K+channels are essential for a variety of cellular functions in both excitable and nonexcitable cells, and K+channel gene alteration has been recently described in cardiac and neurological disorders. To explore further the relations between hereditary human diseases and K+channels, we isolated from a human cosmid library the gene encoding the inwardly rectifying K+channel α-subunit Kir 2.2 (KCNJ12). PCR analysis performed on this clone indicates that the entire open reading frame is contained in one unique exon. A polymorphic (CA)16sequence was localized 2.2 kb upstream of the ATG start codon. Fluorescencein situhybridization on human metaphases assigns the gene to band 17p11.1. The implication of a deletion of the Kir 2.2 gene in the Smith–Magenis syndrome, which is also localized at 17p11, is unlikely since a Kir 2.2-linked microsatellite sequence could be amplified from the DNA of a Smith–Magenis syndrome affected patient bearing a 17p interstitial deletion.