Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2004 Sep;36(9):989-93.
doi: 10.1038/ng1414. Epub 2004 Aug 15.

Mutations in a member of the Ras superfamily of small GTP-binding proteins causes Bardet-Biedl syndrome

Yanli Fan  1 , Muneer A Esmail, Stephen J Ansley, Oliver E Blacque, Keith Boroevich, Alison J Ross, Susan J Moore, Jose L Badano, Helen May-Simera, Deanna S Compton, Jane S Green, Richard Alan Lewis, Mieke M van Haelst, Patrick S Parfrey, David L Baillie, Philip L Beales, Nicholas Katsanis, William S Davidson, Michel R Leroux
Affiliations

Mutations in a member of the Ras superfamily of small GTP-binding proteins causes Bardet-Biedl syndrome

Yanli Fan et al. Nat Genet. 2004 Sep.

Abstract

RAB, ADP-ribosylation factors (ARFs) and ARF-like (ARL) proteins belong to the Ras superfamily of small GTP-binding proteins and are essential for various membrane-associated intracellular trafficking processes. None of the approximately 50 known members of this family are linked to human disease. Using a bioinformatic screen for ciliary genes in combination with mutational analyses, we identified ARL6 as the gene underlying Bardet-Biedl syndrome type 3, a multisystemic disorder characterized by obesity, blindness, polydactyly, renal abnormalities and cognitive impairment. We uncovered four different homozygous substitutions in ARL6 in four unrelated families affected with Bardet-Biedl syndrome, two of which disrupt a threonine residue important for GTP binding and function of several related small GTP-binding proteins. Analysis of the Caenorhabditis elegans ARL6 homolog indicates that it is specifically expressed in ciliated cells, and that, in addition to the postulated cytoplasmic functions of ARL proteins, it undergoes intraflagellar transport. These findings implicate a small GTP-binding protein in ciliary transport and the pathogenesis of a pleiotropic disorder.

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

Publication types

Associated data

LinkOut - more resources