ATP-sensitive K+ (KATP) channels are implicated in the coupling of metabolic energy to membrane potential, thereby regulating many essential cell functions. Here, we demonstrate that a subunit of human KATP channel, KCNJ8/Kir6.1, is expressed preferentially in the human heart. Somatic cell-hybrid mapping and fluorescence in-situ hybridization (FISH) localize human KCNJ8 to the short arm of human chromosome 12, at 12p12. Partial characterization of the human Kir6. 1 gene demonstrates that there is one large intron in the coding region and at least two additional introns in the 5' untranslated region resulting in transcripts that have differential expression in human tissues examined. Our studies provide information on the complexity of the Kir6.1 transcript in the 5' UTR that may be useful for future investigations on the tissue-specific regulation and function of this KATP channel gene.