CLCN1
Chloride Voltage-Gated Channel 1
Gene Information Card
| Symbol | CLCN1 |
|---|---|
| Full Name | Chloride Voltage-Gated Channel 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 7q34 |
| NCBI Gene ID | 1180 ncbi.nlm.nih.gov/gene/1180 |
| Ensembl ID | ENSG00000186510 |
| UniProt ID | P35523 |
| OMIM ID | 118425 |
| HGNC ID | 2019 |
| Aliases | CLC1, CLC-1, ClC-1 |
Description
The CLCN1 gene encodes the voltage-gated chloride channel ClC-1, which is predominantly expressed in skeletal muscle. This channel is essential for stabilizing the resting membrane potential and repolarizing muscle fibers after contraction. Loss-of-function mutations in CLCN1 lead to myotonia congenita, characterized by muscle stiffness and delayed relaxation. The gene is located on chromosome 7q34 and belongs to the CLC family of chloride channels.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Myotonia Congenita (Thomsen disease, autosomal dominant) | Dominant-negative or loss-of-function mutations reduce chloride conductance, causing hyperexcitability of the sarcolemma and delayed muscle relaxation. | ClinVar, OMIM |
| Myotonia Congenita (Becker disease, autosomal recessive) | Biallelic loss-of-function mutations severely impair chloride channel function, leading to more pronounced myotonia and transient weakness. | ClinVar, OMIM |
| Congenital Myotonia (general) | Mutations in CLCN1 disrupt chloride ion flow, prolonging muscle action potentials and causing repetitive discharges. | NCBI Gene, OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Skeletal muscle | 29.8 | High |
| Heart | 1.2 | Low |
| Brain | 0.5 | Not detected |
| Liver | 0.1 | Not detected |
| Kidney | 0.3 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| LHCN-M2 (skeletal muscle myoblast) | 30.1 | High expression |
| HSMM (skeletal muscle satellite cells) | 28.5 | High expression |
| A549 (lung carcinoma) | 0.2 | Not detected |
| HEK 293 (embryonic kidney) | 0.1 | Not detected |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1437_1450del (p.Arg479_Leu484del) | Deletion | Rare | Loss-of-function; associated with autosomal recessive myotonia congenita |
| c.2680C>T (p.Arg894Ter) | Nonsense | Rare | Loss-of-function; truncation of ClC-1 protein |
| c.1238T>G (p.Phe413Cys) | Missense | Rare | Dominant-negative; reduces chloride conductance in Thomsen disease |
| c.689G>A (p.Gly230Glu) | Missense | Rare | Loss-of-function; associated with Becker myotonia congenita |
Mutation functional classification
Loss of Function (LOF)
Most CLCN1 mutations are loss-of-function, reducing or abolishing chloride conductance, leading to muscle hyperexcitability and myotonia.
Gain of Function (GOF)
No gain-of-function mutations have been reported for CLCN1.
Dominant Negative (DN)
Dominant-negative mutations (e.g., p.Phe413Cys) impair the function of wild-type subunits in the homodimeric channel, causing autosomal dominant myotonia congenita (Thomsen disease).
View complete mutation data：
Gene Ontology (GO)
| • voltage-gated chloride channel activity (GO:0005247) | • chloride transport (GO:0006821) |
| • integral component of membrane (GO:0016021) | • plasma membrane (GO:0005886) |
| • transmembrane transport (GO:0055085) | • muscle contraction (GO:0006936) |
Pathways
• REACTOME:R-HSA-2672351 – Stimuli-sensing channels
• REACTOME:R-HSA-1296072 – Voltage gated chloride channels
• KEGG:hsa04742 – Taste transduction (minor role)
• KEGG:hsa04260 – Cardiac muscle contraction (indirect)
Protein Summary
The ClC-1 protein is a homodimeric voltage-gated chloride channel with 988 amino acids. Each subunit contains 18 transmembrane helices and a cytoplasmic CBS domain. The channel mediates chloride ion efflux to repolarize skeletal muscle fibers after action potentials. Mutations in CLCN1 disrupt channel function, causing myotonia congenita. The protein is primarily localized to the sarcolemma and T-tubules of skeletal muscle.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CLCN1 Knockout HEK293 Cell Line | EDJ-KQ2129 | Human | 1180 | Details Get a Quote |
| CLCN1 Knockout HeLa Cell Line | EDJ-KQ52924 | Human | 1180 | Details Get a Quote |
| CLCN1 Knockout A-549 Cell Line | EDJ-KQ61391 | Human | 1180 | Details Get a Quote |
| CLCN1 Knockout HCT 116 Cell Line | EDJ-KQ69886 | Human | 1180 | Details Get a Quote |
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