SLC12A1

More than 40 mutations in the SLC12A1 gene have been identified in people with Bartter syndrome type I. This form of the disorder is very severe, causing life-threatening health problems that become apparent before or soon after birth.

Most of the SLC12A1 gene mutations responsible for Bartter syndrome change single protein building blocks (amino acids) in the NKCC2 protein. Other mutations delete amino acids from the protein or lead to the production of an abnormally short version of the NKCC2 protein. Each of the known mutations prevents the NKCC2 protein from transporting ions into kidney cells. As a result, the kidneys cannot reabsorb salt normally and excess salt is lost through the urine (salt wasting). The abnormal salt loss disrupts the normal balance of sodium, potassium, and other ions in the body. These imbalances underlie the major features of Bartter syndrome.

Studies suggest that normal variants (polymorphisms) in the SLC12A1 gene may help explain variations in blood pressure seen in different people. Certain rare polymorphisms appear to protect against high blood pressure (hypertension), and researchers speculate that other genetic variants might increase the risk of developing high blood pressure. Changes in the SLC12A1 gene may affect blood pressure by altering the kidneys' ability to reabsorb salt into the bloodstream.