Reviewed February 2011
What is the official name of the SLC12A3 gene?
The official name of this gene is “solute carrier family 12 (sodium/chloride transporters), member 3.”
SLC12A3 is the gene's official symbol. The SLC12A3 gene is also known by other names, listed below.
What is the normal function of the SLC12A3 gene?
The SLC12A3 gene provides instructions for making a protein known as NCC. This protein is a sodium chloride co-transporter, which means that it moves charged atoms (ions) of sodium (Na+) and chlorine (Cl-) across cell membranes.
The NCC protein is essential for normal kidney function. It is part of 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 SLC12A3 gene share characteristics with other genes?
The SLC12A3 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 SLC12A3 gene related to health conditions?
- Gitelman syndrome - caused by mutations in the SLC12A3 gene
More than 140 mutations in the SLC12A3 gene have been identified in people with Gitelman syndrome. Most of these mutations change single protein building blocks (amino acids) in the NCC co-transporter protein. These mutations prevent the protein from reaching the cell membrane or alter the protein's ability to transport sodium and chloride ions. Other mutations in the SLC12A3 gene insert or delete genetic material or lead to the production of an abnormally short, nonfunctional version of the NCC protein.
Mutations in the SLC12A3 gene impair the kidneys' ability to reabsorb salt, leading to the loss of excess salt in the urine (salt wasting). Abnormalities of salt transport also affect the reabsorption of other ions, including ions of potassium, magnesium, and calcium. The resulting imbalance of ions in the body underlies the major features of Gitelman syndrome.
- other disorders - associated with the SLC12A3 gene
Some research suggests that normal variants (polymorphisms) in the SLC12A3 gene may help explain differences in blood pressure between people. Certain rare polymorphisms also appear to protect against high blood pressure (hypertension). Changes in the SLC12A3 gene may affect blood pressure by altering the kidneys' ability to reabsorb salt into the bloodstream. However, some studies have not found any association between variants in the SLC12A3 gene and blood pressure.
Where is the SLC12A3 gene located?
Cytogenetic Location: 16q13
Molecular Location on chromosome 16: base pairs 56,899,118 to 56,949,761
The SLC12A3 gene is located on the long (q) arm of chromosome 16 at position 13.
More precisely, the SLC12A3 gene is located from base pair 56,899,118 to base pair 56,949,761 on chromosome 16.
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 SLC12A3?
You and your healthcare professional may find the following resources about SLC12A3 helpful.
Genetic Testing Registry - Repository of genetic test information
- GTR: Genetic tests for SLC12A3 (http://www.ncbi.nlm.nih.gov/gtr/tests/?term=6559%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=(SLC12A3%5BTIAB%5D)%20AND%20((Genes%5BMH%5D)%20OR%20(Genetic%20Phenomena%5BMH%5D))%20AND%20english%5Bla%5D%20AND%20human%5Bmh%5D%20AND%20%22last%203600%20days%22%5Bdp%5D)
- OMIM - Genetic disorder catalog (http://omim.org/entry/600968)
Research Resources - Tools for researchers
- Atlas of Genetics and Cytogenetics in Oncology and Haematology (http://atlasgeneticsoncology.org/Genes/GC_SLC12A3.html)
- Entrez Gene (http://www.ncbi.nlm.nih.gov/gene/6559)
- GeneCards (http://www.genecards.org/cgi-bin/carddisp.pl?id_type=entrezgene&id=6559)
- HUGO Gene Nomenclature Committee (http://www.genenames.org/data/hgnc_data.php?hgnc_id=10912)
What other names do people use for the SLC12A3 gene or gene products?
- NaCl electroneutral thiazide-sensitive cotransporter
- Na-Cl symporter
- solute carrier family 12 member 3
- thiazide-sensitive Na-Cl cotransporter
- thiazide-sensitive sodium-chloride cotransporter
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 SLC12A3?
cell membrane ;
sodium chloride ;
You may find definitions for these and many other terms in the Genetics Home Reference
- Aoi N, Nakayama T, Sato N, Kosuge K, Haketa A, Sato M, Soma M. Case-control study of the role of the Gitelman's syndrome gene in essential hypertension. Endocr J. 2008 May;55(2):305-10. Epub 2008 Mar 25. (http://www.ncbi.nlm.nih.gov/pubmed/18362449?dopt=Abstract)
- Cruz DN, Simon DB, Nelson-Williams C, Farhi A, Finberg K, Burleson L, Gill JR, Lifton RP. Mutations in the Na-Cl cotransporter reduce blood pressure in humans. Hypertension. 2001 Jun;37(6):1458-64. (http://www.ncbi.nlm.nih.gov/pubmed/11408395?dopt=Abstract)
- De Jong JC, Van Der Vliet WA, Van Den Heuvel LP, Willems PH, Knoers NV, Bindels RJ. Functional expression of mutations in the human NaCl cotransporter: evidence for impaired routing mechanisms in Gitelman's syndrome. J Am Soc Nephrol. 2002 Jun;13(6):1442-8. (http://www.ncbi.nlm.nih.gov/pubmed/12039972?dopt=Abstract)
- Entrez Gene (http://www.ncbi.nlm.nih.gov/gene/6559)
- 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)
- Lemmink HH, Knoers NV, Károlyi L, van Dijk H, Niaudet P, Antignac C, Guay-Woodford LM, Goodyer PR, Carel JC, Hermes A, Seyberth HW, Monnens LA, van den Heuvel LP. Novel mutations in the thiazide-sensitive NaCl cotransporter gene in patients with Gitelman syndrome with predominant localization to the C-terminal domain. Kidney Int. 1998 Sep;54(3):720-30. (http://www.ncbi.nlm.nih.gov/pubmed/9734597?dopt=Abstract)
- Lo YF, Nozu K, Iijima K, Morishita T, Huang CC, Yang SS, Sytwu HK, Fang YW, Tseng MH, Lin SH. Recurrent deep intronic mutations in the SLC12A3 gene responsible for Gitelman's syndrome. Clin J Am Soc Nephrol. 2011 Mar;6(3):630-9. doi: 10.2215/CJN.06730810. Epub 2010 Nov 4. (http://www.ncbi.nlm.nih.gov/pubmed/21051746?dopt=Abstract)
- Mastroianni N, De Fusco M, Zollo M, Arrigo G, Zuffardi O, Bettinelli A, Ballabio A, Casari G. Molecular cloning, expression pattern, and chromosomal localization of the human Na-Cl thiazide-sensitive cotransporter (SLC12A3). Genomics. 1996 Aug 1;35(3):486-93. (http://www.ncbi.nlm.nih.gov/pubmed/8812482?dopt=Abstract)
- Riveira-Munoz E, Chang Q, Godefroid N, Hoenderop JG, Bindels RJ, Dahan K, Devuyst O; Belgian Network for Study of Gitelman Syndrome. Transcriptional and functional analyses of SLC12A3 mutations: new clues for the pathogenesis of Gitelman syndrome. J Am Soc Nephrol. 2007 Apr;18(4):1271-83. Epub 2007 Feb 28. (http://www.ncbi.nlm.nih.gov/pubmed/17329572?dopt=Abstract)
- Sabath E, Meade P, Berkman J, de los Heros P, Moreno E, Bobadilla NA, Vázquez N, Ellison DH, Gamba G. Pathophysiology of functional mutations of the thiazide-sensitive Na-Cl cotransporter in Gitelman disease. Am J Physiol Renal Physiol. 2004 Aug;287(2):F195-203. Epub 2004 Apr 6. (http://www.ncbi.nlm.nih.gov/pubmed/15068971?dopt=Abstract)
- Simon DB, Nelson-Williams C, Bia MJ, Ellison D, Karet FE, Molina AM, Vaara I, Iwata F, Cushner HM, Koolen M, Gainza FJ, Gitleman HJ, Lifton RP. Gitelman's variant of Bartter's syndrome, inherited hypokalaemic alkalosis, is caused by mutations in the thiazide-sensitive Na-Cl cotransporter. Nat Genet. 1996 Jan;12(1):24-30. (http://www.ncbi.nlm.nih.gov/pubmed/8528245?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
See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.