The Human Aquaporin Gene Family

Aquaporin (AQP) water channel proteins are responsible for osmotically driven water transport across cell membranes of mammalian tissues, lower animals and plants. Recently, the cDNAs encoding ten mammalian AQPs with widely different tissue expression patterns have been cloned. This article reviews the recent progress in molecular cloning, gene organization, chromosomal localization and mutations of human AQPs. Sequence and genomic structure analyses indicate that the AQP gene family contains at least three subgroup. AQPs 0, 1, 2, 4, 5 and 6 have 40-50 percent amino acid homology and their genes contain 4 exons. AQPs 3, 7 and 9 belong to distinct subfamily that contains 6 exons and functions as transporters of small neutral solutes as well as water. AQP8 belongs to the third subgroup with unique exon-intron boundaries. Mutations in AQP2 cause human nephrogenic diabetes insipidus (NDI). The understanding of AQP genetics is important in studying the pathogenesis of diseases related AQP disorders and finding new targets for therapy.