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). Within a single YAC, we have determined the order cen-HPAK3(5'-3')-DCX(3'-5')-DXS7012E-TRPC5(3'-5' )-ter. TRPC5 encodes a 974-residue novel human protein (111.5 kDa predicted mass) and displays 99% homology with mouse TRP5, (MGD-approved symbol Trrp5) a novel member of a family of receptor-activated Ca2+ channels. It contains eight transmembrane domains, including a putative pore region. A transcript larger than 9.5 kb is observed only in fetal and adult human brain, with a relatively higher level in the adult human cerebellum. We devised an efficient method, Incorporation PCR SSCP (IPS), for detection of gene alterations. Five single-nucleotide variations in the TRPC5 gene were identified in males with mental retardation. However, these were found to be polymorphic variants. Exclusive expression of the TRPC5 gene in developing and adult brain suggests a possible role during development and provides a candidate gene for instances of mental retardation and other developmental defects.
Sossey-Alaoui
K
K
J. C. Self Research Institute of Human Genetics, Greenwood Genetic Center, Greenwood, South Carolina 29646, USA.
Lyon
J A
JA
Jones
L
L
Abidi
F E
FE
Hartung
A J
AJ
Hane
B
B
Schwartz
C E
CE
Stevenson
R E
RE
Srivastava
A K
AK
D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain; D015220:Calcium Channels / Q000235:genetics* / Q000302:isolation & purification; D027682:Cation Transport Proteins; D003001:Cloning, Molecular; D004252:DNA Mutational Analysis; D000089662:Doublecortin Protein; D005091:Exons; D015870:Gene Expression; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics; D051379:Mice; D008969:Molecular Sequence Data; D010802:Phylogeny; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D018807:Polymorphism, Single-Stranded Conformational; D016415:Sequence Alignment; D050052:TRPC Cation Channels; D014960:X Chromosome / Q000235:genetics
D015220:Calcium Channels; D027682:Cation Transport Proteins; C000714847:Dcx protein, mouse; D000089662:Doublecortin Protein; D050052:TRPC Cation Channels; C491780:TRPC5 protein, human; C112021:Trpc5 protein, mouse