AQP2

The AQP2 gene provides instructions for making a protein called aquaporin 2. This protein forms a channel that carries water molecules across cell membranes. It is found in the kidneys in structures called collecting ducts, which are a series of small tubes that reabsorb water from the kidneys into the bloodstream.

The aquaporin 2 water channel plays an essential role in maintaining the body's water balance. The placement of these channels is controlled by a hormone called vasopressin or antidiuretic hormone (ADH). When a person's fluid intake is low or when a lot of fluid is lost (for example, through sweating), the body produces more ADH. This hormone triggers chemical reactions that ultimately insert aquaporin 2 water channels into the membrane of collecting duct cells. These channels allow water to be reabsorbed into the bloodstream, which makes the urine more concentrated. When fluid intake is adequate, less ADH is produced. Without signals from ADH, aquaporin 2 water channels are removed from the membrane of collecting duct cells. At these times, less water is reabsorbed into the bloodstream and the urine is more dilute.

nephrogenic diabetes insipidus - caused by mutations in the AQP2 gene

At least 40 mutations in the AQP2 gene have been identified in people with nephrogenic diabetes insipidus.

Most of the known AQP2 gene mutations cause the aquaporin 2 protein to be misfolded into an incorrect 3-dimensional shape. The misfolded protein is trapped within the cell, where it is unable to reach the cell membrane to transport water molecules. A few mutations result in the production of functional aquaporin 2 water channels, but these channels are misrouted within the cell and do not reach the cell membrane.

If aquaporin 2 water channels are not inserted into the membrane of collecting duct cells, the kidneys are unable to respond to signals from ADH. As a result, collecting ducts do not reabsorb water as they should, and the body makes excessive amounts of urine. These problems with water balance are characteristic of nephrogenic diabetes insipidus.