ARC

Summary

ARC (activity regulated cytoskeleton associated protein, HGNC:648) is a protein-coding gene on chromosome 8q24.3, encoding Activity-regulated cytoskeleton-associated protein (Q7LC44). Master regulator of synaptic plasticity that self-assembles into virion-like capsids that encapsulate RNAs and mediate intercellular RNA transfer in the nervous system.

Enables mRNA binding activity and structural molecule activity. Involved in cell migration; cytoskeleton organization; and regulation of cell morphogenesis. Located in cytoplasm and plasma membrane. Part of virus-like capsid.

Source: NCBI Gene 23237 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 29 total
• MANE Select transcript: NM_015193

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:648
Approved symbol	ARC
Name	activity regulated cytoskeleton associated protein
Location	8q24.3
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0278, Arg3.1
Ensembl gene	ENSG00000198576
Ensembl biotype	protein_coding
OMIM	612461
Entrez	23237

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 1 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000356613, ENST00000581404

RefSeq mRNA: 2 — MANE Select: NM_015193 NM_001412852, NM_015193

CCDS: CCDS34950

Canonical transcript exons

ENST00000356613 — 3 exons

Exon	Start	End
ENSE00001418346	142611049	142611857
ENSE00001429918	142612108	142612252
ENSE00001431435	142612484	142614479

Expression profiles

Bgee: expression breadth ubiquitous, 168 present calls, max score 90.87.

FANTOM5 (CAGE): breadth broad, TPM avg 5.6502 / max 1503.9893, expressed in 560 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
95412	5.4026	494
95409	0.1097	39
95410	0.0967	44
95411	0.0412	16

Top tissues by expression

280 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
adenohypophysis	UBERON:0002196	90.87	gold quality
pituitary gland	UBERON:0000007	90.16	gold quality
right frontal lobe	UBERON:0002810	86.06	gold quality
prefrontal cortex	UBERON:0000451	85.19	gold quality
Brodmann (1909) area 10	UBERON:0013541	84.08	silver quality
cingulate cortex	UBERON:0003027	83.46	gold quality
anterior cingulate cortex	UBERON:0009835	83.25	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.10	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	82.04	gold quality
ganglionic eminence	UBERON:0004023	81.99	gold quality
frontal cortex	UBERON:0001870	81.85	gold quality
neocortex	UBERON:0001950	81.79	gold quality
ventricular zone	UBERON:0003053	81.72	gold quality
cerebral cortex	UBERON:0000956	80.19	gold quality
Brodmann (1909) area 9	UBERON:0013540	80.18	gold quality
Ammon’s horn	UBERON:0001954	80.11	gold quality
primary visual cortex	UBERON:0002436	79.85	gold quality
amygdala	UBERON:0001876	79.55	gold quality
putamen	UBERON:0001874	78.95	gold quality
forebrain	UBERON:0001890	78.75	gold quality
telencephalon	UBERON:0001893	78.26	gold quality
mucosa of stomach	UBERON:0001199	76.96	gold quality
caudate nucleus	UBERON:0001873	76.45	gold quality
skin of abdomen	UBERON:0001416	76.43	gold quality
occipital lobe	UBERON:0002021	75.88	gold quality
brain	UBERON:0000955	75.56	gold quality
nucleus accumbens	UBERON:0001882	75.55	gold quality
central nervous system	UBERON:0001017	75.35	gold quality
hypothalamus	UBERON:0001898	75.18	gold quality
upper lobe of left lung	UBERON:0008952	75.09	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-CURD-46	yes	202.87
E-ANND-3	yes	4.61

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 28)

• Arc/MS2 mRNA assembles into particles that move independently, bidirectionally, and intermittently. These observations identify several phases of Arc mRNA movement that serve as potential points for regulating Arc mRNA localization. (PMID:17120280)
• Arc Expression Is Increased in medial frontal cortex of patients with Alzheimer’s Disease. (PMID:22036569)
• Strong fibrinogen and Abeta deposition is demonstrated in small- and medium-sized vessels, but not in large cerebral arteries, of 24-month-old transgenic arcAbeta mice. (PMID:22302811)
• analysis of dynamic, multifaceted control of Arc synthesis during mAchR signaling (PMID:22584581)
• we report a novel ARC single nucleotide polymorphism associated with a reduced risk of developing Alzheimer disease. (PMID:22622366)
• Degradation of Arc by clathrin-localized Triad3A regulates the availability of synaptic AMPA receptors. (PMID:24945773)
• Arc is a flexible multi-domain protein that exists in monomeric and oligomeric forms, compatible with a diverse, hub-like role in plasticity-related processes. (PMID:25748042)
• mRNA levels of ARC and SGK1 did not differ significantly between the schizophrenia or control samples. (PMID:26038830)
• we propose that the peculiar characteristics of Arc protein, such as its optimal expression after ongoing experience or familiar behavior could explain how familiarization and recognition memories are stored and preserved in the mammalian brain–{REVIEW} (PMID:26380114)
• this is the first report associating an ARC SNP with schizophrenia and supports recent large-scale GWAS findings implicating the ARC complex in schizophrenia risk (PMID:26474411)
• We tested whether ARC variants are associated with six measures of cognitive functioning in 670 healthy subjects in the Norwegian Cognitive NeuroGenetics (NCNG) by extracting data from its Genome-Wide Association Study (GWAS). (PMID:26516611)
• ARC confers resistance to sunitinib in renal cell carcinoma through alternate angiogenesis pathways (PMID:26995091)
• Study identified several rare mutations that reduced ARC expression in schizophrenia patients. Furthermore, DNA methylation of ARC in schizophrenia patients may be associated with a downregulation of ARC mRNA expression. These findings suggest that multiple rare ARC variants and DNA methylation of ARC might contribute to the pathogenesis of schizophrenia. (PMID:27464451)
• missense mutations in TRIAD3 abolished the interaction of TRIAD3A with Arc, disrupting Arc ubiquitination, and consequently Arc degradation. (PMID:27995769)
• Our results indicated that the Arc gene would confer susceptibility to Alzheimer disease in Han Chinese, probably through changing the protein structure or affecting the Arc expression in brain tissues, which would finally contribute to the pathogenesis and development of AD. (PMID:28108859)
• The ARC complex revealed association with verbal and total IQ in child. (PMID:28671113)
• The findings have important implications for the structural organization of ARC with respect to distinct functions, such as postsynaptic signal transduction and virus-like capsid formation (PMID:30028513)
• Our data highlighted that PCAT6 acts as a key activator of ARC expression by forming a complex with EZH2, inhibiting cell apoptosis and contributing to colon cancer progression. These findings elucidated that PCAT6 may be a novel prognostic predictor and therapeutic target of colon cancer (PMID:30569799)
• Activity-Regulated Cytoskeleton-Associated Protein (Arc/Arg3.1) is Transiently Expressed after Heat Shock Stress and Suppresses Heat Shock Factor 1. (PMID:30796345)
• Multiscale Imaging Reveals Aberrant Functional Connectome Organization and Elevated Dorsal Striatal Arc Expression in Advanced Age. (PMID:31826916)
• Structure of Drosophila melanogaster ARC1 reveals a repurposed molecule with characteristics of retroviral Gag. (PMID:31911950)
• Activity-regulated cytoskeleton-associated protein predicts symptom response to cognitive behavioral therapy among individuals with first-episode psychosis. (PMID:32145691)
• Arc self-association and formation of virus-like capsids are mediated by an N-terminal helical coil motif. (PMID:33175445)
• Arc and Homer1 are involved in comorbid epilepsy and depression: A microarray data analysis. (PMID:35665606)
• NMDA Receptor-Arc Signaling Is Required for Memory Updating and Is Disrupted in Alzheimer’s Disease. (PMID:36796600)
• Gut-derived 4-hydroxyphenylacetic acid attenuates sepsis-induced acute kidney injury by upregulating ARC to inhibit necroptosis. (PMID:37714058)
• Arc regulates brain damage and neuroinflammation via Sirt1 signaling following subarachnoid hemorrhage. (PMID:37820952)
• Tau regulates Arc stability in neuronal dendrites via a proteasome-sensitive but ubiquitin-independent pathway. (PMID:38552740)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Arc	ENSMUSG00000022602
rattus_norvegicus	Arc	ENSRNOG00000043465

Protein

Protein identifiers

Activity-regulated cytoskeleton-associated protein — Q7LC44 (reviewed: Q7LC44)

Alternative names: Activity-regulated gene 3.1 protein homolog

All UniProt accessions (1): Q7LC44

UniProt curated annotations — full annotation on UniProt →

Function. Master regulator of synaptic plasticity that self-assembles into virion-like capsids that encapsulate RNAs and mediate intercellular RNA transfer in the nervous system. ARC protein is released from neurons in extracellular vesicles that mediate the transfer of ARC mRNA into new target cells, where ARC mRNA can undergo activity-dependent translation. ARC capsids are endocytosed and are able to transfer ARC mRNA into the cytoplasm of neurons. Acts as a key regulator of synaptic plasticity: required for protein synthesis-dependent forms of long-term potentiation (LTP) and depression (LTD) and for the formation of long-term memory. Regulates synaptic plasticity by promoting endocytosis of AMPA receptors (AMPARs) in response to synaptic activity: this endocytic pathway maintains levels of surface AMPARs in response to chronic changes in neuronal activity through synaptic scaling, thereby contributing to neuronal homeostasis. Acts as a postsynaptic mediator of activity-dependent synapse elimination in the developing cerebellum by mediating elimination of surplus climbing fiber synapses. Accumulates at weaker synapses, probably to prevent their undesired enhancement. This suggests that ARC-containing virion-like capsids may be required to eliminate synaptic material. Required to transduce experience into long-lasting changes in visual cortex plasticity and for long-term memory. Involved in postsynaptic trafficking and processing of amyloid-beta A4 (APP) via interaction with PSEN1. In addition to its role in synapses, also involved in the regulation of the immune system: specifically expressed in skin-migratory dendritic cells and regulates fast dendritic cell migration, thereby regulating T-cell activation.

Subunit / interactions. Homooligomer; homooligomerizes into virion-like capsids. Interacts with SH3GL1/endophilin-2, SH3GL3/endophilin-3 and DNM2/DYN2. Interacts with CAMK2B (in the kinase inactive state); leading to target ARC to inactive synapses. Interacts with PSEN1.

Subcellular location. Extracellular vesicle membrane. Postsynaptic cell membrane. Synapse. Postsynaptic density. Early endosome membrane. Cell projection. Dendrite. Cytoplasm. Cytoskeleton. Cell cortex. Dendritic spine. Cytoplasmic vesicle. Secretory vesicle. Acrosome. Clathrin-coated vesicle membrane.

Post-translational modifications. Palmitoylation anchors the protein into the membrane by allowing direct insertion into the hydrophobic core of the lipid bilayer. Ubiquitinated by UBE3A, leading to its degradation by the proteasome, thereby promoting AMPA receptors (AMPARs) expression at synapses. Ubiquitinated by RNF216 at Lys-268 and Lys-269 limiting ARC protein levels induced by synaptic activity and thus regulating ARC-dependent forms of synaptic plasticity. Phosphorylation at Ser-260 by CaMK2 prevents homooligomerization into virion-like capsids by disrupting an interaction surface essential for high-order oligomerization. Phosphorylation by CaMK2 inhibits synaptic activity.

Domain organisation. The protein is evolutionarily related to retrotransposon Gag proteins: it contains large N- and C-terminal domains that form a bi-lobar architecture similar to the capsid domain of human immunodeficiency virus (HIV) gag protein. It contains structural elements found within viral Gag polyproteins originated from the Ty3/gypsy retrotransposon family and retains the ability to form virion-like capsid structures that can mediate mRNA transfer between cells. Tetrapod and fly Arc protein-coding genes originated independently from distinct lineages of Ty3/gypsy retrotransposons.

Similarity. Belongs to the ARC/ARG3.1 family.

RefSeq proteins (2): NP_001399781, NP_056008* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR023263	Arc	Family
IPR040814	Arc_C-lobe	Domain
IPR045557	Arc_N	Domain
IPR048965	Arc_N-lobe	Domain

Pfam: PF18162, PF19284, PF21395

UniProt features (27 total): helix 12, region of interest 3, mutagenesis site 2, turn 2, modified residue 2, cross-link 2, chain 1, strand 1, coiled-coil region 1, compositionally biased region 1

Structure

Experimental structures (PDB)

8 structures.

PDB	Method	Resolution (Å)
6YTU	X-RAY DIFFRACTION	0.95
8QF4	X-RAY DIFFRACTION	1.02
6TNQ	X-RAY DIFFRACTION	1.3
8QF5	X-RAY DIFFRACTION	1.5
6TN7	X-RAY DIFFRACTION	1.67
7R1Z	X-RAY DIFFRACTION	1.94
6TQ0	X-RAY DIFFRACTION	1.95
7R23	X-RAY DIFFRACTION	2.77

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q7LC44-F1	66.72	0.10

Antibody-complex structures (SAbDab): 4 — 7R1Z, 7R23, 8QF4, 8QF5

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (4): 260, 278, 268, 269

Mutagenesis-validated functional residues (2):

Position	Phenotype
268	complete loss of rnf216-mediated ubiquitination; when associated by a-269.
269	complete loss of rnf216-mediated ubiquitination; when associated by a-268.

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-9031628	NGF-stimulated transcription
R-HSA-162582	Signal Transduction
R-HSA-166520	Signaling by NTRKs
R-HSA-187037	Signaling by NTRK1 (TRKA)
R-HSA-198725	Nuclear Events (kinase and transcription factor activation)
R-HSA-9006934	Signaling by Receptor Tyrosine Kinases

MSigDB gene sets: 250 (showing top): GSE45365_NK_CELL_VS_BCELL_UP, MORF_RAGE, GOBP_DENDRITE_DEVELOPMENT, GOBP_MEMORY, GOBP_COGNITION, GOBP_BEHAVIOR, GOBP_REGULATION_OF_CELL_MORPHOGENESIS, GOCC_SECRETORY_GRANULE, GOBP_REGULATION_OF_NEURONAL_SYNAPTIC_PLASTICITY, MODULE_45, GOBP_DENDRITIC_SPINE_DEVELOPMENT, GOBP_NEUROGENESIS, GOBP_VESICLE_MEDIATED_TRANSPORT, MODULE_16, NAGASHIMA_NRG1_SIGNALING_UP

GO Biological Process (19): endocytosis (GO:0006897), cytoskeleton organization (GO:0007010), endoderm development (GO:0007492), long-term memory (GO:0007616), anterior/posterior pattern specification (GO:0009952), cell migration (GO:0016477), regulation of cell morphogenesis (GO:0022604), regulation of neuronal synaptic plasticity (GO:0048168), modulation of chemical synaptic transmission (GO:0050804), mRNA transport (GO:0051028), protein homooligomerization (GO:0051260), long-term synaptic potentiation (GO:0060291), dendritic spine morphogenesis (GO:0060997), regulation of dendritic spine morphogenesis (GO:0061001), regulation of postsynaptic neurotransmitter receptor internalization (GO:0099149), vesicle-mediated intercellular transport (GO:0110077), regulation of long-term synaptic potentiation (GO:1900271), regulation of long-term synaptic depression (GO:1900452), positive regulation of AMPA receptor activity (GO:2000969)

GO Molecular Function (4): mRNA binding (GO:0003729), structural molecule activity (GO:0005198), RNA binding (GO:0003723), protein binding (GO:0005515)

GO Cellular Component (24): acrosomal vesicle (GO:0001669), cytoplasm (GO:0005737), cytosol (GO:0005829), plasma membrane (GO:0005886), cell cortex (GO:0005938), postsynaptic density (GO:0014069), actin cytoskeleton (GO:0015629), clathrin-coated vesicle membrane (GO:0030665), early endosome membrane (GO:0031901), neuronal cell body (GO:0043025), dendritic spine (GO:0043197), membrane raft (GO:0045121), postsynaptic membrane (GO:0045211), neuronal ribonucleoprotein granule (GO:0071598), glutamatergic synapse (GO:0098978), virus-like capsid (GO:0170047), extracellular vesicle (GO:1903561), endosome (GO:0005768), cytoskeleton (GO:0005856), membrane (GO:0016020), dendrite (GO:0030425), cytoplasmic vesicle (GO:0031410), cell projection (GO:0042995), synapse (GO:0045202)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Nuclear Events (kinase and transcription factor activation)	1
Signaling by Receptor Tyrosine Kinases	1
Signaling by NTRKs	1
Signaling by NTRK1 (TRKA)	1
Signal Transduction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of synaptic plasticity	4
cellular anatomical structure	4
vesicle-mediated transport	2
regulation of anatomical structure morphogenesis	2
cytoplasm	2
cell periphery	2
postsynapse	2
vesicle budding from membrane	1
membrane invagination	1
import into cell	1
organelle organization	1
tissue development	1
memory	1
regionalization	1
cell motility	1
cell morphogenesis	1
chemical synaptic transmission	1
regulation of trans-synaptic signaling	1
RNA transport	1
protein complex oligomerization	1
positive regulation of synaptic transmission	1
neuron projection development	1
neuron projection morphogenesis	1
dendrite morphogenesis	1
dendritic spine development	1
dendritic spine organization	1
regulation of neuron projection development	1
dendritic spine morphogenesis	1
regulation of postsynapse organization	1
regulation of receptor internalization	1
regulation of biological quality	1
postsynaptic neurotransmitter receptor internalization	1
intercellular transport	1
long-term synaptic potentiation	1
long-term synaptic depression	1
AMPA glutamate receptor activity	1
positive regulation of ion transmembrane transporter activity	1
regulation of AMPA receptor activity	1
RNA binding	1
molecular_function	1

Protein interactions and networks

STRING

1084 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ARC	SH3GL3	Q99963	885
ARC	DNM2	P50570	884
ARC	GRIA1	P42261	812
ARC	SH3GL1	Q99961	767
ARC	FMR1	Q06787	744
ARC	CAMK2B	Q13554	738
ARC	GRIN2B	Q13224	704
ARC	BDNF	P23560	683
ARC	CAMK2A	Q9UQM7	656
ARC	CACNG2	Q9Y698	647
ARC	UBE3A	P78355	623
ARC	EGR1	P18146	622
ARC	FOS	P01100	622
ARC	DLG4	P78352	612
ARC	HOMER1	Q86YM7	597

IntAct

19 interactions, top by confidence:

A	B	Type	Score
CSRP2	ARC	psi-mi:“MI:0915”(physical association)	0.560
ARC	SH2D4A	psi-mi:“MI:0915”(physical association)	0.560
TBX18	ARC	psi-mi:“MI:0915”(physical association)	0.560
S100P	ARC	psi-mi:“MI:0915”(physical association)	0.560
ARC	FER	psi-mi:“MI:0914”(association)	0.530
DLG4	ARC	psi-mi:“MI:0915”(physical association)	0.400
KRT15	ARC	psi-mi:“MI:0915”(physical association)	0.370
INSYN1	CCDC85C	psi-mi:“MI:0914”(association)	0.350
KRAS	ESYT2	psi-mi:“MI:2364”(proximity)	0.270
CSRP2	ARC	psi-mi:“MI:0915”(physical association)	0.000
S100P	ARC	psi-mi:“MI:0915”(physical association)	0.000
SH2D4A	ARC	psi-mi:“MI:0915”(physical association)	0.000
TBX18	ARC	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (35): ARC (Two-hybrid), RNF216 (Affinity Capture-Western), ARC (Affinity Capture-Western), ARC (Affinity Capture-Western), FER (Affinity Capture-MS), TMEM55A (Affinity Capture-MS), FAM83B (Affinity Capture-MS), SSFA2 (Affinity Capture-MS), NDE1 (Affinity Capture-MS), ARC (Affinity Capture-Western), ARC (Affinity Capture-Western), ARC (Affinity Capture-Western), ARC (Proximity Label-MS), ARC (Reconstituted Complex), ARC (Two-hybrid)

ESM2 similar proteins: A6QLK5, A6ZKI3, D2HBJ8, O15519, O94955, O95751, P0CW24, P10272, Q0V9G5, Q17QF6, Q17RB0, Q1JQ94, Q2TBA3, Q5RD56, Q5RER6, Q5XGZ2, Q63053, Q6NTR6, Q6P5G6, Q6SEH4, Q6SEH5, Q70Z35, Q7JV70, Q7K1U0, Q7LC44, Q7TPY9, Q86TG7, Q8AWC3, Q8C1C8, Q8CA95, Q8N165, Q8N635, Q8ND90, Q8QZR7, Q8TCU6, Q8VHZ4, Q8WNV3, Q96PV4, Q9BWD3, Q9BYG7

Diamond homologs: Q63053, Q7LC44, Q8AWC3, Q9WV31

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

29 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	21
Likely benign	2
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

164 predictions. Top by Δscore:

Variant	Effect	Δscore
8:142612248:TGGAG:T	acceptor_gain	1.0000
8:142612253:C:CA	acceptor_loss	1.0000
8:142612253:C:CC	acceptor_gain	1.0000
8:142612120:T:A	donor_gain	0.9900
8:142612249:GGAG:G	acceptor_gain	0.9900
8:142612250:GAG:G	acceptor_gain	0.9900
8:142612251:AG:A	acceptor_gain	0.9900
8:142612102:CGTTA:C	donor_loss	0.9800
8:142612103:GTTA:G	donor_loss	0.9800
8:142612104:TTA:T	donor_loss	0.9800
8:142612105:TA:T	donor_loss	0.9800
8:142612106:A:AT	donor_loss	0.9800
8:142612107:CCTGT:C	donor_loss	0.9800
8:142612249:GGAGC:G	acceptor_gain	0.9800
8:142612250:GAGCT:G	acceptor_gain	0.9800
8:142612251:AGCTG:A	acceptor_gain	0.9800
8:142612252:GCTG:G	acceptor_gain	0.9800
8:142612108:C:G	donor_loss	0.9700
8:142612253:C:A	acceptor_gain	0.9700
8:142612254:T:A	acceptor_gain	0.9700
8:142612478:GCTCA:G	donor_loss	0.9700
8:142612479:CTCA:C	donor_loss	0.9700
8:142612480:TCA:T	donor_loss	0.9700
8:142612481:CA:C	donor_loss	0.9700
8:142612483:C:CT	donor_loss	0.9700
8:142612248:TGGA:T	acceptor_gain	0.9600
8:142612169:AGCC:A	donor_gain	0.9400
8:142611858:C:CC	acceptor_gain	0.9300
8:142612255:G:C	acceptor_gain	0.9000
8:142611855:GAC:G	acceptor_gain	0.8800

AlphaMissense

2570 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:142613460:A:G	F271S	1.000
8:142613472:A:G	F267S	1.000
8:142613515:A:G	W253R	1.000
8:142613515:A:T	W253R	1.000
8:142613601:A:G	L224P	1.000
8:142613612:G:C	F220L	1.000
8:142613612:G:T	F220L	1.000
8:142613614:A:G	F220L	1.000
8:142613229:A:G	L348P	0.999
8:142613369:G:C	F301L	0.999
8:142613369:G:T	F301L	0.999
8:142613371:A:G	F301L	0.999
8:142613471:G:C	F267L	0.999
8:142613471:G:T	F267L	0.999
8:142613473:A:G	F267L	0.999
8:142613480:C:A	W264C	0.999
8:142613480:C:G	W264C	0.999
8:142613482:A:G	W264R	0.999
8:142613482:A:T	W264R	0.999
8:142613510:C:A	W254C	0.999
8:142613510:C:G	W254C	0.999
8:142613512:A:G	W254R	0.999
8:142613512:A:T	W254R	0.999
8:142613513:C:A	W253C	0.999
8:142613513:C:G	W253C	0.999
8:142613613:A:G	F220S	0.999
8:142613926:A:G	W116R	0.999
8:142613926:A:T	W116R	0.999
8:142613958:A:G	L105P	0.999
8:142614013:A:G	W87R	0.999

dbSNP variants (sampled 300 via entrez): RS1000029399 (8:142614156 A>C), RS1000233723 (8:142612799 G>C), RS1003170115 (8:142615044 G>C), RS1003242235 (8:142615412 G>A), RS1003309256 (8:142614821 C>T), RS1003412354 (8:142616419 G>A), RS1004225557 (8:142614693 C>T), RS1004258053 (8:142614554 C>T), RS1004502488 (8:142612903 C>T), RS1004554712 (8:142613141 C>T), RS1005428363 (8:142612527 C>T), RS1005818994 (8:142614603 A>G), RS1006095898 (8:142614748 C>A,G,T), RS1006482407 (8:142611197 C>T), RS1006686953 (8:142616014 G>A,C)

Disease associations

OMIM: gene MIM:612461 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST007329_7	Automobile speeding propensity	7.000000e-10
GCST009440_6	Age-related cognitive decline (attention/processing speed) (slope of z-scores)	2.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0008579	risk-taking behaviour
EFO:0007710	cognitive decline measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

62 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Cadmium Chloride	decreases expression, increases expression	3
sodium arsenite	affects methylation, increases expression	2
Cisplatin	affects cotreatment, increases expression, decreases expression	2
Copper	affects binding, decreases expression, increases expression	2
Tobacco Smoke Pollution	increases expression	2
Aflatoxin B1	increases expression, decreases methylation	2
aristolochic acid I	increases expression	1
OTX015	increases expression	1
TAK-243	increases sumoylation	1
methylmercuric chloride	increases expression	1
propionaldehyde	increases expression	1
2-methyl-4-isothiazolin-3-one	increases expression	1
beta-lapachone	increases expression	1
butyraldehyde	increases expression	1
benzo(e)pyrene	increases methylation	1
ferrous chloride	increases expression	1
aflatoxin B2	decreases methylation	1
cupric oxide	increases expression	1
gallium arsenide	increases expression	1
pentanal	increases expression	1
15-acetyldeoxynivalenol	increases expression	1
aluminum maltolate	increases expression, decreases reaction	1
2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one	decreases reaction, increases expression	1
nutlin 3	affects cotreatment, increases expression	1
abrine	increases expression	1
(4-amino-1,4-dihydro-3-(2-pyridyl)-5-thioxo-1,2,4-triazole)copper(II)	increases expression	1
licochalcone B	increases expression	1
jinfukang	affects cotreatment, increases expression, decreases expression	1
NSC 689534	affects binding, increases expression	1
(+)-JQ1 compound	increases expression	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.