ARC

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

Basic information

Region (hg38): 8:142611049-142614479

Links

ENSG00000198576 ∙ NCBI:23237 ∙ OMIM:612461 ∙ HGNC:648 ∙ Uniprot:Q7LC44 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Transcripts

Transcript IDs starting with ENST are treated as Ensembl, all others as RefSeq. Showing 3 of 3.

Transcript ID	Protein ID	Coding exons	MANE Select	MANE Plus Clinical
NM_015193.5	NP_056008.1	1	yes	-
ENST00000356613.4	ENSP00000349022.2	1	yes	-
NM_001412852.1	NP_001399781.1	1	-	-

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ARC gene.

• not_specified (20 variants)
• not_provided (3 variants)

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. These statistics are base on transcript: NM_015193.5. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				2	1	3
missense			23			23
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	23	2	1

GnomAD

Source: gnomAD

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
		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: 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}.
• 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

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

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