Chromosome location and characterization of the human nicotinic acetylcholine receptor subunit alpha (alpha) 9 (CHRNA9) gene.

The human nicotinic acetylcholine receptor (nAChR) subunit alpha9 gene (CHRNA9) codes for a component of the AChR in hair cells of the inner ear. While no direct evidence presently links this gene to known hearing disorders, it may underlie individual susceptibility to acoustic inner ear injury, and is associated with the autoimmune skin disorder Pemphigus vulgaris. Future studies will depend upon a thorough characterization of the nAChR alpha9 gene. CHRNA9 was localized to chromosome 4p15.1-->p14 by FISH analysis. Radiation hybrid mapping further localized the gene between markers D4S405 and D4S496 (Stanford G3 panel), and between markers WI-3875 and D4S1231 (Genebridge 4 panel), representing a distance of approximately 3.1 cR. The D4S405 marker has been linked to a non-syndromic form of hereditary hearing loss, DFNB-25. The gene contains five exons, separated by four introns. Exons 1-5 are 78, 145, 154, 532 and 877 bases, respectively. Introns 1-4 are 294, 1239, 11517, and 4571 bases, respectively. The intron-exon splice junction sites correlate identically with those of the rat alpha9 gene and are nearly identical to those of the human alpha10 gene. Sequence promoter analysis reveals a number of potential regulatory elements, including several in common with the nAChR alpha10 gene, whose expressed protein is assumed to combine with alpha9 in the inner ear.