CLCN2
Chloride Voltage-Gated Channel 2
Gene Information Card
| Symbol | CLCN2 |
|---|---|
| Full Name | chloride voltage-gated channel 2 |
| Gene Type | protein-coding |
| Chromosomal Location | 3q27.1 |
| NCBI Gene ID | 1181 ncbi.nlm.nih.gov/gene/1181 |
| Ensembl ID | ENSG00000114859 |
| UniProt ID | P51788 |
| OMIM ID | 600570 |
| HGNC ID | 2020 |
| Aliases | ClC-2, ECA3, ECA2 |
Description
CLCN2 encodes the chloride voltage-gated channel 2 (ClC-2), a member of the ClC family of chloride channels. This channel is involved in regulating chloride ion transport across cell membranes, playing a critical role in neuronal excitability, fluid secretion, and cell volume regulation. Mutations in CLCN2 are associated with leukodystrophy and idiopathic generalized epilepsy.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Leukodystrophy, hypomyelinating, 2 (HLD2) | Loss-of-function mutations impair chloride conductance in oligodendrocytes, disrupting myelin formation | OMIM #608804 |
| Epilepsy, idiopathic generalized, susceptibility to (ECA3) | Altered channel gating leads to neuronal hyperexcitability | OMIM #600570 |
| Epilepsy, juvenile myoclonic (ECA2) | Missense variants reduce channel function, contributing to seizure susceptibility | ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Kidney | 8.3 | Medium |
| Lung | 6.1 | Low |
| Heart | 4.7 | Low |
| Liver | 3.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y | 10.2 | Neuroblastoma cell line |
| HEK293 | 7.8 | Embryonic kidney cells |
| U-87 MG | 9.1 | Glioblastoma cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.61C>T (p.Arg21Trp) | Missense | <0.01% | Loss of function; associated with epilepsy |
| c.355G>A (p.Gly119Arg) | Missense | <0.01% | Impaired channel activity; leukodystrophy |
| c.1313G>A (p.Arg438His) | Missense | <0.01% | Reduced chloride conductance; epilepsy |
Mutation functional classification
Loss of Function (LOF)
Most reported pathogenic mutations reduce or abolish chloride channel activity, leading to hypomyelination or neuronal hyperexcitability.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported in CLCN2.
Dominant Negative (DN)
Some missense variants may exert dominant-negative effects by interfering with wild-type channel assembly.
View complete mutation data：
Gene Ontology (GO)
| • voltage-gated chloride channel activity | • chloride transmembrane transport |
| • ion channel complex | • plasma membrane |
| • regulation of membrane potential |
Pathways
• Chloride channelopathies
• Ion transport by P-type ATPases
• Neurotransmitter release cycle
Protein Summary
The ClC-2 protein is a 898-amino acid transmembrane chloride channel that forms homodimers. It is activated by hyperpolarization, cell swelling, and acidic pH. ClC-2 is widely expressed, with highest levels in brain and kidney, and plays roles in neuronal chloride homeostasis and renal salt transport.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CLCN2 Knockout HEK293 Cell Line | EDC09609 | Human | 1181 | Details Get a Quote |
| CLCN2 Knockout A-549 Cell Line | EDJ-KQ25235 | Human | 1181 | Details Get a Quote |
| CLCN2 Knockout HCT 116 Cell Line | EDJ-KQ25237 | Human | 1181 | Details Get a Quote |
| CLCN2 Knockout HeLa Cell Line | EDJ-KQ25238 | Human | 1181 | Details Get a Quote |
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