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CLCNKB

Reviewed February 2011

What is the official name of the CLCNKB gene?

The official name of this gene is “chloride channel, voltage-sensitive Kb.”

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

What is the normal function of the CLCNKB gene?

The CLCNKB gene belongs to the CLC family of genes, which provide instructions for making chloride channels. These channels, which transport negatively charged chlorine atoms (chloride ions), play a key role in a cell's ability to generate and transmit electrical signals. Some CLC channels regulate the flow of chloride ions across cell membranes, while others transport chloride ions within cells.

The CLCNKB gene provides instructions for making a chloride channel called ClC-Kb. These channels are found predominantly in the kidneys. ClC-Kb is one of several proteins that work together to regulate the movement of ions into and out of kidney cells. The transport of chloride ions by ClC-Kb channels is part of the mechanism by which the 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.

ClC-Kb channels are also located in the inner ear, where they play a role in normal hearing.

Does the CLCNKB gene share characteristics with other genes?

The CLCNKB gene belongs to a family of genes called CLCN (chloride channels, voltage-sensitive).

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 CLCNKB gene related to health conditions?

Bartter syndrome - caused by mutations in the CLCNKB gene

More than 30 mutations in the CLCNKB gene have been identified in people with Bartter syndrome type III. This form of the condition, which is also described as classical Bartter syndrome, begins in childhood and tends to be less severe than other types of Bartter syndrome.

Many of the mutations responsible for Bartter syndrome type III delete the entire CLCNKB gene. Other mutations change single protein building blocks (amino acids) in the ClC-Kb channel or lead to an abnormally short, nonfunctional version of ClC-Kb. A loss of functional ClC-Kb channels impairs the transport of chloride ions in the kidneys. 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 ions in the body. This imbalance underlies many of the major features of Bartter syndrome type III.

Several people with a more severe form of Bartter syndrome have had mutations in both the CLCNKB gene and a closely related gene called CLCNKA. The CLCNKA gene provides instructions for making a very similar chloride channel, ClC-Ka, that is also found in the kidneys and inner ear. A combination of CLCNKA and CLCNKB gene mutations causes a life-threatening form of the disorder known as Bartter syndrome type IV or antenatal Bartter syndrome with sensorineural deafness. In addition to salt wasting, this form of the disorder is characterized by hearing loss that results from a loss of ClC-Ka and ClC-Kb function in the inner ear.

Gitelman syndrome - associated with the CLCNKB gene

Mutations in the CLCNKB gene are a rare cause of Gitelman syndrome. Like the mutations responsible for Bartter syndrome, the genetic changes associated with Gitelman syndrome impair the kidneys' ability to reabsorb salt, leading to 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 leads to the characteristic features of Gitelman syndrome.

other disorders - associated with the CLCNKB gene

A common variation (polymorphism) in the CLCNKB gene has been associated with salt-sensitive hypertension, a form of high blood pressure related to increased levels of salt in the blood. The polymorphism replaces the amino acid threonine with the amino acid serine at position 481 in the ClC-Kb channel (also written as Thr481Ser or T481S). This genetic change increases the activity of the ClC-Kb channel, which directs the kidneys to reabsorb more salt into the bloodstream. The excess salt raises blood pressure and increases the risk of developing hypertension.

Where is the CLCNKB gene located?

Cytogenetic Location: 1p36

Molecular Location on chromosome 1: base pairs 16,043,735 to 16,057,325

The CLCNKB gene is located on the short (p) arm of chromosome 1 at position 36.

The CLCNKB gene is located on the short (p) arm of chromosome 1 at position 36.

More precisely, the CLCNKB gene is located from base pair 16,043,735 to base pair 16,057,325 on chromosome 1.

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 CLCNKB?

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

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

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

  • chloride channel Kb
  • chloride channel, kidney, B
  • chloride channel protein ClC-Kb
  • ClC-K2
  • CLCKB
  • ClC-Kb
  • CLCKB_HUMAN
  • hClC-Kb

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 CLCNKB?

acids ; amino acid ; calcium ; cell ; channel ; chloride ; chloride channels ; gene ; hypertension ; ions ; kb ; kidney ; NaCl ; polymorphism ; potassium ; protein ; sensorineural ; serine ; sodium ; sodium chloride ; syndrome ; threonine ; voltage ; 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

  • Enríquez R, Adam V, Sirvent AE, García-García AB, Millán I, Amorós F. Gitelman syndrome due to p.A204T mutation in CLCNKB gene. Int Urol Nephrol. 2010 Dec;42(4):1099-102. doi: 10.1007/s11255-010-9850-4. Epub 2010 Oct 8. (http://www.ncbi.nlm.nih.gov/pubmed/20931281?dopt=Abstract)
  • Jeck N, Konrad M, Peters M, Weber S, Bonzel KE, Seyberth HW. Mutations in the chloride channel gene, CLCNKB, leading to a mixed Bartter-Gitelman phenotype. Pediatr Res. 2000 Dec;48(6):754-8. (http://www.ncbi.nlm.nih.gov/pubmed/11102542?dopt=Abstract)
  • Jeck N, Waldegger P, Doroszewicz J, Seyberth H, Waldegger S. A common sequence variation of the CLCNKB gene strongly activates ClC-Kb chloride channel activity. Kidney Int. 2004 Jan;65(1):190-7. (http://www.ncbi.nlm.nih.gov/pubmed/14675050?dopt=Abstract)
  • Jeck N, Waldegger S, Lampert A, Boehmer C, Waldegger P, Lang PA, Wissinger B, Friedrich B, Risler T, Moehle R, Lang UE, Zill P, Bondy B, Schaeffeler E, Asante-Poku S, Seyberth H, Schwab M, Lang F. Activating mutation of the renal epithelial chloride channel ClC-Kb predisposing to hypertension. Hypertension. 2004 Jun;43(6):1175-81. Epub 2004 May 17. (http://www.ncbi.nlm.nih.gov/pubmed/15148291?dopt=Abstract)
  • Kieferle S, Fong P, Bens M, Vandewalle A, Jentsch TJ. Two highly homologous members of the ClC chloride channel family in both rat and human kidney. Proc Natl Acad Sci U S A. 1994 Jul 19;91(15):6943-7. (http://www.ncbi.nlm.nih.gov/pubmed/8041726?dopt=Abstract)
  • Konrad M, Vollmer M, Lemmink HH, van den Heuvel LP, Jeck N, Vargas-Poussou R, Lakings A, Ruf R, Deschênes G, Antignac C, Guay-Woodford L, Knoers NV, Seyberth HW, Feldmann D, Hildebrandt F. Mutations in the chloride channel gene CLCNKB as a cause of classic Bartter syndrome. J Am Soc Nephrol. 2000 Aug;11(8):1449-59. (http://www.ncbi.nlm.nih.gov/pubmed/10906158?dopt=Abstract)
  • Krämer BK, Bergler T, Stoelcker B, Waldegger S. Mechanisms of Disease: the kidney-specific chloride channels ClCKA and ClCKB, the Barttin subunit, and their clinical relevance. Nat Clin Pract Nephrol. 2008 Jan;4(1):38-46. Review. (http://www.ncbi.nlm.nih.gov/pubmed/18094726?dopt=Abstract)
  • NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/1188)
  • Nozu K, Inagaki T, Fu XJ, Nozu Y, Kaito H, Kanda K, Sekine T, Igarashi T, Nakanishi K, Yoshikawa N, Iijima K, Matsuo M. Molecular analysis of digenic inheritance in Bartter syndrome with sensorineural deafness. J Med Genet. 2008 Mar;45(3):182-6. doi: 10.1136/jmg.2007.052944. (http://www.ncbi.nlm.nih.gov/pubmed/18310267?dopt=Abstract)
  • Schlingmann KP, Konrad M, Jeck N, Waldegger P, Reinalter SC, Holder M, Seyberth HW, Waldegger S. Salt wasting and deafness resulting from mutations in two chloride channels. N Engl J Med. 2004 Mar 25;350(13):1314-9. (http://www.ncbi.nlm.nih.gov/pubmed/15044642?dopt=Abstract)
  • Simon DB, Bindra RS, Mansfield TA, Nelson-Williams C, Mendonca E, Stone R, Schurman S, Nayir A, Alpay H, Bakkaloglu A, Rodriguez-Soriano J, Morales JM, Sanjad SA, Taylor CM, Pilz D, Brem A, Trachtman H, Griswold W, Richard GA, John E, Lifton RP. Mutations in the chloride channel gene, CLCNKB, cause Bartter's syndrome type III. Nat Genet. 1997 Oct;17(2):171-8. (http://www.ncbi.nlm.nih.gov/pubmed/9326936?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: December 22, 2014