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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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ARHGAP25
Rho GTPase activating protein 25
Chromosome 2 · 2p13.3
NCBI Gene: 9938Ensembl: ENSG00000163219.12HGNC: HGNC:28951UniProt: A0A384MTM1
22PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
negative regulation of small GTPase mediated signal transductionphagocytic cupactin filament organizationphagocytosis, engulfmenthypertensionsign or symptomcolorectal carcinomanon-small cell lung carcinoma
✦AI Summary

ARHGAP25 is a Rho GTPase-activating protein that functions as a negative regulator of Rho family small GTPases, particularly Rac, by converting them from an active GTP-bound to an inactive GDP-bound state 12. The protein localizes to lamellipodia where it suppresses Rac-dependent lamellipodia formation and cell spreading, with its activity regulated by septin2 3. ARHGAP25 controls actin cytoskeletal organization and cell migration through direct regulation of Rac1/PAK1 signaling 4. In neutrophils, ARHGAP25 exhibits GTP-GDP cycle-dependent interactions with small GTPases including RAC2 and RHOG, suggesting dynamic regulation of its GAP activity 2. The protein plays significant roles in immune cell function, particularly in phagocyte effector functions and leukocyte infiltration during inflammatory responses 5. ARHGAP25 is implicated in various diseases, including serving as a tumor suppressor in breast cancer through inhibition of Wnt/β-catenin signaling 4, contributing to vasculogenic mimicry regulation in non-small cell lung cancer 6, and modulating contact hypersensitivity responses 5. Additionally, variants in ARHGAP25 have been identified as novel genetic loci associated with Alzheimer's disease risk 7 and as recurrent mutations in T-large granular lymphocyte leukemia 8.

Sources cited
1
ARHGAP25 is a RhoGAP family protein that negatively regulates Rho family GTPases
PMID: 15254788
2
ARHGAP25 serves as a Rac-specific GTPase-activating protein with GTP-GDP cycle-dependent interactions
PMID: 39210013
3
ARHGAP25 localizes to lamellipodia and suppresses Rac-dependent lamellipodia formation and cell spreading
PMID: 40205813
4
ARHGAP25 directly regulates Rac1/PAK1 signaling and acts as a tumor suppressor in breast cancer
PMID: 37326327
5
ARHGAP25 regulates phagocyte effector functions and leukocyte infiltration in contact hypersensitivity
PMID: 40078992
6
ARHGAP25 is involved in vasculogenic mimicry regulation in non-small cell lung cancer
PMID: 36207695
7
ARHGAP25 variants identified as novel genetic loci associated with Alzheimer's disease
PMID: 40691194
8
ARHGAP25 identified as recurrently mutated putative driver in T-large granular lymphocyte leukemia
PMID: 35015834
Disease Associationsⓘ20
hypertensionOpen Targets
0.30Weak
sign or symptomOpen Targets
0.28Weak
colorectal carcinomaOpen Targets
0.08Suggestive
non-small cell lung carcinomaOpen Targets
0.08Suggestive
pancreatic adenocarcinomaOpen Targets
0.07Suggestive
lung cancerOpen Targets
0.07Suggestive
retinitis pigmentosaOpen Targets
0.06Suggestive
osteosarcomaOpen Targets
0.06Suggestive
neoplasmOpen Targets
0.06Suggestive
isolated agammaglobulinemiaOpen Targets
0.05Suggestive
Familial exudative vitreoretinopathyOpen Targets
0.05Suggestive
neutrophil immunodeficiency syndromeOpen Targets
0.05Suggestive
X-linked retinal dysplasiaOpen Targets
0.05Suggestive
choroidal dystrophy, central areolar, 1Open Targets
0.05Suggestive
Recurrent infection due to specific granule deficiencyOpen Targets
0.05Suggestive
Stargardt diseaseOpen Targets
0.05Suggestive
arthritisOpen Targets
0.05Suggestive
Familial drusenOpen Targets
0.04Suggestive
choroideremiaOpen Targets
0.04Suggestive
immunodeficiency 86Open Targets
0.04Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
ARHGAP12Shared pathway60%ARHGAP45Shared pathway50%ARHGAP29Shared pathway40%ARHGAP22Shared pathway40%SH3BP1Shared pathway33%CGNL1Shared pathway33%
Tissue Expression6 tissues
Bone Marrow
100%
Lung
53%
Ovary
23%
Heart
18%
Liver
13%
Brain
6%
Gene Interaction Network
Click a node to explore
ARHGAP25ARHGAP12ARHGAP45ARHGAP29ARHGAP22SH3BP1CGNL1
PROTEIN STRUCTURE
Preparing viewer…
PDB1V89 · NMR
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.63LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.47 [0.36–0.63]
RankingsWhere ARHGAP25 stands among ~20K protein-coding genes
  • #13,604of 20,598
    Most Researched22
  • #4,426of 17,882
    Most Constrained (LOEUF)0.63 · top quartile
Genes detectedARHGAP25
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Machine learning in Alzheimer's disease genetics.
PMID: 40691194
Nat Commun · 2025
1.00
2
Septin2 regulates ARHGAP25-mediated suppression of lamellipodia formation and cell spreading.
PMID: 40205813
FEBS Lett · 2025
0.90
3
Genomic landscape of TCRαβ and TCRγδ T-large granular lymphocyte leukemia.
PMID: 35015834
Blood · 2022
0.80
4
Identification and characterization of ARHGAP24 and ARHGAP25 genes in silico.
PMID: 15254788
Int J Mol Med · 2004
0.70
5
Relationship between the expression of ARHGAP25 and RhoA in non-small cell lung cancer and vasculogenic mimicry.
PMID: 36207695
BMC Pulm Med · 2022
0.60