ARPC4

Chr 3AD

actin related protein 2/3 complex subunit 4

Also known as: ARC20, DEVLO, P20-ARC

NCBI Gene: 10093ENSG00000241553UniProt: P59998OMIM: 604226

This protein is an actin-binding component of the Arp2/3 complex that mediates actin polymerization for cell motility and also promotes nuclear actin polymerization to regulate gene transcription and DNA repair. Mutations cause autosomal dominant developmental delay with language impairment and ocular abnormalities. The gene is highly constrained against loss-of-function variants (pLI 0.97, LOEUF 0.27), indicating intolerance to protein truncation.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismADLOEUF 0.271 OMIM phenotype
Clinical Summary— ARPC4
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.97). One damaged copy is likely sufficient to cause disease.
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint
0.27LOEUF
pLI 0.975
Z-score 3.11
OE 0.00 (0.00–0.27)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
2.21Z-score
OE missense 0.40 (0.31–0.51)
42 obs / 106.0 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.00 (0.00–0.27)
0≤0.351.4
Missense OE0.40 (0.31–0.51)
0≤0.61.4
Synonymous OE0.82
0≤1.21.6
LoF obs/exp: 0 / 11.3Missense obs/exp: 42 / 106.0Syn Z: 0.86
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongARPC4-related microcephaly and developmental delayOTHERAD
DN
0.3892th %ile
GOF
0.3392th %ile
LOF
0.67top 25%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.27

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

ARPC4 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 4 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Akt-phosphorylated UFL1 UFMylates ArpC4 to promote metastasis.
Zhao K et al.·Nat Struct Mol Biol
2025
[Aurora-A overexpression promotes cervical cancer cell invasion and metastasis by activating the NF-κBp65/ARPC4 signaling axis].
Yue Y et al.·Nan Fang Yi Ke Da Xue Xue Bao
2025
Cytochalasin B Mitigates the Inflammatory Response in Lipopolysaccharide-Induced Mastitis by Suppressing Both the ARPC3/ARPC4-Dependent Cytoskeletal Changes and the Association Between HSP70 and the NLRP3 Inflammasome.
Wang A et al.·Int J Mol Sci
2025Open Access
A recurrent, de novo pathogenic variant in ARPC4 disrupts actin filament formation and causes microcephaly and speech delay.
Laboy Cintron D et al.·HGG Adv
2022Open Access
ARPC4 promotes bladder cancer cell invasion and is associated with lymph node metastasis.
Xu N et al.·J Cell Biochem
2020
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients