Detailed analyses of transcripts encoding various isoforms of the huma
n potassium (K-1, inward rectifying) channel ROM-K (also referred to a
s K(ir)1.1) revealed the existence of at least five distinct transcrip
ts [Shuck et al., J. Biol. Chem. 269 (1994) 24261-24270]. These five h
ROM-K transcripts appear to be the result of alternative splicing of f
ive exons. The nucleotide sequence of the genomic DNA including and sp
anning these exons (the KCNJ1 locus) was obtained directly from lambda
and P1 clones (a total of 40 kb). The organization of the hKCNJ1 gene
was determined by combining this sequence information with data obtai
ned from primer extension and RT-PCR experiments. It appears that the
hKCNJ1 gene utilizes multiple promoters, with promoter-like elements f
ound 5' of exons 1, 4, or 5. The promoter 5' of exon 5 was unexpected;
thus, it appears that the hKCNJ1 gene is capable of producing six dis
tinct hROM-K transcripts via the use of three promoters and alternativ
e splicing of five exons. Comparisons of the rat and human ROM-K cDNA
sequences find human homologs (orthologs) for two of the three distinc
t rROM-K transcripts. A search of the complete human KCNJ1 sequence wi
th the exon sequence that defines the other rROM-K transcript located
a region of shared nucleotides, a putative sixth exon, in the hKCNJ1 g
ene. This finding suggests that the rKCNJ1 gene may contain an exon th
at is no longer or infrequently used in transcripts derived from the h
KCNJ1 gene.