Genomic Organization and Chromosomal Assignment of the Human Voltage-Gated Na⁺ Channel β₁ Subunit Gene (SCN1B)

Voltage-gated sodium (Na⁺) channels are essential for the generation and propagation of action potentials in striated muscle and neuronal tissues. Biochemically, Na⁺ channels consist of a large α subunit and one or two smaller β subunits. The α subunit alone can exhibit all of the functional attributes of a voltage-gated Na⁺ channel, but requires a β₁ subunit for normal inactivation kinetics. While genetic mutations in the skeletal muscle Na⁺ channel α-subunit gene can cause human disease, it is not known whether hereditary defects in the β₁ subunit underlie any inherited syndromes. To help explore this further, we have carried out an analysis of the detailed structure of the human β₁ subunit gene (SCN1B) including the delineation of intron-exon boundaries hy genomic DNA cloning and sequence analysis. The complete coding region of SCN1B is found in ∼9.0 kb of genomic DNA and consists of five exons (72 to 749 bp) and four introns (90 bp to 5.5 kb). Using a 15.9-kb genomic SCN1B clone, we assigned the gene to the long arm of chromosome 19 (19q13.1-q13.2) by fluorescence in situ hybridization. An intragenic polymorphic (TTA)_n repeat that is positioned between two tandem Alu repetitive sequences was also characterized. The (TTA)_n repeat exhibits 5 distinct alleles and a heterozygosity index of 0.59. This information should be useful in evaluating SCN1B as a candidate gene for hereditary disorders affecting membrane excitability.