Title: Exon organization, coding sequence, physical mapping, and polymorphic intragenic markers for the human neuronal sodium channel gene SCN8A.

Authors: N W Plummer, J Galt, J M Jones, D L Burgess, L K Sprunger, D C Kohrman, M H Meisler

Journal, date & volume: Genomics, 1998 Dec 1 , 54, 287-96

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/9828131

Abstract
The voltage-gated sodium channel SCN8A is associated with inherited neurological disorders in the mouse that include ataxia, dystonia, severe muscle weakness, and paralysis. We report the complete coding sequence and exon organization of the human SCN8A gene. The predicted 1980 amino acid residues are distributed among 28 exons, including two pairs of alternatively spliced exons. The SCN8A protein is evolutionarily conserved, with 98.5% amino acid sequence identity between human and mouse. Consensus sites for phosphorylation of serine/threonine and tyrosine residues are present in cyoplasmic loop domains. The polymorphic (CA)n microsatellite marker D12S2211, with PIC = 0.68, was isolated from intron 10C of SCN8A. Single nucleotide polymorphisms in intron 19 and exon 22 were also identified. We localized SCN8A to chromosome band 12q13.1 by physical mapping on a YAC contig. The cDNA clone CSC-1 was reported by others to be a cardiac-specific sodium channel, but sequence comparison demonstrates that it is derived from exon 24 of human SCN8A. The genetic information described here will be useful in evaluating SCN8A as a candidate gene for human neurological disease.