A GENE FROM THE XP22.3 REGION SHARES HOMOLOGY WITH VOLTAGE-GATED CHLORIDE CHANNELS

In the framework of constructing a comprehensive transcript map of the human Xp22.3 region, we identified an evolutionary conserved CpG isla nd and cloned the corresponding gene. The predicted 760 amino acid pro tein encoded by this gene contains 12 hydrophobic domains and shares s ignificant sequence and structural similarities with ail the previousl y isolated members of a recently identified family of voltage gated ch loride channels (the 'ClC family'). This gene, termed ClCN4 (Chloride Channel 4), contains at least 10 exons spanning 60 to 80 kb on the X c hromosome. In contrast to most genes isolated from the human Xp22.3 re gion, the ClCN4 gene does not share homology with the Y chromosome and it is conserved in mouse and hamster. Expression studies revealed the presence of a 7.5 kb transcript which is particularly abundant in ske letal muscle and is also detectable in brain and heart. These data sug gest that we have identified a new voltage-gated chloride channel whic h is encoded by a gene located in the distal short arm of the X chromo some.