CLCN7
Chloride Voltage-Gated Channel 7
Gene Information Card
| Symbol | CLCN7 |
|---|---|
| Full Name | Chloride Voltage-Gated Channel 7 |
| Gene Type | Protein coding |
| Chromosomal Location | 16p13.3 |
| NCBI Gene ID | 1186 ncbi.nlm.nih.gov/gene/1186 |
| Ensembl ID | ENSG00000103249 |
| UniProt ID | P51798 |
| OMIM ID | 602727 |
| HGNC ID | 2025 |
| Aliases | ClC-7, CLC7, OPTB2 |
Description
The CLCN7 gene encodes the chloride channel 7 (ClC-7) protein, a member of the voltage-gated chloride channel family. ClC-7 is primarily localized to lysosomal membranes and osteoclast ruffled borders, where it mediates chloride ion transport essential for acidification of lysosomes and bone resorption. Mutations in CLCN7 cause autosomal recessive and dominant forms of osteopetrosis, as well as lysosomal storage disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Osteopetrosis, autosomal recessive 4 (OPTB4) | Loss-of-function mutations impair osteoclast acidification, reducing bone resorption and causing dense, brittle bones. | ClinVar, OMIM |
| Osteopetrosis, autosomal dominant 2 (OPTB2) | Dominant-negative mutations disrupt ClC-7 function, leading to mild to moderate osteopetrosis. | ClinVar, OMIM |
| Neuronopathic osteopetrosis | Severe loss-of-function mutations cause lysosomal dysfunction in neurons, leading to neurodegeneration. | OMIM, PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Bone marrow | 10.2 | Medium |
| Brain | 8.5 | Medium |
| Kidney | 7.1 | Medium |
| Liver | 6.3 | Low |
| Lung | 5.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Osteoclasts | 15.0 | High expression; critical for bone resorption |
| HEK 293 | 9.5 | Model for functional studies |
| HeLa | 7.2 | Moderate expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.229G>A (p.Gly77Arg) | Missense | Rare | Dominant-negative; causes OPTB2 |
| c.857A>G (p.Tyr286Cys) | Missense | Rare | Loss-of-function; causes OPTB4 |
| c.1610C>T (p.Pro537Leu) | Missense | Rare | Dominant-negative; associated with neuronopathic osteopetrosis |
Mutation functional classification
Loss of Function (LOF)
Complete loss of ClC-7 activity impairs lysosomal acidification and osteoclast function, leading to severe recessive osteopetrosis.
Gain of Function (GOF)
Not reported for CLCN7.
Dominant Negative (DN)
Mutant ClC-7 subunits disrupt wild-type channel function, causing dominant osteopetrosis (OPTB2).
View complete mutation data：
Gene Ontology (GO)
| • GO:0005247 - voltage-gated chloride channel activity | • GO:0006821 - chloride transport |
| • GO:0016021 - integral component of membrane | • GO:0005764 - lysosome |
| • GO:0035583 - ruffled border |
Pathways
• Lysosomal acidification (Reactome: R-HSA-425986)
• Osteoclast differentiation (KEGG: hsa04380)
Protein Summary
ClC-7 is a 805-amino acid transmembrane protein that forms a homodimeric chloride channel. It requires the accessory subunit Ostm1 for proper function. The protein is essential for lysosomal chloride conductance and acidification, and in osteoclasts, it mediates HCl secretion into the resorption lacuna, enabling bone matrix degradation.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CLCN7 Knockout HEK293 Cell Line | EDJ-KQ3589 | Human | 1186 | Details Get a Quote |
| CLCN7 Knockout HeLa Cell Line | EDJ-KQ18188 | Human | 1186 | Details Get a Quote |
| CLCN7 Knockout A-549 Cell Line | EDJ-KQ25491 | Human | 1186 | Details Get a Quote |
| CLCN7 Knockout HCT 116 Cell Line | EDJ-KQ25492 | Human | 1186 | Details Get a Quote |
| CLCN7 Knockout HAP1 Cell Line | EDC09402 | Human | 1186 | Details Get a Quote |
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