CDNA, GENE STRUCTURE, AND CHROMOSOMAL LOCALIZATION OF HUMAN GAR1 (CNCG3L), A HOMOLOG OF THE 3RD SUBUNIT OF BOVINE PHOTORECEPTOR CGMP-GATED CHANNEL

A unique glutamic acid-rich protein was previously identified in bovin e rod photoreceptors (Sugimoto et al., 1991, Proc. Natl, Acad. Sci. US A 88: 3116-3119) and later suggested to be a third subunit (gamma) of the rod cCMP-gated cation channel (Chen et al., 1994, Proc. Natl. Acad . Sci. USA 91: 11757-11761). Here, we report on the characterization o f the GAR1 gene encoding a human homolog of bovine gamma. Sequence ana lysis of cDNA clones encoding human gamma revealed an open reading fra me predicting a protein of 299 amino acids (similar to 32 kDa), half t he size of the bovine gamma subunit. Comparison of the N-terminal half of bovine gamma with the predicted human gamma sequence revealed 90% identity within the first 31 amino acids, and only 60% homology was fo und throughout the remainder of the protein sequence. As in bovine gam ma, the predicted isoelectric point of the human protein is very acidi c despite the absence of the bovine C-terminal glutamic acid-rich doma in. The integrity of the cDNA sequence was confirmed by analysis of se veral overlapping genomic clones that span the GAR1 gene. The protein coding region of the gene consists of 12 exons spanning similar to 11 kb with exon sequence identical to that of the cDNA clones. PCR of som atic cell hybrid DNA with primer pairs that amplify a portion of the G AR1 gene (locus designation CNCG3L) demonstrate localization to chromo some 16. The location of the gene was further delimited by fluorescenc e in situ hybridization placing the gene at 16q13. Within this same re gion linkage was previously reported with Bardet-Biedl syndrome, a dis ease involving retinal degeneration, suggesting that GAR1 is a good ca ndidate gene for this disorder. (C) 1995 Academic Press, Inc.