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1. Genes as genetic candidates in ADHD

1. Genes as genetic candidates in ADHD

This post is under construction: we are trying to organize the gene candidates by area of effect. After completion we will remove this note again.

One study found 560 genes and 6 miRNA that showed aberrant expression in ADHD compared to non-affected individuals.1 Changes in gene expression cause a deviation in the activity of the gene and thus in the effects mediated by it (e.g. activity of a receptor, transporter, protein). Other studies found many other genes that could be considered, so that a four-digit number of candidate genes can currently be assumed.
An interesting study of 1033 ADHD sufferers versus 950 unaffected individuals reached a result that achieved diagnostically relevant values of accuracy (0.9018), AUC (0.9570), sensitivity (0.8980), and specificity (0.9055) by considering the combined effect of multiple variants with insignificant P values and analyzing them using DeepLearning (“AI”). The study found 96 candidate genes, of which only 14 genes had previously been reported in ADHD-related studies.2

The Chinese ADHDgene database lists genes relevant for ADHD.3 However, it does not seem to have been updated since 2014.

Some of the genes listed below cause rare (orphan) diseases when a gene defect is present. For example, the SYNE1 gene (one of the 560 genes from the study by Nuzziello et al) causes SYNE1 ataxia in 20 out of 100,000 people, so it has a prevalence of 0.02%.4 The following thought experiment should give an idea of the contribution of individual genes to ADHD: If all of the 560 genes named as candidate genes for ADHD were to cause such a rare orphan disorder (each of which would be associated with ADHD symptoms), and if each gene alteration occurred only alone, the sum of these 560 genes would yield a prevalence of 11.2%, which would equal or exceed the prevalence of ADHD

Below we name several candidate genes that may contribute to the development of ADHD. The links of the genes associated with ADHD refer to the OMIM gene database.

Gene Databases:

1. Genes that may be involved in the development of ADHD (candidate genes)

Dopamine

Dopamine synthesis

1.8. Aromatic-L-amino acid decarboxylase, AADC, DOPA decarboxylase gene, DDC (chromosome 9q34.2)

OMIM DOPA decaboxylase gene, DDC

DDC is a candidate gene for ADHD.5

The DDC gene was identified as a candidate gene for ADHD in a 2006 study with p = 0.039.6

In children with hyperactivity (but not in adults), one study found decreased striatal and prefrontal dopa decarboxylase activity.7

1.9. Tyrosine hydroxylase gene (chromosome 11p15.5)

Tyrosine hydroxylase is a candidate gene for ADHD.5

Dopamine storage and release

1.28. 25-KD synaptosomal associated protein gene / SYNAPTOSOMAL-ASSOCIATED PROTEIN, 25-KD; SNAP25 (chromosome 20p12.3; T1065G)

The SNARE protein SNAP-25 - together with syntaxin-1 and synaptobrevin - mediates the release of neurotransmitters from synaptic vesicles in neurons.

OMIM 25-kD synaptosomal associated protein gene / SYNAPTOSOMAL-ASSOCIATED PROTEIN, 25-KD; SNAP25

SNAP25 is a candidate gene for ADHD.58

The SNAP25 gene was identified as a candidate gene for ADHD in a 2006 study with p = 0.035.6

Dopamine effect

1.1. Dopamine receptor D1 gene, DRD1 (chromosome 5q35.2)

OMIM Dopamine receptor D1 gene, DRD1

DRD1 is a candidate gene for ADHD.5

The DRD1 receptor is closely related to the DRD5 receptor, but is found in other brain regions, namely in the striatum, nucleus accumbens, tuberculum olfactorium and frontal cortex - i.e. in brain regions where DRD1 receptors are hardly found.9

Activating effect of D1 and D5 receptors

The dopamine D1 and D5 receptors have activating effects, while the D2 to D4 receptors mediate inhibitory effects. For D1 and D5 receptors, the intracellular signal is mediated by a stimulatory G protein that activates adenylate cyclase. This enhances the conversion of ATP to cAMP. cAMP activates further proteins.
The cascade of activated proteins amplifies the signal received at the receptor.

1.2. Dopamine receptor D2 gene, DRD2 (chromosome 11q23.1; TAQ1A, rs1800497)

OMIM Dopamine receptor D2 gene, DRD2
DRD2 is a candidate gene for ADHD.5

The A allele has been associated with lower receptor density in the striatum in several studies. This means that existing dopamine can be taken up to a lesser extent, which has the same effect as a reduced dopamine level.10
The DRD2-A1 allele is thought to correlate with impulsivity, compulsivity, and addiction.11

One study found significantly increased ADHD and ASD risk overlap in correlation with the DRD2-12 (rs7131465) gene polymorphism.12

1.3. Dopamine receptor D3 gene, DRD3 (chromosome 3q13.31)

OMIM Dopamine receptor D3 gene, DRD3
DRD3 is a candidate gene for ADHD.5

In mice, an effect of the D3 receptor on increased motor activity (hyperactivity) and rearing behavior (“rearing behavior”) was found. Binding of the D3 receptor prevents addictive behavior (craving).

1.4. Dopamine receptor D4 gene, DRD4 (chromosome 11p15.5 exon III, VTNR) (x)

OMIM Dopamine receptor D4 gene, DRD4

DRD4 is a candidate gene for ADHD.138514
DRD4 was identified as a candidate gene for ADHD in a 2006 study with p = 0.055.6
The DRD4-7R variant increases the risk of ADHD by 50% (odds ratio 1.5).15
The 7-repeat allele encodes the dopamine receptor D4 in such a way that it requires 3 times the amount of dopamine to respond. 1617 This acts like an apparent decreased dopamine level in the striatum, which correlates with motivational problems and impulsivity18
In other words, DRD4-7R causes reduced postsynaptic inhibition.1920
A recent report suggests that DRD4-7R is not simply more insensitive to dopamine, but rather interacts with other dopamine receptors. Moreover, DRD4, like all D2-type receptors (D2, D3, and D4), is also thought to respond to norepinephrine as an agonist.21

Inhibitory effect of D2 to D4 receptors

Dopamine D2 to D4 receptors mediate inhibitory effects, while D1 and D5 receptors mediate activating effects. For D2 to D4 receptors, the intracellular signal is mediated via an inhibitory G protein that inhibits adenylate cyclase. This decreases cAMP synthesis and thereby inhibits the downstream signaling pathway. In addition, potassium channels are activated by D2 to D4 receptors, which stabilizes the resting potential of nerve cells, making excitation of a nerve cell less likely.

DRD4-7R increases the reactivity of the ventral striatum as a result.
Thus, DRD4-7R does not cause lower levels of dopamine in the striatum per se, but reduces inhibition of the striatum by responding inhibitively only to higher levels of dopamine.
Surprisingly, however, DRD4-7R has an additional inhibitory effect on a methamphetamine-triggered increase in dopamine and glutamate in the striatum. A methamphetamine-triggered increase in dopamine and glutamate was reduced in mice carrying the DRD4-7R gene.22 In contrast, cocaine did not show reduced dopamine or glutamate increases in DRD4-7R. The dopamine increase on cocaine was marked in all DRD4 variants, whereas the glutamate increase was rather small.
Striatal glutamate stimulates dopamine increase in the striatum.22
Adenosine modulates striatal DA release by stimulating glutamate release at adenosine receptors in the striatum, which increases dopamine levels.23
DRD4-7R causes decreased function and connectivity of brain regions involved in inhibitory control during impulse control task execution, particularly the right inferior frontal gyrus cortex.222425
Flattened corticostriatal neurotransmission impairs GABAergic activity in the striatum during “Go” and “NoGo” tasks and reduces the ability to increase reactivity to reward-related stimuli and suppress reactivity to non-reward or aversive stimuli.26
This increases “interest” in irrelevant stimuli and decreases inhibition of irrelevant responses, as evidenced by distractibility and action and decision impulsivity in ADHD.22 This contradicts representations that DRD4-7R should be associated with ADHD-I subtype.

DRD4-7R and ADHD-I subtype?

It has been argued that DRD4-7R is associated with the ADHD-I subtype.27 To our understanding, this is clearly contradicted by the empirical presentation of Eisenberg28 on the Ariaal people.
According to several reports29, DRD4-7R is thought to be involved only in ADHD with conduct disorder (CD), but not in ADHD without conduct disorder.
This contradicts the presentation of an association with ADHD-I, as ADHD-I is strongly internalizing characterized, whereas CD is strongly externalizing.
However, we consider this association questionable as well. Friedmann further reports on investigations by Eisenberg on the Kenyan people of the Ariaal. The Ariaal have separate tribes of sedentary people and hunters. Research showed that hunters who had a lower responsive dopamine D4 receptor (gene variant DRD4-7R) had above average nutrition compared to the other hunters, while within the sedentary, those with DRD4-7R had below average nutrition.28 Further, more hunters had the DRD4-7R - gene alteration than foragers.30
This strengthens the Hunter/Farmer thesis,31 when read as suggesting that an individual develops optimally when given an environment and tasks that are optimal for their genetic makeup. According to this account, DRD4-7R should correlate with ADHD-HI. Diamond27, on the other hand, sees DRD4-7R as indicative of ADHD-I (ADD).

If DRD4-7R were associated with the ADHD-I subtype, Eisenberg’s results would be inconclusive because then the farmers (collectors) would also have to have an equal number of DRD4-7R mutations.
Eisenberg studied 87 ariaal of a tribe that had recently settled and 65 ariaal of a tribe that was still living as nomads. The fact that a tribe that has always lived as nomads is compared with a tribe that has recently settled distorts the test setting enormously. A tribe that has only recently fundamentally changed its way of life cannot be as successful within that way of life as a tribe that has always maintained its way of life. That members of the tribe that has recently fundamentally changed its way of life will be worse nourished than members of the tribe that has maintained its way of life this way since time immemorial is to be expected, or at least depends on a great many factors that have nothing to do with genetic makeup. Therefore, the statement that those members (with the DRD4-7R gene variant) of the tribe that have recently settled were worse nourished than members (with the DRD4-7R gene variant) of the tribe that has always lived as nomads is not a robust statement that this is because of the gene variant.
In addition, the frequency of the DRD4-7R mutation did not differ between the two strains - it was just under 20% in each, which is the normal distribution in humans.

We hypothesize that DRD4-7R is linked to increased impulsivity, which is more typical of the ADHD-HI subtype.
DRD4-7R is associated with Novelty Seeking.32 Novelty Seeking correlates with high impulsivity.

A cohort study found that DRD4-7R correlated with high levels of hyperactivity/impulsivity quite generally.33

DRD4-7R causes less formation of gyri and sulci (gyrification) in the PFC of ADHD sufferers.34

DRD4-7R is only about 40,000 to 50,000 years old and has since spread far more rapidly than would be expected from random gene transmission. This suggests that DRD4-7R is an extremely successful gene.2035

DRD4-4R and DRD4-7R appear to strongly and differentially affect the functionality of the D2-short receptor variant.36

A review on the epigenetic causation of ADHD points to the relevance of DRD4.37

1.5. Dopamine receptor D5 gene, DRD5 (chromosome 4p16.1-p15.3; CARepeat, 148 bp)

OMIM Dopamine receptor D5 gene, DRD5

DRD5 is a candidate gene for ADHD.85

The DRD5 receptor is closely related to the DRD1 receptor, but is found in other (primarily limbic) brain regions, namely the hippocampus, mamillary nuclei, anterior pretectal nuclei, and all brain regions where DRD1 receptors are scarce.9
DRD5 is widely distributed in the brain and is significantly more affine for dopamine than the D1 receptor. The DRD5-148-bp allele is associated with ADHD in 18.5 kb at the end of the 5′-flank.38
DRD5 appears to moderate the hypothalamus and parts of motor control.39

Dopamine degradation

Dopamine Reuptake

1.6. SLC6A3 (DAT1) SOLUTE CARRIER FAMILY 6 (NEUROTRANSMITTER TRANSPORTER, DOPAMINE), MEMBER 3; (dopamine transporter gene) (chromosome 5p15.3; 10-R allele, VNTR)

OMIM SLC6A3 (DAT1) SOLUTE CARRIER FAMILY 6 (NEUROTRANSMITTER TRANSPORTER, DOPAMINE), MEMBER 3;

The dopamine transporter (DAT), which plays the major role in dopamine reuptake, is found primarily in the striatum40 and is much more abundant there than in the PFC.

The DAT gene is frequently cited as an ADHD candidate gene.138514 The DAT1 gene was identified as a candidate gene for ADHD in a 2006 study with p = 0.005.6
A particular DAT1 variant is thought to be primarily associated with the ADHD-HI subtype.27 Binding of DAT, which is largely determined by the DAT1 gene, is associated with motor hyperactivity, but not with inattention.13 In the ADHD-HI subtype (with hyperactivity), the striatum is primarily affected. The caudate nucleus is conspicuously reduced in size.41
A certain DAT1 gene variant causes an excessive number of dopamine transporters. An excessive number of dopamine transporters causes the dopamine released presynaptically (by the sending neuron) to be taken up again by the excess DAT like a vacuum cleaner from the presynapse (the sending neuron) before it could be taken up postsynaptically (by the receiving neuron). The correctly released amount of dopamine therefore does not arrive at the postsynaptic dopamine receptors, which is why they do not receive the required amount of decision information (which would only be triggered if a sufficient number of the receptors had received dopamine).2842
The polymorphisms of the DAT gene in question occur significantly more frequently in families of ADHD sufferers (n = 329). A combination of 3 specific polymorphisms was associated with a 2.5-fold frequency of ADHD.43
Certain DAT1 variants cause a disposition for lower birth weight and ADHD susceptibility.44
DAT Val559, unlike the DAT Ala559 variant, is thought to be associated with increased dopamine transport, which may be relevant in ADHD, autism, and bipolar disorder.45
The DAT1 rs27048 (C)rs429699 (T) haplotype was associated with altered functional connectivity of the left dorsal caudate nucleus in visual memory performance of adolescents with ADHD in one study.46

1.18. Norepinephrine transporter gene, SOLUTE CARRIER FAMILY 6 (NEUROTRANSMITTER TRANSPORTER, NORADRENALINE), MEMBER 2; SLC6A2, NET (chromosome 16q12.2)

OMIM Norepinephrine transporter gene, SOLUTE CARRIER FAMILY 6 (NEUROTRANSMITTER TRANSPORTER, NORADRENALINE), MEMBER 2; SLC6A2, NET

SLC6A2 is a candidate gene for ADHD.547

The NET gene was identified as a candidate gene for ADHD in a 2006 study with p = 0.012.6

Children with ADHD with the SLC6A2 rs36011 (T) / rs1566652 (G) haplotype showed abnormalities in intrinsic brain activity of the sensorimotor and dorsal attention networks that correlated with impairments in visual memory and visual attention.48

NET1-rs3785143 is reported to be associated with increased emptional lability in ADHD.49

Dopamine metabolization

1.10. Monoamine oxidase A gene, MAOA (chromosome Xp11.3) (x)

OMIM Monoamine oxidase A gene, MAOA

MAO-A is a candidate gene for ADHD.5

The MAO-A gene controls the formation of the enzyme monoaminooxydase-A. The MAO-A gene was identified as a candidate gene for ADHD with p = 0.02 in a 2006 study.6
A certain variant of the MAO-A gene doubles the risk of aggression and antisocial behavior if those affected were themselves exposed to violence (or let’s say more generally: intense stress) in childhood. It occurs more frequently in boys because men - unlike women - do not have a second copy of this gene that could mitigate the defect.
This MAO-A gene variant is also associated with ADHD. However, we consider this to be a comorbidity that frequently occurs together with ADHD-HI (not with ADHD-I) and not a part of ADHD. So does Steinhausen regarding social behavior disorders,50 which is the most common comorbidity. However, Steinhausen describes the comorbidity of social behavior disorders as a subtype of ADHD, which we disagree with due to the delineability of the remaining genetic basis. Further arguing for a pure comorbidity and against an ADHD-HI subtype is that medications for aggression disorders and antisocial behavior are typically dopamine D2 receptor antagonists (antipsychotic medications), which reduce the effect of dopamine uptake at the postsynaptic neuron at the (inhibitory*) D2 receptor, whereas ADHD is more likely to have too little receptor affinity (see above).

1.11. Monoamine oxidase B gene (chromosome Xp11.4-p11.3)

MAO-B is a candidate gene for ADHD.5

In contrast to MAO-A inhibitors, MAO-B inhibitors have been shown to be ineffective in ADHD.51

1.12. Catechol-O-methyltransferase; COMT (chromosome 22q11.21)

OMIM Catechol-O-methyltransferase; COMT

COMT is a candidate gene for ADHD.5

1.12.1. COMT Val158Val

The COMT gene variant Val158Val causes increased degradation of dopamine and norepinephrine, leading to dopamine deficiency in the PFC, which in turn, however, may cause increased dopaminergic activity in the mesolimbic system.5253 54 55 .56

1.12.2. COMT Met158Met

The COMT Met158 Met variant correlates with antisocial behavior in ADHD.57

This could explain why this gene variant is only observed in ADHD with comorbid antisocial behavior, but to our knowledge not in ADHD in general. In addition, this gene variant is associated with borderline and (via increased dopaminergic activity of the mesolimbic system) the positive symptoms of schizophrenia.
This gene variant directly impairs working memory, which in turn indirectly controls delay aversion and directly controls executive functions and attentional control, and together with the latter, the processing of auditory stimuli, which are prerequisites for language processing. On the question whether this COMT gene variant correlates with ADHD, there are more contradictory than confirming studies, which, however, did not consider working memory.58
This gene variant is further relevant in antisocial behavior disorder associated with ADHD, but not in ADHD without antisocial behavior disorder.53 However, in our understanding, antisocial behavior disorder is a comorbid disorder and not part of ADHD.

1.12.3. COMT Val108/158 Met

The COMT Val108/158 Met polymorphism reduces the activity of the enzyme in degrading dopamine to one quarter. This variant correlates with a more focused and efficient cerebrovascular response in working memory tasks 59
This variant is not associated with ADHD, in which dopamine levels are too low, but with schizophrenia, in which dopamine levels in the synaptic cleft are elevated.

1.279. STS, STEROID SULFATASE

Steroid sulfatase causes the degradation of dopamine by sulfation. More about this Sulfation by sulfotransferases In the article Dopamine degradation.

The STS gene is an ADHD gene candidate.6061

Dopamine regulation

1.31. Calcyon (CALY) gene / DOPAMINE RECEPTOR D1-INTERACTING PROTEIN; DRD1IP gene (chromosome 10q26) (x)

Calcylone is involved in the regulation of the D1 receptor.62

OMIM Calcyon (CALY) gene / DOPAMINE RECEPTOR D1-INTERACTING PROTEIN; DRD1IP gene

CALY / DRD1IP is a candidate gene for ADHD.5

1.64. POTASSIUM CHANNEL, VOLTAGE-GATED, SHAW-RELATED SUBFAMILY, MEMBER 1; KCNC1 (chromosome 11p15.1)

The KCNC1 protein is a member of a family of integral membrane proteins that mediate voltage-dependent permeability of potassium ions in excitable membranes. KCNC1 influences dopamine-DARPP32 feedback to the cAMP pathway.63
Alternative splicing appears to result in two isoforms with different C termini.
Diseases associated with KCNC1 are epilepsy, Progressive Myoclonic 7, and Spinocerebellar Ataxia 13

OMIM POTASSIUM CHANNEL, VOLTAGE-GATED, SHAW-RELATED SUBFAMILY, MEMBER 1

  • SNP: rs3893215 position: 7721406; In intron of KCNC164
    p: 2.56E-05

1.78. MTHFR (5,10-METHYLENETETRAHYDROFOLATE REDUCTASE)

The enzyme methylenetetrahydrofolate reductase (MTHFR) reduces 5,10-methylene-FH4 with the help of NAD(P)H to 5-methyl-FH4. Since this produces the methylating agent 5-methyl-FH4, MTHFR is indispensable in many metabolic pathways, including the degradation of harmful homocysteine to methionine, and in bacterial methane formation.
Humans express MTHFR in many tissue types, from where the protein is released into the blood. Variants and mutations of the MTHFR gene can lead to decreased, and less commonly increased, MTHFR synthesis and efficacy. MTHFR deficiency can

  • be the cause of neural tube malformations such as spina bifida in the newborn in pregnant women
  • Trigger homocystinuria
  • Increase risk of stroke
  • Increase colorectal cancer risk.

Homocysteine decreases dopamine levels in the striatum.65

OMIM MTHFR (5,10-METHYLENETETRAHYDROFOLATE REDUCTASE)

The 1298A > C polymorphism of the MTHFR gene has been associated with an increased risk of ADHD, but not the MTHFR 677 C > T polymorphism.66

The MTHFR 1298A > C polymorphism is associated with increased homocysteine levels, probably due to decreased degradation of homocysteine by this polymorphism.67

ADHD correlates with elevated homocysteine levels (and decreased vitamin B12 levels).6869
B12 deficiency can increase homopcysteine levels.70

1.81. ARTN, Artemin; 1p34.1

ARTN (artemin, enovin, neublastin) is a neurotrophic factor from the glial cell line-derived neurotrophic factor family of ligands, a group of ligands within the TGF-beta superfamily of signaling molecules. ARTN promotes survival of a number of peripheral neuron populations and at least one population of CNS dopaminergic neurons. ARTN frequently expresses near these neurons. ARTN is a ligand for the RET receptor and utilizes GFR-alpha 3 as a coreceptor. ARTN plays a role in axonal development.
ARTN is involved in the structural development and plasticity of several types of neurons, including the dopaminergic neurons of the ventral mesencephalon. ARTN plays an important role in the migration, proliferation and differentiation of sympathetic neurons during development.

OMIM ARTN, Artemin; 1p34.1

Increased expression and decreased methylation in ADHD.71

1.85. KCNJ6, POTASSIUM CHANNEL, INWARDLY RECTIFYING, SUBFAMILY J, MEMBER 6

OMIM KCNJ6, POTASSIUM CHANNEL, INWARDLY RECTIFYING, SUBFAMILY J, MEMBER 6

KCNJ6 regulates the excitability of dopaminergic neurons and is expressed in brain regions involved in ADHD.
KCNJ6 rs7275707 is associated with ADHD in children and correlates with increased reward dependence.
Both KCNJ6 rs7275707 and KCNJ6 rs6517442 affected EEG in the N-back task in ADHD.
KCNJ6 rs6517442 affected ventral striatum activation during reward anticipation.72

1.127. GPR139, Probable G-protein coupled receptor 139

Other names: G(q)-coupled orphan receptor GPRg1, G-protein-coupled receptor PGR3

GPR139 is active in the plasma membrane. GPR139 is involved in G protein-coupled receptor signaling (especially Gq/11 as well as somewhat weaker G12/13), phospholipase C-activating G protein-coupled receptor signaling and signal transduction. GPR139 may play a role in motor activity, food intake, alcohol dependence and hyperalgesia and phenylketonuria (PKU)
Endogenous agonists are probably the aromatic amino acids L-Trp and L-Phe and ACTH/α-MSH-related peptides. GPR139 appears to increase cAMP and cause an ERK phosphorylation reaction.
GPR139 appears to form receptor heterodimers with the dopamine D2 receptor and moderate D2 activation.73

The GPR139 receptor is expressed almost exclusively in the brain, particularly in the ventrolateral region of the putamen caudatus, the nucleus habenularis, the zona incerta, and the nucleus mammillaris medialis,74 according to another source in the striatum, thalamus, hypothalamus, pituitary, and habenula of the CNS.73

GPR139 appears to be associated with:73

  • Schizophrenia
  • ADHD and inattention symptoms
  • Depression
  • fetal development

One study found this gene to be one of the 51 most likely gene candidates for ADHD.75

Norepinephrine

Noradrenaline synthesis

1.7. Dopamine beta-hydroxylase gene, DBH (chromosome 9q34.2; Taql A)

The enzyme dopamine-β-hydroxylase catalyzes the oxidation of dopamine to norepinephrine.

DBH is a candidate gene for ADHD.8645

Norepinephrine action

1.46. ALPHA-1A-ADRENERGIC RECEPTOR; ADRA1A (chromosome 8p21.2)

OMIM ALPHA-1A-ADRENERGIC RECEPTOR; ADRA1A

The HES1 gene was identified as a candidate gene for ADHD in a 2006 study with p = 0.017.6

1.17. ALPHA-2A-ADRENERGIC RECEPTOR; ADRA2A (chromosome 10q25.2)

OMIM ALPHA-2A-ADRENERGIC RECEPTOR; ADRA2A

ADRA2A is a candidate gene for ADHD.56447

1.69. ALPHA-2C-ADRENERGIC RECEPTOR; ADRA2C (chromosome 4p16.3)

OMIM ALPHA-2C-ADRENERGIC RECEPTOR

Source64

1.44. BETA-2-ADRENERGIC RECEPTOR; ADRB2 (chromosome 5q32)

OMIM BETA-2-ADRENERGIC RECEPTOR; ADRB2

The ADRB2 gene was identified as a candidate gene for ADHD in a 2006 study with p = 0.013.6

Norepinephrine degradation

Norepinephrine reuptake

1.18. Norepinephrine transporter gene, SOLUTE CARRIER FAMILY 6 (NEUROTRANSMITTER TRANSPORTER, NORADRENALINE), MEMBER 2; SLC6A2, NET (chromosome 16q12.2)

The noradenaline transporter reuptakes more dopamine than noradrenaline in the PFC. See therefore above under dopamine reuptake

Serotonin

Serotonin synthesis

1.16. Tryptophan hydroxylase gene (chromosome 11p15.1)

Tryptophan hydroxylase is a candidate gene for ADHD.5

1.77. Tryptophan hydroxylase-1 gene; TPH1 (chromosome 11p15.1)

OMIM Tryptophan hydroxylase-1 gene; TPH1

One study found that the rare 218A-6526G haplotype of TPH1 was significantly more likely not to be transmitted in subjects with ADHD.76

Another study failed to find involvement of the more common haplotypes of TPH1 or TPH2 in ADHD-C.77

1.21. Tryptophan hydroxylase 2 gene, TPH2 (chromosome 12q21.1)

OMIM Tryptophan hydroxylase 2 gene, TPH2

TPH2 is a candidate gene for ADHD.64

The TPH2 gene was identified as a candidate gene for ADHD in a 2006 study with p = 0.003.6 Another study could not confirm this for either TPH1 or TPH2.77

Stress naive TPH2-/- mice (TPH2-KO mice) showed decreased dopamine levels in hippocampus and PFC.78
In TPH2+/- mice, stress resulted in decreased dopamine levels:79

  • In the hippocampus and striatum compared with stress-naive TPH2+/- mice.
  • In amygdala and PFC compared to stressed TPH2+/+ mice

The changes in the dopaminergic system of stressed TPH2+/- mice were markedly different from those in TPH2+/+ animals and strongly resembled those in TPH2-/- mice.

Stressed TPH2-/- mice showed no particular changes in norepinephrine levels in amygdala, PFC, hippocampus, dorsal raphe nuclei, or striatum. They merely showed (as did TPH2+/+ mice) the usual increased norepinephrine levels in the PFC, hippocampus, and striatum compared with nonstressed mice of the respective genotype.79

Serotonin effect

1.13. 5-HYDROXYTRYPTAMINE RECEPTOR 1B; serotonin receptor 1B, HTR1B (chromosome 6q14.1)

OMIM 5-HYDROXYTRYPTAMINE RECEPTOR 1B

HTR-1B is a candidate gene for ADHD.645

1.51. 5-HYDROXYTRYPTAMINE RECEPTOR 1E; HTR1E (chromosome 6q14.3)

OMIM 5-HYDROXYTRYPTAMINE RECEPTOR 1E; HTR1E

The HTRE1E gene was identified as a candidate gene for ADHD in a 2006 study with p = 0.051.6

1.14. 5-HYDROXYTRYPTAMINE RECEPTOR 2A; serotonin receptor 2A, HTR2A (chromosome 13q14.2)

OMIM 5-HYDROXYTRYPTAMINE RECEPTOR 2A

HTR-2A is a candidate gene for ADHD.645

Serotonin degradation

Serotonin Reuptake

1.15. SOLUTE CARRIER FAMILY 6 (NEUROTRANSMITTER TRANSPORTER, SEROTONIN), MEMBER 4; SLC6A4; serotonin transporter gene (5-HTT gene) (chromosome 17q11.2; 5-HTTLPR long)(x)

OMIM SOLUTE CARRIER FAMILY 6 (NEUROTRANSMITTER TRANSPORTER, SEROTONIN), MEMBER 4; SLC6A4;

SLC6A4 is a candidate gene for AD(HHD).6458

Serotonin Metablization

1.20. Tryptophan-2,3-dioxynase gene (chromosome 4q32.1)

The enzyme tryptophan-2,3-dioxygenase (TDO) oxidizes L - tryptophan by binding to two oxygen atoms. This is the first and at the same time rate-determining reaction step in the degradation of tryptophan.

The tryptophan 2,3-dioxynase gene is a candidate gene for ADHD.80

Steroids

1.19. Androgen receptor gene (chromosome Xq11-q12)

The androgen receptor gene is a candidate gene for ADHD.80

GABA

1.22. GABA receptor alpha3 gene (chromosome Xq28)

OMIM GABA receptor alpha3 gene

GABA receptor-A3 is a candidate gene for ADHD.5

OMIM indicates function in relation to physical and psychological pain sensing, as well as motor impairment and tolerence.

1.23. GABA receptor beta 3 gene (chromosome 15q11.2-q.12)

OMIM GABA receptor beta 3 gene

GABA receptor-B3 is a candidate gene for ADHD.5

OMIM points out that GABA receptors are zinc-controlled and a particularly zinc-insensitive polymorphism is known. OMIM does not mention ADHD, but autism, to which ADHD has a high comorbidity.
There are thoughts that ADHD and autism may share common neurological roots.81
Zinc deficiency can cause ADHD (similar) symptoms.

1.35. Cadherin13 (CDH13) gene (chromosome 16q23.3)

Cadherin-13 affects GABAergic function in the hippocampus and cognition.82

OMIM: Cadherin13 (CDH13) gene

CDH 13 is a candidate gene for ADHD.83

  • SNP rs7187223, position 81015234; Intergenic, within 203 kb upstream from CDH1364
    P: 5.21E-05.
  • SNP s116411, position 81304438; In Intron of CDH13 64
    P: 7.40E-06
  • SNP rs6565113, position 81665146; intron of CDH13 64
  • One study found CDH13 (variant rs8055161) to be one of the 20 most likely among 96 candidate genes 2

1.116. KIF21B, Kinesin Family Member 21B

Other names: KIAA0449, Kinesin-Like Protein KIF21B, DKFZP434J212

The protein KIF21B is a member of the kinesin superfamily. Kinesins are ATP-dependent, microtubule-based motor proteins involved in the intracellular transport of membranous organelles

KIF21B is associated with

  • inflammatory bowel diseases (single nucleotide polymorphisms)
  • Multiple sclerosis (single nucleotide polymorphisms)

KIF21B is a plus-end directed microtubule-dependent motor protein with processive activity. KIF21B is involved in the regulation of microtubule dynamics, synapse function, and neuronal morphology, including dendritic tree branching and spine formation. KIF21B plays a role in learning and memory. KIF21B is involved in the transmission of the gamma-aminobutyric acid (GABA(A)) receptor to the cell surface.

One study found this gene to be one of the 51 most likely gene candidates for ADHD.75

Acetylcholine

Acetylcholine action

1.32. Alpha-7 neuronal nicotinic acetylcholine receptor (CHRNA7) gene

The protein neuronal acetylcholine receptor subunit alpha-7 (nAChRα7) is a subunit of certain nicotinic acetylcholine receptors (nAchR).

OMIM Alpha-7 neuronal nicotinic acetylcholine receptor (CHRNA7) gene

CHRNA 7 is a candidate gene for ADHD.84

1.50. CHOLINERGIC RECEPTOR, NEURONAL NICOTINIC, ALPHA POLYPEPTIDE 4; CHRNA4 (chromosome 20q13.33)

OMIM CHOLINERGIC RECEPTOR, NEURONAL NICOTINIC, ALPHA POLYPEPTIDE 4; CHRNA4

The SHRNA4 gene was identified as a candidate gene for ADHD in a 2006 study with p = 0.05.664

Acetylcholine degradation

1.40. CHT, SOLUTE CARRIER FAMILY 5 (CHOLINE TRANSPORTER), MEMBER 7; SLC5A7 - coding variant Ile89Val (rs1013940)

OMIM CHT, SOLUTE CARRIER FAMILY 5 (CHOLINE TRANSPORTER), MEMBER 7; SLC5A7

This polymorphism has a two- to threefold frequency in ADHD sufferers (n = 100; P = 0.02) and is supposed to correlate with the ADHD-C of ADHD (OR = 3.16; P = 0.01), whereas coding variant SNP 3’ (rs333229) was significantly less frequent in ADHD sufferers than in nonaffected individuals (n = 60; P = 0.004).85

Glutamate

1.39. Glutamate receptor metabotropic 1 (GRM1) gene (chromosome 6p24-3)

OMIM:Glutamate receptor metabotropic 1 (GRM1) gene

GRM1 is a candidate gene for ADHD.86

1.34. Glutamate receptor metabotropic 5 (GRM5) gene (chromosome 11q14..2 - 14.3) (33, p. 55)

OMIM Glutamate receptor metabotropic 5 (GRM5) gene

GRM5 is a candidate gene for ADHD.865 One study found this gene to be one of the 51 most likely gene candidates for ADHD.75

1.38. Glutamate receptor metabotropic 7 (GRM7) gene (chromosome 3p26.1)

OMIM Glutamate receptor metabotropic 7 (GRM7) gene

GRM7 is a candidate gene for ADHD.86

The GMR7 rs3792452 polymorphism affects methylphenidate response in children with ADHD.87

Cannabinoids

1.37. Cannaboid receptor 1 (CNR1) gene (chromosome 6q14-q15)

OMIM Cannaboid receptor 1 (CNR1) gene

CNR1 is a candidate gene for ADHD.83

Traceamine

1.42. Phenylethanolamine, N-methyltransferase gene, PNMT (chromosome 17q12)

OMIM Phenylethanolamines, N-methyltransferase gene, PNMT

The PNMT gene was identified as a candidate gene for ADHD in a 2006 study with p = 0.008.6

Glycine

1.89. SLC6A9, SOLUTE CARRIER FAMILY 6 (NEUROTRANSMITTER TRANSPORTER, GLYCINE), MEMBER 9

OMIM SLC6A9, SOLUTE CARRIER FAMILY 6 (NEUROTRANSMITTER TRANSPORTER, GLYCINE), MEMBER 9

For SLC6A9, one study found an alteration in expression in ADHD.1

Nitric Oxide

1.36. Nitric Oxide synthase 1 (NOS1) gene (chromosome 12q24.22) (87)

The protein Nitric Oxide synthase 1 belongs to the family of nitric oxide synthases, which synthesize nitric oxide from L-arginine. Nitric oxide is a biological mediator of neurotransmission, antimicrobial and antitumor activities, among others. Nitric oxide exhibits many neurotransmitter properties in the brain and peripheral nervous system. It is involved in

  • Neurotoxicity in relation to strokes
  • neurodegenerative diseases
  • neuronal regulation of smooth muscle, including peristalsis, and penile erection.

OMIM Nitric Oxide synthase 1 (NOS1) gene

Nitric oxide (NO) has been implicated in schizophrenia, ADHD, and possibly mood disorders:88

Genetically determined decreased NO signaling in the PFC is associated with schizophrenia and cognition problems. Here, NOS1 as well as its interaction partner NOS1AP play a role.
Reduced NOS1 expression in the striatum due to a length polymorphism in the NOS1 promoter (NOS1 ex1f-VNTR) correlates with impulsivity
Associations of NOS1 with mood disorders is possible. NO metabolites in blood may serve as biomarkers for major depression and bipolar disorder. .

NOS 1 (short allele) is a candidate gene for increased impulsivity and thus ADHD.8389

Neurotransmitter storage and release

1.114. CPLX2, Complexin 2

Other names: CPX-2, DKFZp547D155, Complexin II, Complexin-2

CPLX2 is a cytosolic protein and plays a role in the exocytosis of synaptic vesicles. It binds to and disrupts syntaxin, a part of the SNAP receptor, allowing the release of transmitters. CPLX2 inhibits the formation of synaptic vesicle clusters at the active zone to the presynaptic membrane in postmitotic neurons. CPLX2 promotes a late step in the exocytosis of various cytoplasmic vesicles, such as synaptic vesicles and other secretory vesicles. CPLX2 is involved in the exocytosis of mast cells.90

CPLX2 is associated with

  • Schizophrenia
  • Epilepsy, familial temporal lobe, 7

One study found this gene to be one of the 51 most likely gene candidates for ADHD.75

Brain development

1.33. Nuclear distribution gene E homologue 1 (NDE1) gene

NDE1 is required for centrosome duplication and mitotic spindle formation and function. NDE1is essential for the development of cerebral cortex and can regulate the production of neurons.

OMIM Nuclear distribution gene E homologue 1 (NDE1) gene

NDE1 is a candidate gene for ADHD.84

1.106. MAP1B, Microtubule Associated Protein 1B

Other names: PPP1R102, MAP5, Protein Phosphatase 1, Regulatory Subunit 102

The protein MAP1B belongs to the family of microtubule-associated proteins that are thought to be involved in microtubule assembly, which is an essential step in neurogenesis. MAP1B is a precursor polypeptide that presumably forms the final heavy chain of MAP1B and the light chain of LC1 after proteolytic processing. MAP1B knockout mouse studies suggest an important role in nervous system development and function. MAP1B facilitates tyrosination of alpha-tubulin in neuronal microtubules. Phosphorylated MAP1B appears to play a role in the cytoskeletal changes associated with neurite outgrowth. MMAP1B acts as a positive cofactor in DAPK1-mediated autophagic vesicle formation and membrane blebbing.91
MAP1B is associated with

  • Periventricular nodular heterotopia 9
  • Deafness, Autosomal Dominant 83

One study found this gene to be one of the 51 most likely gene candidates for ADHD.75

1.107. MOBP, Myelin-Associated Oligodendrocyte Basic Protein

The protein MOBP is thought to facilitate actin and myosin binding activity. MOBP appears to be a structural component of the myelin sheath (possibly by binding the negatively charged acidic phospholipids of the cytoplasmic membrane) and involved in the development of the nervous system. It is probably found in the mitochondrion and is active in the cortical actin cytoskeleton

MOBP is associated with frontotemporal dementia and cocaine abuse

One study found this gene to be one of the 51 most likely gene candidates for ADHD.92

1.56. ASTROTACTIN 2; ASTN2 (chromosome 9q33.1)

The proteins astrotactin-1 and 2 (ASTN-1 and ASTN-2) are integral membrane perforin-like proteins. They play a critical role in neurodevelopment. Genetic variations in these proteins are associated with a number of neurodevelopmental disorders and other neurological pathologies, including advanced onset of Alzheimer’s disease. ASTN-2 (unlike ASTN-1) binds inositol triphosphates , suggesting a mechanism for membrane recognition or regulation of its activity by secondary messengers

OMIM ASTROTACTIN 2; ASTN2

  • SMP: rs10983238 position: 118373504; In intron of ASTN264
    p: 1.37E-07
    One study found this gene to be one of the 51 most likely gene candidates for ADHD.75

1.110. TCF4, Transcription Factor 4

Other names: BHLHb19, ITF2, Class B Basic Helix-Loop-Helix Protein 19, Immunoglobulin Transcription Factor 2, SL3-3 Enhancer Factor 2, SEF2-1B, E2-2, ITF-2

The protein TCF4 is a basic helix-loop-helix transcription factor. It recognizes an ephrussi box (“E-box”) binding site (“CANNTG”). TCFG4 is widely expressed and may play an important role in nervous system development. TCF4 is involved in the initiation of neuronal differentiation. TCF4 binds to the immunoglobulin enhancer Mu-E5/KE5 motif. TCF4 binds to the E-box in the somatostatin receptor 2 initiator element (SSTR2-INR) and the E-box (5’-CANNTG-3’) to activate transcription

TCF4 is associated with

  • Pitt-Hopkins syndrome
  • endothelial corneal dystrophy of Fuchs

One study found this gene to be one of the 51 most likely gene candidates for ADHD.75

1.111. TLL2, Tolloid Like 2

Other names: Tolloid-Like Protein 2, EC 3.4.24.19, EC 3.4.24, EC 3.4.24, KIAA0932

The protein TLL2 is astacin-like zinc-dependent metalloprotease and member of the metzincin family subfamily. TLL2 is a predominant protease and specifically processes pro-lysyl oxidase. TLL2 is required for embryonic development and influences the development of dorsal-ventral patterning and dre skeleton formation.

TLL2 is associated with

  • Powassan encephalitis
  • Louping Ill.

One study found this gene to be one of the 51 most likely gene candidates for ADHD.75

1.117. TENM4, Teneurin Transmembrane Protein 4

Other names: Ten-M4, KIAA1302, TEN4, ODZ4, Protein Odd Oz/Ten-M Homolog 4, Tenascin-M4

The protein TENM4 plays a role in establishing proper neuronal connectivity during development. TENM4 is involved in the formation of the anterior-posterior axis during gastrulation. TENM4 regulates oligodendrocyte differentiation and cellular process formation and myelination of small diameter axons in the central nervous system (CNS). TENM4 promotes activation of focal adhesion kinase. TENM4 may function as a cellular signal transducer.

TENM4 is associated with tremor.

One study found this gene to be one of the 51 most likely gene candidates for ADHD.75

1.120. ANKS1B, Ankyrin Repeat And Sterile Alpha Motif Domain Containing 1B

Other names: AIDA-1, EB-1, Cajalin-2, ANKS2, Ankyrin Repeat And Sterile Alpha Motif Domain-Containing Protein 1B

ANKS1B is a multidomain protein found primarily in the brain and testis. ANKS1B interacts with the amyloid beta protein precursor (AbetaPP) and may play a role in normal brain development and in the development of Alzheimer’s disease. Isoform 2 may be involved in the regulation of nucleoplasmic coilin-protein interactions in neuronal and transformed cells. Isoform 3 may regulate global protein synthesis by altering the number of nucleoli. Isoform 4 may play a role as a modulator of APP processing. Overexpression may downregulate APP processing.93

ANKS1B is associated with

  • Alzheimer
  • pre-B-cell acute lymphoblastic leukemia

One study found this gene to be one of the 51 most likely gene candidates for ADHD.75

Growth factors, neurogenesis

1.25. Neurotrophin-3 (NTF3) gene (chromosome 12p13.31)

OMIM Neurotrophin-3 (NTF3) gene

NTF3 is a candidate gene for ADHD.594

1.71. NEUROTROPHIN 4; NTF4 (chromosome 19q13.33)

OMIM NEUROTROPHIN 4; NTF4

Source64

1.71.1. NEUROTROPHIN 5; NTF5 (chromosome 19q13.33)

OMIM NEUROTROPHIN 5; NTF5

Source64

1.26. Brain-derived-neurothropic-factor (BDNF) gene (chromosome11p14.1) (X)

OMIM Brain-derived-neurothropic-factor (BDNF) gene

BDNF is a candidate gene for ADHD.594

The BDNF gene is involved in the formation of the dopamine D3 receptor (see OMIM on DRD3) in the nucleus accumbens during development and adolescence.
In children with ADHD, poorer performance on the Stroop test of executive function correlated BDNF GG genotype rs2030324.95 One study found a positive correlation between BDNF gene polymorphism rs10835210 and ADHD-HI and a negative correlation of BDNF-rs12291186 with one or both mutant alleles with ADHD.96

1.27. Brain-specific angiogenesis inhibitor 1-associated protein (BAIAP2) gene

OMIM Brain-specific angiogenesis inhibitor 1-associated protein (BAIAP2) gene

BAIAP2 is a candidate gene for ADHD.597

1.70. NERVE GROWTH FACTOR; NGF (chromosome 1p13.2)

OMIM NERVE GROWTH FACTOR

Source64

1.72. GLIAL CELL LINE-DERIVED NEUROTROPHIC FACTOR; GDNF (chromosome 5p13.2)

OMIM GLIAL CELL LINE-DERIVED NEUROTROPHIC FACTOR; GDNF

Source64

1.54. UNC5, C. ELEGANS, HOMOLOG OF, B; UNC5B (chromosome 10q22.1)

UNC-5 is a receptor for netrins. Netrins are a class of proteins involved in axon guidance. UNC-5 uses repulsion to direct axons, while the other netrin receptor, UNC-40, attracts axons to the source of netrin production.

OMIM UNC5, C. ELEGANS, HOMOLOG OF, B; UNC5B

  • SNP: rs16928529 position: 72652991; In intron of UNC5B64
    p: 3.90E-06

1.61. GLYPICAN 6; GPC6 (chromosome 13q31.3-q32.1)

Glypicans are a family of glycosylphosphatidylinositol-anchored heparan sulfate proteoglycans. Glypicans are involved in the control of cell growth and division. Glypican 6 is a putative cell surface coreceptor for growth factors, extracellular matrix proteins, proteases and anti-proteases.
Mutations of glypican 6 are associated with omodysplasia 1.

OMIM GLYPICAN 6; GPC6

  • SNP: rs7995215 Position: 93206507; In intron of GPC664
    P: 1.35E-08
    One study found this gene to be one of the 51 most likely gene candidates for ADHD.75

Circadian rhythm

1.29. Circadian Locomotor Output Cycles Protein Kaput (CLOCK) gene (chromosome 4q12) (x)

OMIM Circadian Locomotor Output Cycles Protein Kaput (CLOCK) gene

CLOCK is a candidate gene for ADHD.5

1.47. PERIOD, DROSOPHILA, HOMOLOG OF, 2; PER2 (chromosome 2q37.3)

OMIM PERIOD, DROSOPHILA, HOMOLOG OF, 2; PER2

The PER2 gene was identified as a candidate gene for ADHD in a 2006 study with p = 0.017.6

1.73. VASOACTIVE INTESTINAL PEPTIDE RECEPTOR 2; VIPR2 (chromosome 7q36.3)

VIPR2 and VIPR1 (192321) encode receptors for the neuropeptide vasoactive intestinal peptide (VIP; 192320) and also bind pituitary adenylate cyclase activating polypeptide (PACAP; 102980) with the same affinity as VIP

The human VIP2 receptor binds to PACAP38, PACAP27, VIP, and heldermin, each of which activates adenylate cyclase. GTP inhibits the binding of the peptide

Food intake triggers a neuronal signal of the gut with antimicrobial and metabolic responses. This signal is controlled by innate lymphoid cells type 3 (ILC3). Food intake rapidly activates a population of intestinal neurons that produce VIP. Projections of VIP-producing neurons in the lamina propria are in close proximity to clusters of ILC3 that selectively express VIPR2. VIPR2 inhibits IL22 synthesis. This has the effect of reducing the level of epithelial cell-derived antimicrobial peptides while increasing the expression of lipid-binding proteins and transporters. Thus, during food consumption, activation of VIP-producing neurons promotes the growth of segmented filamentous bacteria associated with the epithelium and increases lipid absorption. This establishes a nutrition- and circadian-regulated dynamic neuroimmune circuit in the gut that moderatesz between IL22-mediated innate immune protection and nutrient absorption efficiency

Rare copy number variants (CNVs) of VIPR2 are associated with schizophrenia-
Microduplications of 7q36.3 correlated with increased VIPR2 transcription and increased cyclic AMP signaling

Vipr2 -/- mice (VPR2-KO mice) are unable to maintain normal resting/activity circadian rhythms and show no circadian expression of the central clock genes Per1 (602260), Per2 (603426), and Cry1 (601933) and the clock-controlled gene encoding arginine vasopressin (AVP; 192340) in the suprachiasmatic nuclei. In addition, VPR2-KO mice showed no acute induction of Per1 and Per2 by nocturnal illumination

OMIM VASOACTIVE INTESTINAL PEPTIDE RECEPTOR 2; VIPR2

Source37

1.79. KAT2B, LYSINE ACETYLTRANSFERASE 2B

The protein KAT2B (lysine acetyltransferase 2B) is involved in:98

  • Apoptotic pathway signaling in synovial fibroblasts
  • Signaling pathway of regulation of activated PAH-2p34 by proteasome-mediated degradation
  • Protein kinase binding
  • KAT2B is a histone acetyltransferase (HAT) and thus increases transcriptional coactivator activity
  • Has significant histone acetyltransferase activity with nuclear histones (H3 and H4) and also with nucleosome nuclear particles
  • Also acetylates non-histone proteins, such as ACLY, MAPRE1/EB1, PLK4, RRP9/U3-55K and TBX5
  • Inhibits cell cycle progression and counteracts mitogenic activity of the adenoviral oncoprotein E1A
  • Acts as a circadian transcriptional coactivator, enhancing the activity of circadian transcriptional activators: NPAS2-ARNTL/BMAL1 and CLOCK-ARNTL/BMAL1 heterodimers
  • Acetylation of TBX5, thereby participating in heart and limb development
    • Acetylation regulates nucleocytoplasmic shuttling of TBX5
  • inhibits centrosome amplification by mediating acetylation of PLK4
  • Acetylates RRP9/U3-55K, a key subunit of the U3 snoRNP complex, impairing pre-rRNA processing
  • Acetylates MAPRE1/EB1 to promote dynamic kinetochore-microtubule interactions in early mitosis
  • Acetylated spermidine
  • is recruited by the viral protein Tat upon HIV-1 infection. Regulates the transactivating activity of Tat and may help induce chromatin remodeling of proviral genes.

KAT2B is associated with disease:

  • Holt-Oram syndrome
  • spinocerebellar ataxia 7

OMIM KAT2B, LYSINE ACETYLTRANSFERASE 2B

KAT2B is a candidate gene for ADHD.99

Immune system

1.57. CUB AND SUSHI MULTIPLE DOMAINS 2; CSMD2 (chromosome 1p35.1)

The protein CSMD2 appears to be involved in the control of the complement cascade of the immune system. It may serve as a tumor suppressor for colorectal cancer. Gene defects are associated with schizophrenia

OMIM CUB AND SUSHI MULTIPLE DOMAINS 2

  • SNP: rs2281597 position: 34132445; In intron of CSMD264
    p: 5.41E-07
    One study found this gene to be one of the 51 most likely gene candidates for ADHD.75

1.112. TRIM26, Tripartite Motif Containing 26

Other names: RNF95, ZNF173, Tripartite Motif-Containing Protein 26, Zinc Finger Protein 173

The TRIM26 protein is a member of the TRIM (tripartite motif) family. The TRIM motif comprises three zinc-binding domains, a RING, a B-box type 1 and a B-box type 2, and a coiled-coil region. TRIM26 is found in cytoplasmic bodies. The RING domain suggests that TRIM26 may have DNA-binding activity. TRIM26 is an E3 ubiquitin-protein ligase that regulates IFN-beta production and antiviral response downstream of various DNA-encoded pattern recognition receptors (PRRs). TRIM26 promotes IRF3 nuclear ubiquitination and proteasomal degradation. TRIM26 links TBK1 and NEMO during the innate response to viral infection, leading to activation of TBK1

TRIM26 is associated with neural tube defects.

One study found this gene to be one of the 51 most likely gene candidates for ADHD.75

Stress Systems

HPA axis

1.74. NUCLEAR RECEPTOR SUBFAMILY 3, GROUP C, MEMBER 1; NR3C1 (GLUCOCORTICOID RECEPTOR; GCCR; GR GCR; GRL) Chromosome: 5q31.3

OMIM NUCLEAR RECEPTOR SUBFAMILY 3, GROUP C, MEMBER 1; NR3C1 (GLUCOCORTICOID RECEPTOR; GCCR; GR GCR; GRL)

The GR-9β haplotype of the glucocorticoid receptor gene NR3C1 causes increased GRβ expression100 and has been associated with ADHD.101 However, the GRβ variant does not bind cortisol, is transcriptionally inactive, and is considered a dominant-negative inhibitor of the functional GRα variant.102
The GR-9β-stabilizing polymorphism has been associated with increased ACTH and cortisol stress responses.103

The combined inhibitory effect of the GR-9β haplotype and stress exposure may reduce GR activity to pathologically low levels, contributing to ADHD-related behaviors. The GR-9β haplotype of the glucocorticoid receptor gene NR3C1 is associated with increased ADHD risk. In carriers of this haplotype, stress exposure and ADHD severity correlate more strongly than in noncarriers. This gene-environment interaction was further enhanced when affected individuals were also carriers of the homozygous 5-HTTLPR L allele rather than the S allele.104

In contrast, the Bcll GG haplotype of GR showed a flattened cortisol stress response in males and a greatly increased cortisol stress response in females (although the subjects were all using hormonal contraception).103

1.75. FK506-BINDING PROTEIN 5; FKBP5 (chromosome 6p21.31)

OMIM FK506-BINDING PROTEIN 5; FKBP5

The FKBP5 gene modulates glucocorticoid receptor sensitivity.
In terms of damage from long-term exposure to stress, there is a significant difference whether stress occurs during the developmental phase of the brain or in adulthood. Downregulation in adulthood has fewer long-term consequences. Epigenetic demethylation of the FKBP5 gene, which modulates glucocorticoid receptor sensitivity,105 is mediated by stress only during the differentiation and proliferation phase of neurons (i.e., childhood and adolescence), but no longer in mature neurons (i.e., adults).106

The FKBP5 gene polymorphisms rs1360780, rs4713916, and rs3800737 cause increased FKBP51 concentrations in blood and thus an enhanced cortisol response to psychosocial stress. HPA axis re-regulation is slowed and remains incomplete for prolonged periods, even with repeated stress exposure. In contrast, the FKBP5 gene polymorphism Bcl1 shows an anticipatory cortisol response to psychosocial stress.107

1.60. CADHERIN 23; CDH23 (chromosome 10q22.1)

The CDH23 gene encodes a member of the cadherin superfamily, which includes calcium-dependent cell-cell adhesion glycoproteins.
CDH23 is associated with adenomas of the hypohyseal gland (second stage of the HPA axis). Pituitary adenomas have a prevalence of 14 to 22%.108

OMIM CADHERINE 23

  • SNP: rs11594082 position: 72969259; In intron of CDH2364
    p: 1.00E-05

Broadly effective mechanisms

Transcription

1.95. RERE

The RERE protein is critical for normal development before birth. RERE dysfunction likely alters the activity of many genes involved in pre-birth development. These changes prevent normal development of tissues in the brain, eyes, heart, and other organs. The RERE protein interacts with other proteins called transcription factors that control the activity (transcription) of certain genes. The RERE protein helps ensure that these transcription factors turn on (activate) and turn off (repress) a number of genes that are important for early development, ensuring that genes are activated (expressed) at the right time and place for proper tissue formation. Research suggests that the RERE protein plays a role in brain, eye, inner ear, heart and kidney development.109

One study found this gene to be one of the 51 most likely candidate genes for AD(HHD).75

1.45. HAIRY/ENHANCER OF SPLIT, DROSOPHILA, HOMOLOG OF, 1; HES1 (chromosome 3q29)

The HES1 protein belongs to the bHLH (basic helix-loop-helix) family of transcription factors. It is a transcriptional repressor of genes that require a bHLH protein for their transcription. As a member of the bHLH family, it is a transcriptional repressor that affects cell proliferation and differentiation in embryogenesis. HES1 regulates its own expression via a negative feedback loop and oscillates with a periodicity of approximately 2 hours.

OMIM HAIRY/ENHANCER OF SPLIT, DROSOPHILA, HOMOLOG OF, 1; HES1

The HES1 gene was identified as a candidate gene for ADHD in a 2006 study with p = 0.016.6

1.86. FEZF1, FEZ FAMILY ZINC FINGER PROTEIN 1

The protein FEZF1 is a transcriptional repressor. In mice, FEZF1 is expressed in the forebrain during early embryonic development.
FEZF1 represses the transcription factor HES5, which contributes to the control of neural stem cell differentiation. FEZF1 helps divide the caudal forebrain into three distinct parts during development prethalamus, thalamus and pretectum: FEZF1-KO mice have no prethalamus and a smaller thalamus.
A loss-of-function mutation in FEZF1 causes Kallmann syndrome.
As axons develop and migrate in the early embryo, FEZF1 enables olfactory neuron axons to connect to the central nervous system in the mouse model. During neuronal development, GnRH neurons migrate through one of these olfactory axon pathways, and loss of function of FEZF1 therefore leads to loss of GnRH neurons in the brain, the hallmark of Kallmann syndrome.110

OMIM FEZF1, FEZ FAMILY ZINC FINGER PROTEIN 1

FEZF1 is a candidate gene for ADHD.111

1.93. TAF1, TAF1 RNA POLYMERASE II, TATA BOX-BINDING PROTEIN-ASSOCIATED FACTOR, 250-KD

Other names: TAFII250, DYT3/TAF1, NSCL2, TAF2A, KAT4, BA2R, CCG1, CCGS, TAF1 RNA Polymerase II, TATA Box Binding Protein (TBP)-Associated Factor, 250kDa, Transcription Initiation Factor TFIID Subunit 1, TBP-Associated Factor 250 KDa, Cell Cycle Gene 1 Protein, EC 2.7.11.1, TAF(II)250

The TAF1 protein:

  • is the largest subunit and the core scaffold of the basal transcription factor complex TFIID
  • contains novel N- and C-terminal Ser/Thr kinase domains that can autophosphorylate or transphosphorylate other transcription factors
  • phosphorylates TP53 at ‘Thr-55’, leading to MDM2-mediated degradation of TP53
  • phosphorylates GTF2A1 and GTF2F1 at Ser residues
  • has DNA-binding activity
  • essential for the progression of the G1 phase of the cell cycle
  • shows histone acetyltransferase activity towards histones H3 and H4
  • binds to core promoter sequences comprising the transcription start site
  • binds to activators and other transcriptional regulators, affecting the rate of transcription initiation
  • contains two independent protein kinase domains at the N- and C-terminus
  • possesses acetyltransferase activity
  • may act as a ubiquitin-activating/conjugating enzyme
  • controls apoptotic pathways in synovial fibroblasts

Mutations of TAF1 lead to

  • Dystonia 3, torsion, X-linked, a dystonia-parkinsonism disorder
  • Intellectual development disorder, X-linked, syndrome 33

OMIM TAF1, TAF1 RNA POLYMERASE II, TATA BOX-BINDING PROTEIN-ASSOCIATED FACTOR, 250-KD

For TAF1, one study found an alteration in expression in ADHD.1

1.143. ZNF763, Zinc Finger Protein 763

Other NAmen: ZNF440L, Zinc Finger Protein 440 Like, DNA-Binding Protein, ZNF

The protein ZNF763 is likely to be involved in transcriptional regulation through RNA polymerase II. ZNF763 appears to have DNA-binding transcription factor activity and sequence-specific DNA-binding activity in the cis-regulatory region of RNA polymerase II. ZNF763 is thought to be localized in the nucleus.112

ZNF763 is a candidate gene for ADHD.113

1.134. ZNF615, Zinc Finger Protein 615

Other name: FLJ33710

The protein ZNF615 facilitates DNA-binding transcription activator activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA-binding activity. ZNF615 is thought to be involved in the regulation of transcription by RNA polymerase II. ZNF615 is probably active in the nucleus.114

One study found this gene to be one of the 51 most likely gene candidates for ADHD.75

1.139. POLR1H, RNA Polymerase I Subunit H

Other names: Tctex-6, HTEX-6, HZR14, RPA12, A12, ZNRD1, DNA-Directed RNA Polymerase I Subunit RPA12, DNA-Directed RNA Polymerase I Subunit H, Zinc Ribbon Domain Containing 1, RNA Polymerase I Small Specific Subunit Rpa12, Transcription-Associated Zinc Ribbon Protein, Zinc Ribbon Domain-Containing Protein 1, TCTEX6, HTEX6, Rpa12, TEX6, ZR14, ZNRD1, ZINC RIBBON DOMAIN-CONTAINING PROTEIN 1, MOUSE, HOMOLOG OF; A12.2

The protein POLR1H is a DNA-directed RNA polymerase I subunit. This may play a role in regulating cell proliferation. POLR1H catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. POLR1H is a component of RNA polymerase I.115 RNA polymerase (Pol) I produces ribosomal (r)RNA, an essential component of the cellular protein synthesis machinery that drives cell growth and underlies many basic cellular processes. Transcription by Pol I is subject to a number of intricate control mechanisms that influence rRNA production. Pol I-specific transcription factors direct Pol I to the rDNA promoter and contribute to multiple rounds of transcription initiation, promoter escape, elongation, and termination.116
POLR1H is associated with

  • Cancer progression
  • HIV
  • Asthma
  • Nasal polyps
  • Aspirin intolerance
  • Plantar warts

OMIM ZNRD1, ZINC RIBBON DOMAIN-CONTAINING PROTEIN 1

One study found this gene to be one of the 51 most likely gene candidates for ADHD.75

Receptor activity

1.41. Arrestin beta 2 gene, ARRB2 (chromosome 17p13.2)

The protein β-arrestin (also β-arrestin 1, arrestin 2) regulates the activity of G protein-coupled receptors (GPCRs). It causes

  • reduced GPCR activation
  • Endocytosis of the GPCR
  • Connection of GPCR signaling pathway with Src signaling pathway
  • Connection ERK signal pathway and the Akt signal pathway.

OMIM Arrestin beta 2 gene, ARRB2

The ARRB2 gene was identified as a candidate gene for ADHD in a 2006 study with p = 0.004.6

Neurotransmitter storage

1.49. SYNAPTOPHYSIN; SYP (chromosome Xp11.23)

Synaptophysin is found in synaptic vesicles of neurons in brain, spinal cord, and retina, and in similar vesicles in adrenal medulla and motor endplate.
The function of synaptophysin is poorly understood. It appears to form a channel in the membrane of neurons, allowing the uptake of neurotransmitters from the cytosol into the synaptic vesicles.

OMIM SYNAPTOPHYSIN; SYP

The SYP gene was identified as a candidate gene for ADHD in a 2006 study with p = 0.045.6

Purine metabolism

1.115. NT5C2, 5’-nucleotidase, cytosolic II

Other names: CN-II, PNT5, SPG65, NT5B, GMP, Spastic Paraplegia 45 (Autosomal Recessive), Cytosolic Nucleoside Phosphotransferase 5’N, 5’-Nucleotidase (Purine), Cytosolic Type B, Cytosolic IMP/GMP-Specific 5’-Nucleotidase, Cytosolic Purine 5’-Nucleotidase

The protein NT5C2 is a hydrolase and a cytosolic 5’-nucleotidase with broad specificity. NT5C2 plays an important role in cellular purine metabolism. NT5C2 mainly acts on inosine 5’-monophosphate and other purine nucleotides. NT5C2 catalyzes the dephosphorylation of 6-hydroxypurine nucleoside 5’-monophosphates. NT5C2 possesses phosphotransferase activity by which it can transfer a phosphate from a donor nucleoside monophosphate to an acceptor nucleoside, preferably inosine, deoxyinosine, and guanosine.117

NT5C2 is associated with

  • Chemotherapy resistance in relapsed T-cell acute lymphoblastic leukemia.
  • Spastic paraplegia 45, autosomal recessive
  • Paraplegia

One study found this gene to be one of the 51 most likely gene candidates for ADHD.75

Adhesion

1.30. Latrophilin-3 (LPHN3) gene / ADHESION G PROTEIN-COUPLED RECEPTOR L3; ADGRL3 gene (chromosome 4q13.1)

Latrophilin-3 (LPHN3), a G protein-coupled receptor, belongs to the adhesion receptor subfamily. LPHN3 regulates synaptic function and serves to maintain in brain regions that mediate locomotor activity, attention, and place and path memory

OMIM Latrophilin-3 (LPHN3) gene / ADHESION G PROTEIN-COUPLED RECEPTOR L3; ADGRL3 gene

ADGRL3 is a candidate gene for ADHD.5118119
Lphn3 binds to Gαi1, Gαi2, Gαs, Gαq, and Gα13 In particular, gene variants that cause impaired Gα13 binding appear to be relevant in ADHD.120

Other

1.24. Ciliary neurotrophic factor receptor gene CNFTR (chromosome 9p13.3)

The Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) is a protein fixed on the surface of cells, a so-called chloride channel. Mutations in the CFTR gene in humans lead, among other things, to the absence or impaired function of the channel, which can cause cystic fibrosis and congenital aplasia of the vas deferens (CAVD).

OMIM Ciliary neurotrophic factor receptor gene CNFTR

CNFTR is a candidate gene for ADHD.5

1.48. FATTY ACID DESATURASE 2; FADS2 (chromosome 11q12.2)

The enzyme fatty acid desaturase removes two hydrogen atoms from a fatty acid, forming a carbon-carbon double bond

OMIM FATTY ACID DESATURASE 2; FADS2

The FADS2 gene was identified as a candidate gene for ADHD in a 2006 study with p = 0.039.6

1.52. METASTASIS-ASSOCIATED GENE 3; MTA3 (chromosome 2)

MTA3 appears to be associated with cellular circulation

OMIM METASTASIS-ASSOCIATED GENE 3; MTA3

  • SNP: rs930421 position: 42834743; exon of MTA3 64
    p: 5.64E-06
    Associated with all ADHD symptoms
  • SNP: rs6719977 Position: 42839307; Within 2 kb downstream of MTA3 64
    p: 1.67E-06
    Associated with hyperactivity and impulsivity

1.53. SPERMATOGENESIS-ASSOCIATED PROTEIN 13; SPATA13 (ARHGEF29, FLJ31208) (chromosome 13q12.12)

Other names: Spermatogenesis Associated 13, ARHGEF29, ASEF2, APC-Stimulated Guanine Nucleotide Exchange Factor

The protein SPATA13 facilitates guanyl nucleotide exchange factor activity for the GTPases RHOA, RAC1, and CDC42 and identical protein binding activity. SPATA13 is involved in cell migration, formation of cell processes bound to the plasma membrane, regulation of cell migration, and adhesion formation and degradation through a mechanism dependent on RAC1, PI3K, RHOA, and AKT1. SPATA13 increases both RAC1 and CDC42 activity, but decreases the amount of active RHOA. SPATA13 is required for the upregulation of MMP9 via the JNK pathway in colorectal tumor cells. SPATA13 is involved in tumor angiogenesis and may play a role in intestinal adenoma formation and tumor progression. SPATA13 is found in several cellular components, including filopodium, lamellipodium, and curl membrane.121
SPATA13 is associated with

  • Optical atrophy 3, autosomal dominant
  • Dravet syndrome

OMIM SPERMATOGENESIS-ASSOCIATED PROTEIN 13; SPATA13

  • SNP: rs17079773 Position: 23496384; In intron of SPATA13 64
    Associated with inattention
    p: 4.71E-06

1.43. SOLUTE CARRIER FAMILY 9 (SODIUM/HYDROGEN EXCHANGER, FLJ35613, NHE9, isoform 9, member 9); SLC9A9 (chromosome 3q24)

The SLC9A9 gene encodes a sodium/proton exchanger belonging to the solute carrier 9 family of proteins. The encoded protein is localized in the late recycling endosomes and appears to be relevant for the maintenance of cation homeostasis. Mutations are associated with autism and attention-deficit/hyperactivity disorder.

OMIM SOLUTE CARRIER FAMILY 9 (SODIUM/HYDROGEN EXCHANGER), MEMBER 9; SLC9A9

The SLC9A9 gene was identified as a candidate gene for ADHD with p = 0.01 in a 2006 study.6 Another study found SLC9A9 (variant rs7621206) to be one of the 20 most likely among 96 candidate genes 2

1.58. INTEGRIN, ALPHA-E; ITGAE, CD103 (chromosome 17p3.2)

Integrins are membrane proteins. As transmembrane proteins, they cross the cell membrane, in which they are firmly anchored. They form an important function in cell signal transduction. They connect individual cells with each other and cells with the extracellular matrix (adhesion). Integrins are therefore also called adhesion molecules

Integrin protein alpha E (ITGAE) binds integrin beta 7 (β7- ITGB7) to form the complete heterodimeric integrin molecule αEβ7. The β7-subunit can bind with other integrin α-chains, such as α4 (CD49d).

OMIM INTEGRIN, ALPHA-E

  • SNP: rs220470 position: 3611724; In intron of ITGAE64
    P: 1.34E-07
    One study found this gene to be one of the 51 most likely gene candidates for ADHD.75

1.59. INTEGRIN, ALPHA-11; ITGA11 (chromosome 15q23)

Integrins are membrane proteins. As transmembrane proteins, they cross the cell membrane, in which they are firmly anchored. They form an important function in cell signal transduction. They connect individual cells with each other and cells with the extracellular matrix (adhesion). Integrins are therefore also called adhesion molecules

The protein ITGA11 contains an I-domain. It is expressed in muscle tissue and dimerizes in vitro with beta-1 integrin, which appears to bind collagen. Therefore, ITGA11 may be involved in binding muscle tissue to the extracellular matrix. Alternative transcriptional splice variants have been found.

OMIM INTEGRIN, ALPHA-11

  • Rs7164335 66502086 In intron of ITGA1164
    p: 1.30E-07
    One study found this gene to be one of the 51 most likely gene candidates for ADHD.75

1.62. CATENIN ALPHA-2; CTNNA2 (chromosome 2p12)

The protein CTNNA2 enables actin filament binding activity. It is involved in the following functions:

  • Inhibition of Arp2/3 complex-mediated actin nucleation and Arp2/3-mediated actin polymerization Thus, it suppresses excessive actin branching that would affect neurite growth and stability.122
  • Regulation of neuron migration / development of the nervous system
  • Regulation of the development of neuron projections
  • Link between cadherin adhesion receptors and the cytoskeleton to regulate cell-cell adhesion and differentiation in the nervous system.
  • Regulation of cortical neuronal migration and neurite growth.
  • Regulation of morphological plasticity of synapses and lamination of cerebellum and hippocampus during development.
  • Control of the startle modulation.

It is involved in the following disorder patterns:

  • complex cortical dysplasia with other brain malformations 9 (CDCBM9)
  • Hereditary Breast Ovarian Cancer Syndrome

OMIM CATENIN, ALPHA-2

  • SNP: rs13395022 position: 79735768; In intron of CTNNA264
    p: 9.68E-06

1.63. NEURON NAVIGATOR 2; NAV2 (APC down-regulated 1, FLJ10633, FLJ11030, FLJ23707, HELAD1, KIAA1419, POMFIL2, RAINB1, helicase, pore membrane and/or filament interacting like protein 2, retinoic acid inducible gene in neuroblastoma 1; chromosome 11p15.1)

Neuron Navigator 2 (NAV2) protein is a member of the neuron navigator protein family-NAV2 is widely expressed in the central nervous system (CNS), particularly common in the developing cerebellum. NAV2 is critical for cytoskeletal dynamics and neurite growth. Nav2 deficiency causes cerebellar hypoplasia in mice with abnormal folding due to impaired axonal outgrowth, corpus callosum hypo-dysgenesis, and agenesis of olfactory bulbs. NAV2 deficiency is associated with cellular migration deficits. NAV2 abnormalities are usually lethal.123

OMIM NEURON NAVIGATOR 2

  • SNP: rs874426 Position: 19526139; In intron of NAV264
    p: 3.75E-06

1.65. POTASSIUM CHANNEL-INTERACTING PROTEIN 4, KCNIP4, (chromosome 4p15.3-p15.2)

The protein KCNIP4 is a member of the family of voltage-dependent potassium (Kv) channel-interacting proteins (KCNIPs), which belong to the recoverin branch of the EF-hand superfamily. KCNIP family members are small calcium-binding proteins with EF-Hand-like domains that differ from each other by the N-terminus. They are integral subunit components of native Kv4 channel complexes. They may regulate A-type currents and thus neuronal excitability in response to changes in intracellular calcium. This protein member also interacts with presenilin. Several alternatively spliced transcript variants encoding different isoforms have been identified for this gene. It has been implicated in cardiac excitation conduction, regulation of nuclear beta-catenin signaling, and transcription of target genes . .
124

KCNIP4 is associated with

  • Synovial angioma
  • congenital capillary malformations

OMIM POTASSIUM CHANNEL-INTERACTING PROTEIN 4, KCNIP4

  • SNP rs876477 position: 20766026; intron of KCNIP464
    p: 2.69E-05

1.66. POTASSIUM CHANNEL-INTERACTING PROTEIN 1; KCNIP1

The protein KCNIP1 (Potassium Voltage-Gated Channel Interacting Protein 1) is linked to cardiac conduction. Associated diseases are epilepsy, idiopathic generalized and diastolic hypertension

OMIM POTASSIUM CHANNEL-INTERACTING PROTEIN 1; KCNIP1

  • SNP: rs1541665 position: 170075495; intron of KCNIP164
    p: 5.60E-05

1.67. DIPEPTIDYL PEPTIDASE X; DPP10 (chromosome 2q14.1)

The DPP10 protein is a single-pass type II membrane protein of the S9B family in clan SC of serine proteases. It appears to have no detectable protease activity, most likely due to the absence of the conserved serine residue normally present in the catalytic domain of serine proteases. However, it binds specific voltage-gated potassium channels and alters their expression and biophysical properties. DPP10 mutations are correlated with asthma and autism spectrum disorders.

OMIM DIPEPTIDYL PEPTIDASE X; DPP10

  • SNP: rs272000 116372265; Within 50 kb downstream of DPP1064
    p: 9.10E-06

1.68. FRAGILE HISTIDINE TRIAD GENE; FHIT (chromosome 3p14.2)

The gene fragile histidine triad protein (FHIT, bis(5’-adenosyl)-triphosphatase)belongs to the family of histidine triad genes. FHIT encodes a diadenosine P1,P3-bis(5’-adenosyl) triphosphate adenylohydrolase involved in purine metabolism. Aberrant transcripts of this gene were found in about half of all esophageal, gastric, and colon carcinomas. FHIT acts as a tumor suppressor, also synergistically with the tumor suppressor VHL, and protects against chemically induced lung cancer and in HER2/neu-induced breast cancer.

OMIM FRAGILE HISTIDINE TRIAD GENE; FHIT

  • SNP: rs6791644 60746148; In intron of FHIT64
    p: 8.32E-06

1.76. DIRAS FAMILY, GTP-BINDING RAS-LIKE PROTEIN 2; DIRAS2 (chromosome 9q22.2)

The protein DIRAS2 belongs to a branch of the functionally diverse Ras superfamily of monomeric GTPases. It shows low GTPase activity and is predominantly present in the GTP-bound form

OMIM DIRAS FAMILY, GTP-BINDING RAS-LIKE PROTEIN 2; DIRAS2

DIRAS2 is a candidate gene for ADHD.125

1.80. TRANSMEMBRANE PROTEIN 161B; TMEM161B

The protein TMEM161B appears to

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

GeneCards Summary for TMEM161B Gene
TMEM161B (transmembrane protein 161B) is a protein coding gene. Diseases associated with TMEM161B include brachial plexus neuritis and bruxism. Gene Ontology (GO) annotations for this gene include nucleic acid binding. An important paralog of this gene is TMEM161A.

UniProtKB/Swiss-Prot Summary for TMEM161B Gen
Essential for the maintenance of normal cardiac rhythm in the developing heart and for neonatal survival (By similarity). Inhibits potassium and calcium currents in cardiomyocytes, contributing to timely repolarization of the action potential, thereby maintaining a normal cardiac rhythm (By similarity). T161B_HUMAN,Q8NDZ6

TMEM161B is considered aks candidate gene for depression and for personality expressions.126

TMEM161B is a candidate gene for ADHD.99

1.82. PPD1, p53-induced death domain protein, LRDD, LEUCINE-RICH REPEATS- AND DEATH DOMAIN-CONTAINING PROTEIN; 11p15.5

The protein encoded by this gene contains a leucine-rich repeat and a death domain. This protein has been shown to interact with other death domain proteins, such as Fas (TNFRSF6)-associated through death domain (FADD) and MAP kinase-activating death domain-containing protein (MADD), and thus may function as an adaptor protein in cell death-related signaling processes. Expression of the mouse counterpart of this gene was found to be positively regulated by the tumor suppressor p53 and to induce cell apoptosis in response to DNA damage, suggesting a role for this gene as an effector of p53-dependent apoptosis. Three alternatively spliced transcript variants encoding different isoforms have been reported. In addition to its pro-apoptotic function, it may also be involved in DNA repair as part of a protein complex formed together with the catalytic subunit of DNA-PK (DNA-PKcs) and caspase 2.127

OMIM LRDD / PIDD1, LEUCINE-RICH REPEATS- AND DEATH DOMAIN-CONTAINING PROTEIN; 11p15.5

Increased expression and decreased methylation in ADHD.71

1.83. C2orf82 (ASCL830, UNQ830, SNORC secondary ossification center associated regulator of chondrocyte maturation)

Probably

  • involved in cartilage development
  • found in the extracellular area
  • integral part of the membrane
  • active in the cell periphery.

Finds

  • in the collagen-containing extracellular matrix
  • in the cytoplasm

Decreased expression and increased methylation in ADHD.71

1.84. CADM1, CELL ADHESION MOLECULE 1 (TSLC1, IGSF4)

The protein CADM1 enables signal receptor binding activity. CADM1 is involved in

  • Cell recognition
  • positive regulation of cytokine production
  • promotes the cytotoxicity of natural killer (NK) cells
  • promotes the secretion of interferon-gamma (IFN-gamma)
  • Organization of cell adhesion (cell connections).
  • relevant for the survival of mast cells
  • mediates binding to and communication with nerves in mast cells
  • acts as a synaptic cell adhesion molecule
  • plays a role in the formation of dendritic spines and in synapse formation
  • May be involved in neuronal migration, axon growth, pathfinding, and fasciculation on axons of differentiating neurons

Located in the plasma membrane
Used for breast cancer and prostate cancer.

Associated diseases:

  • Cervix Uteri Carcinoma In Situ
  • Retroperitoneal Fibrosis

OMIM CADM1, CELL ADHESION MOLECULE 1

The CADM1 rs10891819 genotype (T alleles) correlated negatively with errors in the Stroop test in one study, consequently positive with inhibitory ability and therefore ADHD-protective.128

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

FEZF1-AS1 is not a protein gene but an RNA gene of the lncRNA class. FEZF1-AS1 is associated with the following diseases

  • ductal adenocarcinoma of the pancreas
  • Stomach cancer.

OMIM FEZF1-AS1

rs3958046 of FEZF1-AS1 is a candidate gene for ADHD.111129

rs11767283 correlates with age at first sexual intercourse
rs11767283 correlates with nutrition
rs145467198 correlates with heel bone mineral density
rs7779018 correlates with schizophrenia

1.88. 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 membrane-bound type II glycoproteins that appear to be specific exclusively for the donor substrate UDP-galactose. All transfer galactose in a beta1,4 bond to similar acceptor sugars: GlcNAc, Glc, and Xyl
B4GalT2 serves

  • Metabolism and Transport to the Golgi and Subsequent Modification
  • Galactosyltransferase activity
  • Synthesis of complex N-linked oligosaccharides in many glycoproteins as well as the carbohydrate components of glycolipids
  • N-acetyllactosamine synthase activity
    Its substrate specificity is affected by alpha-lactalbumin, but it is not expressed in lactating breast tissue

Three transcript variants encoding two different isoforms have been found for this gene.
Bit B4GALT2 is associated with Ehlers-Danlos syndrome,

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

For B4GALT2, one study found an alteration in expression in ADHD.1

1.90. TLE1, TRANSDUCIN-LIKE ENHANCER OF SPLIT 1

The protein TLE1 is part of the beta-catenin-TCF complex. It is found in the cytosol and nucleoplasm.
TLE1

  • enables identical protein binding activity and transcriptional corepressor activity
  • binds to a number of transcription factors
  • Inhibition of transcriptional activation mediated by FOXA2 and by CTNNB1 and TCF family members in Wnt signaling
  • Amplification of FOXG1/BF-1- and HES1-mediated transcriptional repression
  • Inhibition of NF-kappa-B / kappa-B kinase signal transduction and expression
  • Anoikis inhibition
  • influences developmental Notch signaling pathway
  • affects RNA polymerase I promoter opening
  • Coactivator for ESRRG

TLE1 is associated with the diseases

  • Nuclear binding factor Acute myeloid leukemia
  • Glomerular tumor

OMIM TLE1, TRANSDUCIN-LIKE ENHANCER OF SPLIT 1

For TLE1, one study found an alteration in expression in ADHD.1 TLE1 had already attracted attention as a candidate gene for ADHD in another study.130

1.91. ANK3, ANKYRIN 3, Node Of Ranvier, Ankyrin-G, MRT37

The protein ankyrin-3 is immunologically distinct from the ankyrins ANK1 and ANK2. It is found at the axonal initial segment and at the nodes of Ranvier of neurons in the central and peripheral nervous system
In the nervous system, ankyrin-G is specifically found at the neuromuscular junction, the initial portion of the axon, and the nodes of Ranvier. Within the nodes of Ranvier, where action potentials are actively transmitted, ANK3 is an intermediate binding partner for neurofascin and voltage-gated sodium channels. ANK3 is required for the normal accumulation of voltage-gated sodium channels at the axon hillock and for the initiation of action potentials.131

ANK3 is associated with

  • Brugada syndrome, a form of cardiac arrhythmia.
  • bipolar disorder
  • intellectual disability.

OMIM ANK3, ANKYRIN 3

For ANK3, one study found an alteration in expression in ADHD.1 One study found this gene to be one of the 51 most likely gene candidates for ADHD.75

1.92. TRIO, TRIPLE FUNCTIONAL DOMAIN

Some isoforms of calirin and trio colocalized with immature secretory granules in mouse and rat neuroendocrine cells and modulated their cargo secretion
Overexpression of their N-terminal GEF domains enhanced secretion from the immature granules such that the cells lost their secretory cargo in the absence of secretory tagogum (the agent that caused their secretion). This response required GEF activity and was mimicked by the calirin/Trio substrates Rac1 and RhoG. Selective pharmacological inhibition of endogenous GEF activity reduced secretagogue-independent release of hormone precursors and resulted in accumulation of the product peptide in mature secretory granules. Modulation of cargo secretion from immature granules by calirin/TRIO provides secretory cells with additional control over the amounts of peptide released and expands the range of physiological responses that can be triggered. .

TRIO (amino acids 1227-1407) catalyzes the nucleotide exchange for Rac1. The all-alpha-helical protein has a structure very different from other exchange factors. Based on site-directed mutagenesis, the authors identified functionally important residues of the DH domain. They are all highly conserved and located in close proximity on 2 alpha helices. In addition, Liu et al. (1998) discovered a unique ability of the pleckstrin homology (PH) domain to enhance nucleotide exchange in DH domain-containing proteins

OMIM TRIO, TRIPLE FUNCTIONAL DOMAIN

In TRIO, one study found a change in expression in ADHD.1

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

SYNE1 is one of the largest genes in the human genome and therefore particularly susceptible to mutations or gene defects. Its longest isoform comprises 146 exons, which code for the synaptic nuclear envelope protein 1 with 8797 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 connect the plasma membrane to the actin cytoskeleton. SYNE1 encodes a protein that is important for maintaining the cerebellum - the part of the brain that coordinates complex body movements. Truncated recessive mutations in SYNE1 result in a slowly progressive, relatively pure cerebellar ataxia with few extracerebellar symptoms (spinocerebellar ataxia, autosomal recessive 8; SCAR8/autosomal recessive cerebellar ataxia type 1, ARCA1)132((

OMIM SYNE1, SPECTRIN REPEAT-CONTAINING NUCLEAR ENVELOPE PROTEIN 1

For SYNE1, one study found an alteration in expression in ADHD.1 One study found this gene to be one of the 51 most likely gene candidates for ADHD.75

1.96. BMPR1B (Bone morphogenetic protein receptor type-1B, CDw293, Cluster of differentiation w293)

BMPR1B is a member of the transmembrane serine/threonine kinase family of bone morphogenetic protein (BMP) receptors. The ligands of this receptor are BMPs of the TGF-beta superfamily. BMPs are involved in endochondral bone formation and embryogenesis. These proteins relay their signals by forming heteromeric complexes of two different types of serine (threonine) kinase receptors: type I receptors of about 50-55 kD and type II receptors of about 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.133

BMPR1B gene mutations have been associated with primary pulmonary hypertension.

BMPR1B is found in prepartilaginous condensations (in the chick embryo). BMPR1B is the major signal transducer 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.

One study found this gene to be one of the 51 most likely gene candidates for ADHD.75

1.97. CACNA1C, Calcium Voltage-Gated Channel Subunit Alpha1 C

Other names: CACH2, CACN2, CACNL1A1, CCHL1A1, LQT8, TS, Calcium Channel, Voltage-Dependent, L Type, Alpha 1C Subunit

Pore-forming alpha-1C subunit of the voltage-gated calcium channel that gives rise to L-type calcium currents. Mediates influx of calcium ions into the cytoplasm, thereby triggering calcium release from the sarcoplasm. Important for excitation-contraction coupling in the heart. Required for normal cardiac development and normal cardiac rhythm regulation. Required for normal contraction of smooth muscle cells in blood vessels and intestine. Essential for normal blood pressure regulation through its role in contraction of arterial smooth muscle cells.134
Acts as a receptor for influenza viruses.Could be relevant for enabling virus entry when sialylated and expressed on lung tissue

One study found this gene to be one of the 51 most likely gene candidates for ADHD.75

1.98. CACNB2, Calcium Voltage-Gated Channel Auxiliary Subunit Beta 2

Other names: CACNLB2, MYSB, Voltage-Dependent L-Type Calcium Channel Subunit Beta-2, Calcium Channel, Voltage-Dependent, Beta 2 Subunit

The protein CACNB2 is related to the signaling pathways

  • the sensory processing of sound
  • the CREB Pathway

CACNB2 contributes to calcium channel function by increasing peak calcium current, shifting the voltage dependence of activation and inactivation, modulating G-protein inhibition, and controlling membrane targeting of the alpha-1 subunit.

One study found this gene to be one of the 51 most likely gene candidates for ADHD.75
Mutations in the CACNB2 gene have been further associated with ADHD in addition to:135

  • Brugada syndrome 4
  • Autism
  • bipolar disorder
  • major depressive disorder
  • Schizophrenia
  • Lambert-Eaton Myasthenia Syndrome136

1.99. DNM1, Dynamin 1

Other names: DNM, EC 3.6.5.5, Dynamin-1, EIEE31, DEE31

The DNM1 protein is a member of the dynamin subfamily of GTP-binding proteins. DNM1 has unique mechanochemical properties used for membrane tubulation and disruption, and is involved in clathrin-mediated endocytosis and other vesicular trafficking processes. Actin and other cytoskeletal proteins act as binding partners for the encoded protein, which can also self-assemble, resulting in stimulation of GTPase activity.137
DNM1 is associated with integrin pathway signaling and nervous system development.

Mutations in DNM1 are associated with

  • a severe form of childhood epilepsy (developmental and epileptic encephalopathy)
  • Lennox-Gastaut Syndrome

Most pathogenic variants are missense variants that have been shown to affect endocytosis of synaptic vesicles in a dominant-negative manner.

One study found this gene to be one of the 51 most likely gene candidates for ADHD.75

1.100. DPP6, dipeptidyl aminopeptidase-like protein 6

Other names: Dipeptidyl Peptidase Like 6, DPPX, DPL1, Dipeptidyl Aminopeptidase-Like Protein 6, Dipeptidyl Peptidase VI, Dipeptidyl Peptidase 6, Dipeptidyl Peptidase 6, DPP VI

DPP6 is a single-pass type II membrane protein of the S9B family in clan SC of serine proteases. DPP6 has no detectable protease activity, most likely due to the absence of the conserved serine residue normally present in the catalytic domain of serine proteases. However, it binds specific voltage-gated potassium channels and alters their expression and biophysical properties.138
DPP6

  • promotes cell surface expression of the potassium channel KCND2
  • modulates the activity and gating properties of the potassium channel KCND2
  • has no dipeptidylaminopeptidase activity

Diseases associated with DPP6 are:

  • Intellectual Developmental Disorder, Autosomal Dominant 33
  • Ventricular Fibrillation, Paroxysmal Familial, 2.

One study found this gene to be one of the 51 most likely gene candidates for ADHD.75

1.101. EMP2, Epithelial Membrane Protein 2

Other names: XMP, Protein XMP, EMP-2

EMP2 is a tetraspan protein of the PMP22/EMP family. EMP2 regulates the composition of the cell membrane. It influences

  • Endocytosis
  • Cell signaling
  • Cell proliferation
  • Cell migration
  • Cell adhesion
  • Cell death
  • Cholesterol homeostasis
  • Albumin excretion in urine
  • Embryo implantation
  • promotes angiogenesis and vasculogenesis by inducing VEGFA through a HIF1A-dependent pathway
  • inhibits caveolin-1 by increasing lysosomal degradation
  • activates PTK2, thereby regulating focal adhesion density, F-actin conformation, and cell adhesiveness
  • modulates the function of certain integrin isomers in the plasma membrane
  • regulates the surface expression of MHC1 and ICAM1.

EMP2 is associated with the diseases

  • nephrotic syndrome type 10 (NPHS10)
  • genetic steroid-resistant nephrotic syndrome. Related pathways include nephrotic syndrome. Gene Ontology (GO) annotations for this gene include protein kinase binding and kinase binding. An important paralog of this gene is PMP22.

One study found this gene to be one of the 51 most likely gene candidates for ADHD.75

1.102. HAS3, hyaluronan synthase 3

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 appears to be a regulator of hyaluronan synthesis.

One study found this gene to be one of the 51 most likely gene candidates for ADHD.75

1.103. 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 protein ITIH3 is a subunit of the heavy chain of the pre-alpha-trypsin inhibitor complex. By binding hyaluronic acid, this complex can stabilize the extracellular matrix. It appears to form response to increased platelet cytosolic Ca2+ and cell adhesion_cell-matrix glycoconjugates. It is associated with serine-type endopeptidase inhibitor activity and endopeptidase inhibitor activity.139

ITIH3 is associated with

  • Schizophrenia
  • major depressive disorder

One study found this gene to be one of the 51 most likely gene candidates for ADHD.75

1.104. STT3A, STT3 Oligosaccharyltransferase Complex Catalytic Subunit A

Witere names: STT3-A, TMC, Integral Membrane Protein 1, ITM1, Dolichyl-Diphosphooligosaccharide Protein Glycosyltransferase Subunit STT3A, STT3A, Catalytic Subunit Of The Oligosaccharyltransferase Complex, Dolichyl-Diphosphooligosaccharide Protein Glycotransferase, Oligosaccharyl Transferase Subunit STT3A, Transmembrane Protein TMC

The protein STT3A is a catalytic subunit of the N-oligosaccharyltransferase (OST) complex that transfers glycan chains to asparagine residues of target proteins in the endoplasmic reticulum. It is associated with CFTR activation by S-nitrosoglutathione (normal and CF) and translation of structural proteins.
STT3A is associated with

  • congenital disorder of glycosylation, type Iw, autosomal recessive
  • congenital disorder of glycosylation, type Iw, autosomal dominant

One study found this gene to be one of the 51 most likely gene candidates for ADHD.75

1.105. MAN2A2, Mannosidase Alpha Class 2A Member 2

Other names: MANA2X, mannosyl-oligosaccharide 1,3-1,6-alpha-mannosidase, alpha-mannosidase IIx, alpha-mannosidase 2x, EC 3.2.1.114

The protein MAN2A2 is thought to enable alpha-mannosidase activity. It appears to be involved in N-glycan processing, by catalyzing the first step in the biosynthesis of complex N-glycans. MANA2A2 is involved in protein deglycosylation. It is thought to be an integrative component of the membrane and active in the Golgi membrane.
Glycosylases are a group of enzymes that includes glucosidases, mannosidases and heparanases. There are two glucosidase subtypes, both of which are found in the intestine. They hydrolyze terminal (1,4)-alpha-glucoside bonds and (1,6)-beta-glucoside bonds, releasing alpha-glucose and beta-glucose.
MAN2A2 is associated with abdominal obesity - Metabolic Syndrome Quantitative Trait Locus 2.140

One study found this gene to be one of the 51 most likely gene candidates for ADHD.75

1.108. NCL, nucleolin

Other names: Nsr1, C23, Protein C23

NCL is the major eukaryotic nucleolar phosphoprotein and is involved in ribosome synthesis and maturation. It is mainly located in dense fibrillar regions of the nucleolus. NCL induces chromatin decondensation by binding to histone H1. NCL appears to play a role in pre-rRNA transcription and ribosome assembly and to be involved in the process of transcription elongation.
NCL is associated with

  • Childhood ependymoma
  • Spinal muscular atrophy

One study found this gene to be one of the 51 most likely gene candidates for ADHD.75
Another study found NCL (variant rs16828074) to be the most likely of 96 candidate genes.2

1.109. PPP2R2B, Protein Phosphatase 2 Regulatory Subunit Bbeta

Other names: PR55-BETA, PR52B, Serine/Threonine Protein Phosphatase 2A 55 KDa Regulatory Subunit B Beta Isoform, PP2A Subunit B Isoform Beta, B55beta, SCA12, Protein Phosphatase 2 (Formerly 2A), Regulatory Subunit B (PR 52), Beta Isoform, Protein Phosphatase 2, Regulatory Subunit B, Beta, PP2A Subunit B Isoform PR55-Beta, PP2A Subunit B Isoform B55-Beta

The protein PPP2R2B belongs to the family of protein Ser/Thr phosphatases are a group of enzymes that catalyze the removal of phosphate groups from serine and/or threonine residues by hydrolysis of phosphoric acid monoesters. They counteract the action of kinases and phosphorylases, are involved in signal transduction and in the inhibition of cell growth and division
PPP2R2B modulates substrate selectivity and catalytic activity as well as the localization of the catalytic enzyme in a specific subcellular compartment. Isoform 2 is required for the promotion of proapoptotic activity and regulates neuronal survival by balancing mitochondrial fission and fusion

PPP2R2B is associated with

  • autosomal dominant spinocerebellar ataxia 12 (SCA12; degeneration of cerebellum and sometimes brainstem and spinal cord; poor coordination of speech and body movements)
  • autosomal dominant cerebellar ataxia

One study found this gene to be one of the 51 most likely gene candidates for ADHD.75

1.113. ATP2C2, ATPase Secretory Pathway Ca2+ Transporting 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 protein ATP2C2 enables the activity of the P-type calcium transporter and the P-type manganese transporter. ATP2C2 appears to be involved in transmembrane transport of calcium ions, cellular calcium ion homeostasis, and manganese ion 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. Within a catalytic cycle, it takes up Ca(2+) or Mn(2+) ions on the cytoplasmic side of the membrane and releases them to the lumenal side. The transfer of ions across the membrane is coupled to ATP hydrolysis and is accompanied by transient phosphorylation that shifts the conformation of the pump from an inward to an outward state ATP2C2 induces Ca(2+) influx independently of its ATP-driven pump function. ATP2C2 interacts with the Ca(2+) channel ORAI1 at the basolateral membrane of mammary epithelial cells and mediates Ca(2+) influx independently of the Ca(2+) content of the endoplasmic reticulum or Golgi stores. ATP2C2 may facilitate transepithelial transport of large amounts of Ca(2+) for milk secretion through activation of Ca(2+) influx channels at the plasma membrane and active Ca(2+) transport at the Golgi apparatus.141

ATP2C2 is associated with

  • specific language disorders
  • Dyslexia.

One study found this gene to be one of the 51 most likely gene candidates for ADHD.75 Another study found it among 96 candidate genes.

1.118. MPP6, MAGUK p55 subfamily member 6

The protein MPP6 is a member of the family of peripheral membrane-associated guanylate kinases (MAGUK, membrane-associated guanylate kinase homologues). These are involved in tumor suppression and receptor clustering by forming multiprotein complexes containing various groups of transmembrane, cytoskeletal, and cytoplasmic signaling proteins.

One study found this gene to be one of the 51 most likely gene candidates for ADHD.75

1.119. CNNM2, Cyclin And CBS Domain Divalent Metal Cation Transport Mediator 2

Other names: ACDP2, Ancient Conserved Domain-Containing Protein 2, Metal Transporter CNNM2, Cyclin M2, Cyclin-M2, HOMGSMR, HOMG6

The protein CNNM2 is a transporter for divalent metal cations. CNNM2 mediates the transport of divalent metal cations in the order Mg(2+) > Co(2+) > Mn(2+) > Sr(2+) > Ba(2+) > Cu(2+) > Fe(2+). CNNM2 is a member of the family of proteins containing ancient conserved domains. Members of this protein family contain a cyclin box motif and have structural similarity to cyclins. CNNM2 may play an important role in magnesium homeostasis by mediating epithelial transport and renal reabsorption of Mg2+.

CNNM2 is associated with

  • Hypomagnesemia
  • Renal and hypomagnesemia
  • Seizures
  • mental retardation

One study found this gene to be one of the 51 most likely gene candidates for ADHD.75

1.121. AS3MT, Arsenite Methyltransferase

Other names: CYT19, S-adenosyl-L-methionine:arsenic(III) methyltransferase, arsenic (+3 oxidation state) methyltransferase, methylarsonite methyltransferase, S-adenosylmethionine:arsenic (III) methyltransferase, methyltransferase Cyt19, EC 2.1.1.137

The protein AS3MT plays a role in arsenic metabolism. AS3MT catalyzes the transfer of a methyl group from S-adenosyl-L-methionine (AdoMet) to trivalent arsenic, resulting in methylated and dimethylated arsenic compounds. AS3MT methylates arsenite to methylarsonate, Me-AsO(3)H(2), which is reduced by methylarsonate reductase to methylarsonite, Me-As(OH)2. Methylarsonite is also a substrate and is converted to the much less toxic compound dimethylarsinate (cacodylate), Me(2)As(O)-OH.

AS3MT is associated with

  • Borst-Jadassohn intraepidermal carcinoma
  • Attention Deficit Hyperactivity Disorder

One study found this gene to be one of the 51 most likely gene candidates for ADHD.75

1.122. CSMD1, CUB And Sushi Multiple Domains 1

Other names: KIAA1890, PPP1R24, Protein Phosphatase 1, Regulatory Subunit 24, CUB And Sushi Domain-Containing Protein 1, CUB And Sushi Multiple Domains Protein 1

The protein CSMD1 is thought to be involved in learning and memory, branching of mammary glands during pregnancy, and development of reproductive organs. CSMD1 is probably an integral component of the membrane. CSMD1 is a potential suppressor of squamous cell carcinoma.142

CSMD1 is associated with

  • Autism
  • Schizophrenia

One study found this gene to be one of the 51 most likely candidate genes for ADHD.75 One study found CSMD1 (variant rs6559123) as one of the 20 most likely among 96 ADHD candidate genes 2

1.123. PALB2, Partner and localizer of BRCA2

Other names: PALB2, FANCN

The protein PALB2 gene is responsible for genome maintenance (repair of double-strand breaks). PALB2 binds and colocalizes with Breast Cancer 2 Early Onset Protein (BRCA2) in nuclear foci and likely enables stable intranuclear localization and accumulation of BRCA2

PALB2 gene is associated with

  • increased risk of breast cancer
  • familial pancreatic cancer
  • Ovarian Cancer
  • Fanconi anemia
  • reduced fertility (demonstrated in mice)

One study found this gene to be one of the 51 most likely gene candidates for ADHD.75

1.124. ZNF385D, Zinc Finger Protein 385D

Other names: Zinc Finger Protein 659, ZNF659, FLJ22419

The protein ZNF385D enables sequence-specific double-stranded DNA-binding activity. ZNF385D is thought to be active in the nucleus
ZNF385D is associated with

  • Reading disability
  • Attention Deficit Hyperactivity Disorder

One study found this gene to be one of the 51 most likely gene candidates for ADHD.75

1.125. FERMT3, FERM Domain Containing Kindlin 3

Other names: KIND3, MIG2B, URP2, UNC112C, UNC-112 Related Protein 2, Fermitin Family Homolog 3, Unc-112-Related Protein 2

The protein FERMT3 is a member of the Kindlins family of proteins that mediate protein-protein interactions in integrin activation, thereby playing a role in cell adhesion, migration, differentiation, and proliferation. FERMT3 plays a key role in the regulation of hemostasis and thrombosis. FERMT3 may also contribute to the maintenance of the erythrocyte membrane skeleton. FERMT3 plays a central role in cell adhesion in hematopoietic cells. FERMT3 acts by activating integrin beta-1-3 (ITGB1, ITGB2 and ITGB3). FERMT3 is required for integrin-mediated platelet adhesion and leukocyte adhesion to endothelial cells and for the activation of integrin beta-2 (ITGB2) in polymorphonuclear granulocytes (PMNs). Isoform 2 may act as a repressor of NF-kappa-B and apoptosis.143
FERMT3 is associated with

  • Leukocyte adhesion deficiency, type Iii
  • Kindler syndrome

One study found this gene to be one of the 51 most likely gene candidates for ADHD.75

1.126. CHMP7, Charged Multivesicular Body Protein 7

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

The protein CHMP7 is involved in the late transport of endosomes to vacuoles, in the abscission of the midbody, and in mitotic nuclear division. CHMP7 is found in the cytosol, nuclear envelope, and nucleoplasm. CHMP7 is part of the ESCRT III complex. CHMP7 colocalizes with chromatin. CHMP7 is required for 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 mitotic spindle degradation during late anaphase. CHMP7 is recruited to the newly forming nuclear envelope during anaphase by LEMD2. CHMP7 plays a role in the endosomal sorting pathway.144

GeneCards summary for CHMP7 gene
CHMP7 is associated with

  • cerebellar ataxia type 48
  • Attention Deficit/Hyperactivity Disorder

One study found this gene to be one of the 51 most likely gene candidates for ADHD.75

1.128. 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 protein MUCL3 is thought to be localized in the cytoplasm and plasma membrane. It appears to be an integral component of the membrane. MUCL3 possibly modulates NF-kappaB signaling and plays a role in cell growth.145
MUCL3 is associated with

  • Panbronchiolitis, diffuse
  • spinocerebellar ataxia, autosomal recessive 8

One study found this gene to be one of the 51 most likely gene candidates for ADHD.75

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

Other names: HIWI2, Piwi-Like Protein 4, FLJ36156, Miwi2

The protein PIWIL4 belongs to the Argonaute family of proteins that play a role in the development and maintenance of germline stem cells. PIWIL4 plays a central role during spermatogenesis by repressing transposable elements and preventing their mobilization, which is essential for germline integrity. PIWIL4 acts through the piRNA metabolic process, which mediates the repression of transposable elements during meiosis through the formation of complexes of piRNAs and Piwi proteins, and controls the methylation and subsequent repression of transposons. PIWIL4 directly binds piRNAs, a class of RNAs with 24 to 30 nucleotides generated by a Dicer-independent mechanism and derived primarily from transposons and other sequence repeat elements. PIWIL4 is associated with secondary piRNAs antisense. 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 called 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 nucleus. PIWIL4 may be involved in the chromatin-modifying pathway by inducing ‘Lys-9’ methylation of histone H3 at some loci. PIWIL4 further plays a role in regulating somatic cell activities and pancreatic beta cell function and insulin secretion. PIWIL4 is involved in the maintenance of cell morphology and functional integrity of the retinal epithelium through the Akt/GSK3alpha/beta signaling pathway. PIWIL4, when overexpressed, acts as an oncogene by inhibiting apoptosis and promoting cell proliferation in tumors.146
PIWIL4 is associated with

  • Spermatogenic Failure (male infertility)
  • Cervical cancer.

One study found this gene to be one of the 51 most likely gene candidates for ADHD.75

1.130. AK8, adenylate kinase 8

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

The protein AK8 enables AMP binding activity and kinase activity for nucleobase-containing compounds. AK8 is involved in nucleoside diphosphate phosphorylation and 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 has the highest activity toward AMP and weaker activity toward dAMP, CMP, and dCMP. AK8 further shows broad nucleoside diphosphate kinase activity.147

AK8 is associated with reticular dysgenesis
One study found this gene to be one of the 51 most likely gene candidates for ADHD.75

1.131. CFAP221, Cilia And Flagella Associated Protein 221

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

The protein CFAP221 probably activates calmodulin-binding activity and appears to be involved in cilia formation. It is probably active upstream of or within the CSF circulation, the assembly of the motile cilium, and mucociliary clearance.CFAP221 is probably found in the axoneme, in the extracellular region, and in the flagellum of spermatozoa.148
CFAP221 is associated with

  • ciliary dyskinesia
  • cerebral degeneration

One study found this gene to be one of the 51 most likely gene candidates for ADHD.75

1.132. CEP112, Centrosomal Protein 112

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

CEP112 is a coiled-coil domain-containing protein and belongs to the cell division control 42 family of effector proteins. In neurons, it is localized to the cytoplasm of dendrites and is also enriched in the nucleus, where it interacts with the RNA polymerase III transcriptional repressor Maf1 to regulate surface expression of the gamma-aminobutyric acid A receptor. In addition, the protein has been identified as a component of the human centrosome.149
CEP112 is associated with

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

One study found this gene to be one of the 51 most likely gene candidates for ADHD.75

1.133. KIF6, Kinesin Family Member 6

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

The protein KIF6 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 homodimeric molecules with two N-terminal head domains that move along 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 conoran heart disease.

One study found this gene to be one of the 51 most likely gene candidates for ADHD.75

1.135. NCKAP5, NCK Associated Protein 5

Other names: NAP5, ERIH1, ERIH2

The protein NCKAP5 is thought to be involved in microtubule bundle formation and microtubule depolymerization, as well as being active at the microtubule plus end.150
NCKAP5 is associated with

  • ADHD
  • drug-induced lupus erythematosus

One study found this gene to be one of the 51 most likely gene candidates for ADHD.75

1.136. SPATA33, Spermatogenesis Associated 33

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

The protein SPATA33 is thought to be active upstream of or within cellular protein localization, fertilization, and flagellar sperm motility. SPATA33 appears to be localized in the sperm mitochondrial envelope and active in the cytoplasm and nucleus.151152
SPATA33 is associated with Fanconi anemia, complementation group A.

One study found this gene to be one of the 51 most likely gene candidates for ADHD.75

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 protein CDK10 belongs to the CDK subfamily of the Ser/Thr protein kinase family. 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 restricted 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 actin cytoskeleton organization by phosphorylating regulators of actin dynamics such as PKN2. CDK10 is a negative regulator of ciliogenesis by phosphorylating PKN2 and promoting RhoA signaling.153
CDK10 is associated with

  • Al-Kaissi Syndrome
  • Toe syndactyly
  • Telecanthus
  • anogenital and renal malformations

One study found this gene to be one of the 51 most likely gene candidates for ADHD.75

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 Protei, E3 Ubiquitin-Protein Ligase PPP1R11, TCTEX5

The protein PPP1R11 is a specific inhibitor of protein phosphatase-1 (PP1) with differential sensitivity to the metal-independent and metal-dependent forms of PP1. PPP1R11 is an atypical E3 ubiquitin-protein 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 clearance of Gram-positive bacteria, acting in part by ubiquitinating and degrading TLR2.154

OMIM PPP1R11, PROTEIN PHOSPHATASE 1, REGULATORY SUBUNIT 11

One study found this gene to be one of the 51 most likely gene candidates for ADHD.75

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 protein NME5 is thought to facilitate nucleoside diphosphate kinase activity. NME5 is thought to be involved in the negative regulation of oxidative stress-induced intrinsic apoptotic signaling and spermatid development. NME5 is thought to be active upstream of or within cilia assembly, epithelial cilia movement involved in extracellular fluid movement, and ventricular system development. NME5 is thought to be found in the cilium. NME5 does not appear to have NDK kinase activity. NME5 protects against cell death by Bax and alters cellular levels of several antioxidant enzymes including Gpx5. NME5 may play a role in spermiogenesis by increasing the ability of late stage spermatids to eliminate reactive oxygen species.155
NME5 is associated with

  • Nemalin myopathy 5
  • primary ciliary dyskinesia

OMIM NME5, NME/NM23 FAMILY, MEMBER 5

NME5 is a candidate gene for ADHD.113

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 ABHD5 Gene

The protein ABHD5 is defined, among other things, by an alpha/beta hydrolase fold. ABHD5 contains three sequence motifs corresponding to a catalytic triad found in the esterase/lipase/thioesterase subfamily. ABHD5 functions in phosphatidic acid biosynthesis, ABHD5 possibly regulates cellular storage of triacylglycerol by activating the phospholipase PNPLA2 , and is involved in keratinocyte differentiation. ABHD5 regulates lipid droplet fusion.
ABHD5 is a coenzyme A-dependent lysophosphatidic acid acyltransferase that catalyzes the transfer of an acyl group to a lysophosphatidic acid. ABHD5 functions preferentially with:156

  • as 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 has a regulatory function in lipid metabolism. Among other things, it stimulates lipolysis.
ABHD5 is expressed in adipose tissue, liver, neurons and epidermis, among others.

In adipose tissue, ABHD5 is bound to perilipin-1. Β-adrenergic stimulation activates protein kinase A, which phosphorylates perilipin-1. This causes dissociation of ABHD5 and perilipin-1, and 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 adipocytes: ABHD5 interacts with adipophilin (perilipin-2) and perilipin-5, among others. ABHD5 converts lysophosphatidic acid to phosphatidic acid by means of acyl-CoA-dependent lysophosphatidic acid acyltransferase activity (LPAAT).157
ABHD5 is associated with Chanarin-Dorfman syndrome, a triglyceride storage disorder with impaired oxidation of long-chain fatty acids, and lipid storage disease.

OMIM ABHD5, ABHYDROLASE DOMAIN-CONTAINING 5

ABHD5 is a candidate gene for ADHD.113

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 and 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 modulating cellular differentiation.158
GMPR2 is associated with urethra cancer.

OMIM GMPR2, GUANOSINE MONOPHOSPHATE REDUCTASE 2

GMPR2 is a candidate gene for ADHD.113

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:159

  • was found in connection with the centrosome
  • colocalized with gamma-tubulin
  • is a protein in the BLOC-1 complex
    • plays a role in the formation of lysosomal organelles (e.g. dense granules of platelets and melanosomes)
  • BLOC-1 complex
    • traffics (together with AP-3 complex) membrane protein cargoes into vesicles formed in cell bodies for transport into neurites and nerve terminals
    • is probably also involved (in conjunction with SNARE proteins) in neurite extension
    • is part of the BORC complex; possibly relevant in 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 (reduced skull size)

Microcephaly is often associated with ADHD
BLOC1S2 is a candidate gene for ADHD.113

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 protein KIAA0319L may be involved in axon guidance through interaction with RTN4R.
KIAA0319L acts as a receptor for adeno-associated viruses and is involved in adeno-associated virus infection through the endocytosis system.160
KIAA0319L is associated with

  • Dyslexia
  • limited scleroderma

KIAA0319L is a candidate gene for ADHD.113

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 protein FMNL3 contains a formin homology 2 domain and shares 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 developmental angiogenesis. FMNL3 triggers actin cytoskeleton restructuring in quiescent endothelial cells without altering microtubule orientation.161
FMNL3 is associated with

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

FMNL3 is a candidate gene for ADHD.113

1.147. CCDC138, Coiled-Coil Domain Containing 138

Other name: FLJ32745

CCDC138 is expressed at low levels in almost all human tissues, including lymphocytes in peripheral blood, fetal thymus, thymus, testis, ovary, feral brain, colon, mammary gland, and bone marrow. Elevated concentrations in some cancer tissues. CCDC138 is a soluble protein that accumulates in the nucleus of a cell. CCDC138 is involved in the initiation of labor in the myometrium.
The protein CCDC138 is associated with162

  • Chromosome 3Q13.31 deletion syndrome
  • Fundus dystrophy

CCDC138 is a candidate gene for ADHD.113

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 protein TMBIM6 facilitates endoribonuclease inhibitor activity and ubiquitin-protein ligase binding activity. TMBIM6 is involved in:163

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

TMBIM6 is associated with

  • chronic congestive splenomegaly (an enlargement of the spleen)
  • Inclusion conjunctivitis (an inflammation of the conjunctiva)

TMBIM6 is a candidate gene for ADHD.113

Xxxxx Uncategorized xxxxx

1.149. SV2A

SV2A is a candidate gene for ADHD.113

1.150. TARBP1

TARBP1 is a candidate gene for ADHD.113

1.151. TATDN3

TATDN3 is a candidate gene for ADHD.113

1.152. ALS2CR8

ALS2CR8 is a candidate gene for ADHD.113

1.153. ST3GAL3

ST3GAL3 is a candidate gene for ADHD.113164

1.154. ELAVL4

ELAVL4 is a candidate gene for ADHD.113

1.155. NBEAL1

NBEAL1 is a candidate gene for ADHD.113

1.156. FGFR3

FGFR3 is a candidate gene for ADHD.113

1.157. ACAD11

ACAD11 is a candidate gene for ADHD.113

1.158. CNPY2

CNPY2 is a candidate gene for ADHD.113

1.159. TMEM206

TMEM206 is a candidate gene for ADHD.113

1.160. BST1

BST1 is a candidate gene for ADHD.113

1.161. RASSF4

RASSF4 is a candidate gene for ADHD.113

1.162. SLC6A12

SLC6A12 is a candidate gene for ADHD.113

1.163. RAPGEF5

RAPGEF5 is a candidate gene for ADHD.113

1.164. MVP

MVP is a candidate gene for ADHD.113

1.165. RPS20

RPS20 is a candidate gene for ADHD.113

1.166. RASGRP4

RASGRP4 is a candidate gene for ADHD.113

1.167. MAP1A, Microtubule-associated protein 1A

MAP1A is a candidate gene for ADHD.165

1.168. FBXO25, F-BOX ONLY PROTEIN 25

OMIM FBXO25, F-BOX ONLY PROTEIN 25

Overexpression of FBXO25 could potentially correlate with hyperactivity, according to one study.166

1.169. TRAPPC9, TRAFFICKING PROTEIN PARTICLE COMPLEX, SUBUNIT 9

OMIM TRAPPC9, TRAFFICKING PROTEIN PARTICLE COMPLEX, SUBUNIT 9

TRAPPC9 is a candidate gene for ADHD.164

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

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

MEF2C is a candidate gene for ADHD.164

1.171. TNRC6B, TRINUCLEOTIDE REPEAT-CONTAINING GENE 6B

OMIM TNRC6B, TRINUCLEOTIDE REPEAT-CONTAINING GENE 6B

TNRC6B is a candidate gene for ADHD.167

1.172. 22Q11.2

Individuals with 22q11.2 deletion syndrome (DS) are at increased risk for comorbid mental disorders such as ADHD, schizophrenia, depression, or intellectual disability.168

1.173. EPHA5

One study found EPHA5 (variant rs4860671) as one of 96 candidate genes.2

1.174. RIMS1

One study found RIMS1 (variant rs4707940) as one of 96 candidate genes.2

1.175. NRG3

One study found NRG3 (variant rs12244269) as one of 96 candidate genes.2

1.176. TENM4

One study found TENM4 (variant rs1944959) as one of 96 candidate genes.2

1.177. STXBP6

One study found STXBP6 (variant rs17200947)as one of 96 candidate genes.2

1.178. MFDGA2

One study found MDGA2 (variant rs12232114) as one of 96 candidate genes.2

1.179. RBFOX1

One study found RBFOX1 (variant rs9935453) to be one of 96 candidate genes.2

1.180. LIG4

One study found LIG4 (variant rs9514807) as one of 96 candidate genes.2

1.181. NEDD4L

One study found NEDD4L (variant rs1620068) as one of 96 candidate genes.2

1.182. BMP2

One study found BMP2 (variant rs952793) as one of 96 candidate genes.2

1.182. FAM19A4

One study found FAM19A4 (variant rs9871910) as one of 96 candidate genes.2

1.183. ATXN8OS

One study found ATXN8OS (variant rs2498502) as one of 96 candidate genes.2

1.184. PPP1R26-AS1

One study found PPP1R26-AS1 (variant rs895192) as one of 96 candidate genes.2

1.185. BCR

One study found BCR (variant rs140502) as one of 96 candidate genes.2

1.186. ZBTB7C

One study found ZBTB7C (variant rs11662736) as one of 96 candidate genes.169

1.187. TSPAN11

One study found TSPAN11 (variant rs11051194) as one of 96 candidate genes.2

1.188. GRIP1

One study found GRIP1 (variant rs4913506) as one of 96 candidate genes.2

1.189. PRDM2

One study found PRDM2 (variant rs7519796) as one of 96 candidate genes.2

1.190. LINC00609

One study found LINC00609 (variant rs1537424) as one of 96 candidate genes.2

1.191. NAV1

One study found NAV1 (variant rs2078097) to be one of 96 candidate genes.2

1.192. LOC100507468

One study found LOC100507468 (variant rs1195234) as one of 96 candidate genes.2

1.193. LINC00609

One study found LINC00609 (variant rs1537424) as one of 96 candidate genes.2

1.194. LINC00355

One study found LINC00355 (variant rs9528776) as one of 96 candidate genes.2

1.195. GIMAP6

One study found GIMAP6 (variant rs1403220) as one of 96 candidate genes.2

1.196. LIG4

One study found LIG4 (variant rs9514807) as one of 96 candidate genes.2

1.197. LOC101927967

One study found LOC101927967 (variant rs1819004) as one of 96 candidate genes.2

1.198. IFNG-AS1

One study found IFNG-AS1 (variant rs17629076) as one of 96 candidate genes.2

1.199. CSMD1

One study found CSMD1 (variant rs6559123) as one of 96 candidate genes.2

1.200. LOC101929484

One study found LOC101929484 (variant rs2343365) as one of 96 candidate genes.2

1.201. LOC100133050

One study found LOC100133050 (variant rs7717154) as one of 96 candidate genes.2

1.202. MDGA2

One study found MDGA2 (variant rs12232114) as one of 96 candidate genes.2

1.203. TBX3

One study found TBX3 (variant rs4534630) as one of 96 candidate genes.2

1.204. C6orf123

One study found C6orf123 (variant rs543930) as one of 96 candidate genes.2

1.205. LINC01364

One study found LINC01364 (variant rs12745339) as one of 96 candidate genes.2

1.206. FSCB

One study found FSCB (variant rs1957260) as one of 96 candidate genes.2

1.207. GAN

One study found GAN (variant rs3809632) as one of 96 candidate genes.2

1.208. FSIP2

One study found FSIP2 (variant rs12998684) as one of 96 candidate genes.2

1.209. LPAR1

One study found LPAR1 (variant rs9919025) as one of 96 candidate genes.2

1.210. MYO1G

One study found MYO1G (variant rs6958168) as one of 96 candidate genes.2

1.211. NXPE2

One study found NXPE2 (variant rs4938140) as one of 96 candidate genes.2

1.212. LYPD1

One study found LYPD1 (variant rs7561232) as one of 96 candidate genes.2

1.213. LOC101929184

One study found LOC101929184 (variant rs12757080) as one of 96 candidate genes.2

1.214. WNK1

One study found WNK1 (variant rs7295704) to be one of 96 candidate genes.2

1.215. LOC101927797

One study found LOC101927797 (variant rs2824866) as one of 96 candidate genes.2

1.216. LOC101928769

One study found LOC101928769 (variant rs6865656) as one of 96 candidate genes.2

1.217. MIR4255

One study found MIR4255 (variant rs11264025) as one of 96 candidate genes.2

1.218. TG

One study found TG (variant rs61744749) as one of 96 candidate genes.2

1.219. MEP1A

One study found MEP1A (variant rs7760667) to be one of 96 candidate genes.2

1.220. ZMYM4

One study found ZMYM4 (variant rs3768336) as one of 96 candidate genes.2

1.221. DIAPH3

One study found DIAPH3 (variant rs2321867) as one of 96 candidate genes.2

1.222. SP140L

One study found SP140L (variant rs11688362 and variant rs6732684) as one of 96 candidate genes.2

1.223. FAM120A

One study found FAM120A (variant rs1556416) as one of 96 candidate genes.2

1.224. LINC01377

One study found LINC01377 (variant rs469546) as one of 96 candidate genes.2

1.225. GRIK3

One study found GRIK3 (variant rs1032722) as one of 96 candidate genes.2

1.226. GAN

One study found GAN (variant rs9926795) as one of 96 candidate genes.2

1.227. CTNNA3

One study found CTNNA3 (variant rs7094454) as one of 96 candidate genes.2

1.228. SULT6B1

One study found SULT6B1 (variant rs4670667) as one of 96 candidate genes.2

1.229. NRG3

One study found NRG3 (variant rs12244269) as one of 96 candidate genes.2

1.230. TLR4

One study found TLR4 (variant rs10121605) as one of 96 candidate genes.2

1.231. RBFOX1

One study found RBFOX1 (variant rs9935453) to be one of 96 candidate genes.2

1.232. CNTN5

One study found CNTN5 (variant rs2515376) as one of 96 candidate genes.2

1.233. EPHA7

One study found EPHA7 (variant rs16870710) as one of 96 candidate genes.2

1.234. ADORA2A, ADENOSINE A2A RECEPTOR

OMIM ADENOSINE A2A RECEPTOR; ADORA2A

One study reports a possible significant association between the A2AAR gene polymorphism rs35320474 and ADHD.170

1.235. IPO8

One study found IPO8 (variant rs16906369) as one of 96 candidate genes.2

1.236. TBC1D13

One study found TBC1D13 (variant rs12235388) as one of 96 candidate genes.2

1.237. SLC44A1

One study found SLC44A1 (variant rs10991581) as one of 96 candidate genes.2

1.238. CDH13

One study found CDH13 (variant rs8055161) as one of 96 candidate genes.2

1.239. CASC17

One study found CASC17 (variant rs7224246) to be one of 96 candidate genes.2

1.240. PCSK6

One study found PCSK6 (variant rs2020951) as one of 96 candidate genes.2

1.241. DSC3

One study found DSC3 (variant rs2729396) as one of 96 candidate genes.2

1.242. MYO5B

One study found MYO5B (variant rs1787319) as one of 96 candidate genes.2

1.243. EPHA6

One study found EPHA6 (variant rs2053246) as one of 96 candidate genes.2

1.244. PLXNC1

One study found PLXNC1 (variant rs10859690) to be one of 96 candidate genes.2

1.245. FSTL5

One study found FSTL5 (variant rs17504151) as one of 96 candidate genes.2

1.246. CYFIP1

One study found CYFIP1 (variant rs11632784) as one of 96 candidate genes.2

1.247. TUSC1

One study found TUSC1 (variant rs2498716) as one of 96 candidate genes.2

1.248. NOTCH2

One study found NOTCH2 (variant rs2453044) as one of 96 candidate genes.2

1.249. OPRK1

One study found OPRK1 (variant rs7461467) as one of 96 candidate genes.2

1.250. ACAA2

One study found ACAA2 (variant rs617619) as one of 96 candidate genes.2

1.251. RIMS1

One study found RIMS1 (variant rs4707940) as one of 96 candidate genes.2

1.252. NEDD4L

One study found NEDD4L (variant rs1620068) as one of 96 candidate genes.2

1.253. KC6

One study found KC6 (variant rs16974432) as one of 96 candidate genes.2

1.254. NAT2

One study found NAT2 (variant rs12676224) as one of 96 candidate genes.2

1.255. LINC00970

One study found LINC00970 (variant rs16861817) as one of 96 candidate genes.2

1.256. ALG10

One study found ALG10 rs1843014) as one of 96 candidate genes.2

1.257. MTRR

One study found MTRR (variant rs924977) as one of 96 candidate genes.2

1.258. ADAMDEC1

One study found ADAMDEC1 (variant rs4872233) as one of 96 candidate genes.2

1.259. CLIC4

One study found CLIC4 (variant rs2223365) as one of 96 candidate genes.2

1.260. SLC13A5

One study found SLC13A5 (variant rs41463346) as one of 96 candidate genes.2

1.261. LOC101928769

One study found LOC101928769 (variant rs2968194) as one of 96 candidate genes.2

1.262. ACSL3

One study found ACSL3 (variant rs10498143) as one of 96 candidate genes.2

1.263. TRAPPC11

One study found TRAPPC11 (variant rs10018951) as one of 96 candidate genes.2

1.264. METTL8

One study found METTL8 (variant rs17218608) as one of 96 candidate genes.2

1.265. ZNF777

One study found ZNF777 (variant rs17852167) as one of 96 candidate genes.2

1.266. TFAP2D

One study found TFAP2D (variant rs78648104) to be one of 96 candidate genes.2

1.267. OTOR

One study found OTOR (variant rs6105651) as one of 96 candidate genes.2

1.268. KCNC2

One study found KCNC2 (variant rs17114649) as one of 96 candidate genes.2

1.269. EEPD1

One study found EEPD1 (variant rs2726059) as one of 96 candidate genes.2

1.270. MAD2L1

One study found MAD2L1 (variant rs1553692) as one of 96 candidate genes.2

1.271. FLRT2

One study found FLRT2 (variant rs17712565) as one of 96 candidate genes.2

1.272. PLD5

One study found PLD5 (variant rs4658830) as one of 96 candidate genes.2

1.273. ADAMDEC1

One study found ADAMDEC1 (variant rs7012077) as one of 96 candidate genes.2

1.274. CASC20

One study found CASC20 (variant rs6038589) to be one of 96 candidate genes.2

1.275. BMP2

One study found BMP2 (variant rs952793) as one of 96 candidate genes.2

1.276. COBLL1

One study found COBLL1 (variant rs139834711) as one of 96 candidate genes.2

1.277. PAPOLA

One study found PAPOLA (variant rs7160641)as one of 96 candidate genes.2

1.278. NCL

One study found NCL (variant rs16828074) as one of 96 candidate genes.2
miRNAs have been substantially implicated in the development of ADHD in children and adults.171

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


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  61. Kent, Emerton, Bhadravathi, Weisblatt, Pasco, Willatt, McMahon, Yates (2008): X-linked ichthyosis (steroid sulfatase deficiency) is associated with increased risk of attention deficit hyperactivity disorder, autism and social communication deficits. J Med Genet. 2008 Aug;45(8):519-24. doi: 10.1136/jmg.2008.057729. PMID: 18413370.

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  63. KCNC1 Gene - Potassium Voltage-Gated Channel Subfamily C Member 1; Gene Cards

  64. Banaschewski, Becker, Scherag, Franke, Coghill (2010): Eur Child Adolesc Psychiatry. 2010 Mar; 19(3): 237–257; doi: 10.1007/s00787-010-0090-z; PMCID: PMC2839490; Molecular genetics of attention-deficit/hyperactivity disorder: an overview

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  68. Yektaş, Alpay, Tufan (2019): Comparison of serum B12, folate and homocysteine concentrations in children with autism spectrum disorder or attention deficit hyperactivity disorder and healthy controls. Neuropsychiatr Dis Treat. 2019 Aug 6;15:2213-2219. doi: 10.2147/NDT.S212361. eCollection 2019.

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  70. Pusceddu, Herrmann, Kleber, Scharnagl, März, Herrmann (2019): Telomere length, vitamin B12 and mortality in persons undergoing coronary angiography: the Ludwigshafen risk and cardiovascular health study. Aging (Albany NY). 2019 Sep 6;11(17):7083-7097. doi: 10.18632/aging.102238.

  71. Pineda-Cirera, Shivalikanjli, Cabana-Domínguez, Demontis, Rajagopal, Børglum, Faraone, Cormand, Fernàndez-Castillo (2019): Exploring genetic variation that influences brain methylation in attention-deficit/hyperactivity disorder. Transl Psychiatry. 2019 Oct 3;9(1):242. doi: 10.1038/s41398-019-0574-7.

  72. Ziegler, Röser, Renner, Hahn, Ehlis, Weber, Dempfle, Walitza, Jacob, Romanos, Fallgatter, Reif, Lesch (2019): KCNJ6 variants modulate reward-related brain processes and impact executive functions in attention-deficit/hyperactivity disorder. Am J Med Genet B Neuropsychiatr Genet. 2019 May 17. doi: 10.1002/ajmg.b.32734.

  73. Vedel, Nøhr, Gloriam, Bräuner-Osborne (2020): Pharmacology and function of the orphan GPR139 G protein-coupled receptor. Basic Clin Pharmacol Toxicol. 2020 Jun;126 Suppl 6(Suppl 6):35-46. doi: 10.1111/bcpt.13263. PMID: 31132229; PMCID: PMC7318219.

  74. Probable G-protein coupled receptor 139, UniProt

  75. Lotan, Fenckova, Bralten, Alttoa, Dixson, Williams, van der Voet (2014): Neuroinformatic analyses of common and distinct genetic components associated with major neuropsychiatric disorders. Front Neurosci. 2014 Nov 6;8:331. doi: 10.3389/fnins.2014.00331. eCollection 2014.

  76. Li, Wang, Zhou, Zhang, Yang, Wang, Faraone (2006): Association between tryptophan hydroxylase gene polymorphisms and attention deficit hyperactivity disorder in Chinese Han population. Am J Med Genet B Neuropsychiatr Genet. 2006 Mar 5;141B(2):126-9.

  77. Johansson, Halmøy, Mavroconstanti, Jacobsen, Landaas, Reif, Jacob, Boreatti-Hümmer, Kreiker, Lesch, Kan, Kooij, Kiemeney, Buitelaar, Franke, Ribases, Bosch, Bayes, Casas, Ramos-Quiroga, Cormand, Knappskog, Haavik (2010): Common Variants in the TPH1 and TPH2 Regions Are Not Associated With Persistent ADHD in a Combined Sample of 1,636 Adult Cases and 1,923 Controls From Four European Populations. AMERICAN JOURNAL OF MEDICAL GENETICS, 1008, 2010. DOI 10.1002/ajmg.b.31067

  78. Gutknecht, Araragi, Merker, Waider, Sommerlandt, Mlinar, Baccini, Mayer, Proft, Hamon, Schmitt, Corradetti, Lanfumey, Lesch (2012): Impacts of brain serotonin deficiency following Tph2 inactivation on development and raphe neuron serotonergic specification. PLoS One. 2012;7(8):e43157. doi: 10.1371/journal.pone.0043157. PMID: 22912815; PMCID: PMC3422228.

  79. Strekalova, Svirin, Waider, Gorlova, Cespuglio, Kalueff, Pomytkin, Schmitt-Boehrer, Lesch, Anthony (2021): Altered behaviour, dopamine and norepinephrine regulation in stressed mice heterozygous in TPH2 gene. Prog Neuropsychopharmacol Biol Psychiatry. 2021 Jun 8;108:110155. doi: 10.1016/j.pnpbp.2020.110155. PMID: 33127424.

  80. Krause, Krause (2014): ADHS im Erwachsenenalter, Kapitel 4: Genetik

  81. Panagiotidi, Overton, Stafford (2017): Co-Occurrence of ASD and ADHD Traits in an Adult Population.J Atten Disord. 2017 Aug 1:1087054717720720. doi: 10.1177/1087054717720720; n = 334

  82. Rivero, Selten, Sich, Popp, Bacmeister, Amendola, Negwer, Schubert, Proft, Kiser, Schmitt, Gross, Kolk, Strekalova, van den Hove, Resink, Nadif Kasri, Lesch (2015): Cadherin-13, a risk gene for ADHD and comorbid disorders, impacts GABAergic function in hippocampus and cognition. Transl Psychiatry. 2015 Oct 13;5(10):e655. doi: 10.1038/tp.2015.152. PMID: 26460479; PMCID: PMC4930129.

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  85. English, HahnIan, Gizer, Mazei-Robison, Steele, Kurnik, SteinIrwin, Waldman, Blakely (2009): Choline transporter gene variation is associated with attention-deficit hyperactivity disorder; Journal of Neurodevelopmental Disorders, December 2009, Volume 1, Issue 4, pp 252–263

  86. Elia, Glessner, Wang, Takahashi, Shtir, Hadley, Sleiman, Zhang, Kim, Robison, Lyon, Flory, Bradfield, Imielinski, Hou, Frackelton, Chiavacci, Sakurai, Rabin, Middleton, Thomas, Garris, Mentch, Freitag, Steinhausen (2012): Genome-wide copy number variation study associates metabotropic glutamate receptor gene networks with attention deficit hyperactivity disorder; Nature Genetics 44, 78–84, (2012); doi:10.1038/ng.1013, n > 5000

  87. Subin, Bung-Nyun, Soo-Churl, Jae-Won, Inhyang, Min-Sup, Hee-Jeong, Hyun, Hoon (2014): The Metabotropic Glutamate Receptor Subtype 7 rs3792452 Polymorphism Is Associated with the Response to Methylphenidate in Children with Attention-Deficit/Hyperactivity Disorder; Journal of Child and Adolescent Psychopharmacology. May 2014, 24(4): 223-227. doi:10.1089/cap.2013.0079.

  88. Freudenberg, Alttoa, Reif (2015): Neuronal nitric oxide synthase (NOS1) and its adaptor, NOS1AP, as a genetic risk factors for psychiatric disorders. Genes Brain Behav. 2015 Jan;14(1):46-63. doi: 10.1111/gbb.12193. PMID: 25612209.

  89. Hoogman, Aarts, Zwiers, Slaats-Willemse, Naber, Onnink, Cools, Kan, Buitelaar, Franke (2011): Nitric oxide synthase genotype modulation of impulsivity and ventral striatal activity in adult ADHD patients and healthy comparison subjects. Am J Psychiatry. 2011 Oct;168(10):1099-106. doi: 10.1176/appi.ajp.2011.10101446. PMID: 21724667.

  90. CPLX2, Complexin 2, GeneCards

  91. MAP1B, Microtubule Associated Protein 1B, GeneCards

  92. Lotan, FenMOBPckova, Bralten, Alttoa, Dixson, Williams, van der Voet (2014): Neuroinformatic analyses of common and distinct genetic components associated with major neuropsychiatric disorders. Front Neurosci. 2014 Nov 6;8:331. doi: 10.3389/fnins.2014.00331. eCollection 2014.

  93. ANKS1B, Ankyrin Repeat And Sterile Alpha Motif Domain Containing 1B. GeneCards

  94. Banaschewski, Becker, Scherag, Franke, Coghill (2010): Eur Child Adolesc Psychiatry. 2010 Mar; 19(3): 237–257; doi: 10.1007/s00787-010-0090-z; PMCID: PMC2839490; Molecular genetics of attention-deficit/hyperactivity disorder: an overview

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  96. Luo, Jiang, Cao, Xiong, Yang, Zhang, Shen (2020): Association between BDNF gene polymorphisms and attention deficit hyperactivity disorder in school-aged children in Wuhan, China. J Affect Disord. 2020 Mar 1;264:304-309. doi: 10.1016/j.jad.2020.01.017. PMID: 32056765.

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  105. Binder, Bradley, Liu, Epstein, Deveau, Mercer, Tang, Gillespie, Heim, Nemeroff, Schwartz, Cubells, Ressler (2008): Association of FKBP5 polymorphisms and childhood abuse with risk of posttraumatic stress disorder symptoms in adults. JAMA 2008; 299: 1291–305.

  106. Klengel, Mehta, Anacker, Rex-Haffner, Pruessner, Pariante, Pace, Mercer, Mayberg, Bradley, Nemeroff, Holsboer, Heim, Ressler, Rein, Binder (2013): Allelespecific FKBP5 DNA demethylation mediates gene-childhood trauma interactions. Nat Neurosci 2013; 16: 33–41.

  107. Ising, Depping, Siebertz, Lucae, Unschuld, Kloiber, Horstmann, Uhr, Muller-Myhsok, Holsboer (2008): Polymorphisms in the FKBP5 gene region modulate recovery from psychosocial stress in healthy controls. European Journal of Neuroscience, 28: 389-398. doi:10.1111/j.1460-9568.2008.06332.x

  108. Zhang Q, Peng C, Song J, Zhang Y, Chen J, Song Z, Shou X, Ma Z, Peng H, Jian X, He W, Ye Z, Li Z, Wang Y, Ye H, Zhang Z, Shen M, Tang F, Chen H, Shi Z, Chen C, Chen Z, Shen Y, Wang Y, Lu S, Zhang J, Li Y, Li S, Mao Y, Zhou L, Yan H, Shi Y, Huang C, Zhao Y. Germline Mutations in CDH23, Encoding Cadherin-Related 23, Are Associated with Both Familial and Sporadic Pituitary Adenomas. Am J Hum Genet. 2017 May 4;100(5):817-823. doi: 10.1016/j.ajhg.2017.03.011. PMID: 28413019; PMCID: PMC5420349.

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  112. ZNF763, Zinc Finger Protein 763, GeneCards

  113. 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.

  114. ZNF615, Zinc Finger Protein 615, GeneCards

  115. POLR1H, RNA Polymerase I Subunit H; GeneCards

  116. Goodfellow, Zomerdijk (20139. Basic mechanisms in RNA polymerase I transcription of the ribosomal RNA genes. Subcell Biochem. 2013;61:211-36. doi: 10.1007/978-94-007-4525-4_10. PMID: 23150253; PMCID: PMC3855190. REVIEW

  117. NT5C2, 5’-Nucleotidase, Cytosolic II, GeneCards

  118. Bruxel, Moreira-Maia, Akutagava-Martins, Quinn, Klein, Franke, Ribasés, Rovira, Sánchez-Mora, Kappel, Mota, Grevet, Bau, Arcos-Burgos, Rohde, Hutz (2020): Meta-analysis and systematic review of ADGRL3 (LPHN3) polymorphisms in ADHD susceptibility. Mol Psychiatry. 2020 Feb 12. doi: 10.1038/s41380-020-0673-0. PMID: 32051549.

  119. Regan, Williams, Vorhees (2021): Latrophilin-3 disruption: Effects on brain and behavior. Neurosci Biobehav Rev. 2021 Aug;127:619-629. doi: 10.1016/j.neubiorev.2021.04.030. PMID: 34022279; PMCID: PMC8292202. REVIEW

  120. Moreno-Salinas, Holleran, Ojeda-Muñiz, Correoso-Braña, Ribalta-Mena, Ovando-Zambrano, Leduc, Boucard (2022): Convergent selective signaling impairment exposes the pathogenicity of latrophilin-3 missense variants linked to inheritable ADHD susceptibility. Mol Psychiatry. 2022 Apr 7. doi: 10.1038/s41380-022-01537-3. PMID: 35393556.

  121. SPATA13, SPERMATOGENESIS-ASSOCIATED PROTEIN 13, GeneCards

  122. Schaffer, Breuss, Caglayan, Al-Sanaa, Al-Abdulwahed, Kaymakçalan, Yılmaz, Zaki, Rosti, Copeland, Baek, Musaev, Scott, Ben-Omran, Kariminejad, Kayserili, Mojahedi, Kara, Cai, Silhavy, Elsharif, Fenercioglu, Barshop, Kara, Wang, Stanley, James, Nachnani, Kalur, Megahed, Incecik, Danda, Alanay, Faqeih, Melikishvili, Mansour, Miller, Sukhudyan, Chelly, Dobyns, Bilguvar, Jamra, Gunel, Gleeson (2018): Biallelic loss of human CTNNA2, encoding αN-catenin, leads to ARP2/3 complex overactivity and disordered cortical neuronal migration. Nat Genet. 2018 Aug;50(8):1093-1101. doi: 10.1038/s41588-018-0166-0. Epub 2018 Jul 16. PMID: 30013181; PMCID: PMC6072555.

  123. Accogli, Lu, Musante, Scudieri, Rosenfeld, Severino, Baldassari, Iacomino, Riva, Balagura, Piccolo, Minetti, Roberto, Xia F, Razak, Lawrence, Hussein, Chang EY, Holick, Calì, Aliberto, De-Sarro, Gambardella, Network UD, Group SS, Emrick, McCaffery, Clagett-Dame, Marcogliese, Bellen, Lalani, Zara, Striano, Salpietro (2022): Loss of Neuron Navigator 2 Impairs Brain and Cerebellar Development. Cerebellum. 2022 Feb 26. doi: 10.1007/s12311-022-01379-3. PMID: 35218524.

  124. KCNIP4 Gene - Potassium Voltage-Gated Channel Interacting Protein 4; GeneCards

  125. Grünewald, Becker, Camphausen, O’Leary, Lesch, Freudenberg, Reif (2018): Expression of the ADHD candidate gene Diras2 in the brain., J Neural Transm (Vienna). 2018 Feb 27. doi: 10.1007/s00702-018-1867-3.

  126. TMEM161B transmembrane protein 161B [ Homo sapiens (human) ]

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  128. Jin, Liu, Chen, Gao, Li, Wang, Qian (2019): The Implicated Roles of Cell Adhesion Molecule 1 (CADM1) Gene and Altered Prefrontal Neuronal Activity in Attention-Deficit/Hyperactivity Disorder: A “Gene-Brain-Behavior Relationship”? Front Genet. 2019 Sep 26;10:882. doi: 10.3389/fgene.2019.00882. eCollection 2019.

  129. FEZF1-AS1 Gene - FEZF1 Antisense RNA 1, GeneCards

  130. Schimmelmann. Hinney. Scherag. Pütter. Pechlivanis. Cichon. Jöckel. Schreiber. Wichmann. Albayrak. Dauvermann. Konrad. Wilhelm. Herpertz-Dahlmann. Lehmkuhl. Sinzig. Renner. Romanos. Warnke. Lesch. Reif. Hebebrand (2013): Bipolar disorder risk alleles in children with ADHD. Journal of Neural Transmission, November 2013, Volume 120, Issue 11, pp 1611–1617

  131. ANKYRIN 3, Wikipedia, 27.05.22

  132. 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.

  133. BMPR1B, Wikipedia, 18.05.22

  134. CACNA1C Gene - Calcium Voltage-Gated Channel Subunit Alpha1 C; GeneCards

  135. Cross-Disorder Group of the Psychiatric Genomics Consortium. Identification of risk loci with shared effects on five major psychiatric disorders: a genome-wide analysis. Lancet. 2013 Apr 20;381(9875):1371-1379. doi: 10.1016/S0140-6736(12)62129-1. Epub 2013 Feb 28. Erratum in: Lancet. 2013 Apr 20;381(9875):1360. Erratum in: Lancet. 2013 Apr 20;381(9875):1360. PMID: 23453885; PMCID: PMC3714010.

  136. CACNB2 Gene - Calcium Voltage-Gated Channel Auxiliary Subunit Beta 2, GeneCards

  137. DNM1, Wikipedia, 28.05.22

  138. DPP6, Wikipedia, 28.05.22

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

  140. MAN2A2, Mannosidase Alpha Class 2A Member 2, GeneCards

  141. ATP2C2, ATPase Secretory Pathway Ca2+ Transporting 2, GeneCards

  142. CSMD1, CUB And Sushi Multiple Domains 1, GeneCards

  143. FERMT3, FERM Domain Containing Kindlin 3, GeneCards

  144. CHMP7, Charged Multivesicular Body Protein 7, GeneCards

  145. MUCL3, GeneCards

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

  147. AK8, Adenylate Kinase 8, GeneCards

  148. CFAP221, Cilia And Flagella Associated Protein 221, GeneCards

  149. CEP112, Centrosomal Protein 112, GeneCards

  150. NCKAP5, NCK Associated Protein 5, GeneCards

  151. SPATA33, Spermatogenesis Associated 33, GeneCards

  152. SPATA33, OMIM

  153. CDK10, Cyclin Dependent Kinase 10; GeneCards

  154. PPP1R11, PROTEIN PHOSPHATASE 1, REGULATORY SUBUNIT 11, GeneCards

  155. NME5, NME/NM23 FAMILY, MEMBER 5; GeneCards

  156. ABHD5, GeneCards

  157. ABHD5; DocCheck Flexikon

  158. GMPR2, GeneCards

  159. BLOC1S2 , GeneCards

  160. KIAA0319L , GeneCards

  161. FMNL3, GeneCards

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