The human ATP-binding cassette (ABC) transporter superfamily

The ATP-binding cassette (ABC) transporter superfamily contains membrane pr oteins that translocate a variety of substrates across extra- and intra-cel lular membranes. Genetic variation in these genes is the cause of or contri butor to a wide variety of human disorders with Mendelian and complex inher itance, including cystic Fibrosis, neurological disease, retinal degenerati on, cholesterol and bile transport defects, anemia, and drug response. Cons ervation of the ATP-binding domains of these genes has allowed the identifi cation of new members of the superfamily based on nucleotide and protein se quence homology. Phylogenetic analysis is used to divide all 48 known ABC t ransporters into seven distinct subfamilies of proteins. For each gene, the precise map location on human chromosomes, expression data, and localizati on within the superfamily has been determined. These data allow predictions to be made as to potential functions or disease phenotypes associated with each protein. In this paper, we review the current state of knowledge on a ll human ABC genes in inherited disease and drug resistance. In addition, t he availability of the complete Drosophila genome sequence allows the compa rison of the known human ABC genes with those in the fly genome. The combin ed data enable an evolutionary analysis of the superfamily. Complete charac terization of all ABC from the human genome and from model organisms will l ead to important insights into the physiology and the molecular basis of ma ny human disorders.