Адам ағзасындағы ATP7A гені және Менкес ауруы

Protein coding gene in humans

ATP7A, also known as Menkes' protein (MNK), is a copper transporting P type ATPase which uses the energy arising from ATP hydrolysis to transport Cu(I) across cell membranes. The ATP7A protein is a transmembrane protein and is expressed in the intestine and all tissues except liver. In the intestine, ATP7A regulates Cu(I) absorption in the human body by transporting Cu(I) from the small intestine into the blood. In other tissues, ATP7A shuttles between the Golgi apparatus and the cell membrane to maintain proper Cu(I) concentrations (since there is no free Cu(I) in the cell, Cu(I) ions are all tightly bound) in the cell and provides certain enzymes with Cu(I) (e. g. peptidyl α monooxygenase, tyrosinase, and lysyl oxidase). The X linked, inherited, lethal genetic disorder of the ATP7A gene causes Menkes disease, a copper deficiency resulting in early childhood death.

ATP7A is important for regulating copper Cu(I) in mammals. Researchers have identified different ATP7A mutations that cause Menkes disease and occipital horn syndrome (OHS), the milder form of Menkes disease. Many of these mutations delete part of the gene and are predicted to produce a shortened ATP7A protein that is unable to transport Cu(I). Other mutations insert additional DNA base pairs or use the wrong base pairs, which leads to ATP7A proteins that do not function properly. A comprehensive resource of clinically annotated genetic variants in ATP7A gene has been made available confirming to the American College of Medical Genetics and Genomics guidelines for interpretation of sequence variants.

A proton pump inhibitor, Omeprazole, has been shown to block ATP7A, in addition to its more established role of blocking ATP4A.