CLIC4: Chloride Intracellular Channel 4 – Ion Channel and Signaling Regulator
A comprehensive biomedical resource on CLIC4 gene, protein, expression, mutations, and associated diseases.
Gene Information Card
| Symbol | CLIC4 |
|---|---|
| Full Name | Chloride Intracellular Channel 4 |
| Gene Type | Protein coding |
| Chromosomal Location | 1p36.11 |
| NCBI Gene ID | 25932 ncbi.nlm.nih.gov/gene/25932 |
| Ensembl ID | ENSG00000169564 |
| UniProt ID | Q9Y696 |
| OMIM ID | 606536 |
| HGNC ID | 2063 |
| Aliases | p64H1, CLIC4L, H1, huH1 |
Description
CLIC4 (Chloride Intracellular Channel 4) encodes a member of the chloride intracellular channel family. The protein functions as an ion channel regulated by oxidation-reduction state and is involved in cell cycle regulation, apoptosis, and angiogenesis. It localizes to the cytoplasm, nucleus, and plasma membrane, and plays roles in cellular signaling, differentiation, and tumor suppression.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (multiple types) | Altered CLIC4 expression affects cell proliferation, migration, and invasion; acts as a tumor suppressor in some contexts. | NCBI Gene, COSMIC |
| Neurological disorders | CLIC4 implicated in neuronal differentiation and synaptic function; dysregulation linked to neurodevelopmental conditions. | OMIM, ClinVar |
| Cardiovascular disease | CLIC4 modulates endothelial cell function and angiogenesis; associated with vascular remodeling. | UniProt, NCBI Gene |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 15.2 | Medium |
| Heart | 12.8 | Medium |
| Lung | 18.5 | High |
| Liver | 9.1 | Low |
| Kidney | 14.3 | Medium |
| Testis | 20.1 | High |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 16.4 | High expression |
| HeLa | 12.1 | Moderate expression |
| A549 | 14.7 | High expression |
| MCF7 | 10.3 | Moderate expression |
| SH-SY5Y | 18.9 | High expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.287G>A (p.Arg96His) | Missense | <0.1% | Altered channel activity; potential loss of function |
| c.412C>T (p.Pro138Ser) | Missense | <0.1% | Unknown functional effect |
| c.523_524insA | Frameshift | <0.1% | Predicted loss of function |
Mutation functional classification
Loss of Function (LOF)
Frameshift and nonsense mutations predicted to truncate protein; missense variants may impair channel gating or stability.
Gain of Function (GOF)
Not well documented; some missense variants may enhance activity but evidence is limited.
Dominant Negative (DN)
Not reported for CLIC4.
View complete mutation data：
Gene Ontology (GO)
| • chloride channel activity | • intracellular chloride channel activity |
| • voltage-gated chloride channel activity | • protein binding |
| • identical protein binding | • plasma membrane |
| • cytoplasm | • nucleus |
| • cell cycle | • apoptotic process |
| • angiogenesis |
Pathways
• Chloride channel complex
• Ion transport
• Apoptosis signaling
• VEGF signaling pathway
Protein Summary
CLIC4 is a 253-amino acid protein that exists in both soluble and membrane-associated forms. It undergoes redox-dependent structural changes to form chloride channels. The protein interacts with multiple partners including actin, tubulin, and signaling kinases, influencing cytoskeletal dynamics, cell cycle progression, and apoptosis. CLIC4 is widely expressed and its dysregulation contributes to cancer, neurological, and cardiovascular pathologies.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CLIC4 Knockout HEK293 Cell Line | EDJ-KQ8309 | Human | 25932 | Details Get a Quote |
| CLIC4 Knockout HeLa Cell Line | EDJ-KQ32961 | Human | 25932 | Details Get a Quote |
| CLIC4 Knockout A-549 Cell Line | EDJ-KQ34277 | Human | 25932 | Details Get a Quote |
| CLIC4 Knockout HCT 116 Cell Line | EDJ-KQ34278 | Human | 25932 | Details Get a Quote |
