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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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ARHGAP1
Rho GTPase activating protein 1
Chromosome 11 · 11p11.2
NCBI Gene: 392Ensembl: ENSG00000175220.13HGNC: HGNC:673UniProt: Q07960
136PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
small GTPase-mediated signal transductionsorting endosomeGTPase activator activityprotein bindingheart diseasehypertrophic cardiomyopathypulmonary embolismneurodegenerative disease
✦AI Summary

ARHGAP1 (Rho GTPase-activating protein 1) is a GAP protein that inactivates Rho family GTPases by converting them from active GTP-bound to inactive GDP-bound states, with Cdc42 as the preferred substrate 1. The protein localizes to multiple cellular compartments including the cytoplasm, plasma membrane, and endosomal structures, and participates in cadherin binding and signal transduction regulation 2. Mechanistically, ARHGAP1 modulates actin filament dynamics and endocytic transport. In influenza-infected cells, ARHGAP1 is transported with viral ribonucleoproteins via Rab11a-mediated endocytic pathways, where it stabilizes actin filaments to promote budozone formation 2. In neuronal contexts, Cdc42GAP deficiency impairs cognitive function and dendritic spine density through elevated Cdc42 signaling, suggesting ARHGAP1 regulates synaptic plasticity 1. Disease relevance includes Alzheimer's disease, where Cdc42GAP deficiency promotes tau hyperphosphorylation and amyloid accumulation through GSK-3β activation 1. In diabetic retinopathy, ARHGAP1 influences disease progression via body mass index, C-reactive protein, and hypertension regulation 3. Conversely, ARHGAP1 overexpression suppresses cervical carcinoma cell proliferation, migration, and invasion 4, while circRNA-mediated ARHGAP1 upregulation promotes breast cancer progression 5. In ischemic cardiomyopathy, ARHGAP1 overexpression induces myocardial apoptosis through Bcl-2 pathway modulation 6.

Sources cited
1
Cdc42GAP (ARHGAP1) converts Cdc42 from GTP-bound to GDP-bound state; deficiency impairs cognitive behavior, causes synaptic loss, and increases Alzheimer's disease-like pathology including tau hyperphosphorylation and amyloid accumulation
PMID: 37254741
2
ARHGAP1 is transported with viral ribonucleoproteins via Rab11a-mediated endocytic transport and stabilizes actin filaments to promote budozone formation in influenza-infected cells
PMID: 35475647
3
ARHGAP1 is a core causal target for diabetic retinopathy that influences disease progression via regulation of body mass index, C-reactive protein, and hypertension
PMID: 41340073
4
ARHGAP1 overexpression inhibits cervical carcinoma cell proliferation, migration, and invasion by downregulating tumor-related proteins including MMP2, ZEB1, and cyclin B1
PMID: 28223826
5
CircRNA-mediated ARHGAP1 upregulation promotes breast cancer cell proliferation, metastasis, and EMT through miR-542-3p sponging
PMID: 34402683
6
ARHGAP1 overexpression induces apoptosis of cardiac myocytes in ischemic cardiomyopathy by regulating Bcl-2 and BAX
PMID: 31664016
7
ARHGAP1 associates with insulin secretory granules as a cytosolic factor, with preferential association with younger granules
PMID: 38421874
Disease Associationsⓘ20
heart diseaseOpen Targets
0.35Weak
hypertrophic cardiomyopathyOpen Targets
0.33Weak
pulmonary embolismOpen Targets
0.33Weak
neurodegenerative diseaseOpen Targets
0.32Weak
cardiomyopathyOpen Targets
0.29Weak
Pulmonary InfarctionOpen Targets
0.28Weak
deep vein thrombosisOpen Targets
0.27Weak
Alzheimer diseaseOpen Targets
0.22Weak
lysosomal storage diseaseOpen Targets
0.22Weak
multiple sclerosisOpen Targets
0.22Weak
Parkinson diseaseOpen Targets
0.22Weak
schizophreniaOpen Targets
0.18Weak
heart failureOpen Targets
0.17Weak
Familial exudative vitreoretinopathyOpen Targets
0.14Weak
aneurysmOpen Targets
0.10Suggestive
venous thromboembolismOpen Targets
0.06Suggestive
hypertensionOpen Targets
0.06Suggestive
essential hypertensionOpen Targets
0.06Suggestive
cervical carcinomaOpen Targets
0.05Suggestive
ventricular fibrillationOpen Targets
0.05Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
TRIP10Protein interaction100%BNIP2Protein interaction93%WASProtein interaction92%IQGAP1Protein interaction91%ARHGDIAProtein interaction90%NDEL1Protein interaction87%
Tissue Expression6 tissues
Heart
100%
Ovary
41%
Liver
39%
Lung
38%
Bone Marrow
30%
Brain
25%
Gene Interaction Network
Click a node to explore
ARHGAP1TRIP10BNIP2WASIQGAP1ARHGDIANDEL1
PROTEIN STRUCTURE
Preparing viewer…
PDB1TX4 · 1.65 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.60LoF Tolerant
pLIⓘ
0.14Tolerant
Observed/Expected LoF0.42 [0.30–0.60]
RankingsWhere ARHGAP1 stands among ~20K protein-coding genes
  • #3,399of 20,598
    Most Researched136 · top quartile
  • #4,124of 17,882
    Most Constrained (LOEUF)0.60 · top quartile
Genes detectedARHGAP1
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Multi-omics integrated analysis identifies causal risk factors and therapeutic targets for diabetic retinopathy.
PMID: 41340073
J Transl Med · 2025
1.00
2
ARHGAP1 overexpression inhibits proliferation, migration and invasion of C-33A and SiHa cell lines.
PMID: 28223826
Onco Targets Ther · 2017
0.90
3
Cdc42GAP deficiency contributes to the Alzheimer's disease phenotype.
PMID: 37254741
Brain · 2023
0.80
4
CD97 maintains tumorigenicity of glioblastoma stem cells via mTORC2 signaling and is targeted by CAR Th9 cells.
PMID: 39637858
Cell Rep Med · 2024
0.70
5
Rho GTPase‑activating protein 1 promotes apoptosis of myocardial cells in an ischemic cardiomyopathy model.
PMID: 31664016
Kardiol Pol · 2019
0.60