CLCN3
Chloride Voltage-Gated Channel 3
Gene Information Card
| Symbol | CLCN3 |
|---|---|
| Full Name | Chloride Voltage-Gated Channel 3 |
| Gene Type | Protein coding |
| Chromosomal Location | 4q33 |
| NCBI Gene ID | 1182 ncbi.nlm.nih.gov/gene/1182 |
| Ensembl ID | ENSG00000109519 |
| UniProt ID | P51790 |
| OMIM ID | 600580 |
| HGNC ID | 2021 |
| Aliases | ClC-3, ClC3 |
Description
CLCN3 encodes a member of the voltage-gated chloride channel (CLC) family. The encoded protein functions as a chloride ion channel and is involved in various cellular processes including ion homeostasis, cell volume regulation, and acidification of intracellular organelles. Mutations in CLCN3 have been associated with neurodevelopmental disorders and epilepsy.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Neurodevelopmental disorder with epilepsy and brain atrophy | Loss-of-function mutations impair chloride conductance, disrupting neuronal ion homeostasis | ClinVar, OMIM |
| Epileptic encephalopathy, early infantile | Biallelic missense variants reduce channel activity, leading to neuronal hyperexcitability | ClinVar, PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Heart | 8.3 | Medium |
| Kidney | 7.1 | Medium |
| Liver | 4.2 | Low |
| Lung | 5.6 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y | 10.2 | Neuroblastoma cell line |
| HEK 293 | 9.8 | Embryonic kidney cells |
| HeLa | 6.5 | Cervical carcinoma cells |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1582C>T (p.Arg528Trp) | Missense | Rare | Loss of chloride conductance |
| c.1015G>A (p.Gly339Arg) | Missense | Rare | Reduced channel activity |
| c.1240_1242del (p.Phe414del) | Deletion | Rare | Dominant-negative effect |
Mutation functional classification
Loss of Function (LOF)
Missense variants (e.g., p.Arg528Trp) reduce or abolish chloride ion conductance.
Gain of Function (GOF)
Not reported in CLCN3.
Dominant Negative (DN)
Deletion variant p.Phe414del exerts dominant-negative effect on wild-type channel function.
View complete mutation data：
Gene Ontology (GO)
| • voltage-gated chloride channel activity | • chloride transmembrane transport |
| • intracellular chloride ion homeostasis | • plasma membrane |
| • endosome membrane | • lysosome membrane |
Pathways
• Ion transport by P-type ATPases
• Chloride channelopathies
Protein Summary
The CLCN3 protein (ClC-3) is a 818-amino acid voltage-gated chloride channel that forms homodimers and heterodimers with other CLC family members. It localizes to plasma membranes and intracellular vesicles, mediating chloride flux essential for neuronal excitability, cell volume regulation, and organellar acidification.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CLCN3 Knockout HEK293 Cell Line | EDJ-KQ4291 | Human | 1182 | Details Get a Quote |
| CLCN3 Knockout A-549 Cell Line | EDJ-KQ26777 | Human | 1182 | Details Get a Quote |
| CLCN3 Knockout HCT 116 Cell Line | EDJ-KQ26778 | Human | 1182 | Details Get a Quote |
| CLCN3 Knockout HeLa Cell Line | EDJ-KQ26779 | Human | 1182 | Details Get a Quote |
Displaying Records 1 To 4 Of 4 Records
