ACTR3

protein-coding

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

Gene summary

The specific function of this gene has not yet been determined; however, the protein it encodes is known to be a major constituent of the ARP2/3 complex. This complex is located at the cell surface and is essential to cell shape and motility through lamellipodial actin assembly and protrusion. Three transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Mar 2013]

MANE transcript

NM_005721.5

Inheritance

—

ClinVar variants

U:28B:1

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0

Max pathogenic AF

—

Genomic locus

chr2:113,890,063-113,962,596

External References & Databases

Ensembl (ENSG00000115091)

Transcript & Mutation Effects

hg38 • Region Span ~72.5 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 ACTR3 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 17

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_005721.5. 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.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar	1 clinvar		2
missense			21 clinvar			21
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			6 clinvar			6
Total	0	0	28	1	0	29

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 56 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_005721.5	RefSeq	NP_005712.1	12	MANE Select
ENST00000263238.7	Ensembl	ENSP00000263238.2	12	MANE Select
NM_001277140.1	RefSeq	NP_001264069.1	10	Standard
ENST00000415792.5	Ensembl	ENSP00000407912.1	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Tight junction - Homo sapiens (human)
Association Between Physico-Chemical Features and Toxicity Associated Pathways
Developmental Biology
Signal Transduction
Vesicle-mediated transport

Biological Process

establishment or maintenance of cell polarity
asymmetric cell division
meiotic chromosome movement towards spindle pole
meiotic cytokinesis
Arp2/3 complex-mediated actin nucleation

Molecular Function

structural constituent of cytoskeleton
protein binding
ATP binding
actin filament binding

Cellular Component

nucleus
cytoplasm
cytosol
Arp2/3 protein complex
brush border

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000263238
Coding exons: 12
Length: 72637
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	3.61	76	230	0.330	0.0000120	2730
Missense (PolyPhen)		20	94.725	0.21114		1122
Synonymous	0.429	70	74.7	0.937	0.00000373	776
Loss of Function	4.65	0	25.2	0.00	0.00000133	310

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: ATP-binding component of the Arp2/3 complex, a multiprotein complex that mediates actin polymerization upon stimulation by nucleation-promoting factor (NPF) (PubMed:9000076). The Arp2/3 complex mediates the formation of branched actin networks in the cytoplasm, providing the force for cell motility (PubMed:9000076). Seems to contact the pointed end of the daughter actin filament (PubMed:9000076). 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:17220302, 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). Plays a role in ciliogenesis (PubMed:20393563). {ECO:0000269|PubMed:17220302, ECO:0000269|PubMed:20393563, ECO:0000269|PubMed:29925947, ECO:0000269|PubMed:9000076}.;

Recessive Scores

pRec: 0.142

Intolerance Scores

LoFtool: 0.0643
RVIS EVS: 0.13
RVIS percentile EVS: 62.74

Essentials

Essential (CRISPR): E
Essential (CRISPR2): E
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.937

Gene Damage Prediction

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