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25 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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ARPC4
actin related protein 2/3 complex subunit 4
Chromosome 3 · 3p25.3
NCBI Gene: 10093Ensembl: ENSG00000241553.14HGNC: HGNC:707UniProt: P59998
152PubMed Papers
21Diseases
0Drugs
0Pathogenic Variants
CLINICAL
OMIM Disease Gene
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein-macromolecule adaptor activityactin filament bindingstructural constituent of cytoskeletonprotein bindingneurodegenerative diseasedevelopmental delay, language impairment, and ocular abnormalitiesmicrocephalycutaneous Leishmaniasis
✦AI Summary

ARPC4 is a core structural subunit of the Arp2/3 complex that mediates actin polymerization and branched actin network formation, driving cell motility 1. Beyond cytoplasmic functions, ARPC4 regulates nuclear actin polymerization to facilitate gene transcription, DNA repair, and homologous recombination of double-strand breaks 2. In cancer biology, ARPC4 promotes metastatic progression through multiple mechanisms: Akt-phosphorylated UFL1 catalyzes ARPC4 UFMylation to enhance lamellipodia formation and cell migration 3, while elevated ARPC4 expression in bladder cancer correlates with lymph node metastasis and cell invasion capacity 4. ARPC4 also functions downstream of mTORC1/mTORC2 signaling in pancreatic cancer, promoting actin-dependent acinar-to-ductal metaplasia and early carcinogenesis 5. Conversely, ARPC4 depletion in epidermis causes psoriasis-like disease through Nrf2 hyperactivation 6, and ARPC4 knockdown impairs CAR T cell resistance in glioblastoma 7. Clinical relevance extends to kidney transplant acute rejection, where ARPC4 serves as a diagnostic biomarker 8. Additionally, bacterial toxins target ARPC4 for ADP-ribosylation to inhibit Arp2/3 complex function 9.

Sources cited
1
ARPC4 is an actin-binding component of Arp2/3 complex mediating branched actin network formation and cell motility
PMID: 9230079
2
Arp2/3 complex promotes nuclear actin polymerization for gene transcription and homologous recombination repair of DNA damage
PMID: 29925947
3
Akt-phosphorylated UFL1 UFMylates ARPC4 to promote lamellipodia formation, cell migration, invasion and metastasis
PMID: 40419786
4
ARPC4 expression is elevated in bladder cancer, correlates with lymph node metastasis, and its knockdown reduces cell proliferation, migration, invasion and pseudopodia formation
PMID: 31190401
5
mTORC1 and mTORC2 converge on the Arp2/3 complex through ARPC4 to promote acinar-to-ductal metaplasia and KrasG12D-driven pancreatic carcinogenesis
PMID: 33388318
6
ARPC4 knockout in epidermis causes psoriasis-like disease with Nrf2 hyperactivation and altered actin cytoskeleton
PMID: 29113991
7
ARPC4 knockdown in glioblastoma enhances B7-H3-targeting CAR T cell efficacy through TNFSF15 upregulation
PMID: 38561797
8
ARPC4 is identified as a mitophagy-related diagnostic biomarker for acute rejection following kidney transplantation
PMID: 40596704
9
Bacterial toxins ADP-ribosylate ARPC4 and other Arp2/3 complex components to inhibit complex function
PMID: 36429089
Disease Associationsⓘ21
neurodegenerative diseaseOpen Targets
0.56Moderate
developmental delay, language impairment, and ocular abnormalitiesOpen Targets
0.55Moderate
microcephalyOpen Targets
0.37Weak
cutaneous LeishmaniasisOpen Targets
0.37Weak
Alzheimer diseaseOpen Targets
0.35Weak
Parkinson diseaseOpen Targets
0.35Weak
lysosomal storage diseaseOpen Targets
0.35Weak
multiple sclerosisOpen Targets
0.35Weak
genetic disorderOpen Targets
0.19Weak
eye swellingOpen Targets
0.07Suggestive
response to xenobiotic stimulusOpen Targets
0.06Suggestive
hemoglobin D diseaseOpen Targets
0.05Suggestive
uncombable hair syndromeOpen Targets
0.05Suggestive
Blackfan-Diamond anemiaOpen Targets
0.05Suggestive
hereditary persistence of fetal hemoglobin-sickle cell disease syndromeOpen Targets
0.05Suggestive
Hereditary persistence of fetal hemoglobin - beta-thalassemiaOpen Targets
0.05Suggestive
alpha thalassemia-intellectual disability syndrome type 1Open Targets
0.05Suggestive
Alpha-thalassemia - intellectual disability syndrome linked to chromosome 16Open Targets
0.05Suggestive
hemoglobin E diseaseOpen Targets
0.05Suggestive
delta-beta-thalassemiaOpen Targets
0.05Suggestive
Developmental delay, language impairment, and ocular abnormalitiesUniProt
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
GMFGProtein interaction100%CDC42Protein interaction100%ACTR3Protein interaction100%ACTR2Protein interaction100%ACTA1Protein interaction99%ACTG1Protein interaction99%
Tissue Expression6 tissues
Lung
100%
Brain
87%
Bone Marrow
80%
Liver
73%
Ovary
56%
Heart
45%
Gene Interaction Network
Click a node to explore
ARPC4GMFGCDC42ACTR3ACTR2ACTA1ACTG1
PROTEIN STRUCTURE
Preparing viewer…
PDB9I2B · 3.00 Å · EM
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.36Moderately Constrained
pLIⓘ
1.00Intolerant
Observed/Expected LoF0.14 [0.06–0.36]
RankingsWhere ARPC4 stands among ~20K protein-coding genes
  • #2,967of 20,598
    Most Researched152 · top quartile
  • #1,626of 17,882
    Most Constrained (LOEUF)0.36 · top 10%
Genes detectedARPC4
Sources retrieved25 papers
Response time—
📄 Sources
25▼
1
Akt-phosphorylated UFL1 UFMylates ArpC4 to promote metastasis.
PMID: 40419786
Nat Struct Mol Biol · 2025
1.00
2
Expression of the ARPC4 subunit of human Arp2/3 severely affects mycobacterium tuberculosis growth and suppresses immunogenic response in murine macrophages.
PMID: 23894563
PLoS One · 2013
0.90
3
ARPC4 promotes bladder cancer cell invasion and is associated with lymph node metastasis.
PMID: 31190401
J Cell Biochem · 2020
0.80
4
Silencing of the ARP2/3 complex disturbs pancreatic cancer cell migration.
PMID: 23267127
Anticancer Res · 2013
0.72
5
mTORC1 and mTORC2 Converge on the Arp2/3 Complex to Promote Kras
PMID: 33388318
Gastroenterology · 2021
0.70