ATP7A

The ATP7A gene provides instructions for making a protein that is important for regulating copper levels in the body. This protein is found in most cells except liver cells. In the small intestine, the ATP7A protein helps control the absorption of copper from food. In other cells, the ATP7A protein has a dual role and shuttles between two cellular locations. The protein normally resides in a cell structure called the Golgi apparatus, which modifies newly produced proteins, including enzymes. In the Golgi apparatus, the ATP7A protein supplies copper to certain enzymes that are critical for the structure and function of bone, skin, hair, blood vessels, and the nervous system. If copper levels in the cell environment are elevated, however, the ATP7A protein moves to the cell membrane and eliminates excess copper from the cell.

Menkes syndrome - caused by mutations in the ATP7A gene

Researchers have identified more than 100 ATP7A mutations that cause Menkes syndrome and occipital horn syndrome (a less severe form of Menkes syndrome). Many of these mutations delete part of the gene and likely produce a shortened ATP7A protein that is unable to transport copper. Other mutations insert additional DNA building blocks (base pairs) or use the wrong building blocks, which leads to ATP7A proteins that do not function properly.

Altered proteins that result from ATP7A mutations impair the absorption of copper from food, fail to supply copper to certain enzymes, or get stuck in the cell membrane and are unable to shuttle back and forth from the Golgi apparatus. As a result of the disrupted activity of the ATP7A protein, copper is poorly distributed to cells in the body. Copper accumulates in some tissues, such as the small intestine and kidneys, while the brain and other tissues have unusually low levels. The decreased supply of copper can reduce the activity of numerous copper-containing enzymes that are necessary for the structure and function of bone, skin, hair, blood vessels, and the nervous system.