SLC12A3

The SLC12A3 gene provides instructions for making a protein known as NCC. This protein is a sodium chloride co-transporter, which means that it moves charged atoms (ions) of sodium (Na⁺) and chlorine (Cl^-) across cell membranes.

The NCC protein is essential for normal kidney function. It is part of the mechanism by which kidneys reabsorb salt (sodium chloride or NaCl) from the urine back into the bloodstream. The retention of salt affects the body's fluid levels and helps maintain blood pressure.

Gitelman syndrome - caused by mutations in the SLC12A3 gene

More than 140 mutations in the SLC12A3 gene have been identified in people with Gitelman syndrome. Most of these mutations change single protein building blocks (amino acids) in the NCC co-transporter protein. These mutations prevent the protein from reaching the cell membrane or alter the protein's ability to transport sodium and chloride ions. Other mutations in the SLC12A3 gene insert or delete genetic material or lead to the production of an abnormally short, nonfunctional version of the NCC protein.

Mutations in the SLC12A3 gene impair the kidneys' ability to reabsorb salt, leading to the loss of excess salt in the urine (salt wasting). Abnormalities of salt transport also affect the reabsorption of other ions, including ions of potassium, magnesium, and calcium. The resulting imbalance of ions in the body underlies the major features of Gitelman syndrome.

other disorders - associated with the SLC12A3 gene

Some research suggests that normal variants (polymorphisms) in the SLC12A3 gene may help explain differences in blood pressure between people. Certain rare polymorphisms also appear to protect against high blood pressure (hypertension). Changes in the SLC12A3 gene may affect blood pressure by altering the kidneys' ability to reabsorb salt into the bloodstream. However, some studies have not found any association between variants in the SLC12A3 gene and blood pressure.