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Genetics Home Reference: your guide to understanding genetic conditions
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CLCN5

Reviewed September 2012

What is the official name of the CLCN5 gene?

The official name of this gene is “chloride channel, voltage-sensitive 5.”

CLCN5 is the gene's official symbol. The CLCN5 gene is also known by other names, listed below.

What is the normal function of the CLCN5 gene?

The CLCN5 gene provides instructions for making a protein called ClC-5 that transports charged atoms (ions) across cell membranes. Specifically, ClC-5 exchanges negatively charged atoms of chlorine (chloride ions) for positively charged atoms of hydrogen (protons or hydrogen ions). Based on this function, ClC-5 is known as a H+/Cl- exchanger.

ClC-5 is found primarily in the kidneys, particularly in structures called proximal tubules. These structures help to reabsorb nutrients, water, and other materials that have been filtered from the bloodstream. The kidneys reabsorb needed materials into the blood and excrete everything else into the urine.

Within proximal tubule cells, ClC-5 is embedded in specialized compartments called endosomes. Endosomes are formed at the cell surface to carry proteins and other molecules to their destinations within the cell. ClC-5 transports hydrogen ions into endosomes and chloride ions out, which helps these compartments maintain the proper acidity level (pH). Endosomal pH levels must be tightly regulated for proximal tubule cells to function properly.

How are changes in the CLCN5 gene related to health conditions?

Dent disease - caused by mutations in the CLCN5 gene

About 150 mutations in the CLCN5 gene have been found to cause Dent disease 1, a chronic kidney disorder that can cause kidney failure. Most of the mutations lead to the production of an abnormally short, nonfunctional version of ClC-5 or prevent cells from producing any of this protein. A loss of ClC-5 alters the regulation of endosomal pH, which disrupts the overall function of proximal tubule cells and prevents them from reabsorbing proteins and other materials into the bloodstream. As a result, proteins are lost through the urine (tubular proteinuria). A failure to reabsorb calcium and other nutrients into the bloodstream can cause bone defects, kidney stones, and related health problems in people with Dent disease 1. Abnormal proximal tubule function ultimately leads to kidney failure in most affected individuals.

Where is the CLCN5 gene located?

Cytogenetic Location: Xp11.23-p11.22

Molecular Location on the X chromosome: base pairs 49,687,224 to 49,863,891

The CLCN5 gene is located on the short (p) arm of the X chromosome between positions 11.23 and 11.22.

The CLCN5 gene is located on the short (p) arm of the X chromosome between positions 11.23 and 11.22.

More precisely, the CLCN5 gene is located from base pair 49,687,224 to base pair 49,863,891 on the X chromosome.

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 CLCN5?

You and your healthcare professional may find the following resources about CLCN5 helpful.

  • Educational resources - Information pages

    • Molecular Biology of the Cell (fourth edition, 2002): Transport into the Cell from the Plasma Membrane: Endocytosis (http://www.ncbi.nlm.nih.gov/books/NBK26870/)
    • National Institute of Diabetes and Digestive and Kidney Diseases: The Kidneys and How They Work (http://kidney.niddk.nih.gov/kudiseases/pubs/yourkidneys/index.aspx)
    • Neuromuscular Disease Center, Washington University: Chloride channels (http://neuromuscular.wustl.edu/mother/chan.html)
  • Gene Reviews - Clinical summary (http://www.ncbi.nlm.nih.gov/books/NBK99494/)

  • Genetic Testing Registry - Repository of genetic test information

    • GTR: Genetic tests for CLCN5 (http://www.ncbi.nlm.nih.gov/gtr/tests/?term=1184%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=((CLCN5%5BTIAB%5D)%20OR%20(CLC-5%5BTIAB%5D)%20OR%20(CLC5%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/300008)

  • Research Resources - Tools for researchers

    • Entrez Gene (http://www.ncbi.nlm.nih.gov/gene/1184)
    • GeneCards (http://www.genecards.org/cgi-bin/carddisp.pl?id_type=entrezgene&id=1184)
    • HUGO Gene Nomenclature Committee (http://www.genenames.org/data/hgnc_data.php?hgnc_id=2023)

What other names do people use for the CLCN5 gene or gene products?

  • chloride channel 5
  • chloride channel protein 5
  • chloride transporter ClC-5
  • CLC5
  • clC-5
  • CLCK2
  • CLCN5_HUMAN
  • DENTS
  • hCIC-K2
  • hClC-K2
  • H(+)/Cl(-) exchange transporter 5
  • NPHL1
  • NPHL2
  • XLRH
  • XRN

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 CLCN5?

acidity ; calcium ; cell ; channel ; chloride ; chronic ; endosomes ; excrete ; gene ; hydrogen ions ; intracellular ; ions ; kidney ; kidney stones ; pH ; protein ; proteinuria ; proximal ; rickets ; voltage

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

References

  • Christensen EI, Devuyst O, Dom G, Nielsen R, Van der Smissen P, Verroust P, Leruth M, Guggino WB, Courtoy PJ. Loss of chloride channel ClC-5 impairs endocytosis by defective trafficking of megalin and cubilin in kidney proximal tubules. Proc Natl Acad Sci U S A. 2003 Jul 8;100(14):8472-7. Epub 2003 Jun 18. (http://www.ncbi.nlm.nih.gov/pubmed/12815097?dopt=Abstract)
  • Claverie-Martín F, Ramos-Trujillo E, García-Nieto V. Dent's disease: clinical features and molecular basis. Pediatr Nephrol. 2011 May;26(5):693-704. doi: 10.1007/s00467-010-1657-0. Epub 2010 Oct 10. (http://www.ncbi.nlm.nih.gov/pubmed/20936522?dopt=Abstract)
  • Cox JP, Yamamoto K, Christie PT, Wooding C, Feest T, Flinter FA, Goodyer PR, Leumann E, Neuhaus T, Reid C, Williams PF, Wrong O, Thakker RV. Renal chloride channel, CLCN5, mutations in Dent's disease. J Bone Miner Res. 1999 Sep;14(9):1536-42. (http://www.ncbi.nlm.nih.gov/pubmed/10469281?dopt=Abstract)
  • Devuyst O, Christie PT, Courtoy PJ, Beauwens R, Thakker RV. Intra-renal and subcellular distribution of the human chloride channel, CLC-5, reveals a pathophysiological basis for Dent's disease. Hum Mol Genet. 1999 Feb;8(2):247-57. (http://www.ncbi.nlm.nih.gov/pubmed/9931332?dopt=Abstract)
  • Entrez Gene (http://www.ncbi.nlm.nih.gov/gene/1184)
  • Fisher SE, van Bakel I, Lloyd SE, Pearce SH, Thakker RV, Craig IW. Cloning and characterization of CLCN5, the human kidney chloride channel gene implicated in Dent disease (an X-linked hereditary nephrolithiasis). Genomics. 1995 Oct 10;29(3):598-606. (http://www.ncbi.nlm.nih.gov/pubmed/8575751?dopt=Abstract)
  • Lloyd SE, Pearce SH, Fisher SE, Steinmeyer K, Schwappach B, Scheinman SJ, Harding B, Bolino A, Devoto M, Goodyer P, Rigden SP, Wrong O, Jentsch TJ, Craig IW, Thakker RV. A common molecular basis for three inherited kidney stone diseases. Nature. 1996 Feb 1;379(6564):445-9. (http://www.ncbi.nlm.nih.gov/pubmed/8559248?dopt=Abstract)
  • Lourdel S, Grand T, Burgos J, González W, Sepúlveda FV, Teulon J. ClC-5 mutations associated with Dent's disease: a major role of the dimer interface. Pflugers Arch. 2012 Feb;463(2):247-56. doi: 10.1007/s00424-011-1052-0. Epub 2011 Nov 15. Review. (http://www.ncbi.nlm.nih.gov/pubmed/22083641?dopt=Abstract)
  • Picollo A, Pusch M. Chloride/proton antiporter activity of mammalian CLC proteins ClC-4 and ClC-5. Nature. 2005 Jul 21;436(7049):420-3. (http://www.ncbi.nlm.nih.gov/pubmed/16034421?dopt=Abstract)
  • Wellhauser L, D'Antonio C, Bear CE. ClC transporters: discoveries and challenges in defining the mechanisms underlying function and regulation of ClC-5. Pflugers Arch. 2010 Jul;460(2):543-57. doi: 10.1007/s00424-009-0769-5. Epub 2010 Jan 5. Review. (http://www.ncbi.nlm.nih.gov/pubmed/20049483?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: September 2012
Published: June 17, 2013