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Genetics Home Reference: your guide to understanding genetic conditions
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CLCN7

Reviewed September 2010

What is the official name of the CLCN7 gene?

The official name of this gene is “chloride channel, voltage-sensitive 7.”

CLCN7 is the gene's official symbol. The CLCN7 gene is also known by other names, listed below.

What is the normal function of the CLCN7 gene?

The CLCN7 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 CLCN7 gene provides instructions for making a chloride channel called ClC-7. These channels are abundant in cells throughout the body. They are particularly important for the normal function of osteoclasts, which are specialized cells that break down bone tissue. Osteoclasts are involved in bone remodeling, a normal process in which old bone is removed and new bone is created to replace it. Bones are constantly being remodeled, and the process is carefully controlled to ensure that bones stay strong and healthy.

ClC-7 channels help regulate the relative acidity (pH) of osteoclasts. These channels transport two negatively charged chloride ions out of these cells for every positively charged hydrogen atom (hydrogen ion) that flows in. In this way, ClC-7 channels help balance the acidic environment that osteoclasts use to dissolve bone tissue. The pH inside and outside osteoclasts must be carefully controlled for these cells to break down bone effectively.

Does the CLCN7 gene share characteristics with other genes?

The CLCN7 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 CLCN7 gene related to health conditions?

osteopetrosis - caused by mutations in the CLCN7 gene

More than 50 mutations in the CLCN7 gene have been identified in people with osteopetrosis. Mutations in this gene can cause several different forms of the disorder: autosomal recessive osteopetrosis (ARO), which is the most severe form; autosomal dominant osteopetrosis (ADO), which tends to be milder; and a moderate form known as intermediate autosomal osteopetrosis (IAO).

Mutations in the CLCN7 gene impair the function of ClC-7 channels. The defective channels cannot transport chloride ions effectively, which disrupts the regulation of pH in osteoclasts. As a result, osteoclasts are unable to break down bone normally. When old bone is not broken down as new bone is formed, bones throughout the skeleton become unusually dense. The bones are also structurally abnormal, making them prone to fracture. These problems with bone remodeling underlie all of the major forms of osteopetrosis.

Where is the CLCN7 gene located?

Cytogenetic Location: 16p13

Molecular Location on chromosome 16: base pairs 1,444,932 to 1,475,083

The CLCN7 gene is located on the short (p) arm of chromosome 16 at position 13.

The CLCN7 gene is located on the short (p) arm of chromosome 16 at position 13.

More precisely, the CLCN7 gene is located from base pair 1,444,932 to base pair 1,475,083 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 CLCN7?

You and your healthcare professional may find the following resources about CLCN7 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 CLCN7 gene or gene products?

  • chloride channel 7
  • chloride channel protein 7
  • CLC7
  • CLC-7
  • CLCN7_HUMAN
  • FLJ26686
  • FLJ39644
  • FLJ46423
  • H(+)/Cl(-) exchange transporter 7
  • OPTA2
  • OPTB4
  • PPP1R63

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 CLCN7?

acidity ; atom ; autosomal ; autosomal dominant ; autosomal recessive ; bone remodeling ; cell ; channel ; chloride ; chloride channels ; gene ; ions ; pH ; protein ; proton ; recessive ; tissue ; 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

  • Cleiren E, Bénichou O, Van Hul E, Gram J, Bollerslev J, Singer FR, Beaverson K, Aledo A, Whyte MP, Yoneyama T, deVernejoul MC, Van Hul W. Albers-Schönberg disease (autosomal dominant osteopetrosis, type II) results from mutations in the ClCN7 chloride channel gene. Hum Mol Genet. 2001 Dec 1;10(25):2861-7. (http://www.ncbi.nlm.nih.gov/pubmed/11741829?dopt=Abstract)
  • Del Fattore A, Peruzzi B, Rucci N, Recchia I, Cappariello A, Longo M, Fortunati D, Ballanti P, Iacobini M, Luciani M, Devito R, Pinto R, Caniglia M, Lanino E, Messina C, Cesaro S, Letizia C, Bianchini G, Fryssira H, Grabowski P, Shaw N, Bishop N, Hughes D, Kapur RP, Datta HK, Taranta A, Fornari R, Migliaccio S, Teti A. Clinical, genetic, and cellular analysis of 49 osteopetrotic patients: implications for diagnosis and treatment. J Med Genet. 2006 Apr;43(4):315-25. Epub 2005 Aug 23. (http://www.ncbi.nlm.nih.gov/pubmed/16118345?dopt=Abstract)
  • Frattini A, Pangrazio A, Susani L, Sobacchi C, Mirolo M, Abinun M, Andolina M, Flanagan A, Horwitz EM, Mihci E, Notarangelo LD, Ramenghi U, Teti A, Van Hove J, Vujic D, Young T, Albertini A, Orchard PJ, Vezzoni P, Villa A. Chloride channel ClCN7 mutations are responsible for severe recessive, dominant, and intermediate osteopetrosis. J Bone Miner Res. 2003 Oct;18(10):1740-7. (http://www.ncbi.nlm.nih.gov/pubmed/14584882?dopt=Abstract)
  • Gene Review: CLCN7-Related Osteopetrosis (http://www.ncbi.nlm.nih.gov/books/NBK1127)
  • Kornak U, Kasper D, Bösl MR, Kaiser E, Schweizer M, Schulz A, Friedrich W, Delling G, Jentsch TJ. Loss of the ClC-7 chloride channel leads to osteopetrosis in mice and man. Cell. 2001 Jan 26;104(2):205-15. (http://www.ncbi.nlm.nih.gov/pubmed/11207362?dopt=Abstract)
  • NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/1186)
  • Pangrazio A, Pusch M, Caldana E, Frattini A, Lanino E, Tamhankar PM, Phadke S, Lopez AG, Orchard P, Mihci E, Abinun M, Wright M, Vettenranta K, Bariae I, Melis D, Tezcan I, Baumann C, Locatelli F, Zecca M, Horwitz E, Mansour LS, Van Roij M, Vezzoni P, Villa A, Sobacchi C. Molecular and clinical heterogeneity in CLCN7-dependent osteopetrosis: report of 20 novel mutations. Hum Mutat. 2010 Jan;31(1):E1071-80. doi: 10.1002/humu.21167. (http://www.ncbi.nlm.nih.gov/pubmed/19953639?dopt=Abstract)
  • Scheel O, Zdebik AA, Lourdel S, Jentsch TJ. Voltage-dependent electrogenic chloride/proton exchange by endosomal CLC proteins. Nature. 2005 Jul 21;436(7049):424-7. (http://www.ncbi.nlm.nih.gov/pubmed/16034422?dopt=Abstract)
  • Waguespack SG, Hui SL, Dimeglio LA, Econs MJ. Autosomal dominant osteopetrosis: clinical severity and natural history of 94 subjects with a chloride channel 7 gene mutation. J Clin Endocrinol Metab. 2007 Mar;92(3):771-8. Epub 2006 Dec 12. (http://www.ncbi.nlm.nih.gov/pubmed/17164308?dopt=Abstract)
  • Waguespack SG, Koller DL, White KE, Fishburn T, Carn G, Buckwalter KA, Johnson M, Kocisko M, Evans WE, Foroud T, Econs MJ. Chloride channel 7 (ClCN7) gene mutations and autosomal dominant osteopetrosis, type II. J Bone Miner Res. 2003 Aug;18(8):1513-8. (http://www.ncbi.nlm.nih.gov/pubmed/12929941?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 2010
Published: September 15, 2014