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CLCN1

chloride voltage-gated channel 1

The CLCN1 gene provides instructions for creating chloride channels, crucial for the proper electrical signalling and relaxation of skeletal muscles. The CLCN1 gene encodes a chloride channel protein known as ClC-1, which is exclusively found in skeletal muscles.

Chromosome 7q34 Autosomal recessive HGNC:2019 Tier C
CLCN1 7q34 p arm q arm 7

CLCN1 is located on the long (q) arm of chromosome 7, at band 7q34. Arm ratio per GRCh38 - banding schematic.

Explore chromosome 7 in the library →

Available at Jeen Health

Clinical tests that include this

Carrier Screening panel
CLCN1 is 1 of 1,008 genes on this panel
Expanded carrier screening for recessive and X-linked conditions

Overview

The CLCN1 gene provides the genetic blueprint for a specific type of chloride channel protein, ClC-1, which is found in skeletal muscles. These channels are integral to the normal functioning of muscles, controlling the movement of chloride ions across muscle cell membranes. By regulating this ion flow, CLC-1 channels help stabilise the electrical potential of muscle cells, which is essential for coordinated muscle contraction and relaxation.

Disruptions to the CLCN1 gene can lead to conditions affecting muscle function, specifically myotonia congenita. Understanding the role of CLCN1 is therefore key to comprehending the mechanisms behind certain inherited muscle disorders.

What the gene does

The CLCN1 gene is responsible for producing the ClC-1 chloride channel. This channel is specifically located in skeletal muscles, which are responsible for voluntary movement. The primary function of ClC-1 channels is to facilitate the controlled flow of negatively charged chloride ions into muscle cells.

This influx of chloride ions is critical for maintaining the stability of the cell's electrical charge. By stabilising the resting membrane potential, the ClC-1 channel prevents excessive excitability of muscle fibres, which in turn helps to prevent abnormal and sustained muscle contractions. Essentially, the channel ensures that after a muscle contracts, it can relax properly, contributing to the coordinated and efficient movement of the body. Each ClC-1 channel is formed from two identical protein subunits, each contributing to the overall regulation of chloride ion movement.

Video: Genetics 101

Chromosome location

The CLCN1 gene is situated on the long arm of chromosome 7 at position 7q34. This specific genomic location places it within a region that can be inherited, and variants within this gene are known to be passed down through families in an autosomal recessive pattern for certain conditions.

Protein structure

The CLCN1 protein is composed of 988 amino acids. It features several key structural elements including a Disordered region spanning amino acids 65-92, and another from 713-764, with a further disordered region from 880-988. Important for its function, the protein contains three Selectivity filter part_1, part_2, and part_3 motifs, located at amino acids 188-192, 230-234, and 482-486, respectively. Additionally, two CBS (cystathionine beta-synthase) domains are present: CBS 1 from amino acids 609-668, and CBS 2 from amino acids 821-876, which are typically involved in regulatory processes.

Domain map · 988 amino acids
Selectivity filter part_1 (188–192)Selectivity filter part_2 (230–234)Selectivity filter part_3 (482–486)CBS 1 (609–668)CBS 2 (821–876)Selectivity filter par188–192CBS 1609–668CBS 2821–8761~494988
Motif - short conserved sequence
Domain - independent functional unit
🧬 Explore 3D structure on AlphaFold
UniProt:P35523Length:988 aaStructure:AlphaFold

Key variants

Variations within the CLCN1 gene can alter the structure or function of the ClC-1 chloride channel. Over 150 different gene variants have been identified in individuals with myotonia congenita. These genetic changes can impair the channel's ability to regulate chloride ion flow, leading to muscle excitability issues.

The table below shows the top 10 pathogenic or likely-pathogenic variants currently classified in ClinVar for CLCN1.
View all on ClinVar →

Sample of pathogenic variants

10 pathogenic / likely-pathogenic variants from ClinVar, ranked by review status (expert-panel-reviewed first). This is a sample; recurrent founder variants in a specific population may not appear here - see the full ClinVar listing via the link above.

Variant (HGVS) Protein change Classification Evidence Associated condition
c.1264G>T
single nucleotide variant
 p.Glu422Ter Pathogenic ★★☆☆ Congenital myotonia, autosomal dominant form
c.127C>T
single nucleotide variant
 p.Gln43Ter Pathogenic/Likely pathogenic ★★☆☆ Congenital myotonia, autosomal recessive form
c.1696G>A
single nucleotide variant
 p.Ala566Thr Pathogenic/Likely pathogenic ★★☆☆ Congenital myotonia, autosomal recessive form
c.2203_2216del
Deletion
 p.Thr735fs Pathogenic/Likely pathogenic ★★☆☆ Congenital myotonia, autosomal recessive form
c.302-2A>C
single nucleotide variant
 - Pathogenic/Likely pathogenic ★★☆☆ Congenital myotonia, autosomal dominant form
c.32del
Deletion
 p.Gly11fs Pathogenic/Likely pathogenic ★★☆☆ Congenital myotonia, autosomal dominant form
c.37C>T
single nucleotide variant
 p.Gln13Ter Pathogenic/Likely pathogenic ★★☆☆ Congenital myotonia, autosomal recessive form
c.444dup
Duplication
 p.Ser149fs Pathogenic ★★☆☆ Congenital myotonia, autosomal recessive form
c.450C>A
single nucleotide variant
 p.Tyr150Ter Pathogenic ★★☆☆ Congenital myotonia, autosomal recessive form
c.696+1G>A
single nucleotide variant
 - Pathogenic ★★☆☆ Congenital myotonia, autosomal recessive form

Evidence stars indicate ClinVar review status. Individual variant interpretation should always be performed by a qualified clinical laboratory - many variants remain classified as Variants of Uncertain Significance (VUS) pending more research.

Associated conditions

Variants in the CLCN1 gene are primarily associated with myotonia congenita. This condition manifests in two main forms: Myotonia congenita (Becker, recessive) and Myotonia congenita (Thomsen, dominant). The autosomal recessive form, known as Becker disease, typically results from changes affecting both copies of the CLCN1 gene.

Inheritance pattern

Conditions caused by pathogenic CLCN1 variants typically follow autosomal recessive inheritance.

♀ Carrier parent 1 altered copy ♂ Carrier parent 1 altered copy Affected Carrier Carrier Unaffected Affected Carrier Unaffected Circles = females · Squares = males

When both parents are carriers, each child has a 25% chance of being affected, 50% of being a carrier, and 25% of being unaffected.

Carrier frequency by population How common is heterozygous CLCN1 carrier status across ancestry groups?

UK clinical status

The CLCN1 gene is recognised within the NHS Genomic Medicine Service, being listed on the Skeletal Muscle Channelopathies panel. This indicates its importance in the diagnosis and understanding of inherited muscle channel disorders within the UK healthcare system.

Green-listed
High evidence · clinically actionable in NHS testing
Included in NHS GMS signed-off panels
Skeletal muscle channelopathy · R76 NHS GMS →
NHS Genomic Medicine Service Jeen carrier screening

Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory

Frequently asked questions

What is the main function of the CLCN1 gene?

The CLCN1 gene provides instructions for the ClC-1 chloride channel, which is found in skeletal muscles. This channel helps regulate the flow of chloride ions, stabilising the electrical charge of muscle cells and enabling normal muscle contraction and relaxation.

What health conditions are associated with CLCN1 gene variants?

Variants in the CLCN1 gene are associated with myotonia congenita, which can present as Myotonia congenita (Becker, recessive) or Myotonia congenita (Thomsen, dominant). These conditions affect muscle function, causing prolonged muscle contractions.

How common are CLCN1 gene variants?

Over 150 different variants in the CLCN1 gene have been identified in individuals diagnosed with myotonia congenita, with most leading to the autosomal recessive form known as Becker disease.

References

  1. Imbrici P, Altamura C, Pessia M. ClC-1 chloride channels: state-of-the-art research and future challenges. Frontiers in cellular neuroscience. 2015. PMID: 25964741
  2. Colding-Jørgensen E. Phenotypic variability in myotonia congenita. Muscle & nerve. 2005. PMID: 15786415
  3. Dunø M, Colding-Jørgensen E, Grunnet M. Difference in allelic expression of the CLCN1 gene and the possible influence on the myotonia congenita phenotype. European journal of human genetics : EJHG. 2004. PMID: 15162127
  4. Grunnet M, Jespersen T, Colding-Jørgensen E. Characterization of two new dominant ClC-1 channel mutations associated with myotonia. Muscle & nerve. 2003. PMID: 14639587
  5. Jentsch TJ, Stein V, Weinreich F. Molecular structure and physiological function of chloride channels. Physiological reviews. 2002. PMID: 11917096
  6. Pusch M. Myotonia caused by mutations in the muscle chloride channel gene CLCN1. Human mutation. 2002. PMID: 11933197
  7. Zhang J, Bendahhou S, Sanguinetti MC. Functional consequences of chloride channel gene (CLCN1) mutations causing myotonia congenita. Neurology. 2000. PMID: 10690989
  8. Zhang J, George AL Jr, Griggs RC. Mutations in the human skeletal muscle chloride channel gene (CLCN1) associated with dominant and recessive myotonia congenita. Neurology. 1996. PMID: 8857733
  9. Adam MP, Bick S, Mirzaa GM. Myotonia Congenita. 1993. PMID: 20301529
Educational content. This page is not medical or genetic advice, is not individually reviewed by a clinician for each reader, and should not replace a consultation with a qualified healthcare professional or genetic counsellor. If you are considering genetic testing or acting on a test result, book a consultation.
Data sources Last updated 27 September 2026. Content compiled from HGNC · MedlinePlus Genetics · ClinGen · Genomics England PanelApp · NHS National Genomic Test Directory · ClinVar · UniProt · AlphaFold .