SLC12A1 gene

solute carrier family 12 member 1

The SLC12A1 gene provides instructions for making a protein known as NKCC2. This protein is a Na+/K+/2Cl- cotransporter, which means that it moves charged atoms (ions) of sodium (Na+), potassium (K+), and chlorine (Cl-) into cells.

The NKCC2 protein is essential for normal kidney function. The NKCC2 protein works with other transport proteins to regulate the movement of ions into and out of kidney cells. Together, these proteins provide 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.

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.

Cytogenetic Location: 15q21.1, which is the long (q) arm of chromosome 15 at position 21.1

Molecular Location: base pairs 48,206,302 to 48,304,078 on chromosome 15 (Homo sapiens Updated Annotation Release 109.20200522, GRCh38.p13) (NCBI)

Cytogenetic Location: 15q21.1, which is the long (q) arm of chromosome 15 at position 21.1
  • BSC1
  • bumetanide-sensitive sodium-(potassium)-chloride cotransporter 2
  • kidney-specific Na-K-Cl symporter
  • Na-K-2Cl cotransporter
  • NKCC2
  • S12A1_HUMAN
  • solute carrier family 12 (sodium/potassium/chloride transporter), member 1
  • solute carrier family 12 (sodium/potassium/chloride transporters), member 1