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Normal Function
The CLCNKA 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 CLCNKA gene provides instructions for making a chloride channel called ClC-Ka. These channels are found predominantly in the kidneys. ClC-Ka 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-Ka 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-Ka channels are also located in the inner ear, where they play a role in normal hearing.
Health Conditions Related to Genetic Changes
Bartter syndrome
Several people with Bartter syndrome have had mutations in both the CLCNKA gene and a closely related gene called CLCNKB. The CLCNKB gene provides instructions for making a very similar chloride channel, ClC-Kb, 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 called Bartter syndrome type IV. This condition is also known as antenatal Bartter syndrome with sensorineural deafness because affected individuals have hearing loss caused by abnormalities in the inner ear.
Mutations in the CLCNKA and CLCNKB genes prevent the ClC-Ka and ClC-Kb channels from transporting 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, including a failure to grow and gain weight at the expected rate (failure to thrive), dehydration, constipation, and increased urine production (polyuria). A loss of ClC-Ka and ClC-Kb function in the inner ear is responsible for the hearing loss characteristic of Bartter syndrome type IV.
More About This Health ConditionOther disorders
Studies suggest that several normal variants (polymorphisms) in the CLCNKA gene may be associated with salt-sensitive hypertension, a form of high blood pressure related to increased levels of salt in the blood. However, this association between CLCNKA polymorphisms and hypertension has not been confirmed. Changes in the CLCNKA gene may affect blood pressure by altering the kidneys' ability to reabsorb salt into the bloodstream.
Other Names for This Gene
- chloride channel Ka
- chloride channel protein ClC-Ka
- chloride channel, kidney, A
- chloride channel, voltage-sensitive Ka
- ClC-K1
- CLCK1
- CLCKA_HUMAN
- hClC-Ka
Additional Information & Resources
Tests Listed in the Genetic Testing Registry
Scientific Articles on PubMed
Catalog of Genes and Diseases from OMIM
References
- Barlassina C, Dal Fiume C, Lanzani C, Manunta P, Guffanti G, Ruello A, Bianchi G, Del Vecchio L, Macciardi F, Cusi D. Common genetic variants and haplotypes in renal CLCNKA gene are associated to salt-sensitive hypertension. Hum Mol Genet. 2007 Jul 1;16(13):1630-8. doi: 10.1093/hmg/ddm112. Epub 2007 May 17. Citation on PubMed
- 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. doi: 10.1073/pnas.91.15.6943. Citation on PubMed or Free article on PubMed Central
- Kramer 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. doi: 10.1038/ncpneph0689. Citation on PubMed
- 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. Citation on PubMed
- 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. doi: 10.1056/NEJMoa032843. No abstract available. Citation on PubMed
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