Genetics of ATP-binding cassette transporters

The ATP-binding cassette (ABC) superfamily consists of membrane proteins that transport a wide variety of substrates across membranes. Mutations in ABC transporters cause or contribute to a number of different Mendelian disorders, including adrenoleukodystrophy, cystic fibrosis, retinal degeneration, cholesterol, and bile transport defects. In addition, the genes are involved in an increasing number of complex disorders. The proteins play essential roles in the protection of organisms from toxic metabolites and compounds in the diet and are involved in the transport of compounds across the intestine, blood-brain barrier, and the placenta. There are 48 ABC genes in the human genome divided into seven subfamilies based in gene structure, amino acid alignment, and phylogenetic analysis. These seven subfamilies are found in all other sequenced eukaryotic genomes and are of ancient origin. Further characterization of all ABC genes from humans and model organisms will lead to additional insights into normal physiology and human disease.