ARC
activity regulated cytoskeleton associated protein, the group of Gag like LTR retrotransposon derived genes
Basic information
Region (hg38): 8:142611049-142614479
Links
Phenotypes
GenCC
Source:
No genCC data.
ClinVar
This is a list of variants' phenotypes submitted to
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the ARC gene is commonly pathogenic or not.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
|---|---|---|---|---|---|---|
| synonymous | 3 | |||||
| missense | 8 | |||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region | 0 | |||||
| non coding | 1 | |||||
| Total | 0 | 0 | 8 | 2 | 2 |
Variants in ARC
This is a list of pathogenic ClinVar variants found in the ARC region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 8-142612823-G-A | Benign (Apr 20, 2019) | |||
| 8-142613097-C-T | not specified | Uncertain significance (Jan 03, 2025) | ||
| 8-142613125-G-C | not specified | Uncertain significance (Oct 10, 2023) | ||
| 8-142613152-C-T | not specified | Uncertain significance (Oct 10, 2023) | ||
| 8-142613243-C-T | Likely benign (Dec 31, 2019) | |||
| 8-142613269-G-A | not specified | Uncertain significance (Feb 28, 2023) | ||
| 8-142613351-G-C | not specified | Uncertain significance (Jun 03, 2022) | ||
| 8-142613358-T-C | not specified | Uncertain significance (Nov 25, 2024) | ||
| 8-142613399-C-T | Likely benign (Jul 01, 2022) | |||
| 8-142613735-G-A | Benign (Jul 11, 2018) | |||
| 8-142613886-C-T | not specified | Uncertain significance (Mar 15, 2024) | ||
| 8-142614013-A-C | not specified | Uncertain significance (Nov 08, 2021) | ||
| 8-142614036-A-T | not specified | Uncertain significance (Jun 13, 2023) | ||
| 8-142614171-C-T | not specified | Uncertain significance (Jan 18, 2025) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| ARC | protein_coding | protein_coding | ENST00000356613 | 1 | 4429 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.594 | 0.405 | 125535 | 0 | 3 | 125538 | 0.0000119 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 2.60 | 144 | 262 | 0.549 | 0.0000183 | 2520 |
| Missense in Polyphen | 64 | 142.23 | 0.44998 | 1427 | ||
| Synonymous | 1.42 | 108 | 129 | 0.840 | 0.0000101 | 791 |
| Loss of Function | 2.98 | 3 | 15.8 | 0.190 | 8.32e-7 | 145 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.0000289 | 0.0000289 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.0000548 | 0.0000544 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.00000931 | 0.00000881 |
| Middle Eastern | 0.0000548 | 0.0000544 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- 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}.;
- Pathway
- Amphetamine addiction - Homo sapiens (human);Serotonin and anxiety;BDNF-TrkB Signaling;Serotonin and anxiety-related events
(Consensus)
Recessive Scores
- pRec
- 0.140
Intolerance Scores
- loftool
- 0.0428
- rvis_EVS
- -0.36
- rvis_percentile_EVS
- 28.63
Haploinsufficiency Scores
- pHI
- 0.116
- hipred
- Y
- hipred_score
- 0.743
- ghis
- 0.506
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- H
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.903
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Arc
- Phenotype
- behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); embryo phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); growth/size/body region phenotype;
Gene ontology
- Biological process
- endocytosis;cytoskeleton organization;endoderm development;learning;long-term memory;anterior/posterior pattern specification;cell migration;regulation of cell morphogenesis;regulation of neuronal synaptic plasticity;mRNA transport;protein homooligomerization;long-term synaptic potentiation;dendritic spine morphogenesis;regulation of dendritic spine morphogenesis;regulation of postsynaptic neurotransmitter receptor internalization;vesicle-mediated intercellular transport;regulation of long-term synaptic potentiation;regulation of long-term synaptic depression;positive regulation of AMPA receptor activity
- Cellular component
- acrosomal vesicle;cytoplasm;plasma membrane;cell cortex;actin cytoskeleton;cell junction;early endosome membrane;neuronal cell body;dendritic spine;membrane raft;postsynaptic density membrane;postsynaptic endosome;glutamatergic synapse;extracellular vesicle
- Molecular function
- mRNA binding