WNK4

Reviewed December 2011

What is the official name of the WNK4 gene?

The official name of this gene is “WNK lysine deficient protein kinase 4.”

WNK4 is the gene's official symbol. The WNK4 gene is also known by other names, listed below.

What is the normal function of the WNK4 gene?

The WNK4 gene provides instructions for making a protein that plays a role in blood pressure regulation by helping control the amount of sodium and potassium in the body. The WNK4 protein acts as a kinase, which is an enzyme that changes the activity of other proteins by adding a cluster of oxygen and phosphorus atoms (a phosphate group) at specific positions.

The WNK4 protein regulates channels in the cell membrane that control the transport of sodium or potassium into and out of cells, which occurs primarily in the kidneys. Sodium channels help transport sodium into specialized cells of the kidney, from which it is transferred to the blood. This transfer helps keep sodium in the body through a process called reabsorption. Potassium channels handle excess potassium that has been transferred from the blood into the kidney cells. The channels transport the potassium out of the cells in a process called secretion, so that it can be removed from the body in the urine. The WNK4 protein blocks (inhibits) sodium reabsorption and potassium secretion.

How are changes in the WNK4 gene related to health conditions?

pseudohypoaldosteronism type 2 - caused by mutations in the WNK4 gene: Mutations in the WNK4 gene can cause pseudohypoaldosteronism type 2 (PHA2), a condition characterized by high blood pressure (hypertension) and high levels of potassium in the blood (hyperkalemia). The mutations involved in this condition change single protein building blocks (amino acids) in the WNK4 protein, which leads to an abnormal protein that no longer inhibits sodium channels but inhibits potassium channels more strongly. These mutations cause increased sodium reabsorption and decreased potassium secretion, resulting in hypertension and hyperkalemia.
other disorders - increased risk from variations of the WNK4 gene: Studies have associated normal variations in the WNK4 gene with an increased risk of high blood pressure (hypertension) in people without pseudohypoaldosteronism type 2. A combination of genetic variations and environmental factors likely influence the development of this complex condition.

Where is the WNK4 gene located?

Cytogenetic Location: 17q21-q22

Molecular Location on chromosome 17: base pairs 40,932,648 to 40,949,083

The WNK4 gene is located on the long (q) arm of chromosome 17 between positions 21 and 22.

More precisely, the WNK4 gene is located from base pair 40,932,648 to base pair 40,949,083 on chromosome 17.

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 WNK4?

You and your healthcare professional may find the following resources about WNK4 helpful.

Genetic Testing Registry - Repository of genetic test information
- GTR: Genetic tests for WNK4 (http://www.ncbi.nlm.nih.gov/gtr/tests/?term=65266%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=(WNK4%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/601844)
Research Resources - Tools for researchers
- Entrez Gene (http://www.ncbi.nlm.nih.gov/gene/65266)
- GeneCards (http://www.genecards.org/cgi-bin/carddisp.pl?id_type=entrezgene&id=65266)
- HUGO Gene Nomenclature Committee (http://www.genenames.org/data/hgnc_data.php?hgnc_id=14544)

What other names do people use for the WNK4 gene or gene products?

PHA2B
PRKWNK4
protein kinase lysine-deficient 4
protein kinase with no lysine 4
serine/threonine-protein kinase WNK4
WNK4_HUMAN

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 WNK4?

acids ; cell ; cell membrane ; enzyme ; gene ; hyperkalemia ; hypertension ; kidney ; kinase ; oxygen ; phosphate ; phosphorus ; potassium ; protein ; secretion ; serine ; sodium ; threonine

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/65266)
Kokubo Y, Kamide K, Inamoto N, Tanaka C, Banno M, Takiuchi S, Kawano Y, Tomoike H, Miyata T. Identification of 108 SNPs in TSC, WNK1, and WNK4 and their association with hypertension in a Japanese general population. J Hum Genet. 2004;49(9):507-15. Epub 2004 Aug 11. (http://www.ncbi.nlm.nih.gov/pubmed/15309683?dopt=Abstract)
OMIM: PROTEIN KINASE, LYSINE-DEFICIENT 4 (http://omim.org/entry/601844)
Ring AM, Cheng SX, Leng Q, Kahle KT, Rinehart J, Lalioti MD, Volkman HM, Wilson FH, Hebert SC, Lifton RP. WNK4 regulates activity of the epithelial Na+ channel in vitro and in vivo. Proc Natl Acad Sci U S A. 2007 Mar 6;104(10):4020-4. Epub 2007 Feb 26. (http://www.ncbi.nlm.nih.gov/pubmed/17360470?dopt=Abstract)
Subramanya AR, Liu J, Ellison DH, Wade JB, Welling PA. WNK4 diverts the thiazide-sensitive NaCl cotransporter to the lysosome and stimulates AP-3 interaction. J Biol Chem. 2009 Jul 3;284(27):18471-80. doi: 10.1074/jbc.M109.008185. Epub 2009 Apr 28. (http://www.ncbi.nlm.nih.gov/pubmed/19401467?dopt=Abstract)
Wilson FH, Disse-Nicodème S, Choate KA, Ishikawa K, Nelson-Williams C, Desitter I, Gunel M, Milford DV, Lipkin GW, Achard JM, Feely MP, Dussol B, Berland Y, Unwin RJ, Mayan H, Simon DB, Farfel Z, Jeunemaitre X, Lifton RP. Human hypertension caused by mutations in WNK kinases. Science. 2001 Aug 10;293(5532):1107-12. (http://www.ncbi.nlm.nih.gov/pubmed/11498583?dopt=Abstract)
Wilson FH, Kahle KT, Sabath E, Lalioti MD, Rapson AK, Hoover RS, Hebert SC, Gamba G, Lifton RP. Molecular pathogenesis of inherited hypertension with hyperkalemia: the Na-Cl cotransporter is inhibited by wild-type but not mutant WNK4. Proc Natl Acad Sci U S A. 2003 Jan 21;100(2):680-4. Epub 2003 Jan 6. (http://www.ncbi.nlm.nih.gov/pubmed/12515852?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.



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