CLCN4
Chloride Voltage-Gated Channel 4
Gene Information Card
| Symbol | CLCN4 |
|---|---|
| Full Name | Chloride Voltage-Gated Channel 4 |
| Gene Type | protein-coding |
| Chromosomal Location | Xp22.2 |
| NCBI Gene ID | 1183 ncbi.nlm.nih.gov/gene/1183 |
| Ensembl ID | ENSG00000173418 |
| UniProt ID | P51793 |
| OMIM ID | 302910 |
| HGNC ID | 2022 |
| Aliases | ClC-4, ClC-4A |
Description
The CLCN4 gene encodes the chloride voltage-gated channel 4 (ClC-4), a member of the ClC family of chloride channels and transporters. ClC-4 functions as a 2Cl-/H+ exchanger, playing a critical role in neuronal chloride homeostasis, synaptic vesicle acidification, and endosomal ion balance. Mutations in CLCN4 are associated with X-linked intellectual disability, epilepsy, and neurodevelopmental disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| X-linked intellectual disability (XLID) | Loss-of-function mutations impair chloride transport, disrupting neuronal excitability and synaptic function. | ClinVar, OMIM |
| Epileptic encephalopathy | Missense mutations alter channel gating, leading to neuronal hyperexcitability. | ClinVar, PubMed |
| Neurodevelopmental disorder with speech delay and behavioral abnormalities | Disrupted endosomal pH regulation affects neurotransmitter release. | OMIM, ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | High |
| Cerebral cortex | 15.3 | High |
| Cerebellum | 10.8 | High |
| Kidney | 6.2 | Medium |
| Lung | 4.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 14.7 | High expression |
| HEK293 (embryonic kidney) | 8.3 | Moderate expression |
| U-87 MG (glioblastoma) | 11.2 | High expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.116C>T (p.Pro39Leu) | Missense | Rare | Loss of function; reduced chloride transport |
| c.200G>A (p.Arg67Gln) | Missense | Rare | Gain of function; altered voltage dependence |
| c.1240C>T (p.Arg414Trp) | Missense | Rare | Dominant-negative effect; impaired dimerization |
Mutation functional classification
Loss of Function (LOF)
Mutations that reduce or abolish ClC-4 chloride transport activity, leading to impaired neuronal chloride homeostasis and synaptic dysfunction.
Gain of Function (GOF)
Mutations that enhance channel activity or alter gating properties, potentially causing neuronal hyperexcitability.
Dominant Negative (DN)
Mutations that interfere with wild-type ClC-4 function, often through defective dimerization or trafficking.
View complete mutation data：
Gene Ontology (GO)
| • voltage-gated chloride channel activity | • chloride transmembrane transport |
| • endosomal lumen acidification | • synaptic vesicle acidification |
| • ion transmembrane transport |
Pathways
• Chloride transport
• Synaptic vesicle cycle
• Endosomal acidification
Protein Summary
The ClC-4 protein is a 760-amino acid transmembrane protein that functions as a 2Cl-/H+ antiporter. It is predominantly expressed in the brain, where it localizes to endosomes, synaptic vesicles, and the plasma membrane. ClC-4 regulates chloride concentration and pH in intracellular compartments, essential for proper neurotransmitter loading and synaptic transmission. Mutations in CLCN4 disrupt these processes, leading to neurodevelopmental disorders.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CLCN4 Knockout HEK293 Cell Line | EDJ-KQ4288 | Human | 1183 | Details Get a Quote |
| CLCN4 Knockout A-549 Cell Line | EDJ-KQ26771 | Human | 1183 | Details Get a Quote |
| CLCN4 Knockout HCT 116 Cell Line | EDJ-KQ26772 | Human | 1183 | Details Get a Quote |
| CLCN4 Knockout HeLa Cell Line | EDJ-KQ26773 | Human | 1183 | Details Get a Quote |
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