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SLC12A1 gene

solute carrier family 12 member 1
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Normal Function

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.

Health Conditions Related to Genetic Changes

Bartter syndrome

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.

More About This Health Condition

Other disorders

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.

Other Names for This Gene

  • 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

Additional Information & Resources

Tests Listed in the Genetic Testing Registry

Scientific Articles on PubMed

Research Resources

References

  • Gamba G, Friedman PA. Thick ascending limb: the Na(+):K (+):2Cl (-) co-transporter, NKCC2, and the calcium-sensing receptor, CaSR. Pflugers Arch. 2009 May;458(1):61-76. doi: 10.1007/s00424-008-0607-1. Epub 2008 Nov 4. Review. Citation on PubMed or Free article on PubMed Central
  • Haas M. The Na-K-Cl cotransporters. Am J Physiol. 1994 Oct;267(4 Pt 1):C869-85. Review. Citation on PubMed
  • Ji W, Foo JN, O'Roak BJ, Zhao H, Larson MG, Simon DB, Newton-Cheh C, State MW, Levy D, Lifton RP. Rare independent mutations in renal salt handling genes contribute to blood pressure variation. Nat Genet. 2008 May;40(5):592-599. doi: 10.1038/ng.118. Epub 2008 Apr 6. Citation on PubMed or Free article on PubMed Central
  • Simon DB, Karet FE, Hamdan JM, DiPietro A, Sanjad SA, Lifton RP. Bartter's syndrome, hypokalaemic alkalosis with hypercalciuria, is caused by mutations in the Na-K-2Cl cotransporter NKCC2. Nat Genet. 1996 Jun;13(2):183-8. Citation on PubMed
  • Starremans PG, Kersten FF, Knoers NV, van den Heuvel LP, Bindels RJ. Mutations in the human Na-K-2Cl cotransporter (NKCC2) identified in Bartter syndrome type I consistently result in nonfunctional transporters. J Am Soc Nephrol. 2003 Jun;14(6):1419-26. Citation on PubMed
  • Vargas-Poussou R, Feldmann D, Vollmer M, Konrad M, Kelly L, van den Heuvel LP, Tebourbi L, Brandis M, Karolyi L, Hebert SC, Lemmink HH, DeschĂȘnes G, Hildebrandt F, Seyberth HW, Guay-Woodford LM, Knoers NV, Antignac C. Novel molecular variants of the Na-K-2Cl cotransporter gene are responsible for antenatal Bartter syndrome. Am J Hum Genet. 1998 Jun;62(6):1332-40. Citation on PubMed or Free article on PubMed Central
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