title: Cloning and characterization of a novel rho-type GTPase-activating protein gene (ARHGAP6) from the critical region for microphthalmia with linear skin defects.
abstract: Microphthalmia with linear skin defects syndrome (MLS) is an X-linked dominant, male-lethal disorder associated with chromosomal rearrangements that result in deletions of the distal short arm of the X chromosome. In an effort to isolate expressed sequences from the 500-kb MLS critical region in Xp22.3, exons were trapped from 14 overlapping cosmids. Using exon connection followed by cDNA library screening, we identified a 2.4-kb contig of cDNA library screening 170 kb of genomic sequence in the MLS deletion region. Northern analysis of this cDNA detected a prominent approximately 4.2-kb transcript and a less abundant approximately 6-kb transcript in all tissues examined, with additional transcripts in skeletal muscle. Sequence analysis revealed a coding region of 601 amino acids contained in 12 exons, with a splice variant isoform of 495 amino acids. The predicted protein sequence of the gene, named ARHGAP6, contains homology to the GTPase-activating (GAP) domain of the rhoGAP family of proteins, which has been implicated in the regulation of actin polymerization at the plasma membrane in several cellular processes. The possible role of the ARHGAP6 protein in the pathogenesis of MLS is discussed.
authors.affiliation: Department of Molecular and Human Genetics, Howard Hughes Medical Institute, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: L
authors.initials: L
authors.lastname: Schaefer
authors.forename: S
authors.initials: S
authors.lastname: Prakash
authors.forename: H Y
authors.initials: HY
authors.lastname: Zoghbi
mesh_terms: D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D017124:Conserved Sequence; D003360:Cosmids / Q000235:genetics; D019143:Evolution, Molecular; D005091:Exons; D019204:GTP-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D020690:GTPase-Activating Proteins; D005821:Genetic Techniques; D006801:Humans; D008850:Microphthalmos / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D012871:Skin Diseases / Q000235:genetics*; D013577:Syndrome; D014018:Tissue Distribution; D018909:src Homology Domains
chemical_list: C109971:ARHGAP6 protein, human; D020690:GTPase-Activating Proteins; C085379:rho GTPase-activating protein; D019204:GTP-Binding Proteins