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 nonsydromic 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 nonsydromic 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 nonsydromic 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.
- ↑ 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; Marazita ML; Beaty TH; Murray JC (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: 934–942. doi:10.1002/bdra.23076. PMC 3501616. PMID 23008150.
- ↑ Myagmar, BE; Umikawa, M; Asato, T; Taira, K; Oshiro, M; Hino, A; Takei, K; Uezato, H; Kariya, K (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.
- ↑ Beaty TH, Murray JC, Marazita ML, Munger RG, Ruczinski I, Hetmanski JB, Liang KY, Wu T, Murray T, Fallin MD, Redett RA, Raymond G, Schwender H, Jin SC, Cooper ME, Dunnwald M, Mansilla MA, Leslie E, Bullard S, Lidral AC, Moreno LM, Menezes R, Vieira AR, Petrin A, Wilcox AJ, Lie RT, Jabs EW, Wu-Chou YH, Chen PK, Wang H, Ye X, Huang S, Yeow V, Chong SS, Jee SH, Shi B, Christensen K, Melbye M, Doheny KF, Pugh EW, Ling H, Castilla EE, Czeizel AE, Ma L, Field LL, Brody L, Pangilinan F, Mills JL, Molloy AM, Kirke PN, Scott JM, Arcos-Burgos M, Scott AF (2010). "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. doi:10.1038/ng.580. PMC 2941216. PMID 20436469.
- ↑ Ludwig KU, Mangold E, Herms S, Nowak S, Reutter H, Paul A, Becker J, Herberz R, AlChawa T, Nasser E, Böhmer AC, Mattheisen M, Alblas MA, Barth S, Kluck N, Lauster C, Braumann B, Reich RH, Hemprich A, Pötzsch S, Blaumeiser B, Daratsianos N, Kreusch T, Murray JC, Marazita ML, Ruczinski I, Scott AF, Beaty TH, Kramer FJ, Wienker TF, Steegers-Theunissen RP, Rubini M, Mossey PA, Hoffmann P, Lange C, Cichon S, Propping P, Knapp M, Nöthen MM (2012). "Genome-wide meta-analyses of nonsyndromic cleft lip with or without cleft palate identify six new risk loci". Nature Genetics. 44 (9): 968–971. doi:10.1038/ng.2360. PMC 3598617. PMID 22863734.
External links
- ARHGAP29 human gene location in the UCSC Genome Browser.
- ARHGAP29 human gene details in the UCSC Genome Browser.