Identification and characterization of the human ortholog of rat STXBP1, a protein implicated in vesicle trafficking and neurotransmitter release

In a screen designed to identify genes expressed preferentially in retina, we identified a cDNA encoding the human ortholog of rat STXBP1 (n- Sec1, Munc-181, rbSec1), a protein implicated in vesicle trafficking and neurotransmitter release. This protein also has similarity to Drosophila Rop (64% aa identity) and Caenorhabditis elegans UNC-18 (58% aa identity). The major human cDNA encodes a protein of 594 amino acids which has 100% amino acid identity with its rat and murine counterparts. Additionally, there is an alternative splice form in humans, arising from the inclusion of an additional exon, which encodes a protein of 603 amino acids and is also 100% identical to the corresponding rat isoform. We found expression of the shorter eDNA in all tissues and cell lines we examined with highest levels in retina and cerebellum. By RTPCR analysis, we found expression of the longer eDNA in neural tissues only. We mapped the structural gene to 9q34.1, a region without obvious candidate phenotypes. However, due to its evolutionary conservation and abundant expression in retina and brain, STXBP1 should be considered a candidate gene for retinal and/ or neural disorders mapping to 9q34.1.