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URL of this page: https://medlineplus.gov/genetics/gene/clcn1/

CLCN1 gene

chloride voltage-gated channel 1

Normal Function

The CLCN1 gene provides instructions for making a type of protein called a chloride channel. 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.

The CLCN1 gene provides instructions for making a chloride channel called ClC-1. These channels are found only in muscles used for movement (skeletal muscles). For the body to move normally, skeletal muscles must tense (contract) and relax in a coordinated way. Muscle contraction and relaxation are controlled by the flow of certain ions into and out of muscle cells. ClC-1 channels, which span the cell membrane, control the flow of chloride ions into these cells. This influx stabilizes the cells' electrical charge, which prevents muscles from contracting abnormally.

ClC-1 channels are made of two identical protein subunits, each produced from the CLCN1 gene. Although each subunit forms a separate opening (pore) that allows chloride ions to pass through, the two proteins work together to regulate the flow of chloride ions into skeletal muscle cells.

Health Conditions Related to Genetic Changes

Myotonia congenita

More than 150 mutations in the CLCN1 gene have been identified in people with myotonia congenita. Most of these mutations cause the autosomal recessive form of the disorder, which is known as Becker disease. Autosomal recessive inheritance means two copies of the gene in each cell are altered. Becker disease results when CLCN1 mutations change the structure or function of both protein subunits that make up the ClC-1 channel. The altered channels greatly reduce the flow of chloride ions into skeletal muscle cells, which triggers prolonged muscle contractions. Abnormally sustained muscle contractions are the hallmark of myotonia.

CLCN1 mutations also cause the autosomal dominant form of myotonia congenita, which is known as Thomsen disease. Autosomal dominant inheritance means one copy of the altered gene in each cell is sufficient to cause the disorder. Studies suggest that the CLCN1 mutations responsible for Thomsen disease change one of the two protein subunits that make up the ClC-1 channel. The altered protein takes on new, but harmful, properties that disrupt the ability of both subunits to regulate chloride ion flow. Reduced movement of chloride ions into skeletal muscle cells leads to myotonia, which underlies the stiffness and other muscle problems in people with myotonia congenita.

Because several CLCN1 mutations can cause either Becker disease or Thomsen disease, doctors usually rely on characteristic signs and symptoms to distinguish the two forms of myotonia congenita.

More About This Health Condition

Other Names for This Gene

  • chloride channel 1, skeletal muscle
  • Chloride channel protein 1
  • Chloride channel protein, skeletal muscle
  • chloride channel, voltage-sensitive 1
  • ClC-1
  • CLC1
  • CLCN1_HUMAN
  • MGC138361
  • MGC142055
  • skeletal muscle chloride channel 1

Additional Information & Resources

Tests Listed in the Genetic Testing Registry

Scientific Articles on PubMed

Catalog of Genes and Diseases from OMIM

Gene and Variant Databases

References

  • Colding-Jorgensen E. Phenotypic variability in myotonia congenita. Muscle Nerve. 2005 Jul;32(1):19-34. doi: 10.1002/mus.20295. Citation on PubMed
  • Duno M, Colding-Jorgensen E, Grunnet M, Jespersen T, Vissing J, Schwartz M. Difference in allelic expression of the CLCN1 gene and the possible influence on the myotonia congenita phenotype. Eur J Hum Genet. 2004 Sep;12(9):738-43. doi: 10.1038/sj.ejhg.5201218. Citation on PubMed
  • Duno M, Vissing J. Myotonia Congenita. 2005 Aug 3 [updated 2021 Feb 25]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews(R) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2024. Available from http://www.ncbi.nlm.nih.gov/books/NBK1355/ Citation on PubMed
  • Grunnet M, Jespersen T, Colding-Jorgensen E, Schwartz M, Klaerke DA, Vissing J, Olesen SP, Duno M. Characterization of two new dominant ClC-1 channel mutations associated with myotonia. Muscle Nerve. 2003 Dec;28(6):722-32. doi: 10.1002/mus.10501. Citation on PubMed
  • Imbrici P, Altamura C, Pessia M, Mantegazza R, Desaphy JF, Camerino DC. ClC-1 chloride channels: state-of-the-art research and future challenges. Front Cell Neurosci. 2015 Apr 27;9:156. doi: 10.3389/fncel.2015.00156. eCollection 2015. Citation on PubMed or Free article on PubMed Central
  • Jentsch TJ, Stein V, Weinreich F, Zdebik AA. Molecular structure and physiological function of chloride channels. Physiol Rev. 2002 Apr;82(2):503-68. doi: 10.1152/physrev.00029.2001. Erratum In: Physiol Rev. 2003 Apr;83(2):following table of contents. Citation on PubMed
  • Pusch M. Myotonia caused by mutations in the muscle chloride channel gene CLCN1. Hum Mutat. 2002 Apr;19(4):423-34. doi: 10.1002/humu.10063. Citation on PubMed
  • Zhang J, Bendahhou S, Sanguinetti MC, Ptacek LJ. Functional consequences of chloride channel gene (CLCN1) mutations causing myotonia congenita. Neurology. 2000 Feb 22;54(4):937-42. doi: 10.1212/wnl.54.4.937. Citation on PubMed
  • Zhang J, George AL Jr, Griggs RC, Fouad GT, Roberts J, Kwiecinski H, Connolly AM, Ptacek LJ. Mutations in the human skeletal muscle chloride channel gene (CLCN1) associated with dominant and recessive myotonia congenita. Neurology. 1996 Oct;47(4):993-8. doi: 10.1212/wnl.47.4.993. Citation on PubMed

The information on this site should not be used as a substitute for professional medical care or advice. Contact a health care provider if you have questions about your health.