Molecular cloning and characterization of TRPC5 (HTRP5), the human homologue of a mouse brain receptor-activated capacitative Ca2+ entry channel

A novel human gene, TRPC5, was cloned from the region of Xq23 that contains loci for nonsyndromic mental retardation (MRX47 and MRX35) and two genes, DCX and HPAK3, implicated in two X-linked disorders (LISX and MRX30). Withi n a single YAC, we have determined the order cen-HPAK3(5'-3')-DCX(3'-5')-DX S7012E-TRPC5(3'-5')-ter. TRPC5 encodes a 974-residue novel human protein (1 11.5 kDa predicted mass) and displays 99% homology with mouse TRP5, (MGD-ap roved symbol Trrp5) a novel member of a family of receptor-activated Ca2+ c hannels. It contains eight transmembrane domains, including a putative pore region. A transcript larger than 9.5 kb is observed only in fetal and adul t human brain, with a relatively higher level in the adult human cerebellum . We devised an efficient method, Incorporation PCR SSCP (IPS), for detecti on of gene alterations. Five single-nucleotide variations in the TRPC5 gene were identified in males with mental retardation. However, these were foun d to be polymorphic variants. Exclusive expression of the TRPC5 gene in dev eloping and adult brain suggests a possible role during development and pro vides a candidate gene for instances of mental retardation and other develo pmental defects. (C) 1999 Academic Press.