title: Genetic variation in human aquaporins and effects on phenotypes of water homeostasis.
abstract: Aquaporins (AQPs) are critical for the transport of water and small solutes. The 13 known human AQPs are divided into those that transport only water molecules, the "orthodox" AQPs, and those that transport glycerol and small solutes in addition to water, the aquaglyceroporins. In humans, genetic variation in AQPs can cause phenotypes of abnormal water homeostasis. Cellular and human studies of naturally-occurring and synthetic mutations have provided insight into the biology and phenotypes of these variants. Many AQPs have not been well-characterized in terms of the effect of genetic variation on protein function and clinical phenotype. In this review, we discuss functional features in human AQPs and summarize previous studies of naturally-occurring variants. We focus on nonsynonymous mutations since they typically have the greatest effect on function. We develop a map of AQP variation and functional features and examine uncharacterized variants by sequence and structure analysis. We find that variation has been studied relative to the AQP pore, terminal domains, and sites critical to posttranslational modifications. Finally, we propose possible variant-based phenotypes for further research. Other open questions relate to the discovery of novel AQP gene variants as well as their functions and phenotypes.
authors.affiliation: Program in Biological and Medical Informatics, University of California, San Francisco, California 94143, USA.
authors.forename: Marco D
authors.initials: MD
authors.lastname: Sorani
authors.forename: Geoffrey T
authors.initials: GT
authors.lastname: Manley
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Giacomini
mesh_terms: D020346:Aquaporins / Q000737:chemistry / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D010641:Phenotype; D017434:Protein Structure, Tertiary; D014882:Water-Electrolyte Balance / Q000235:genetics*
chemical_list: D020346:Aquaporins