Identification of a novel human voltage-gated sodium channel alpha subunitgene, SCN12A

We have cloned a cDNA encoding a novel human voltage-gated sodium channel a subunit gene, SCN12A, from human brain. Two alternative splicing variants for SCN12A have been identified. The longest open reading frame of SCN12A e ncodes 1791 amino acid residues. The deduced amino acid sequence of SCN12A shows 37-73% similarity with various other mammalian sodium channels. The p resence of a serine residue (S360) in the SS2 segment of domain I suggests that SCN12A is resistant to tetrodotoxin (TTX), as in the cases of rat Scn1 0a (rPN3/SNS) and rat Scn11a (NaN/SNS2). SCN12A is expressed predominantly in olfactory bulb, hippocampus, cerebellar cortex, spinal cord, spleen, sma ll intestine, and placenta. Although expression level could not be determin ed, SCN12A is also expressed in dorsal root ganglia (DRG), Both neurons and glial cells express SCN12A. SCN12A maps to human chromosome 3p23-p21.3, Th ese results suggest that SCN12A is a tetrodotoxin-resistant (TTX-R) sodium channel expressed in the central nervous system and nonneural tissues, (C) 2000 Academic Press.