ARPC2

protein-coding

actin related protein 2/3 complex subunit 2, the group of Actin related protein 2/3 complex subunits

Gene summary

This gene encodes one of seven subunits of the human Arp2/3 protein complex. The Arp2/3 protein complex has been implicated in the control of actin polymerization in cells and has been conserved through evolution. The exact role of the protein encoded by this gene, the p34 subunit, has yet to be determined. Two alternatively spliced variants have been characterized to date. Additional alternatively spliced variants have been described but their full length nature has not been determined. [provided by RefSeq, Jul 2008]

MANE transcript

NM_152862.3

Inheritance

—

ClinVar variants

U:33B:1

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0

Max pathogenic AF

—

Genomic locus

chr2:218,217,141-218,254,356

External References & Databases

Ensembl (ENSG00000163466)

Transcript & Mutation Effects

hg38 • Region Span ~37.2 kb

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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 ARPC2 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 19

not providedTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_152862.3. 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.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous					1 clinvar	1
missense			24 clinvar			24
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			8 clinvar			8
Total	0	0	33	0	1	34

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 67 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_152862.3	RefSeq	NP_690601.1	10	MANE Select
ENST00000315717.10	Ensembl	ENSP00000327137.5	10	MANE Select
NM_005731.3	RefSeq	NP_005722.1	10	Standard
ENST00000295685.14	Ensembl	ENSP00000295685.10	10	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Fc gamma R-mediated phagocytosis - Homo sapiens (human)
Salmonella infection - Homo sapiens (human)
Endocytosis - Homo sapiens (human)
Regulation of actin cytoskeleton - Homo sapiens (human)
Bacterial invasion of epithelial cells - Homo sapiens (human)

Biological Process

positive regulation of lamellipodium assembly
actin filament polymerization
Arp2/3 complex-mediated actin nucleation
Fc-gamma receptor signaling pathway involved in phagocytosis
ephrin receptor signaling pathway

Molecular Function

structural constituent of cytoskeleton
protein binding
actin filament binding

Cellular Component

nucleus
endosome
cytosol
Arp2/3 protein complex
focal adhesion

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000295685
Coding exons: 10
Length: 37263
Individuals with no LoFs: 121877
Homozygous LoFs: 0
Heterozygous LoFs: 3
Defined: 121880
p: 0.0000123

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.70	79	182	0.435	0.0000104	1992
Missense (PolyPhen)		13	49.353	0.26341		642
Synonymous	1.40	55	69.9	0.787	0.00000429	542
Loss of Function	3.91	0	17.8	0.00	9.90e-7	207

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000087	0.000087	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0	0.0	absent
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Actin-binding component of the Arp2/3 complex, a multiprotein complex that mediates actin polymerization upon stimulation by nucleation-promoting factor (NPF) (PubMed:9230079). The Arp2/3 complex mediates the formation of branched actin networks in the cytoplasm, providing the force for cell motility (PubMed:9230079). Seems to contact the mother actin filament (PubMed:9230079). In addition to its role in the cytoplasmic cytoskeleton, the Arp2/3 complex also promotes actin polymerization in the nucleus, thereby regulating gene transcription and repair of damaged DNA (PubMed:29925947). The Arp2/3 complex promotes homologous recombination (HR) repair in response to DNA damage by promoting nuclear actin polymerization, leading to drive motility of double-strand breaks (DSBs) (PubMed:29925947). {ECO:0000269|PubMed:29925947, ECO:0000269|PubMed:9230079}.;

Recessive Scores

pRec: 0.178

Intolerance Scores

RVIS EVS: -0.25
RVIS percentile EVS: 35.42

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.801

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium