ARC

protein-coding

activity regulated cytoskeleton associated protein, the group of Gag like LTR retrotransposon derived genes

Gene summary

Enables mRNA binding activity and structural molecule activity. Predicted to be involved in several processes, including long-term memory; positive regulation of AMPA receptor activity; and regulation of synaptic plasticity. Predicted to act upstream of or within anterior/posterior pattern specification and endoderm development. Located in cytoplasm and plasma membrane. Is active in virus-like capsid. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_015193.5

Inheritance

—

ClinVar variants

U:24B:3

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.19

Max pathogenic AF

—

Genomic locus

chr8:142,611,049-142,614,479

External References & Databases

Transcript & Mutation Effects

hg38 • Region Span ~3.4 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ARC variants in ClinVar

2 Conditions Cataloged
not specifiedTotal: 21
not providedTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_015193.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
2
clinvar
1
clinvar
3
missense
24
clinvar
24
nonsense
0
start loss
0
frameshift
0
splice donor/acceptor (+/-2bp)
0
Total00242127
Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 3 of 3 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_015193.5RefSeqNP_056008.11MANE Select
ENST00000356613.4EnsemblENSP00000349022.21MANE Select
NM_001412852.1RefSeqNP_001399781.11Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • Amphetamine addiction - Homo sapiens (human)
  • Serotonin and anxiety
  • BDNF-TrkB Signaling
  • Serotonin and anxiety-related events

Biological Process

  • endocytosis
  • cytoskeleton organization
  • endoderm development
  • learning
  • long-term memory

Molecular Function

  • mRNA binding

Cellular Component

  • acrosomal vesicle
  • cytoplasm
  • plasma membrane
  • cell cortex
  • actin cytoskeleton

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000356613
Coding exons
1
Length
4429
Individuals with no LoFs
125535
Homozygous LoFs
0
Heterozygous LoFs
3
Defined
125538
p
0.0000119
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense2.601442620.5490.00001832520
Missense (PolyPhen)64142.230.449981427
Synonymous1.421081290.8400.0000101791
Loss of Function2.98315.80.1908.32e-7145

Population LoF Frequency

PopulationCAFp-valueStatus
African00.0absent
Latino/Admixed American0.0000290.000029rare
Ashkenazi Jewish00.0absent
East Asian0.0000550.000054rare
Finnish00.0absent
European (Non-Finnish)0.00000930.0000088rare
South Asian00.0absent
Other00.0absent

dbNSFP Gene Annotations

Source: dbNSFP

Function
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 (By similarity). Involved in postsynaptic trafficking and processing of amyloid-beta A4 (APP) via interaction with PSEN1 (By similarity). 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 (By similarity). {ECO:0000250|UniProtKB:Q63053, ECO:0000250|UniProtKB:Q9WV31}.;

Recessive Scores

pRec
0.140

Intolerance Scores

LoFtool
0.0428
RVIS EVS
-0.36
RVIS percentile EVS
28.63

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
H
Indispensability pred.
E
Indispensability score
0.903

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
For research and educational, non-commercial use only. Not for clinical or diagnostic use. GeneBe does not provide medical advice. Data use for AI modeling is prohibited: if used, the cost is $0.001 per byte of downloaded uncompressed data.