CLCN1

The CLCN family of voltage-dependent chloride channel genes comprises nine members (CLCN1-7, Ka and Kb) which demonstrate quite diverse functional characteristics while sharing significant sequence homology. The protein encoded by this gene regulates the electric excitability of the skeletal muscle membrane. Mutations in this gene cause two forms of inherited human muscle disorders: recessive generalized myotonia congenita (Becker) and dominant myotonia (Thomsen).[5]

CLCN1
Identifiers
Aliases	CLCN1, CLC1, chloride voltage-gated channel 1
External IDs	OMIM: 118425 MGI: 88417 HomoloGene: 63 GeneCards: CLCN1
Gene location (Human) Chr. Chromosome 7 (human)[1] Band 7q34 Start 143,316,111 bp[1] End 143,352,083 bp[1]
Gene location (Mouse) Chr. Chromosome 6 (mouse)[2] Band 6 B2.1|6 20.57 cM Start 42,286,685 bp[2] End 42,315,756 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • protein homodimerization activity • voltage-gated ion channel activity • GO:0001948 protein binding • chloride channel activity • voltage-gated chloride channel activity Cellular component • integral component of membrane • membrane • cell membrane • integral component of plasma membrane • chloride channel complex • sarcolemma Biological process • muscle contraction • regulation of ion transmembrane transport • chloride transmembrane transport • ion transport • ion transmembrane transport • neuronal action potential propagation • chloride transport • transmembrane transport Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	1180	12723
Ensembl	ENSG00000188037	ENSMUSG00000029862
UniProt	P35523	Q64347
RefSeq (mRNA)	NM_000083	NM_013491 NM_001363712
RefSeq (protein)	NP_000074	NP_038519 NP_001350641
Location (UCSC)	Chr 7: 143.32 – 143.35 Mb	Chr 6: 42.29 – 42.32 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

Chloride channel protein, skeletal muscle (CLCN1) is a protein that in humans is encoded by the CLCN1 gene.[6] Mutations in this protein cause congenital myotonia.

CLCN1 is critical for the normal function of skeletal muscle cells. 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 ions into and out of muscle cells. CLCN1 forms an ion channel that controls the flow of negatively charged chloride ions into these cells. The main function of this channel is to stabilize the cells' electrical charge, enabling muscles to contract normally.

In people with congenital myotonia due to a mutation in CLCN1, the ion channel admits too few chloride ions into the cell. This shortage of chloride ions causes prolonged muscle contractions, which are the hallmark of myotonia.

See also

• Chloride channel
• Thomsen disease

References

1. GRCh38: Ensembl release 89: ENSG00000188037 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000029862 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. "Entrez Gene: CLCN1 chloride channel 1, skeletal muscle (Thomsen disease, autosomal dominant)".
6. Koch MC, Steinmeyer K, Lorenz C, Ricker K, Wolf F, Otto M, Zoll B, Lehmann-Horn F, Grzeschik KH, Jentsch TJ (Sep 1992). "The skeletal muscle chloride channel in dominant and recessive human myotonia". Science. 257 (5071): 797–800. doi:10.1126/science.1379744. PMID 1379744.

Further reading

• Hudson AJ, Ebers GC, Bulman DE (1995). "The skeletal muscle sodium and chloride channel diseases". Brain. 118 (2): 547–63. doi:10.1093/brain/118.2.547. PMID 7735894.
• Uchida S, Sasaki S, Marumo F (1996). "Chloride transport across kidney epithelia through CLC chloride channels". Nippon Jinzo Gakkai shi. 38 (7): 285–9. PMID 8741388.
• Fahlke C (2000). "Molecular mechanisms of ion conduction in ClC-type chloride channels: lessons from disease-causing mutations". Kidney Int. 57 (3): 780–6. doi:10.1046/j.1523-1755.2000.00915.x. PMID 10720929.
• Pusch M (2002). "Myotonia caused by mutations in the muscle chloride channel gene CLCN1". Hum. Mutat. 19 (4): 423–34. doi:10.1002/humu.10063. PMID 11933197.
• Colding-Jørgensen E (2005). "Phenotypic variability in myotonia congenita". Muscle Nerve. 32 (1): 19–34. doi:10.1002/mus.20295. PMID 15786415.
• Isobe M, Erikson J, Emanuel BS, et al. (1985). "Location of gene for beta subunit of human T-cell receptor at band 7q35, a region prone to rearrangements in T cells". Science. 228 (4699): 580–2. doi:10.1126/science.3983641. PMID 3983641.
• Lehmann-Horn F, Mailänder V, Heine R, George AL (1995). "Myotonia levior is a chloride channel disorder". Hum. Mol. Genet. 4 (8): 1397–402. doi:10.1093/hmg/4.8.1397. PMID 7581380.
• George AL, Sloan-Brown K, Fenichel GM, et al. (1995). "Nonsense and missense mutations of the muscle chloride channel gene in patients with myotonia congenita". Hum. Mol. Genet. 3 (11): 2071–2. PMID 7874130.
• Lorenz C, Meyer-Kleine C, Steinmeyer K, et al. (1994). "Genomic organization of the human muscle chloride channel CIC-1 and analysis of novel mutations leading to Becker-type myotonia". Hum. Mol. Genet. 3 (6): 941–6. doi:10.1093/hmg/3.6.941. PMID 7951242.
• Heine R, George AL, Pika U, et al. (1995). "Proof of a non-functional muscle chloride channel in recessive myotonia congenita (Becker) by detection of a 4 base pair deletion". Hum. Mol. Genet. 3 (7): 1123–8. doi:10.1093/hmg/3.7.1123. PMID 7981681.
• George AL, Crackower MA, Abdalla JA, et al. (1995). "Molecular basis of Thomsen's disease (autosomal dominant myotonia congenita)". Nat. Genet. 3 (4): 305–10. doi:10.1038/ng0493-305. PMID 7981750.
• Steinmeyer K, Lorenz C, Pusch M, et al. (1994). "Multimeric structure of ClC-1 chloride channel revealed by mutations in dominant myotonia congenita (Thomsen)". EMBO J. 13 (4): 737–43. PMC 394869. PMID 8112288.
• Koch MC, Ricker K, Otto M, et al. (1994). "Evidence for genetic homogeneity in autosomal recessive generalised myotonia (Becker)". J. Med. Genet. 30 (11): 914–7. doi:10.1136/jmg.30.11.914. PMC 1016598. PMID 8301644.
• Meyer-Kleine C, Steinmeyer K, Ricker K, et al. (1996). "Spectrum of mutations in the major human skeletal muscle chloride channel gene (CLCN1) leading to myotonia". Am. J. Hum. Genet. 57 (6): 1325–34. PMC 1801423. PMID 8533761.
• Mailänder V, Heine R, Deymeer F, Lehmann-Horn F (1996). "Novel muscle chloride channel mutations and their effects on heterozygous carriers". Am. J. Hum. Genet. 58 (2): 317–24. PMC 1914535. PMID 8571958.
• Pusch M, Steinmeyer K, Koch MC, Jentsch TJ (1996). "Mutations in dominant human myotonia congenita drastically alter the voltage dependence of the CIC-1 chloride channel". Neuron. 15 (6): 1455–63. doi:10.1016/0896-6273(95)90023-3. PMID 8845168.
• Fahlke C, Beck CL, George AL (1997). "A mutation in autosomal dominant myotonia congenita affects pore properties of the muscle chloride channel". Proc. Natl. Acad. Sci. U.S.A. 94 (6): 2729–34. doi:10.1073/pnas.94.6.2729. PMC 20158. PMID 9122265.

External links

• GeneReviews/NCBI/NIH/UW entry on Myotonia Congenita
• CLCN1+protein,+human at the US National Library of Medicine Medical Subject Headings (MeSH)
• Human CLCN1 genome location and CLCN1 gene details page in the UCSC Genome Browser.

This article incorporates text from the United States National Library of Medicine, which is in the public domain.