Amyotrophic Lateral Sclerosis 2 Chromosome Region, Candidate 11 (ALS2CR11)

Als2cr11 is a novel protein, with a probable tetraspanin-like membrane structure, that is localized in photoreceptors and in the postsynaptic outer plexiform layer and that interacts with cytoskeletal proteins. ALS2 contains an ATS1/RCC1-like domain, a RhoGEF domain, and a vacuolar protein sorting 9 (VPS9) domain, all of which are guanine-nucleotide exchange factors that activate members of the Ras superfamily of GTPases. The protein functions as a guanine nucleotide exchange factor for the small GTPase RAB5. The protein localizes with RAB5 on early endosomal compartments, and functions as a modulator for endosomal dynamics. Mutations in this gene result in several forms of juvenile lateral sclerosis and infantile-onset ascending spastic paralysis. Multiple transcript variants encoding different isoforms have been found for this gene.