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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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ARAP2
ArfGAP with RhoGAP domain, ankyrin repeat and PH domain 2
Chromosome 4 · 4p14
NCBI Gene: 116984Ensembl: ENSG00000047365.14HGNC: HGNC:16924UniProt: A7E2A5
36PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
phosphatidylinositol-3,4,5-trisphosphate bindingGTPase activator activityregulation of actin cytoskeleton organizationcytoplasmskin aginginflammatory bowel diseasehypertensionepididymitis
✦AI Summary

ARAP2 is a phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3)-dependent Arf6 GTPase-activating protein (GAP) that regulates actin cytoskeleton dynamics and focal adhesion formation 1. The protein contains both ArfGAP and RhoGAP domains, functioning as an Arf6 GAP while binding RhoA-GTP without exhibiting RhoGAP activity 1. ARAP2 promotes focal adhesion growth by converting Arf6·GTP to Arf6·GDP, thereby suppressing Rac1 activation 2. Unlike ACAP1, another Arf6 GAP with opposing effects, ARAP2 localizes to APPL1-positive endosomes and slows integrin β1 internalization, regulating integrin trafficking through distinct endosomal compartments 3. Clinically, dysregulated ARAP2 expression contributes to disease pathogenesis. Circular RNA derived from ARAP2 (circ-ARAP2) is upregulated in esophageal squamous cell carcinoma, promoting tumor progression through the miR-761/FOXM1 axis, affecting cancer stemness and epithelial-mesenchymal transition 4. ARAP2 also regulates interferon-gamma signaling; tyrosine 415 phosphorylation enables ARAP2 to interact with and restrict the negative regulator SOCS1, enhancing JAK-STAT signaling and exacerbating inflammation during viral infection 5. Genetic variants in ARAP2 are associated with fatty liver development in geese, suggesting involvement in lipid metabolism and potential relevance to non-alcoholic fatty liver disease 6.

Sources cited
1
ARAP2 is a PtdIns(3,4,5)P3-dependent Arf6 GAP that binds RhoA-GTP and regulates focal adhesions and actin stress fibers
PMID: 17077126
2
ARAP2 promotes focal adhesion growth by suppressing Rac1 activation through Arf6 GAP activity
PMID: 23295182
3
ARAP2 and ACAP1 are distinct Arf6 GAPs with opposing effects on integrin trafficking and localize to different endosomal compartments
PMID: 25225293
4
Circular ARAP2 is upregulated in esophageal squamous cell carcinoma and promotes progression through miR-761/FOXM1 pathway
PMID: 35842667
5
Phosphorylated ARAP2 restricts SOCS1 function, enhancing interferon-gamma signaling and inflammation
PMID: 41401070
6
ARAP2 genetic variants are associated with fatty liver development in geese, suggesting metabolic function
PMID: 32868783
7
ARAP2 serves as an Arf6 GAP regulating integrin adhesion complexes and focal adhesion dynamics
PMID: 28362242
Disease Associationsⓘ20
skin agingOpen Targets
0.40Moderate
inflammatory bowel diseaseOpen Targets
0.37Weak
hypertensionOpen Targets
0.31Weak
epididymitisOpen Targets
0.30Weak
orchitisOpen Targets
0.30Weak
cutaneous lupus erythematosusOpen Targets
0.28Weak
metabolic syndromeOpen Targets
0.27Weak
immune system diseaseOpen Targets
0.26Weak
placenta praeviaOpen Targets
0.19Weak
benign chondrogenic neoplasmOpen Targets
0.17Weak
VertigoOpen Targets
0.16Weak
smoking cessationOpen Targets
0.16Weak
liver diseaseOpen Targets
0.16Weak
ankylosing spondylitisOpen Targets
0.15Weak
corneal ulcerOpen Targets
0.15Weak
pituitary gland diseaseOpen Targets
0.15Weak
ovarian neoplasmOpen Targets
0.15Weak
alcohol drinkingOpen Targets
0.15Weak
influenza A (H1N1)Open Targets
0.15Weak
deficiency anemiaOpen Targets
0.14Weak
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
ARHGEF26Shared pathway100%RAB13Protein interaction71%SIGLEC15Shared pathway50%NAA20Shared pathway50%LOC107987545Shared pathway50%ARAP3Shared pathway33%
Tissue Expression6 tissues
Bone Marrow
100%
Brain
21%
Lung
12%
Liver
8%
Heart
3%
Ovary
1%
Gene Interaction Network
Click a node to explore
ARAP2ARHGEF26RAB13SIGLEC15NAA20LOC107987545ARAP3
PROTEIN STRUCTURE
Preparing viewer…
PDB1X40 · NMR
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.88LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.75 [0.64–0.88]
RankingsWhere ARAP2 stands among ~20K protein-coding genes
  • #10,733of 20,598
    Most Researched36
  • #7,886of 17,882
    Most Constrained (LOEUF)0.88
Genes detectedARAP2
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
ARAP2 regulates responses to interferon-gamma by restricting SOCS1.
PMID: 41401070
Cell Rep · 2025
1.00
2
The abnormal expression of circ-ARAP2 promotes ESCC progression through regulating miR-761/FOXM1 axis-mediated stemness and the endothelial-mesenchymal transition.
PMID: 35842667
J Transl Med · 2022
0.90
3
Arf GAPs: A family of proteins with disparate functions that converge on a common structure, the integrin adhesion complex.
PMID: 28362242
Small GTPases · 2019
0.80
4
Analysis of Human Papilloma Virus Content and Integration in Mucoepidermoid Carcinoma.
PMID: 36366450
Viruses · 2022
0.70
5
ARAP2 effects on the actin cytoskeleton are dependent on Arf6-specific GTPase-activating-protein activity and binding to RhoA-GTP.
PMID: 17077126
J Cell Sci · 2006
0.60