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Genetics Home Reference: your guide to understanding genetic conditions
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SLC12A1

Reviewed February 2011

What is the official name of the SLC12A1 gene?

The official name of this gene is “solute carrier family 12 (sodium/potassium/chloride transporters), member 1.”

SLC12A1 is the gene's official symbol. The SLC12A1 gene is also known by other names, listed below.

What is the normal function of the SLC12A1 gene?

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.

Does the SLC12A1 gene share characteristics with other genes?

The SLC12A1 gene belongs to a family of genes called SLC (solute carriers).

A gene family is a group of genes that share important characteristics. Classifying individual genes into families helps researchers describe how genes are related to each other. For more information, see What are gene families? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genefamilies) in the Handbook.

How are changes in the SLC12A1 gene related to health conditions?

Bartter syndrome - caused by mutations in the SLC12A1 gene

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.

other disorders - associated with the SLC12A1 gene

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.

Where is the SLC12A1 gene located?

Cytogenetic Location: 15q15-q21.1

Molecular Location on chromosome 15: base pairs 48,498,497 to 48,596,274

The SLC12A1 gene is located on the long (q) arm of chromosome 15 between positions 15 and 21.1.

The SLC12A1 gene is located on the long (q) arm of chromosome 15 between positions 15 and 21.1.

More precisely, the SLC12A1 gene is located from base pair 48,498,497 to base pair 48,596,274 on chromosome 15.

See How do geneticists indicate the location of a gene? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genelocation) in the Handbook.

Where can I find additional information about SLC12A1?

You and your healthcare professional may find the following resources about SLC12A1 helpful.

  • Genetic Testing Registry - Repository of genetic test information

    • GTR: Genetic tests for SLC12A1 (http://www.ncbi.nlm.nih.gov/gtr/tests/?term=6557%5Bgeneid%5D)

You may also be interested in these resources, which are designed for genetics professionals and researchers.

  • PubMed - Recent literature (http://www.ncbi.nlm.nih.gov/pubmed?term=(SLC12A1%5BTIAB%5D)%20OR%20(NKCC2%5BTIAB%5D)%20AND%20((Genes%5BMH%5D)%20OR%20(Genetic%20Phenomena%5BMH%5D))%20AND%20english%5Bla%5D%20AND%20human%5Bmh%5D%20AND%20%22last%201800%20days%22%5Bdp%5D)
  • OMIM - Genetic disorder catalog (http://omim.org/entry/600839)

  • Research Resources - Tools for researchers

    • Entrez Gene (http://www.ncbi.nlm.nih.gov/gene/6557)
    • GeneCards (http://www.genecards.org/cgi-bin/carddisp.pl?id_type=entrezgene&id=6557)
    • HUGO Gene Nomenclature Committee (http://www.genenames.org/data/hgnc_data.php?hgnc_id=10910)

What other names do people use for the SLC12A1 gene or gene products?

  • 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 member 1

See How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What glossary definitions help with understanding SLC12A1?

acids ; carrier ; chloride ; gene ; hypertension ; ions ; kidney ; Na ; NaCl ; potassium ; protein ; sodium ; sodium chloride ; solute ; syndrome ; wasting

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

  • Entrez Gene (http://www.ncbi.nlm.nih.gov/gene/6557)
  • 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. (http://www.ncbi.nlm.nih.gov/pubmed/18982348?dopt=Abstract)
  • Haas M. The Na-K-Cl cotransporters. Am J Physiol. 1994 Oct;267(4 Pt 1):C869-85. Review. (http://www.ncbi.nlm.nih.gov/pubmed/7943281?dopt=Abstract)
  • 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):592-9. doi: 10.1038/ng.118. Epub 2008 Apr 6. (http://www.ncbi.nlm.nih.gov/pubmed/18391953?dopt=Abstract)
  • 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. (http://www.ncbi.nlm.nih.gov/pubmed/8640224?dopt=Abstract)
  • 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. (http://www.ncbi.nlm.nih.gov/pubmed/12761241?dopt=Abstract)
  • 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, Deschênes 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. (http://www.ncbi.nlm.nih.gov/pubmed/9585600?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: February 2011
Published: June 17, 2013