Biology:ARHGAP29
ARHGAP29 is a gene located on chromosome 1p22 that encodes Rho GTPase activating protein (GAP) 29,[1] a protein that mediates the cyclical regulation of small GTP binding proteins such as RhoA.[2]
Function
ARHGAP29 is expressed in the developing face and may act downstream of IRF6 in craniofacial development.[3]
Structure
ARHGAP29 contains four domains including a coiled-coil region known to interact with Rap2,[4] a C1 domain, the Rho GTPase domain, and a small C-terminal region that interacts with PTPL1.[2]
Clinical Significance
The 1p22 locus containing ARHGAP29 was associated with nonsyndromic cleft lip/palate by genome wide association[5] and meta-analysis.[6] A follow-up study[3] identified rare coding variants including a nonsense and a frameshift variant in patients with nonsyndromic cleft lip/palate. The finding of ARHGAP29's role in craniofacial development was discovered after the adjacent ABCA4 gene lacked functional or expression data to support it as the etiologic gene for nonsyndromic cleft lip/palate even though SNPs in the ABCA4 gene were associated with cleft lip/palate.
References
- ↑ Heasman, SJ; Ridley, AJ (2008). "Mammalian Rho GTPases: new insights into their functions from in vivo studies". Nat Rev Mol Cell Biol 9 (9): 690–701. doi:10.1038/nrm2476. PMID 18719708.
- ↑ 2.0 2.1 Saras, J; Franzen, P; Aspenstrom, P; Hellman, U; Gonez, LJ; Heldin, CH (1997). "A novel GTPase-activating protein for Rho interacts with a PDZ domain of the protein-tyrosine phosphatase PTPL1". J Biol Chem 272 (39): 24333–24338. doi:10.1074/jbc.272.39.24333. PMID 9305890.
- ↑ 3.0 3.1 Leslie, EJ; Mansilla MA; Biggs LC; Schuette K; Bullard S; Cooper M; Dunnwald M; Lidral AC et al. (2012). "Expression and mutation analyses implicate ARHGAP29 as the etiologic gene for the cleft lip with or without cleft palate locus identified by genome-wide association on chromosome 1p22". Birth Defects Research Part A: Clinical and Molecular Teratology 94 (11): 934–942. doi:10.1002/bdra.23076. PMID 23008150.
- ↑ Myagmar, BE; Umikawa, M; Asato, T; Taira, K; Oshiro, M; Hino, A; Takei, K; Uezato, H et al. (2005). "PARG1, a protein-tyrosine phosphatase-associated RhoGAP, as a putative Rap2 effector". Biochem Biophys Res Commun 329 (3): 1046–1052. doi:10.1016/j.bbrc.2005.02.069. PMID 15752761.
- ↑ "A genome-wide association study of cleft lip with and without cleft palate identifies risk variants near MAFB and ABCA4.". Nature Genetics 42 (6): 525–529. 2010. doi:10.1038/ng.580. PMID 20436469.
- ↑ "Genome-wide meta-analyses of nonsyndromic cleft lip with or without cleft palate identify six new risk loci". Nature Genetics 44 (9): 968–971. 2012. doi:10.1038/ng.2360. PMID 22863734.
External links
- ARHGAP29 human gene location in the UCSC Genome Browser.
- ARHGAP29 human gene details in the UCSC Genome Browser.
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