrane
    • Essential for the normal organization of the cardiac basement membrane during embryogenesis and for normal embryonic epicardial and cardiac morphogenesis.

Related signaling pathways:

  • Signal transduction
  • downregulation of FGFR1 signaling
  • Protein-macromolecule adapter activity
  • chemorepellent activity

Paralog: FLRT3
A study identified FLRT2 (variant rs17712565) as one of 96 candidate genes for ADHD.41

1.272. PLD5, Phospholipase D Family Member 5

Other names: Inactive Phosphatidylcholine-Hydrolyzing Phospholipase D5; Inactive Choline Phosphatase 5; Inactive Phospholipase D5; Inactive PLD 5; FLJ40773; Phospholipase D Family, Member 5; PLDC; PLDc

The PLD5 protein likely mediates catalytic activity and is thought to be an integral component of the membrane.169
PLD5 is associated with

  • Nephrotic syndrome, type 7

Paralog: PLD3

A study identified PLD5 (variant rs4658830) as one of 96 ADHD candidate genes.41

1.274. CASC20, Cancer Susceptibility 20

Other names: Cancer Susceptibility Candidate 20; Cancer Susceptibility 20; NONHSAG031223.2; HSALNG0128472; CASC20

CASC20 is an RNA gene that belongs to the lncRNA class.170

A study identified CASC20 (variant rs6038589) as one of 96 ADHD candidate genes.41

1.276. COBLL1, Cordon-Bleu WH2 Repeat Protein-Like 1

Other names: KIAA0977; Cordon-Bleu Protein-Like 1; COBL-Like 1; Cordon-Bleu WH2 Repeat Protein-Like 1; COBLR1

The COBLL1 protein mediates cadherin-binding activity. COBLL1 is located in the extracellular exosome.171
COBLL1 is associated with

  • Age-related macular degeneration, 10

Related metabolic pathways: Actin binding

Paralog: COBL

A study identified COBLL1 (variant rs139834711) as one of 96 ADHD candidate genes.41

1.277. PAPOLA, Poly(A) Polymerase Alpha

Other names: PAP; Polynucleotide Adenylyltransferase Alpha; EC 2.7.7.19; PAP-Alpha; EC 2.7.7

The PAPOLA protein belongs to the family of poly(A) polymerases. PAPOLA is required for the addition of adenosine residues to form the 3’-poly(A) tail of mRNAs, as well as for the endoribonucleolytic cleavage reaction at certain polyadenylation sites. PAPOLA can acquire its specificity through interaction with a cleavage and polyadenylation specificity factor (CPSF) at its C-terminus.172
PAPOLA is affiliated with

  • 46,Xx Sex Reversal 3
  • Combat Disorder

Related signal paths:

  • Processing of Capped, Intronless Pre-mRNA
  • Processing of Pre-mRNA Containing Capped Introns
  • RNA binding
  • Manganese ion binding

Paralog: PAPOLB

A study identified PAPOLA (rs7160641 variant) as one of 96 candidate genes.41

1.280. KDM4A, Lysine Demethylase 4A

Other names: JHDM3A; KIAA0677; TDRD14A; JMJD2A; JMJD2; JmjC Domain-Containing Histone Demethylation Protein 3A; Jumonji C Domain-Containing Histone Demethylase 3A; [Histone H3]-Trimethyl-L-Lysine(36) Demethylase 4A; [Histone H3]-Trimethyl-L-Lysine(9) Demethylase 4A; Jumonji Domain-Containing Protein 2A; Lysine (K)-Specific Demethylase 4A; Lysine-Specific Demethylase 4A; Jumonji Domain-Containing 2A; Tudor Domain-Containing 14A; Jumonji Domain-Containing 2; EC 1.14.11.66; EC 1.14.11.69; C 1.14.11

The KDM4A protein, a member of the Jumonji domain 2 (JMJD2) family, contains a JmjN domain, a JmjC domain, a JD2H domain, two TUDOR domains, and two PHD-type zinc fingers. This nuclear protein functions as a trimethylation-specific demethylase that converts specific trimethylated histone residues to their dimethylated form, and as a transcription repressor.KDM4A is a histone demethylase that specifically demethyulates ‘Lys-9’ and ‘Lys-36’ residues of histone H3, thereby playing a central role in the histone code. KDM4A does not demethylate histone H3 ‘Lys-4’, H3 ‘Lys-27’, or H4 ‘Lys-20’, but it does demethylate trimethylated H3 ‘Lys-9’ and H3 ‘Lys-36’ residues, while having no effect on mono- or dimethylated residues. The demethylation of Lys residues produces formaldehyde and succinate. KDM4A is involved in the transcriptional repression of ASCL2- and E2F-responsive promoters through the recruitment of histone deacetylases and NCOR1, respectively.
[Isoform 2]: Essential for muscle differentiation, it promotes the transcriptional activation of the Myog gene by regulating the removal of repressive chromatin marks at its promoter. It lacks the N-terminal demethylase domain.173
KDM4A is associated with

  • primary hyperoxaluria

Related signaling pathways:

  • Homology-directed repair
  • DNA double-strand break reaction
  • Ubiquitin-protein ligase binding
  • Histone H3 methyl-lysine-36 demethylase activity

Paralog: KDM4C

This gene was identified as a candidate for ADHD in a large-scale GWAS.8
KDM4A has been identified as a candidate gene for ADHD.61.

1.281. KDM4A-AS1, KDM4A Antisense RNA 1

Other names: KDM4A antisense RNA 1; NONHSAG001242.2; HSALNG0003118; KDM4A-AS1

KDM4A-AS1 is an RNA gene that belongs to the lncRNA class.174

This gene was identified as a candidate for ADHD in a large-scale GWAS.8

1.284. CCDC24, Coiled-Coil Domain Containing 24

Other names: Coiled-Coil Domain-Containing Protein 24; MGC45441

The CCDC24 protein likely acts before or during blastocyst hatching.175

This gene was identified as a candidate for ADHD in a large-scale GWAS.8

1.286. IPO13, Importin 13

Other names: RANBP13; KIAA0724; IMP13; Ran-Binding Protein 13; Importin-13; Ran Binding Protein 13; Late Gestation Lung; Karyopherin 13; Karyopherin-13; RanBP13; KAP13; Imp13; Kap13; LGL2

The IPO13 protein is a member of the importin-beta family of nuclear transport proteins. IPO13 mediates the import of specific cargo proteins from the cytoplasm into the nucleus and is dependent on the Ras-related nuclear protein GTPase system. IPO13 is also involved in the nuclear export of the eukaryotic translation initiation factor 1A. IPO13 serves as a receptor for nuclear localization signals (NLS) in cargo substrates. IPO13 presumably mediates the docking of the importin/substrate complex to the nuclear pore complex (NPC) by binding to nucleoporin, whereupon the complex is translocated through the pore via an energy-intensive, Ran-dependent mechanism. On the nucleoplasmic side of the NPC, Ran binds to importin; the importin/substrate complex dissociates, and importin is re-exported from the nucleus into the cytoplasm, where Ran is released through GTP hydrolysis. The directionality of nuclear import appears to be determined by an asymmetric distribution of the GTP- and GDP-bound forms of Ran between the cytoplasm and the nucleus. IPO13 mediates the nuclear import of UBC9, the RBM8A/MAGOH complex, PAX6, and likely other members of the Paired-Homeobox family. IPO13 mediates the nuclear export of eIF-1A, and the cytoplasmic release of eIF-1A is triggered by the loading of import substrates onto IPO13.176
IPO13 is associated with:

  • Partington syndrome
  • Agenesis of the Corpus Callosum, With Abnormal Genitalia
    • Agenesis of the corpus callosum, severe intellectual disability, seizures, and spasticity. Men are severely affected, while women may not be affected or may exhibit a milder phenotype.

Related signal paths are:

  • Binding of small GTPases

Paralog: TNPO3

This gene was identified as a candidate for ADHD in a large-scale GWAS.8

1.307. NT5DC1

A study found evidence that general signal transduction molecules (such as NT5DC1, PSD, SEC23IP, and ZCCHC4) play an important role in the etiology of ADHD. The role of cellular communication appears to be a potential key component in the development of ADHD in both adults and children.177

1.308. PSD

A study found evidence that general signal transduction molecules (such as NT5DC1, PSD, SEC23IP, and ZCCHC4) play an important role in the etiology of ADHD. The role of cellular communication appears to be a potential key component in the development of ADHD in both adults and children.177

1.309. SEC23IP

A study found evidence that general signal transduction molecules (such as NT5DC1, PSD, SEC23IP, and ZCCHC4) play an important role in the etiology of ADHD. The role of cellular communication appears to be a potential key component in the development of ADHD in both adults and children.177

1.310. ZCCHC4

A study found evidence that general signal transduction molecules (such as NT5DC1, PSD, SEC23IP, and ZCCHC4) play an important role in the etiology of ADHD. The role of cellular communication appears to be a potential key component in the development of ADHD in both adults and children.177

1.311. SHANK2, SH3, and Multiple Ankyrin Repeat Domains 2

Other names: CTTNBP1; ProSAP1; SPANK-3; CORTBP1; SHANK; SH3 and Multiple Ankyrin Repeat Domains Protein; Cortactin-Binding Protein 1; Proline-Rich Synapse-Associated Protein 1; Proline-Rich Synapse-Associated Protein 1; Cortactin SH3 Domain-Binding Protein; GKAP/SAPAP Interacting Protein; Cortactin Binding Protein 1; KIAA1022; PROSAP1; CortBP1; AUTS17; Shank2

SHANK2 belongs to the Shank family of synaptic proteins, which may function as molecular scaffolds in the postsynaptic density of excitatory synapses. Shank proteins contain several domains involved in protein-protein interactions, including ankyrin repeats and an SH3 domain. SHANK2 contains a PDZ domain, a consensus sequence for cortactin-SH3-domain-binding peptides, and a sterile alpha motif. The alternative splicing detected in Shank genes has been proposed as a mechanism for regulating the molecular structure of Shank and the spectrum of Shank-interacting proteins in the postsynaptic density of the adult and developing brain. SHANK2 appears to be an adapter protein in the postsynaptic density of excitatory synapses that links postsynaptic membrane receptors—including NMDA receptors and metabotropic glutamate receptors—to the actin-based cytoskeleton. SHANK2 may play a role in the structural and functional organization of the dendritic spine and the synaptic junction.
SHANK2 is associated with

  • Susceptibility to autism spectrum disorders
  • Autism 17
  • Autism Spectrum Disorder

Related signal paths:

  • Protein-protein interactions at synapses
  • Regulation of CFTR activity (normal and CF)
  • SH3 domain binding
  • synaptic receptor-adaptor activity

Paralog: SHANK1

SHANK2 is thought to be involved in ADHD.178179
Overexpression of the extrasynaptic SHANK2A(R462X) variant resulted in ADHD-like behavior.180

1.315. KDM6B, Lysine Demethylase 6B

In a study, KDM6B was found to have one of the highest levels of potential as a risk gene for ADHD and ASD.181

1.316. ZNF148

A de novo truncated ZNF148 variant has been identified as a cause of ASD, ADHD, and intellectual disability.182

1.317. DDX3X

DDX3X syndrome is a genetically caused neurodevelopmental disorder associated with intellectual disability, autism spectrum disorder, speech delays, attention-deficit/hyperactivity disorder, and medical comorbidities.183

1.318. ATP9A

A genetically determined ATP9A deficiency causes ADHD and abnormal endosomal recycling by modulating the activity of RAB5 and RAB11.184

1.322. KDM2B

In a cohort of 21 individuals with heterozygous (presumably) pathogenic KDM2B variants, the following were found to be more common:185

  • Developmental delays
  • intellectual disabilities
  • Autism
  • ADHD
  • congenital organ abnormalities, primarily of the heart, eyes, and urogenital system
  • subtle facial dysmorphisms

There are several hundred other candidate genes that are not listed here.

1.323. SLC6A8 - Creatinine Transporter

A defect in the SLC6A8 gene, which encodes the creatinine transporter, leads to attention and hyperactivity problems in 55% of people with ADHD.186
Mice with a deactivated creatinine transporter in dopaminergic neurons exhibited hyperactivity.187

Two studies found a higher glutamate/glutamine-to-creatinine ratio in ADHD-HI than in ADHD-I.188189

1.324. GMPPB, GDP-Mannose Pyrophosphorylase B

Other names: Mannose-1-phosphate guanyltransferase beta, GTP-mannose-1-phosphate guanylyltransferase beta; EC 2.7.7.13; KIAA1851; LGMDR19; MDDGA14; MDDGB14; MDDGC14190

Elevated levels of the protein GMPPB in the brain are associated with an increased risk of ADHD.191192

1.325. ICA1L, islet cell autoantigen 1-like protein

Elevated levels of the protein ICA1L in the brain are associated with an increased risk of ADHD.191192

1.326. NAA80, N-alpha-acetyltransferase 80

A study found that elevated levels of the protein NAA80 in the brain are associated with an increased risk of ADHD.191

1.327. HYI, Putative hydroxypyruvate isomerase

A study found that elevated levels of the protein HYI in the brain are associated with an increased risk of ADHD.191

1.328. CISD2, CDGSH iron-sulfur domain-containing protein 2

Elevated levels of the CISD2 protein in the brain are associated with an increased risk of ADHD.191192

1.329. TIE1, Tie-1 tyrosine protein kinase receptor

A study found that elevated levels of the protein TIE1 in the CSF and blood plasma are associated with an increased risk of ADHD.191

1.330. RMDN1, Regulator of Microtubule Dynamics Protein 1

A study found that elevated levels of the protein RMDN1 in blood plasma are associated with an increased risk of ADHD.191

1.331. UPF3B

Loss-of-function mutations in UPF3B lead, among other things, to ADHD, intellectual disability (ID, syndromic and non-syndromic), autism, and childhood schizophrenia.193

1.332. KLF13

A case report on a boy with ADHD describes a de novo heterozygous genetic variant in the gene for Krüppel-like factor 13 (KLF13), which belongs to the KLF family and regulates axonal growth, development, and regeneration. This variant appears to influence protein-protein interactions, DNA binding, and transcriptional activation or repression.194

1.333. NUDT3, Nudix, Nucleoside diphosphate-linked moiety X-type motif 3

A GWAS found that rs206936 in the NUDT3 gene increased the risk of ADHD by 39% (OR: 1.39).195
Furthermore, rs206936 from NUDT3 was associated with inattention.
NUDT3 is also a risk gene for obesity.

1.334. GPRC5B, G protein-coupled receptor, family C, group 5, member B

A GWAS found that rs6497416, located in the intronic region of the GPRC5B gene, is a risk allele for ADHD and was associated with hyperactivity/impulsivity.195
GPRC5B belongs to the family of metabotropic glutamate receptors, which have been linked to the etiology of ADHD.
GPRC5B is also a risk gene for obesity.

1.335. GNPDA2, Glucosamine-6-Phosphate Deaminase 2

A GWAS found that rs10938397 in GNPDA2 was associated with inattention.195
GNPDA2 is also a risk gene for obesity.

1.336. MAP2K5, Mitogen-Activated Protein Kinase 5

A GWAS found that a variant of the MAP2K5 gene was associated with inattention and hyperactivity.195
MAP2K5 is also a risk gene for obesity.

1.337. SLC2A3, Solute Carrier Family 2 Member 3, GLUT3

Other names: Solute Carrier Family 2 (Facilitated Glucose Transporter), Member 3; Solute Carrier Family 2, Facilitated Glucose Transporter Member 3; Glucose Transporter Type 3, Brain; GLUT-3196

SLC2A3 (GLUT3) is a candidate gene for ADHD.197198

SLC2A3 was identified as a candidate CNV in a study of 99 children and adolescents with severe ADHD. The study used genome-wide screening for copy number variations (CNVs) to detect microdeletions and microduplications that might play a role in the pathogenesis of ADHD.136
A meta-analysis of a German and a Spanish cohort found an association between the SNP rs12842 and ADHD. While the CNV analysis detected a population-specific enrichment of SLC2A3 duplications only in German ADHD patients, the CNV + rs12842haplotype influenced ADHD risk in both the German and Spanish cohorts. Carriers of the duplication exhibited increased SLC2A3mRNA expression in peripheral blood cells and altered event-related potentials, which reflected deficits in working memory and cognitive response control, as well as an underestimation of the energy content of high-calorie foods.199
A study examined the generation of a human induced pluripotent stem cell (iPSC) line from a woman with ADHD who carried a duplication of SLC2A3.200
A study found evidence that MPH affects GLUT3 expression.201

Heterozygous GLUT3-deficient (GLUT3+/-) mice exhibited ASS symptoms such as increased electroencephalographic seizure activity, impaired spatial learning and working memory, reduced vocalizations, and stereotypies.202

1.338. PDE4D6

The PDE4D6 gene, which encodes brain-specific phosphodiesterase 4D isoform 6, was identified as a candidate CNV in a study of 99 children and adolescents with severe ADHD. The study used genome-wide screening for copy number variations (CNVs) to detect microdeletions and microduplications that might play a role in the pathogenesis of ADHD.136

1.339. PLEKHB1

The PLEKHB1 gene, which encodes a brain-specific pleckstrin homology domain-containing protein and has been shown to function in primary sensory neurons, was identified as a candidate CNV in a study of 99 children and adolescents with severe ADHD. The study used genome-wide screening for copy number variations (CNVs) to detect microdeletions and microduplications that might play a role in the pathogenesis of ADHD.136

1.340. NDUFAF2

The gene for mitochondrial NADH dehydrogenase 1 α subcomplex assembly factor 2 (NDUFAF2) was identified as a candidate CNV in a study of 99 children and adolescents with severe ADHD. The study used genome-wide screening for copy number variations (CNVs) to detect microdeletions and microduplications that might play a role in the pathogenesis of ADHD.136

Non-coding genes: RNA genes

1.87. FEZF1-AS1, FEZF1 antisense RNA 1 (Chromosome 7q31.32)

FEZF1-AS1 is not a protein gene, but rather an RNA gene belonging to the lncRNA class. FEZF1-AS1 is associated with the following diseases:

  • ductal adenocarcinoma of the pancreas
  • Stomach cancer.

OMIM: FEZF1-AS1

rs3958046 in FEZF1-AS1 is a candidate gene for ADHD.203204

rs11767283 correlates with age at first sexual intercourse
rs11767283 is correlated with diet
rs145467198 correlates with heel bone mineral density
rs7779018 is associated with schizophrenia

1.192. LOC100507468

LOC100507468 has 150 functional associations with biological entities spanning 5 categories (organism, disease, phenotype or trait, chemical, cell line, cell type or tissue, gene, protein, or microRNA).205

A study identified LOC100507468 (variant rs1195234) as one of 96 ADHD candidate genes.41

1.194. LINC00355, Long Intergenic Non-Protein-Coding RNA 355

Other names: NONHSAG013685.2; NONHSAG013688.2; NONHSAG013687.2; HSALNG0097622; HSALNG0097626; HSALNG0097627; LINC00355

LINC00355 is an RNA gene that belongs to the lncRNA class.206
LINC00355 is associated with

  • Bladder cancer

A study identified LINC00355 (variant rs9528776) as one of 96 candidate genes for ADHD.41

1.197. LOC101927967, Uncharacterized LOC101927967

Other names: ONHSAG028283.2; SALNG0016229; HSALNG0016258; Lnc-LRRTM4-3

LOC101927967 is an RNA gene and belongs to the lncRNA class.207

A study identified LOC101927967 (variant rs1819004) as one of 96 candidate genes.41

1.198. IFNG-AS1, IFNG Antisense RNA 1

Other names: LincR-Ifng-3’AS; Tmevpg1; NEST; Theiler’s Murine Encephalomyelitis Virus Persistence Candidate Gene 1; FNG Antisense RNA 1; NONHSAG011599.2; HSALNG0092137; GS1-410F4.2; IFNG-AS1

IFNG-AS1 is an RNA gene and belongs to the lncRNA class.208
IFNG-AS1 is associated with

  • Ulcerative colitis
  • Sjögren’s syndrome

A study identified IFNG-AS1 (variant rs17629076) as one of 96 ADHD candidate genes.41

1.200. LOC101929484

We were unable to find any information regarding LOC101929484.

A study identified LOC101929484 (variant rs2343365) as one of 96 ADHD candidate genes.41

1.201. LOC100133050, beta-glucuronidase pseudogene

We were unable to find any information regarding LOC100133050.

A study identified LOC100133050 (variant rs7717154) as one of 96 ADHD candidate genes.41

1.204. C6orf123, LINC01558, Long Intergenic Non-Protein-Coding RNA 1558

Other names: DJ431P23.4; C6orf123; HGC6.2; Long Intergenic Non-Protein Coding RNA 1557; LINC01557; Uncharacterized Protein Encoded by LINC01558; Chromosome 6 Open Reading Frame 123; NONHSAG045429.2; Protein HGC6.2; HSALNG0055207; LINC01558

C6orf123 (LINC01558) is an RNA gene that belongs to the lncRNA class.209

A study identified C6orf123 (variant rs543930) as one of 96 candidate genes for ADHD.41

1.205. LINC01364, Long Intergenic Non-Protein-Coding RNA 1364

Other names: NONHSAG001996.2; SALNG0004963; LINC01364

LINC01364 is an RNA gene that belongs to the lncRNA class.210

A study identified LINC01364 (variant rs12745339) as one of 96 candidate genes for ADHD.41

1.213. LOC101929184

We were unable to find any information regarding LOC101929184,

A study identified LOC101929184 (variant rs12757080) as one of 96 ADHD candidate genes.41

1.215. LOC101927797

We were unable to find any information regarding LOC101927797.

A study identified LOC101927797 (variant rs2824866) as one of 96 ADHD candidate genes.41

1.216. LINC02229:9, LOC101928769

Other names: NSG00000250313; RP11-5P22.3; ENSG00000250313.2; OTTHUMG00000162359.2; LINC02229211

LINC02229 is an RNA gene and belongs to the lncRNA class.212

LOC101928769 appears to correlate with a reduced hippocampal volume.213

A study identified LOC101928769 (variant rs6865656 and variant rs2968194) as one of 96 ADHD candidate genes.41

1.217. MIR4255, MicroRNA 4255

Other names: Hsa-Mir-4255; MIMAT0016885; Hsa-MiR-4255; MI0015863

MIR4255 is an RNA gene belonging to the miRNA class.214

MicroRNAs (miRNAs) are short (20–24 nt) noncoding RNAs that are involved in the post-transcriptional regulation of gene expression in multicellular organisms by influencing both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs), which can be either protein-coding or non-coding. The primary transcript is cleaved by the enzyme Drosha, a ribonuclease III, to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is in turn cleaved by the cytoplasmic ribonuclease Dicer to produce the mature miRNA and antisense miRNA star products (miRNA-*). The mature miRNA is incorporated into an RNA-induced silencing complex (RISC), which recognizes target mRNAs through incomplete base pairing with the miRNA and, in most cases, leads to translation inhibition or destabilization of the target mRNA. RefSeq depicts the probable microRNA stem-loop structure. [Provided by RefSeq, Sep 2009]

A study identified MIR4255 (variant rs11264025) as one of 96 ADHD candidate genes.41

1.224. LINC01377, Long Intergenic Non-Protein-Coding RNA 1377

Other names: NONHSAG039702.2; CTD-2029E14.1; HSALNG0039710; Lnc-IRX1-5

LINC01377 is an RNA gene that belongs to the lncRNA class.215

A study identified LINC01377 (variant rs469546) as one of 96 candidate genes for ADHD.41

1.239. CASC17, Cancer Susceptibility 17

Other names: LINC00600; Cancer Susceptibility Candidate 17; Cancer Susceptibility 17; Long Intergenic Non-Protein-Coding RNA 600; NONHSAG022649.2; HSALNG0118488; CASC17

CASC17 is an RNA gene and belongs to the class of lncRNAs.216
CASC17 is associated with Robinow syndrome, autosomal recessive type 1.

A study identified CASC17 (variant rs7224246) as one of 96 ADHD candidate genes.41

1.289. LINC02497, Long Intergenic Non-Protein-Coding RNA 2497

Other names: NONHSAG037712.2; HSALNG0033638; LINC02497

LINC02497 is an RNA gene that belongs to the lncRNA class.217

This gene was identified as a candidate for ADHD in a large-scale GWAS.8

1.290. LINC00461, Long Intergenic Non-Protein-Coding RNA 461

Other names: EyeLinc1; ECONEXIN; NDIME; Neural Differentiation Initiation of MEF2C Expression; LOC645323; Evolutionarily Conserved and Expressed in Neural Tissues (ECONEXIN); Evolutionarily Conserved and Expressed in Neural Tissues; Expressed in the Visual Cortex; Visual Cortex-Expressed; NONHSAG040968.2; NONHSAG040969.2; HSALNG0043367; HSALNG0043368; LincRNA 461; LINC00461; Visc-1a; Visc-1b; Visc-2; Visc; VISC

LINC00461 is an RNA gene and belongs to the lncRNA class (mir-9/mir-79 microRNA precursor family RF00237). LINC00461 is an evolutionarily conserved gene that produces alternately spliced long noncoding RNAs, which are primarily expressed in the brain and the visual cortex. These transcripts may be involved in tumorigenesis, as their depletion via siRNA suppresses the division of glioma cells. The transcripts can bind to miR-411-5p and Argonaut 2 and regulate their activity, thereby altering the expression of genes involved in tumor growth.218 “LINC00461 and its mouse homolog NDIME regulate the expression of the MEF2C gene, which encodes the transcription factor ‘myocyte-specific enhancer factor 2C.’ MEF2C is highly expressed in the brain and plays a key role in neurogenesis by inhibiting neuronal cell apoptosis, promoting the formation of neuronal synapses, and influencing the differentiation and maturation of neuronal progenitor cells.”219
LINC00461 is associated with

  • Glioma
  • Cataract 24

LINC00461 was identified as an ADHD candidate gene in a large-scale GWAS.8
LINC00461 is associated with ADHD and ASD.219

1.291. MIR9–2, MicroRNA 9-2

Other names: Hsa-MiR-9-3p; Hsa-MiR-9-5p; Hsa-Mir-9-2; MIRN9-2; Hsa-Mir-9-P2_pre; MIMAT0000441; MIMAT0000442; MI0000467; MiRNA9-2; Mir-9-2; RF00237

MIR9-2 is an RNA gene that belongs to the miRNA class (mir-9/mir-79 microRNA precursor family RF00237). microRNAs (miRNAs) are short (20–24 nt) non-coding RNAs that are involved in the post-transcriptional regulation of gene expression in multicellular organisms by influencing both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs), which can be either protein-coding or non-coding. The primary transcript is cleaved by the enzyme Drosha, a ribonuclease III, to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is in turn cleaved by the cytoplasmic ribonuclease Dicer to produce the mature miRNA and antisense miRNA star products (miRNA*). The mature miRNA is incorporated into an RNA-induced silencing complex (RISC), which recognizes target mRNAs through incomplete base pairing with the miRNA and, in most cases, leads to translation inhibition or destabilization of the target mRNA. RefSeq represents the probable microRNA stem-loop structure.220
MIR9-2 is associated with

  • oral squamous cell carcinoma
  • Glioblastoma

Related signaling pathways:

  • Epithelial-to-mesenchymal transition in colorectal cancer.

This gene was identified as a candidate for ADHD in a large-scale GWAS.8

1.292. LINC02060, Long Intergenic Non-Protein-Coding RNA 2060

Other names: NONHSAG040966.2; HSALNG0043365; CTC-498M16.2; LINC02060

LINC02060 is an RNA gene belonging to the lncRNA class.221
This gene was identified as a candidate for ADHD in a large-scale GWAS.8

1.293. TMEM161B-AS1, TMEM161B Divergent Transcript

Other names: TMEM161B-DT, Linc-POLR3G-8; TMEM161B antisense RNA 1; TMEM161B antisense RNA 1; NONHSAG040958.2; SALNG0043357; HSALNG0043358; CTC-358I24.1; Lnc-RASA1-4

TMEM161B-DT is an RNA gene belonging to the lncRNA class.222
This gene was identified as a candidate for ADHD in a large-scale GWAS.8

1.294. MIR3666, microRNA 3666

Other names: Hsa-Mir-3666; MIMAT0018088; Hsa-MiR-3666; MI0016067

MIR3666 is an RNA gene belonging to the miRNA class. microRNAs (miRNAs) are short (20–24 nt) non-coding RNAs that are involved in the post-transcriptional regulation of gene expression in multicellular organisms by influencing both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs), which can be either protein-coding or non-coding. The primary transcript is cleaved by the enzyme Drosha, a ribonuclease III, to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is in turn cleaved by the cytoplasmic ribonuclease Dicer to produce the mature miRNA and antisense miRNA star products (miRNA*). The mature miRNA is incorporated into an RNA-induced silencing complex (RISC), which recognizes target mRNAs through incomplete base pairing with the miRNA and, in most cases, leads to translation inhibition or destabilization of the target mRNA. RefSeq represents the probable microRNA stem-loop structure.223

This gene was identified as a candidate for ADHD in a large-scale GWAS.8

1.295. LINC01288, Long Intergenic Non-Protein-Coding RNA 1288

Other names: TCONS_00014671; NONHSAG049959.2; HSALNG0064496; LINC01288

LINC01288 is an RNA gene belonging to the lncRNA class.224

This gene was identified as a candidate for ADHD in a large-scale GWAS.8

1.300. LINC01572, Long Intergenic Non-Protein-Coding RNA 1572

Other names: NONHSAG019920.2; NONHSAG019917.2; HSALNG0112544; LINC01572

LINC01572 is an RNA gene belonging to the lncRNA class.225

This gene was identified as a candidate for ADHD in a large-scale GWAS.8

1.301. Intergenic, Locus 2, Chromosome 1, Base position 96602440, Variant rs1222063

This SNP was identified as an ADHD candidate in a large-scale GWAS.8

However, in one study, the frequency distribution of the rs1222063 genotype did not conform to the Hardy-Weinberg equilibrium test (P < 0.05) and was therefore not representative of the population.226

1.302. Intergenic Locus 4, Chromosome 3, Base position 20669071, Variant rs4858241

This SNP was identified as an ADHD candidate in a large-scale GWAS.8

A study found longer Stroop reaction times.226

1.313. LncRNA HULC

Elevated expression of CLOCK, PER1, lncRNA HULC, and lncRNA UCA1 correlated with an evening chronotype, difficulty falling asleep and staying asleep, disorders in the sleep-wake transition, and excessive sleepiness in ADHD. There was no significant association between individual genes and specific sleep parameters.227

1.314. LncRNA UCA1

Elevated expression of CLOCK, PER1, lncRNA HULC, and lncRNA UCA1 correlated with an evening chronotype, difficulty falling asleep and staying asleep, disorders in the sleep-wake transition, and excessive sleepiness in ADHD. There was no significant association between individual genes and specific sleep parameters.227

1.330. SPTBN1

A report on two case studies links SPTBN1 to ADHD.228

1.331. LRRC7

LRRC7 gene variants with reduced or absent function were found in 33 people. Of these, 24% had ADHD and 24% had ASD.229

1.332. KDM5B

In a study, KDM5B was identified as a candidate gene for ADHD with an FDR of 0.04.230

1.333. YLPM1

YLPM1 was identified as a candidate gene for ADHD in a study with an FDR of 0.20.230

1.334. CTNND2

CTNND2 was identified as a candidate gene for ADHD in a study with an FDR of 0.26.230

1.335. GNB2L1

GNB2L1 was identified as a candidate gene for ADHD in a study with an FDR of 0.30.230

1.336. ANTXR1

In a study, ANTXR1 was identified as a candidate gene for ADHD with a probability of p = 1.96 × 10−6 .231

1.337. CHD6

CHD6 was identified as an ADHD candidate gene in a study with a probability of p = 4.50 × 10−6 .231

1.338. SNX17

SNX17 was identified as a candidate gene for ADHD in a study with a probability of p = 7.08 × 10−6 .231

1.339. RAI1

In a study, RAI1 was identified as a candidate gene for ADHD with a probability of p = 1.12 × 10−5 .231

1.340. MMP16

In a study, MMP16 was identified as a candidate gene for ADHD with a probability of p = 1.53 × 10−5 .231

1.341. AGFG1

AGFG1 was identified as a candidate gene for ADHD in a study with a probability of p = 1.94 × 10−5 .231

1.342. CHST15

CHST15 was identified as an ADHD candidate gene in a study with a probability of p = 2.52 × 10−5 .231

1.343. ZMYND11

In a study, ZMYND11 was identified as a candidate gene for ADHD with a probability of p = 3.22 × 10−5 .231

1.344. TNFAIP3

In a study, TNFAIP3 was identified as a candidate gene for ADHD with a probability of p = 3.96 × 10−5 .231

1.345. EP400

In a study, EP400 was identified as a candidate for ADHD with a probability of p = 4.83 × 10−5 .231

1.346. ST8SIA2

ST8SIA2 was identified as a candidate gene for ADHD in a study with a probability of p = 5.79 × 10−5 .231

1.347. IPO5

In a study, IPO5 was identified as a candidate gene for ADHD with a probability of p = 7.00 × 10−5 .231

1.348. PIK3R2

In a study, PIK3R2 was identified as a candidate gene for ADHD with a probability of p = 8.37 × 10−5 .231

1.349. MYT1L

There is some evidence that MYT1L gene variants increase the risk of ADHD.232233 234 The risk of ADHD associated with MYT1L mutations was 30%.235

1.350. LSM6

LSM6 was significantly associated with ADHD.236192

1.351. PDXDC1

PDXDC1 was significantly associated with ADHD.236

1.352. HYAL3

HYAL3 was significantly associated with ADHD.236

1.353. METTL15

METTL15 was significantly associated with ADHD.236

1.354. RPS26

RPS26 was significantly associated with ADHD.236

1.355. RP11-142I20.1

RP11-142I20.1 was significantly associated with ADHD.236

1.356. ABCB9

ABCB9 was significantly associated with ADHD.236

1.357. AP006621.5

AP006621.5 was significantly associated with ADHD.236

1.358. AC000068.5

AC000068.5 was significantly associated with ADHD.236

1.359. LRRC37A15P

LRRC37A15P was significantly associated with ADHD.236

1.360. HYAL3

HYAL3 has been identified as a potential candidate gene for ADHD.237

1.361. NUP43

NUP43 has been identified as a potential candidate for ADHD.237

1.362. PIDD

PIDD has been identified as a potential candidate for ADHD.237

1.363. PNPLA2

PNPLA2 has been identified as a potential candidate for ADHD.237

1.364. NAT6

Elevated levels of the NAT6 protein in the brain are associated with an increased risk of ADHD.192

1.367. CCDC171

CCDC171 in excitatory neurons is a candidate gene for childhood ADHD.238

1.368. PEAK1

PEAK1 in excitatory neurons is a candidate gene for childhood ADHD.238

1.369. DLGAP2

DLGAP2 in inhibitory neurons is a candidate gene for childhood ADHD.238

1.370. ARHGEF7

ARHGEF7 in oligodendrocytes is a candidate gene for childhood ADHD and for persistent ADHD.238

1.371. TLR4

TLR4 in oligodendrocytes is a candidate gene for childhood ADHD.238

1.372. HTR3B

HTR3B in excitatory neurons is a candidate gene for late-diagnosed ADHD.238

1.373. ASTN2

ASTN2 in oligodendrocytes is a candidate gene for late-diagnosed ADHD.238

1.374. RBM6

RBM6 in oligodendrocytes is a candidate gene for late-diagnosed ADHD.238

1.376. FRAT1/FRAT2

FRAT1/FRAT2 has been identified as a candidate gene, particularly for ADHD that persists into adulthood.61.

1.377. CGB1

CGB1 has been identified as a candidate gene, particularly for ADHD that persists into adulthood.61.

1.378. RNF225/ZNF584

RNF225/ZNF584 has been identified as a candidate gene, particularly for ADHD that persists into adulthood.61.

1.379. RSPH3

RSPH3 is involved in neuronal migration in the embryonic brain. RSPH3 has been identified as a candidate gene for ADHD.61.

1.380. CADPS2

CADPS2 is involved in monoamine and neurotrophin neurotransmission. CADPS2 has been identified as a candidate gene for ADHD.61.

1.381. AMN

AMN plays a role in vitamin B12 absorption. AMN has been identified as a candidate gene for ADHD.61.

1.382. FBXL17

FBXL17 is associated with intelligence. FBXL17 has been identified as a candidate gene for ADHD.61.

1.383. GIGYF2

GIGYF2 has been identified as a candidate gene for ADHD.61.

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  11. Synofzik, Smets, Mallaret, Di Bella, Gallenmüller, Baets, Schulze, Magri, Sarto, Mustafa, Deconinck, Haack, Züchner, Gonzalez, Timmann, Stendel, Klopstock, Durr, Tranchant, Sturm, Hamza, Nanetti, Mariotti, Koenig, Schöls, Schüle, de Jonghe, Anheim, Taroni, Bauer (2016): SYNE1 ataxia is a common recessive ataxia with major non-cerebellar features: a large multi-centre study. Brain. 2016 May;139(Pt 5):1378-93. doi: 10.1093/brain/aww079. PMID: 27086870; PMCID: PMC6363274. ↥

  12. SYNE1, GeneCards.org ↥

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  16. BMPR1B, GeneCards.org ↥

  17. Qin L, Ahn KJ, Wine Lee L, de Charleroy C Jr, Crenshaw EB 3rd (2019): Analyses with double knockouts of the Bmpr1a and Bmpr1b genes demonstrate that BMP signaling is involved in the formation of precerebellar mossy fiber nuclei derived from the rhombic lip. PLoS One. 2019 Dec 23;14(12):e0226602. doi: 10.1371/journal.pone.0226602. PMID: 31869353; PMCID: PMC6927620. ↥

  18. Racacho, Byrnes, MacDonald, Dranse, Nikkel, Allanson, Rosser, Underhill, Bulman (2015): Two novel disease-causing variants in BMPR1B are associated with brachydactyly type A1. Eur J Hum Genet. 2015 Dec;23(12):1640-5. doi: 10.1038/ejhg.2015.38. Epub 2015 Mar 11. PMID: 25758993; PMCID: PMC4795202. ↥

  19. Badura-Stronka M, Mróz D, Beighton P, Łukawiecki S, Wicher K, Latos-Bieleńska A, Kozłowski K. Novel mutation in the BMPR1B gene (R486L) in a Polish family and further delineation of the phenotypic features of BMPR1B-related brachydactyly. Birth Defects Res A Clin Mol Teratol. 2015 Jun;103(6):567-72. doi: 10.1002/bdra.23354. PMID: 25776145. ↥

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  24. HAS3, GeneCards.org ↥

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  28. Skandalis SS, Karalis T, Heldin P (2020): Intracellular hyaluronan: Importance for cellular functions. Semin Cancer Biol. 2020 May;62:20-30. doi: 10.1016/j.semcancer.2019.07.002. PMID: 31276783. ↥

  29. Wickramasekara RN, Morrill S, Farhat Y, Smith SJ, Yilmazer-Hanke D (2018): Glutathione and Inter-α-trypsin inhibitor heavy chain 3 (Itih3) mRNA levels in nicotine-treated Cd44 knockout mice. Toxicol Rep. 2018 Jun 22;5:759-764. doi: 10.1016/j.toxrep.2018.06.010. PMID: 29984189; PMCID: PMC6031235. ↥ ↥ ↥ ↥

  30. ITIH3, Inter-Alpha-Trypsin Inhibitor Heavy Chain 3, GeneCards ↥

  31. Brandl EJ, Lett TA, Chowdhury NI, Tiwari AK, Bakanidze G, Meltzer HY, Potkin SG, Lieberman JA, Kennedy JL, Müller DJ (2016): The role of the ITIH3 rs2535629 variant in antipsychotic response. Schizophr Res. 2016 Oct;176(2-3):131-135. doi: 10.1016/j.schres.2016.06.032. PMID: 27396837. ↥

  32. Sasayama D, Hori H, Yamamoto N, Nakamura S, Teraishi T, Tatsumi M, Hattori K, Ota M, Higuchi T, Kunugi H (2014): ITIH3 polymorphism may confer susceptibility to psychiatric disorders by altering the expression levels of GLT8D1. J Psychiatr Res. 2014 Mar;50:79-83. doi: 10.1016/j.jpsychires.2013.12.002. PMID: 24373612. ↥

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  34. Ebana Y, Ozaki K, Inoue K, Sato H, Iida A, Lwin H, Saito S, Mizuno H, Takahashi A, Nakamura T, Miyamoto Y, Ikegawa S, Odashiro K, Nobuyoshi M, Kamatani N, Hori M, Isobe M, Nakamura Y, Tanaka T (2007): A functional SNP in ITIH3 is associated with susceptibility to myocardial infarction. J Hum Genet. 2007;52(3):220-229. doi: 10.1007/s10038-006-0102-5. Epub 2007 Jan 9. PMID: 17211523. ↥

  35. Park S, Park JE, Yoo HJ, Kim JW, Cho SC, Shin MS, Cheong JH, Han DH, Kim BN (2015): Family-based association study of the arsenite methyltransferase gene (AS3MT, rs11191454) in Korean children with attention-deficit hyperactivity disorder. Psychiatr Genet. 2015 Feb;25(1):26-30. doi: 10.1097/YPG.0000000000000064. PMID: 25461954. n = 238 ↥

  36. ATP2C2, ATPase Secretory Pathway Ca2+ Transporting 2, GeneCards ↥

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  38. Andres EM, Neely HL, Hafeez H, Yasmin T, Kausar F, Basra MAR, Raza MH(2021): Study of rare genetic variants in TM4SF20, NFXL1, CNTNAP2, and ATP2C2 in Pakistani probands and families with language impairment. Meta Gene. 2021 Dec;30:100966. doi: 10.1016/j.mgene.2021.100966. PMID: 34540591; PMCID: PMC8444582. ↥

  39. Müller B, Schaadt G, Boltze J, Emmrich F; LEGASCREEN Consortium, Skeide MA, Neef NE, Kraft I, Brauer J, Friederici AD, Kirsten H, Wilcke A (2017): ATP2C2 and DYX1C1 are putative modulators of dyslexia-related MMR. Brain Behav. 2017 Oct 18;7(11):e00851. doi: 10.1002/brb3.851. PMID: 29201552; PMCID: PMC5698869. ↥

  40. Newbury DF, Winchester L, Addis L, Paracchini S, Buckingham LL, Clark A, Cohen W, Cowie H, Dworzynski K, Everitt A, Goodyer IM, Hennessy E, Kindley AD, Miller LL, Nasir J, O’Hare A, Shaw D, Simkin Z, Simonoff E, Slonims V, Watson J, Ragoussis J, Fisher SE, Seckl JR, Helms PJ, Bolton PF, Pickles A, Conti-Ramsden G, Baird G, Bishop DV, Monaco AP (2009):. CMIP and ATP2C2 modulate phonological short-term memory in language impairment. Am J Hum Genet. 2009 Aug;85(2):264-72. doi: 10.1016/j.ajhg.2009.07.004. PMID: 19646677; PMCID: PMC2725236. ↥

  41. Liu, Feng, Li, Cheng, Qian, Wang (2021): Deep learning model reveals potential risk genes for ADHD, especially Ephrin receptor gene EPHA5. Brief Bioinform. 2021 Jun 9:bbab207. doi: 10.1093/bib/bbab207. PMID: 34109382. n = 1.983 ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥

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  43. MPP6, GeneCards.org ↥

  44. Saitoh Y, Kamijo A, Yamauchi J, Sakamoto T, Terada N (2019): The membrane palmitoylated protein, MPP6, is involved in myelin formation in the mouse peripheral nervous system. Histochem Cell Biol. 2019 May;151(5):385-394. doi: 10.1007/s00418-018-1745-y. PMID: 30357511. ↥

  45. Khoury S, Wang QP, Parisien M, Gris P, Bortsov AV, Linnstaedt SD, McLean SA, Tungate AS, Sofer T, Lee J, Louie T, Redline S, Kaunisto MA, Kalso EA, Munter HM, Nackley AG, Slade GD, Smith SB, Zaykin DV, Fillingim RB, Ohrbach R, Greenspan JD, Maixner W, Neely GG, Diatchenko L (2021): Multi-ethnic GWAS and meta-analysis of sleep quality identify MPP6 as a novel gene that functions in sleep center neurons. Sleep. 2021 Mar 12;44(3):zsaa211. doi: 10.1093/sleep/zsaa211. PMID: 33034629; PMCID: PMC7953222. ↥

  46. PALB2, GeneVards.org ↥

  47. ZNF385D, GeneCards.org ↥

  48. Eicher JD, Powers NR, Miller LL, Akshoomoff N, Amaral DG, Bloss CS, Libiger O, Schork NJ, Darst BF, Casey BJ, Chang L, Ernst T, Frazier J, Kaufmann WE, Keating B, Kenet T, Kennedy D, Mostofsky S, Murray SS, Sowell ER, Bartsch H, Kuperman JM, Brown TT, Hagler DJ Jr, Dale AM, Jernigan TL, St Pourcain B, Davey Smith G, Ring SM, Gruen JR (2013): Pediatric Imaging, Neurocognition, and Genetics Study. Genome-wide association study of shared components of reading disability and language impairment. Genes Brain Behav. 2013 Nov;12(8):792-801. doi: 10.1111/gbb.12085. Epub 2013 Oct 9. PMID: 24024963; PMCID: PMC3904347. ↥

  49. Xu C, Aragam N, Li X, Villla EC, Wang L, Briones D, Petty L, Posada Y, Arana TB, Cruz G, Mao C, Camarillo C, Su BB, Escamilla MA, Wang K (2013): BCL9 and C9orf5 are associated with negative symptoms in schizophrenia: meta-analysis of two genome-wide association studies. PLoS One. 2013;8(1):e51674. doi: 10.1371/journal.pone.0051674. Epub 2013 Jan 29. PMID: 23382809; PMCID: PMC3558516. ↥

  50. Lasky-Su J, Neale BM, Franke B, Anney RJ, Zhou K, Maller JB, Vasquez AA, Chen W, Asherson P, Buitelaar J, Banaschewski T, Ebstein R, Gill M, Miranda A, Mulas F, Oades RD, Roeyers H, Rothenberger A, Sergeant J, Sonuga-Barke E, Steinhausen HC, Taylor E, Daly M, Laird N, Lange C, Faraone SV (2008): Genome-wide association scan of quantitative traits for attention deficit hyperactivity disorder identifies novel associations and confirms candidate gene associations. Am J Med Genet B Neuropsychiatr Genet. 2008 Dec 5;147B(8):1345-54. doi: 10.1002/ajmg.b.30867. PMID: 18821565. ↥

  51. CHMP7, Charged Multivesicular Body Protein 7, GeneCards ↥

  52. Malik B, Devine H, Patani R, La Spada AR, Hanna MG, Greensmith L (2019): Gene expression analysis reveals early dysregulation of disease pathways and links Chmp7 to pathogenesis of spinal and bulbar muscular atrophy. Sci Rep. 2019 Mar 5;9(1):3539. doi: 10.1038/s41598-019-40118-3. PMID: 30837566; PMCID: PMC6401132. ↥

  53. Tong JH, Hawi Z, Dark C, Cummins TD, Johnson BP, Newman DP, Lau R, Vance A, Heussler HS, Matthews N, Bellgrove MA, Pang KC (2016): Separating the wheat from the chaff: systematic identification of functionally relevant noncoding variants in ADHD. Mol Psychiatry. 2016 Nov;21(11):1589-1598. doi: 10.1038/mp.2016.2. PMID: 27113999. ↥

  54. Dark C, Williams C, Bellgrove MA, Hawi Z, Bryson-Richardson RJ (2020): Functional validation of CHMP7 as an ADHD risk gene. Transl Psychiatry. 2020 Nov 6;10(1):385. doi: 10.1038/s41398-020-01077-w. PMID: 33159045; PMCID: PMC7648633. ↥

  55. MUCL3, GeneCards ↥

  56. PIWIL4, Piwi Like RNA-Mediated Gene Silencing 4, GeneCards ↥

  57. AK8, Adenylate Kinase 8, GeneCards ↥

  58. CFAP221, Cilia And Flagella Associated Protein 221, GeneCards ↥

  59. Bustamante-Marin XM, Shapiro A, Sears PR, Charng WL, Conrad DF, Leigh MW, Knowles MR, Ostrowski LE, Zariwala MA (2020): Identification of genetic variants in CFAP221 as a cause of primary ciliary dyskinesia. J Hum Genet. 2020 Jan;65(2):175-180. doi: 10.1038/s10038-019-0686-1. PMID: 31636325; PMCID: PMC6920546. ↥

  60. FEZF2 bei GeneCards.org ↥

  61. Rovira P, Demontis D, Sánchez-Mora C, Zayats T, Klein M, Mota NR, Weber H, Garcia-Martínez I, Pagerols M, Vilar-Ribó L, Arribas L, Richarte V, Corrales M, Fadeuilhe C, Bosch R, Martin GE, Almos P, Doyle AE, Grevet EH, Grimm O, Halmøy A, Hoogman M, Hutz M, Jacob CP, Kittel-Schneider S, Knappskog PM, Lundervold AJ, Rivero O, Rovaris DL, Salatino-Oliveira A, da Silva BS, Svirin E, Sprooten E, Strekalova T; ADHD Working Group of the Psychiatric Genomics Consortium; 23andMe Research team; Arias-Vasquez A, Sonuga-Barke EJS, Asherson P, Bau CHD, Buitelaar JK, Cormand B, Faraone SV, Haavik J, Johansson SE, Kuntsi J, Larsson H, Lesch KP, Reif A, Rohde LA, Casas M, Børglum AD, Franke B, Ramos-Quiroga JA, Soler Artigas M, Ribasés M (2020): Shared genetic background between children and adults with attention deficit/hyperactivity disorder. Neuropsychopharmacology. 2020 Sep;45(10):1617-1626. doi: 10.1038/s41386-020-0664-5. PMID: 32279069; PMCID: PMC7419307. METASTUDY ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥

  62. Garber A, Weingarten LS, Abreu NJ, Elloumi HZ, Haack T, Hildebrant C, Martínez-Gil N, Mathews J, Müller AJ, Valenzuela Palafoll I, Steigerwald C, Chung WK (2024): Rare predicted deleterious FEZF2 variants are associated with a neurodevelopmental phenotype. Am J Med Genet A. 2024 Feb 29:e63578. doi: 10.1002/ajmg.a.63578. PMID: 38425142. ↥

  63. CEP112, Centrosomal Protein 112, GeneCards ↥

  64. NCKAP5, NCK Associated Protein 5, GeneCards ↥

  65. SPATA33, Spermatogenesis Associated 33, GeneCards ↥

  66. SPATA33, OMIM ↥

  67. CDK10, Cyclin Dependent Kinase 10; GeneCards ↥

  68. PPP1R11, PROTEIN PHOSPHATASE 1, REGULATORY SUBUNIT 11, GeneCards ↥

  69. NME5, NME/NM23 FAMILY, MEMBER 5; GeneCards ↥

  70. Qi, Wang S1, Zhang, Liu, Wen, Ma, Cheng, Li, Cheng, Du, Liang, Zhao, Ding, Zhang (2019): An integrative analysis of transcriptome-wide association study and mRNA expression profile identified candidate genes for attention-deficit/hyperactivity disorder. Psychiatry Res. 2019 Oct 25:112639. doi: 10.1016/j.psychres.2019.112639. ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥

  71. ABHD5, GeneCards ↥

  72. ABHD5; DocCheck Flexikon ↥

  73. GMPR2, GeneCards ↥

  74. BLOC1S2 , GeneCards ↥

  75. KIAA0319L , GeneCards ↥

  76. FMNL3, GeneCards ↥

  77. CCDC138, Gene Cards ↥

  78. TMBIM6, GeneCards ↥

  79. SV2A, Genecards.org ↥

  80. TARBP1, Genecards.org ↥

  81. TATDN3, Genecards.org ↥

  82. ST3GAL3, Genecards.org ↥

  83. Gordon-Lipkin E, Cohen JS, Srivastava S, Soares BP, Levey E, Fatemi A (2018): ST3GAL5-Related Disorders: A Deficiency in Ganglioside Metabolism and a Genetic Cause of Intellectual Disability and Choreoathetosis. J Child Neurol. 2018 Nov;33(13):825-831. doi: 10.1177/0883073818791099. Epub 2018 Sep 5. PMID: 30185102; PMCID: PMC6188822. ↥ ↥

  84. Svirin E, de Munter J, Umriukhin A, Sheveleva E, Kalueff AV, Svistunov A, Morozov S, Walitza S, Strekalova T (2022):Aberrant Ganglioside Functions to Underpin Dysregulated Myelination, Insulin Signalling, and Cytokine Expression: Is There a Link and a Room for Therapy? Biomolecules. 2022 Oct 7;12(10):1434. doi: 10.3390/biom12101434. PMID: 36291644; PMCID: PMC9599472. REVIEW ↥

  85. Klein, Singgih, van Rens, Demontis, Børglum, Mota, Castells-Nobau, Kiemeney, Brunner, Arias-Vasquez, Schenck, van der Voet, Franke (2020): Contribution of Intellectual Disability-Related Genes to ADHD Risk and to Locomotor Activity in Drosophila. Am J Psychiatry. 2020 Feb 12:appiajp201918050599. doi: 10.1176/appi.ajp.2019.18050599. PMID: 32046534. ↥ ↥ ↥

  86. Demontis, Walters, Martin, Mattheisen, Als, Agerbo, Baldursson, Belliveau, Bybjerg-Grauholm, Bækvad-Hansen, Cerrato, Chambert, Churchhouse, Dumont, Eriksson, Gandal, Goldstein, Grasby, Grove, Gudmundsson, Hansen, Hauberg, Hollegaard, Howrigan, Huang, Maller, Martin, Martin, Moran, Pallesen, Palmer, Pedersen, Pedersen, Poterba, Poulsen, Ripke, Robinson, Satterstrom, Stefansson, Stevens, Turley, Walters, Won H, Wright; ADHD Working Group of the Psychiatric Genomics Consortium (PGC); Early Lifecourse & Genetic Epidemiology (EAGLE) Consortium; 23andMe Research Team, Andreassen, Asherson, Burton, Boomsma, Cormand, Dalsgaard, Franke, Gelernter, Geschwind, Hakonarson, Haavik, Kranzler, Kuntsi, Langley, Lesch, Middeldorp, Reif, Rohde, Roussos, Schachar, Sklar, Sonuga-Barke, Sullivan, Thapar, Tung, Waldman, Medland, Stefansson, Nordentoft, Hougaard, Werge, Mors, Mortensen, Daly, Faraone, Børglum, Neale (2018): Discovery of the first genome-wide significant risk loci for attention deficit/hyperactivity disorder. Nat Genet. 2019 Jan;51(1):63-75. doi: 10.1038/s41588-018-0269-7. PMID: 30478444; PMCID: PMC6481311. ↥

  87. Hall LS, Pain O, O’Brien HE, Anney R, Walters JTR, Owen MJ, O’Donovan MC, Bray NJ (2021): Cis-effects on gene expression in the human prenatal brain associated with genetic risk for neuropsychiatric disorders. Mol Psychiatry. 2021 Jun;26(6):2082-2088. doi: 10.1038/s41380-020-0743-3. Epub 2020 May 4. PMID: 32366953; PMCID: PMC7611670. ↥

  88. ELAVL4, GeneCards.org ↥

  89. FGFR3, GeneCards.org ↥

  90. Stevens HE, Scuderi S, Collica SC, Tomasi S, Horvath TL, Vaccarino FM (2023): Neonatal loss of FGFR2 in astroglial cells affects locomotion, sociability, working memory, and glia-neuron interactions in mice. Transl Psychiatry. 2023 Mar 11;13(1):89. doi: 10.1038/s41398-023-02372-y. PMID: 36906620; PMCID: PMC10008554. ↥

  91. ACAD11, GeneCards.org ↥

  92. CNPY2, GeneCards.org ↥

  93. BST1, GeneCards.org ↥

  94. RASSF4, GeneCards.org ↥

  95. RAPGEF5, GeneCards.org ↥

  96. MVP, GeneCards.org ↥

  97. RPS20, GeneCards.org ↥

  98. RASGRP4, GeneCards.org ↥

  99. MAP1A , GeneCards.org ↥

  100. Satterstrom, Walters, Singh, Wigdor, Lescai, Demontis, Kosmicki, Grove, Stevens, Bybjerg-Grauholm, Bækvad-Hansen, Palmer, Maller; iPSYCH-Broad Consortium, Nordentoft, Mors, Robinson, Hougaard, Werge, Bo Mortensen, Neale, Børglum, Daly (2019): Autism spectrum disorder and attention deficit hyperactivity disorder have a similar burden of rare protein-truncating variants. Nat Neurosci. 2019 Dec;22(12):1961-1965. doi: 10.1038/s41593-019-0527-8. ↥

  101. FBXO25, GeneCards.org ↥

  102. Harich, Klein, Ockeloen, van der Voet, Schimmel-Naber, de Leeuw, Schenck, Franke (2019): From man to fly – convergent evidence links FBXO25 to ADHD and comorbid psychiatric phenotypes. J Child Psychol Psychiatry. 2019 Dec 17. doi: 10.1111/jcpp.13161. ↥

  103. TRAPPC9, GeneCards.org ↥

  104. MEF2C, GeneCards.org ↥

  105. TNRC6B, GeneCards.org ↥

  106. Granadillo, Stegmann, Guo, Xia, Angle, Bontempo, Ranells, Newkirk, Costin, Viront, Stumpel, Sinnema, Panis, Pfundt, Krapels, Klaassens, Nicolai, Li, Jiang, Marco, Canton, Latronico, Montenegro, Leheup, Bonnet, Amudhavalli, Lawson, McWalter, Telegrafi, Pearson, Kvarnung, Wang, Bi, Rosenfeld, Shinawi (2020): Pathogenic variants in TNRC6B Cause a genetic disorder characterised by developmental delay/intellectual disability and a spectrum of neurobehavioural phenotypes including autism and ADHD. J Med Genet. 2020 Oct;57(10):717-724. doi: 10.1136/jmedgenet-2019-106470. PMID: 32152250. ↥

  107. EPHA5, GeneCards.org ↥

  108. RIMS1, GeneCards.org ↥

  109. NRG3, GeneCards.org ↥

  110. TENM4, GnrCards.org ↥

  111. MDGA2, GeneCards.org ↥ ↥

  112. RBFOX1, GeneCards.org ↥

  113. LIG4, GeneCards.org ↥ ↥

  114. NEDD4L, GeneCards.org ↥

  115. BMP2, GeneCards.org ↥

  116. TAFA4, GeneCards.org ↥

  117. ATXN8OS, GeneCards.org ↥

  118. PPP1R26-AS1, GeneCards.org ↥

  119. BCR, GeneCards.org ↥

  120. ZBT7C, GeneCards.org ↥

  121. Liu, Feng, Li, Cheng, Qian, Wang (2021): Deep learning model reveals potential risk genes for ADHD, especially Ephrin receptor gene EPHA5. Brief Bioinform. 2021 Jun 9:bbab207. doi: 10.1093/bib/bbab207. PMID: 34109382. n = 1.983 ↥

  122. TSPAN11, GeneCards.org ↥

  123. GRIP1, GeneCards.org ↥

  124. PRDM2, GeneCards.org ↥

  125. LINC00609, GeneCards.org ↥

  126. NAV1, GeneCards.org ↥

  127. GIMAP6, GeneCards.org ↥

  128. TBX3, GeneCards.org ↥

  129. FSCB , GeneCards.org ↥

  130. GAN, GeneCards.org ↥

  131. FSIP2, GeneCards.org ↥

  132. LPAR1, GeneCards.org ↥

  133. NXPE2, GeneCards.org ↥

  134. WNK1, GeneCards.org ↥

  135. TG, GeneCards.org ↥

  136. Lesch KP, Selch S, Renner TJ, Jacob C, Nguyen TT, Hahn T, Romanos M, Walitza S, Shoichet S, Dempfle A, Heine M, Boreatti-Hümmer A, Romanos J, Gross-Lesch S, Zerlaut H, Wultsch T, Heinzel S, Fassnacht M, Fallgatter A, Allolio B, Schäfer H, Warnke A, Reif A, Ropers HH, Ullmann R (2011): Genome-wide copy number variation analysis in attention-deficit/hyperactivity disorder: association with neuropeptide Y gene dosage in an extended pedigree. Mol Psychiatry. 2011 May;16(5):491-503. doi: 10.1038/mp.2010.29. PMID: 20308990. ↥ ↥ ↥ ↥ ↥

  137. ZMYM4, GeneCards.org ↥

  138. DIAPH3, GeneCards.org ↥

  139. FAM120A , GeneCards.org ↥

  140. CTNNA3, GeneCards.org ↥

  141. IPO8, GeneCards.org ↥

  142. TBC1D13, GdeneCards.org ↥

  143. DSC3, GeneCards.org ↥

  144. EPHA6, GeneCards.org ↥

  145. PLXNC1, GeneCards.org ↥

  146. FSTL5, GeneCards.org ↥

  147. CYFIP1, GeneCards.org ↥

  148. TUSC1, GeneCards.org ↥

  149. NOTCH2, GeneCards.org ↥

  150. OPRK1, GeneCards.org ↥

  151. ACAA2, GeneCards.org ↥

  152. DPH2, GeneCards.org ↥

  153. OCT, GeneCards.org ↥

  154. Ornithintranscarbamylase-Mangel; DocCheck ↥

  155. Lichter-Konecki, Caldovic, Morizono, Simpson, Ah Mew, MacLeod (2013): Ornithine Transcarbamylase Deficiency. 2013 Aug 29 [updated 2022 May 26]. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Mirzaa GM, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2022. PMID: 24006547. REVIEW ↥

  156. KC6, GeneCards.org ↥

  157. LINC00970, GeneCards.org ↥

  158. MTRR, GeneCards.org ↥

  159. ADAMDEC1, GeneCards.org ↥

  160. CLIC4, GeneCards.org ↥

  161. SLC13A5, GeneCards.org ↥

  162. ACSL3, GeneCards.org ↥

  163. METTL8, GeneCards.org ↥

  164. ZNF777, GeneCards.org ↥

  165. TFAP2D, GeneCards.org ↥

  166. EEPD1, GeneCards.org ↥

  167. MAD2L1, GeneCards.org ↥

  168. FLRT2, GeneCards.org ↥

  169. PLD5, GeneCards.org ↥

  170. CASC20, GeneCards.org ↥

  171. COBLL1, GeneCards.org ↥

  172. PAPOLA, GeneCards.org ↥

  173. KDM4A, GeneCards.org ↥

  174. KDM4A-AS1, GeneCards.org ↥

  175. CCDC24, GeneCards.org ↥

  176. IPO13, GeneCards.org ↥

  177. Zayats T, Jacobsen KK, Kleppe R, Jacob CP, Kittel-Schneider S, Ribasés M, Ramos-Quiroga JA, Richarte V, Casas M, Mota NR, Grevet EH, Klein M, Corominas J, Bralten J, Galesloot T, Vasquez AA, Herms S, Forstner AJ, Larsson H, Breen G, Asherson P, Gross-Lesch S, Lesch KP, Cichon S, Gabrielsen MB, Holmen OL, Bau CH, Buitelaar J, Kiemeney L, Faraone SV, Cormand B, Franke B, Reif A, Haavik J, Johansson S (2016): Exome chip analyses in adult attention deficit hyperactivity disorder. Transl Psychiatry. 2016 Oct 18;6(10):e923. doi: 10.1038/tp.2016.196. PMID: 27754487; PMCID: PMC5315553. ↥ ↥ ↥ ↥

  178. Yoo YE, Yoo T, Kang H, Kim E (2022): Brain region and gene dosage-differential transcriptomic changes in Shank2-mutant mice. Front Mol Neurosci. 2022 Oct 13;15:977305. doi: 10.3389/fnmol.2022.977305. PMID: 36311025; PMCID: PMC9612946. ↥

  179. Ma SL, Chen LH, Lee CC, Lai KYC, Hung SF, Tang CP, Ho TP, Shea C, Mo F, Mak TSH, Sham PC, Leung PWL (2021): Genetic Overlap Between Attention Deficit/Hyperactivity Disorder and Autism Spectrum Disorder in SHANK2 Gene. Front Neurosci. 2021 Apr 27;15:649588. doi: 10.3389/fnins.2021.649588. PMID: 33986640; PMCID: PMC8111170. ↥

  180. Eltokhi A, Gonzalez-Lozano MA, Oettl LL, Rozov A, Pitzer C, Röth R, Berkel S, Hüser M, Harten A, Kelsch W, Smit AB, Rappold GA, Sprengel R (2021): Imbalanced post- and extrasynaptic SHANK2A functions during development affect social behavior in SHANK2-mediated neuropsychiatric disorders. Mol Psychiatry. 2021 Nov;26(11):6482-6504. doi: 10.1038/s41380-021-01140-y. Erratum in: Mol Psychiatry. 2021 Jul 8;: PMID: 34021263; PMCID: PMC8760046. ↥

  181. Zhou A, Cao X, Mahaganapathy V, Azaro M, Gwin C, Wilson S, Buyske S, Bartlett CW, Flax JF, Brzustowicz LM, Xing J (2022): Common genetic risk factors in ASD and ADHD co-occurring families. Hum Genet. 2022 Oct 17. doi: 10.1007/s00439-022-02496-z. PMID: 36251081. ↥

  182. Miao C, Du L, Zhang Y, Jia F, Shan L (2022): Novel de novo ZNF148 truncating variant causing autism spectrum disorder, attention deficit hyperactivity disorder and intellectual disability. Clin Genet. 2022 Nov 28. doi: 10.1111/cge.14272. PMID: 36444493. ↥

  183. Levy T, Siper PM, Lerman B, Halpern D, Zweifach J, Belani P, Thurm A, Kleefstra T, Berry-Kravis E, Buxbaum JD, Grice DE (2022): DDX3X Syndrome: Summary of Findings and Recommendations for Evaluation and Care. Pediatr Neurol. 2022 Oct 27;138:87-94. doi: 10.1016/j.pediatrneurol.2022.10.009. PMID: 36434914. ↥

  184. Meng T, Chen X, He Z, Huang H, Lin S, Liu K, Bai G, Liu H, Xu M, Zhuang H, Zhang Y, Waqas A, Liu Q, Zhang C, Sun XD, Huang H, Umair M, Yan Y, Feng D (2023): ATP9A deficiency causes ADHD and aberrant endosomal recycling via modulating RAB5 and RAB11 activity. Mol Psychiatry. 2023 Jan 6:1–13. doi: 10.1038/s41380-022-01940-w. PMID: 36604604; PMCID: PMC9816018. ↥

  185. van Jaarsveld RH, Reilly J, Cornips MC, Hadders MA, Agolini E, Ahimaz P, Anyane-Yeboa K, Bellanger SA, van Binsbergen E, van den Boogaard MJ, Brischoux-Boucher E, Caylor RC, Ciolfi A, van Essen TAJ, Fontana P, Hopman S, Iascone M, Javier MM, Kamsteeg EJ, Kerkhof J, Kido J, Kim HG, Kleefstra T, Lonardo F, Lai A, Lev D, Levy MA, Lewis MES, Lichty A, Mannens MMAM, Matsumoto N, Maya I, McConkey H, Megarbane A, Michaud V, Miele E, Niceta M, Novelli A, Onesimo R, Pfundt R, Popp B, Prijoles E, Relator R, Redon S, Rots D, Rouault K, Saida K, Schieving J, Tartaglia M, Tenconi R, Uguen K, Verbeek N, Walsh CA, Yosovich K, Yuskaitis CJ, Zampino G, Sadikovic B, Alders M, Oegema R (2022): Delineation of a KDM2B-related neurodevelopmental disorder and its associated DNA methylation signature. Genet Med. 2023 Jan;25(1):49-62. doi: 10.1016/j.gim.2022.09.006. PMID: 36322151; PMCID: PMC9825659. ↥

  186. van de Kamp JM, Betsalel OT, Mercimek-Mahmutoglu S, Abulhoul L, Grünewald S, Anselm I, Azzouz H, Bratkovic D, de Brouwer A, Hamel B, Kleefstra T, Yntema H, Campistol J, Vilaseca MA, Cheillan D, D’Hooghe M, Diogo L, Garcia P, Valongo C, Fonseca M, Frints S, Wilcken B, von der Haar S, Meijers-Heijboer HE, Hofstede F, Johnson D, Kant SG, Lion-Francois L, Pitelet G, Longo N, Maat-Kievit JA, Monteiro JP, Munnich A, Muntau AC, Nassogne MC, Osaka H, Ounap K, Pinard JM, Quijano-Roy S, Poggenburg I, Poplawski N, Abdul-Rahman O, Ribes A, Arias A, Yaplito-Lee J, Schulze A, Schwartz CE, Schwenger S, Soares G, Sznajer Y, Valayannopoulos V, Van Esch H, Waltz S, Wamelink MM, Pouwels PJ, Errami A, van der Knaap MS, Jakobs C, Mancini GM, Salomons GS (2013): Phenotype and genotype in 101 males with X-linked creatine transporter deficiency. J Med Genet. 2013 Jul;50(7):463-72. doi: 10.1136/jmedgenet-2013-101658. PMID: 23644449. ↥

  187. Abdulla, Pahlevani, Lundgren, Pennington, Udobi, Seroogy, Skelton (2019): Deletion of the Creatine Transporter (Slc6a8) in Dopaminergic Neurons Leads to Hyperactivity in Mice. J Mol Neurosci. 2019 Sep 13. doi: 10.1007/s12031-019-01405-w. ↥

  188. Ferreira, Palmini, Bau, Grevet, Hoefel, Rohde, Anés, Ferreira, Belmonte-de-Abreu (2009): Differentiating attention-deficit/hyperactivity disorder inattentive and combined types: a (1)H-magnetic resonance spectroscopy study of fronto-striato-thalamic regions. J Neural Transm (Vienna). 2009 May;116(5):623-9. doi: 10.1007/s00702-009-0191-3. zitiert nach Bollmann, Ghisleni, Poil, Martin, Ball, Eich-Höchli, Edden, Klaver, Michels, Brandeis, O’Gorman (2015): Developmental changes in gamma-aminobutyric acid levels in attention-deficit/hyperactivity disorder. Transl Psychiatry. 2015 Jun 23;5:e589. doi: 10.1038/tp.2015.79.: Zusatzgrafik ↥

  189. Sun, Jin, Zang, Zeng, Liu, Li, Seidman, Faraone, Wang (2005): Differences between attention-deficit disorder with and without hyperactivity: a 1H-magnetic resonance spectroscopy study. Brain Dev. 2005 Aug;27(5):340-4.zitiert nach Bollmann, Ghisleni, Poil, Martin, Ball, Eich-Höchli, Edden, Klaver, Michels, Brandeis, O’Gorman (2015): Developmental changes in gamma-aminobutyric acid levels in attention-deficit/hyperactivity disorder. Transl Psychiatry. 2015 Jun 23;5:e589. doi: 10.1038/tp.2015.79.: Zusatzgrafik ↥

  190. GeneCards: GMPPB ↥

  191. Zhang C, Jian L, Li X, Guo W, Deng W, Hu X, Li T (2024): Mendelian randomization analysis of the brain, cerebrospinal fluid, and plasma proteome identifies potential drug targets for attention deficit hyperactivity disorder. EBioMedicine. 2024 Jul;105:105197. doi: 10.1016/j.ebiom.2024.105197. PMID: 38876042; PMCID: PMC11225168. ↥ ↥ ↥ ↥ ↥ ↥ ↥

  192. Liu J (2025): Proteome-wide association studies have predicted that the protein abundance of LSM6, GMPPB, ICA1L, and CISD2 is associated with attention-deficit/hyperactivity disorder. Eur Child Adolesc Psychiatry. 2025 Feb;34(2):721-728. doi: 10.1007/s00787-024-02517-4. PMID: 38954053. ↥ ↥ ↥ ↥ ↥

  193. Jolly LA, Homan CC, Jacob R, Barry S, Gecz J (2013): The UPF3B gene, implicated in intellectual disability, autism, ADHD and childhood onset schizophrenia regulates neural progenitor cell behaviour and neuronal outgrowth. Hum Mol Genet. 2013 Dec 1;22(23):4673-87. doi: 10.1093/hmg/ddt315. PMID: 23821644. ↥

  194. Vinci M, Greco D, Treccarichi S, Chiavetta V, Figura MG, Musumeci A, Greco V, Federico C, Calì F, Saccone S (2024): Bioinformatic Evaluation of KLF13 Genetic Variant: Implications for Neurodevelopmental and Psychiatric Symptoms. Genes (Basel). 2024 Aug 11;15(8):1056. doi: 10.3390/genes15081056. PMID: 39202416; PMCID: PMC11354057. ↥

  195. Albayrak Ö, Pütter C, Volckmar AL, Cichon S, Hoffmann P, Nöthen MM, Jöckel KH, Schreiber S, Wichmann HE, Faraone SV, Neale BM, Herpertz-Dahlmann B, Lehmkuhl G, Sinzig J, Renner TJ, Romanos M, Warnke A, Lesch KP, Reif A, Schimmelmann BG, Scherag A, Hebebrand J, Hinney A; Psychiatric GWAS Consortium: ADHD Subgroup (2013): Common obesity risk alleles in childhood attention-deficit/hyperactivity disorder. Am J Med Genet B Neuropsychiatr Genet. 2013 Jun;162B(4):295-305. doi: 10.1002/ajmg.b.32144. PMID: 23533005. ↥ ↥ ↥ ↥

  196. Gene Cards: SLC2A3 ↥

  197. Mustafin RN, Enikeeva RF, Malykh SB, Valinurov RG, Khusnutdinova EK (2018): Genetika sindroma defitsita vnimaniia i giperaktivnosti [Genetics and epigenetics of attention deficit hyperactivity disorder]. Zh Nevrol Psikhiatr Im S S Korsakova. 2018;118(9):106-110. Russian. doi: 10.17116/jnevro2018118091106. PMID: 30335081. ↥

  198. Daida T, Shin BC, Cepeda C, Devaskar SU (2024): Neurodevelopment Is Dependent on Maternal Diet: Placenta and Brain Glucose Transporters GLUT1 and GLUT3. Nutrients. 2024 Jul 21;16(14):2363. doi: 10.3390/nu16142363. PMID: 39064806; PMCID: PMC11279700. REVIEW ↥

  199. Merker S, Reif A, Ziegler GC, Weber H, Mayer U, Ehlis AC, Conzelmann A, Johansson S, Müller-Reible C, Nanda I, Haaf T, Ullmann R, Romanos M, Fallgatter AJ, Pauli P, Strekalova T, Jansch C, Vasquez AA, Haavik J, Ribasés M, Ramos-Quiroga JA, Buitelaar JK, Franke B, Lesch KP (2017): SLC2A3 single-nucleotide polymorphism and duplication influence cognitive processing and population-specific risk for attention-deficit/hyperactivity disorder. J Child Psychol Psychiatry. 2017 Jul;58(7):798-809. doi: 10.1111/jcpp.12702. PMID: 28224622. METASTUDY ↥

  200. Jansch C, Günther K, Waider J, Ziegler GC, Forero A, Kollert S, Svirin E, Pühringer D, Kwok CK, Ullmann R, Maierhofer A, Flunkert J, Haaf T, Edenhofer F, Lesch KP (2018): Generation of a human induced pluripotent stem cell (iPSC) line from a 51-year-old female with attention-deficit/hyperactivity disorder (ADHD) carrying a duplication of SLC2A3. Stem Cell Res. 2018 Apr;28:136-140. doi: 10.1016/j.scr.2018.02.005. PMID: 29477591. ↥

  201. Schwarz R, Reif A, Scholz CJ, Weissflog L, Schmidt B, Lesch KP, Jacob C, Reichert S, Heupel J, Volkert J, Kopf J, Hilscher M, Weber H, Kittel-Schneider S (2015): A preliminary study on methylphenidate-regulated gene expression in lymphoblastoid cells of ADHD patients. World J Biol Psychiatry. 2015 Apr;16(3):180-9. doi: 10.3109/15622975.2014.948064. PMID: 25162476. ↥

  202. Zhao Y, Fung C, Shin D, Shin BC, Thamotharan S, Sankar R, Ehninger D, Silva A, Devaskar SU (2010): Neuronal glucose transporter isoform 3 deficient mice demonstrate features of autism spectrum disorders. Mol Psychiatry. 2010 Mar;15(3):286-99. doi: 10.1038/mp.2009.51. PMID: 19506559; PMCID: PMC4208914. ↥

  203. Alonso-Gonzalez, Calaza, Rodriguez-Fontenla, Carracedo (2019): Gene-based analysis of ADHD using PASCAL: a biological insight into the novel associated genes. BMC Med Genomics. 2019 Oct 24;12(1):143. doi: 10.1186/s12920-019-0593-5. ↥

  204. FEZF1-AS1 Gene - FEZF1 Antisense RNA 1, GeneCards ↥

  205. LOC100507468, https://maayanlab.cloud ↥

  206. LINC00355, GeneCards.org ↥

  207. LOC101927967, GeneCards.org ↥

  208. IFNG-AS1, GeneCards.org ↥

  209. LINC01558, GeneCards.org ↥

  210. LINC01364, GeneCards.org ↥

  211. LINC02229:9; LNCipedia ↥

  212. LINC02229, GeneCards.org ↥

  213. Hibar DP, Adams HHH, Jahanshad N, Chauhan G, Stein JL, Hofer E, Renteria ME, Bis JC, Arias-Vasquez A, Ikram MK, Desrivières S, Vernooij MW, Abramovic L, Alhusaini S, Amin N, Andersson M, Arfanakis K, Aribisala BS, Armstrong NJ, Athanasiu L, Axelsson T, Beecham AH, Beiser A, Bernard M, Blanton SH, Bohlken MM, Boks MP, Bralten J, Brickman AM, Carmichael O, Chakravarty MM, Chen Q, Ching CRK, Chouraki V, Cuellar-Partida G, Crivello F, Den Braber A, Doan NT, Ehrlich S, Giddaluru S, Goldman AL, Gottesman RF, Grimm O, Griswold ME, Guadalupe T, Gutman BA, Hass J, Haukvik UK, Hoehn D, Holmes AJ, Hoogman M, Janowitz D, Jia T, Jørgensen KN, Karbalai N, Kasperaviciute D, Kim S, Klein M, Kraemer B, Lee PH, Liewald DCM, Lopez LM, Luciano M, Macare C, Marquand AF, Matarin M, Mather KA, Mattheisen M, McKay DR, Milaneschi Y, Muñoz Maniega S, Nho K, Nugent AC, Nyquist P, Loohuis LMO, Oosterlaan J, Papmeyer M, Pirpamer L, Pütz B, Ramasamy A, Richards JS, Risacher SL, Roiz-Santiañez R, Rommelse N, Ropele S, Rose EJ, Royle NA, Rundek T, Sämann PG, Saremi A, Satizabal CL, Schmaal L, Schork AJ, Shen L, Shin J, Shumskaya E, Smith AV, Sprooten E, Strike LT, Teumer A, Tordesillas-Gutierrez D, Toro R, Trabzuni D, Trompet S, Vaidya D, Van der Grond J, Van der Lee SJ, Van der Meer D, Van Donkelaar MMJ, Van Eijk KR, Van Erp TGM, Van Rooij D, Walton E, Westlye LT, Whelan CD, Windham BG, Winkler AM, Wittfeld K, Woldehawariat G, Wolf C, Wolfers T, Yanek LR, Yang J, Zijdenbos A, Zwiers MP, Agartz I, Almasy L, Ames D, Amouyel P, Andreassen OA, Arepalli S, Assareh AA, Barral S, Bastin ME, Becker DM, Becker JT, Bennett DA, Blangero J, van Bokhoven H, Boomsma DI, Brodaty H, Brouwer RM, Brunner HG, Buckner RL, Buitelaar JK, Bulayeva KB, Cahn W, Calhoun VD, Cannon DM, Cavalleri GL, Cheng CY, Cichon S, Cookson MR, Corvin A, Crespo-Facorro B, Curran JE, Czisch M, Dale AM, Davies GE, De Craen AJM, De Geus EJC, De Jager PL, De Zubicaray GI, Deary IJ, Debette S, DeCarli C, Delanty N, Depondt C, DeStefano A, Dillman A, Djurovic S, Donohoe G, Drevets WC, Duggirala R, Dyer TD, Enzinger C, Erk S, Espeseth T, Fedko IO, Fernández G, Ferrucci L, Fisher SE, Fleischman DA, Ford I, Fornage M, Foroud TM, Fox PT, Francks C, Fukunaga M, Gibbs JR, Glahn DC, Gollub RL, Göring HHH, Green RC, Gruber O, Gudnason V, Guelfi S, Håberg AK, Hansell NK, Hardy J, Hartman CA, Hashimoto R, Hegenscheid K, Heinz A, Le Hellard S, Hernandez DG, Heslenfeld DJ, Ho BC, Hoekstra PJ, Hoffmann W, Hofman A, Holsboer F, Homuth G, Hosten N, Hottenga JJ, Huentelman M, Hulshoff Pol HE, Ikeda M, Jack CR Jr, Jenkinson M, Johnson R, Jönsson EG, Jukema JW, Kahn RS, Kanai R, Kloszewska I, Knopman DS, Kochunov P, Kwok JB, Lawrie SM, Lemaître H, Liu X, Longo DL, Lopez OL, Lovestone S, Martinez O, Martinot JL, Mattay VS, McDonald C, McIntosh AM, McMahon FJ, McMahon KL, Mecocci P, Melle I, Meyer-Lindenberg A, Mohnke S, Montgomery GW, Morris DW, Mosley TH, Mühleisen TW, Müller-Myhsok B, Nalls MA, Nauck M, Nichols TE, Niessen WJ, Nöthen MM, Nyberg L, Ohi K, Olvera RL, Ophoff RA, Pandolfo M, Paus T, Pausova Z, Penninx BWJH, Pike GB, Potkin SG, Psaty BM, Reppermund S, Rietschel M, Roffman JL, Romanczuk-Seiferth N, Rotter JI, Ryten M, Sacco RL, Sachdev PS, Saykin AJ, Schmidt R, Schmidt H, Schofield PR, Sigursson S, Simmons A, Singleton A, Sisodiya SM, Smith C, Smoller JW, Soininen H, Steen VM, Stott DJ, Sussmann JE, Thalamuthu A, Toga AW, Traynor BJ, Troncoso J, Tsolaki M, Tzourio C, Uitterlinden AG, Hernández MCV, Van der Brug M, van der Lugt A, van der Wee NJA, Van Haren NEM, van ’t Ent D, Van Tol MJ, Vardarajan BN, Vellas B, Veltman DJ, Völzke H, Walter H, Wardlaw JM, Wassink TH, Weale ME, Weinberger DR, Weiner MW, Wen W, Westman E, White T, Wong TY, Wright CB, Zielke RH, Zonderman AB, Martin NG, Van Duijn CM, Wright MJ, Longstreth WT, Schumann G, Grabe HJ, Franke B, Launer LJ, Medland SE, Seshadri S, Thompson PM, Ikram MA. Novel genetic loci associated with hippocampal volume. Nat Commun. 2017 Jan 18;8:13624. doi: 10.1038/ncomms13624. PMID: 28098162; PMCID: PMC5253632. ↥

  214. MIR4255; GeneCard.org ↥

  215. LINC01377, GeneCards.org ↥

  216. CASC17, GeneCards.org ↥

  217. LINC02497, GeneCards.org ↥

  218. LINC00461, GeneCards.org ↥

  219. Karaivazoglou K, Triantos C, Aggeletopoulou I (2025): Non-Coding RNAs in Neurodevelopmental Disorders-From Diagnostic Biomarkers to Therapeutic Targets: A Systematic Review. Biomedicines. 2025 Jul 24;13(8):1808. doi: 10.3390/biomedicines13081808. PMID: 40868063; PMCID: PMC12384018. REVIEW ↥ ↥

  220. MIR9–2, GeneCards.org ↥

  221. LINC02060, GeneCards.org ↥

  222. TMEM161B-AS1, GeneCards.org ↥

  223. MIR3666, GeneCards.org ↥

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