ARHGAP29

ARHGAP29 is a gene located on chromosome 1p22 that encodes Rho GTPase activating protein (GAP) 29, a protein that mediates the cyclical regulation of small GTP binding proteins such as RhoA.

Function
ARHGAP29 is expressed in the developing face and may act downstream of IRF6 in craniofacial development.

Structure
ARHGAP29 contains four domains including a coiled-coil region known to interact with Rap2, a C1 domain, the Rho GTPase domain, and a small C-terminal region that interacts with PTPL1.

Clinical Significance
A combination of genome wide association, rare coding sequence variants, craniofacial specific expression, and interactions with IRF6 support a role for ARHGAP29 to be the likely etiologic gene for nonsyndromic cleft lip/palate. In a recent study, a nonsense variant, frameshift variant, and fourteen missense variants in ARHGAP29 were collectively overrepresented in individuals with nonsyndromic cleft lip/palate compared to unaffected controls. In addition, ARHGAP29 is located at locus 1p22 which was identified by genome wide association of nonsydromic cleft lip/palate. The finding of ARHGAPs role in craniofacial development was discovered after the adjacent ABCA4 gene lacked functional or expression data to support it as the etiologic gene even though SNPs in the ABCA4 gene were associated with cleft lip/palate.