KCNJ1

The KCNJ1 gene belongs to a large family of genes that produce potassium channels. These channels, which transport positively charged atoms (ions) of potassium into and out of cells, play a key role in a cell's ability to generate and transmit electrical signals.

The specific function of a potassium channel depends on its protein components and its location in the body. Channels made with the KCNJ1 protein, also known as ROMK, are predominantly found in the kidneys. ROMK is one of several proteins that work together to regulate the movement of ions into and out of kidney cells. In particular, the transport of potassium ions by ROMK is necessary for the normal function of another ion transporter called NKCC2 (which is produced from the SLC12A1 gene). This transporter plays an essential role in the reabsorption of 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.

Bartter syndrome - caused by mutations in the KCNJ1 gene

Several dozen mutations in the KCNJ1 gene have been identified in people with Bartter syndrome type II. This form of the disorder causes severe or life-threatening health problems that become apparent before or soon after birth.

Some of the KCNJ1 gene mutations responsible for Bartter syndrome change single protein building blocks (amino acids) in the ROMK protein. These mutations prevent the protein from reaching the cell membrane or alter the channel's ability to transport potassium ions. Other mutations in the KCNJ1 gene delete amino acids from the protein or lead to the production of an abnormally short, nonfunctional version of ROMK.

A loss of functional ROMK affects the normal activity of the NKCC2 protein, preventing it 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.

other disorders - associated with the KCNJ1 gene

Studies suggest that normal variants (polymorphisms) in the KCNJ1 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 high blood pressure. Changes in the KCNJ1 gene may affect blood pressure by altering the kidneys' ability to reabsorb salt into the bloodstream.