ARPC5

protein-coding

actin related protein 2/3 complex subunit 5, 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 p16 subunit, has yet to be determined. Alternatively spliced transcript variants encoding different isoforms have been observed for this gene. [provided by RefSeq, Jul 2012]

MANE transcript

NM_005717.4

Inheritance

ClinVar variants

P:1U:17

Top phenotype

Immunodeficiency 113 with autoimmunity and autoinflammation

gnomAD constraint

pLI —, LoF o/e 0

Max pathogenic AF

—

Genomic locus

chr1:183,620,846-183,635,783

External References & Databases

Ensembl (ENSG00000162704)

Transcript & Mutation Effects

hg38 • Region Span ~14.9 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

immunodeficiency 113 with autoimmunity and autoinflammationSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0957920

Submitter: PanelApp Australia

immunodeficiency 113 with autoimmunity and autoinflammationMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0957920

Submitter: Ambry Genetics

Clinical Genomic Database (CGD)

Immunodeficiency 113 with autoimmunity and autoinflammation AR

Manifestation: Allergy/Immunology/Infectious; Craniofacial; Dermatologic; Hematologic; Neurologic

Intervention: Allergy/Immunology/Infectious

Rationale: Among other findings, the condition can immunologic abnormalities including immunodeficiency and diagnosis may allow preventative measures and early and prompt treatment of infections

Refs: 37349293

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ARPC5 variants in ClinVar

3 Conditions Cataloged

Inborn genetic diseasesTotal: 16

Immunodeficiency 113 with autoimmunity and autoinflammationTotal: 2

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_005717.4. 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						0
missense			16 clinvar			16
nonsense			1 clinvar			1
start loss						0
frameshift	1 clinvar					1
splice donor/acceptor (+/-2bp)						0
Total	1	0	17	0	0	18

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 9 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_005717.4	RefSeq	NP_005708.1	4	MANE Select
ENST00000359856.11	Ensembl	ENSP00000352918.6	4	MANE Select
NM_001270439.2	RefSeq	NP_001257368.1	4	Standard
ENST00000294742.6	Ensembl	ENSP00000294742.6	4	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

smooth muscle cell migration
cell migration
orbitofrontal cortex development
maintenance of cell polarity
actin cytoskeleton organization

Molecular Function

structural constituent of cytoskeleton
protein binding
actin filament binding

Cellular Component

extracellular region
nucleus
cytoplasm
endosome
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000294742
Coding exons: 4
Length: 12492
Individuals with no LoFs: 0
Homozygous LoFs: 0
Heterozygous LoFs: 0
Defined: 0
p: 0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.63	45	87.9	0.512	0.00000422	1003
Missense (PolyPhen)		10	28.832	0.34684		360
Synonymous	-1.21	42	33.1	1.27	0.00000151	302
Loss of Function	2.21	0	5.69	0.00	2.39e-7	73

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
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: 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). 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}.;

Intolerance Scores

RVIS EVS: -0.25
RVIS percentile EVS: 35.42

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.813

Gene Damage Prediction

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