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10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
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ARHGAP29
Rho GTPase activating protein 29
Chromosome 1 Β· 1p22.1-p21.3
NCBI Gene: 9411Ensembl: ENSG00000137962.14HGNC: HGNC:30207UniProt: A0A2X0U4J5
62PubMed Papers
20Diseases
0Drugs
7Pathogenic Variants
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
cytoplasmPDZ domain bindingprotein-containing complexGTPase activator activitycleft palatecleft liporofacial clefthypertension
✦AI Summary

ARHGAP29 is a Rho GTPase-activating protein that inactivates RhoA, RAC1, and CDC42 by promoting GTP hydrolysis to the GDP-bound state 1. Primary function involves converting active Rho GTPases to inactive forms, with preferential activity toward RhoA 2. Mechanistically, ARHGAP29 operates within multiple signaling contexts: it functions as a RAP2A effector in ECM mechanotransduction, where low matrix stiffness activates RAP2, which stimulates ARHGAP29 to suppress YAP/TAZ through LATS1/2 activation 3. In podocytes, ARHGAP29 expression is YAP/TAZ-dependent and regulates RhoA signaling critical for lamellipodia formation and integrin adhesion dynamics 1. ARHGAP29 transcription is regulated by SMARCA4 (SWI/SNF complex) and TBX21, establishing it as a tumor suppressor in triple-negative breast cancer and colorectal cancer by suppressing RhoA hyperactivation 2, 4. In keratinocytes, ARHGAP29 regulates cell morphology, proliferation, and migration through RhoA/ROCK signaling, though it is dispensable for in vivo wound healing 5. Disease relevance includes nonsyndromic cleft lip/palate, where ARHGAP29 variants impair craniofacial development through IRF6 pathway interactions 6, and glioblastoma progression through morphological phenotype switching 7.

Sources cited
1
ARHGAP29 is YAP/TAZ-dependently expressed as a podocyte RhoGAP that regulates RhoA activation, lamellipodia formation, and integrin adhesion complexes
PMID: 37443829
2
RAP2 activates ARHGAP29 at low ECM stiffness to stimulate LATS1/2 and inhibit YAP/TAZ in mechanotransduction
PMID: 30135582
3
SMARCA4 transcriptionally activates ARHGAP29 to suppress RhoA signaling and inhibit triple-negative breast cancer metastasis
PMID: 39992701
4
TBX21 upregulates ARHGAP29 to inhibit GSK3Ξ² phosphorylation and suppress colorectal cancer cell metastasis
PMID: 39744435
5
ARHGAP29 regulates keratinocyte morphology, proliferation, and migration in vitro through RhoA/ROCK signaling but is dispensable for in vivo wound healing
PMID: 39560169
6
ARHGAP29 variants are implicated in nonsyndromic cleft lip/palate etiology with craniofacial expression and IRF6 pathway interactions
PMID: 23008150
7
ARHGAP29 regulates transitional morphological states in glioma through Src kinase signaling and GSK-3 activity affecting phenotype switching
PMID: 40053455
Disease Associationsβ“˜20
cleft palateOpen Targets
0.61Moderate
cleft lipOpen Targets
0.60Moderate
orofacial cleftOpen Targets
0.58Moderate
hypertensionOpen Targets
0.37Weak
neurodegenerative diseaseOpen Targets
0.35Weak
HepatitisOpen Targets
0.32Weak
alcohol drinkingOpen Targets
0.31Weak
essential hypertensionOpen Targets
0.31Weak
breast carcinomaOpen Targets
0.30Weak
drug allergyOpen Targets
0.29Weak
food allergyOpen Targets
0.25Weak
digestive system neoplasmOpen Targets
0.25Weak
external ear diseaseOpen Targets
0.21Weak
genetic disorderOpen Targets
0.19Weak
isolated cleft palateOpen Targets
0.12Weak
breast cancerOpen Targets
0.09Suggestive
renal cell carcinomaOpen Targets
0.07Suggestive
bifid uvulaOpen Targets
0.05Suggestive
isolated asymptomatic elevation of creatine phosphokinaseOpen Targets
0.05Suggestive
white sponge nevus 1Open Targets
0.05Suggestive
Pathogenic Variants7
NM_004815.4(ARHGAP29):c.2547_2550dup (p.Ile851fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 851
NM_004815.4(ARHGAP29):c.1939C>T (p.Arg647Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 647
NM_004815.4(ARHGAP29):c.2481-1G>ALikely pathogenic
ARHGAP29-related disorder
β˜…β˜†β˜†β˜†2022
NM_004815.4(ARHGAP29):c.2109+1G>APathogenic
Nonsyndromic cleft lip with or without cleft palate
β˜…β˜†β˜†β˜†2016
NM_004815.4(ARHGAP29):c.1475C>A (p.Ser492Ter)Pathogenic
Nonsyndromic cleft lip with or without cleft palate
β˜…β˜†β˜†β˜†2016β†’ Residue 492
NM_004815.4(ARHGAP29):c.698-1G>CPathogenic
Nonsyndromic cleft lip with or without cleft palate
β˜…β˜†β˜†β˜†2016
NM_004815.4(ARHGAP29):c.1920+1G>APathogenic
Nonsyndromic cleft lip with or without cleft palate
β˜…β˜†β˜†β˜†
View on ClinVar β†—
Related Genes
RAP2AProtein interaction96%RASIP1Protein interaction95%PTPN13Protein interaction90%PARGProtein interaction86%RHOAProtein interaction82%CDC42Protein interaction80%
Tissue Expression6 tissues
Heart
100%
Lung
76%
Liver
64%
Ovary
37%
Brain
15%
Bone Marrow
3%
Gene Interaction Network
Click a node to explore
ARHGAP29RAP2ARASIP1PTPN13PARGRHOACDC42
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted Β· UniProt Q52LW3
View on AlphaFold β†—
Constraintβ“˜
LOEUFβ“˜
0.45Moderately Constrained
pLIβ“˜
1.00Intolerant
Observed/Expected LoF0.34 [0.26–0.45]
RankingsWhere ARHGAP29 stands among ~20K protein-coding genes
  • #7,429of 20,598
    Most Researched62
  • #3,209of 5,498
    Most Pathogenic Variants7
  • #2,490of 17,882
    Most Constrained (LOEUF)0.45 Β· top quartile
Genes detectedARHGAP29
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
RAP2 mediates mechanoresponses of the Hippo pathway.
PMID: 30135582
Nature Β· 2018
1.00
2
A YAP/TAZ-ARHGAP29-RhoA Signaling Axis Regulates Podocyte Protrusions and Integrin Adhesions.
PMID: 37443829
Cells Β· 2023
0.90
3
SMARCA4 Inhibits Breast Cancer Progression and Metastasis through RHOA Suppression.
PMID: 39992701
Cancer Res Β· 2025
0.80
4
ARHGAP12 and ARHGAP29 exert distinct regulatory effects on switching between two cell morphological states through GSK-3 activity.
PMID: 40053455
Cell Rep Β· 2025
0.70
5
TBX21 inhibits colorectal cancer metastasis through ARHGAP29/GSK3Ξ² inhibitory signaling- and MYCT1/ZO-1 signaling-dependent manner.
PMID: 39744435
Int J Biol Sci Β· 2025
0.60