CLIC5: Chloride Intracellular Channel 5
A multifunctional protein involved in ion transport, cytoskeletal dynamics, and kidney function
Gene Information Card
| Symbol | CLIC5 |
|---|---|
| Full Name | Chloride Intracellular Channel 5 |
| Gene Type | Protein coding |
| Chromosomal Location | 6p21.1 |
| NCBI Gene ID | 53405 ncbi.nlm.nih.gov/gene/53405 |
| Ensembl ID | ENSG00000112782 |
| UniProt ID | Q9NZA1 |
| OMIM ID | 607293 |
| HGNC ID | 13517 |
| Aliases | CLIC5A, CLIC5B, MST130, DFNB102, DFNB103 |
Description
CLIC5 encodes a member of the chloride intracellular channel (CLIC) family of proteins that function as ion channels and also participate in cytoskeletal organization. The protein exists in two isoforms: CLIC5A, which is predominantly expressed in kidney glomerular podocytes and inner ear hair cells, and CLIC5B, which is more widely expressed. CLIC5 interacts with actin and other cytoskeletal components, playing a critical role in maintaining the structural integrity of podocyte foot processes and stereocilia. Mutations in CLIC5 are associated with autosomal recessive deafness and nephrotic syndrome.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Deafness, autosomal recessive 102 (DFNB102) | Loss of CLIC5 function disrupts stereocilia structure in inner ear hair cells, leading to sensorineural hearing loss | ClinVar, OMIM |
| Deafness, autosomal recessive 103 (DFNB103) | Similar mechanism as DFNB102; CLIC5 mutations impair actin-based cytoskeletal organization in cochlear hair cells | ClinVar, OMIM |
| Nephrotic syndrome, type 20 (NPHS20) | CLIC5 deficiency in podocytes causes foot process effacement and glomerular basement membrane abnormalities, resulting in proteinuria and kidney disease | ClinVar, OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Kidney | 12.5 | Medium |
| Inner ear (cochlea) | N/A | High (specific to hair cells) |
| Lung | 8.3 | Low |
| Placenta | 6.7 | Low |
| Testis | 5.9 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Podocytes (kidney) | N/A | High; essential for foot process integrity |
| HEK293 | 10.2 | Moderate |
| HeLa | 7.8 | Low |
| HepG2 | 6.1 | Low |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.148C>T (p.Arg50*) | Nonsense | Rare | Loss of function; associated with DFNB102 |
| c.208G>A (p.Gly70Arg) | Missense | Rare | Loss of function; disrupts protein folding and channel activity |
| c.319C>T (p.Arg107Trp) | Missense | Rare | Loss of function; impairs actin binding |
| c.463_464del (p.Leu155Alafs*12) | Frameshift | Rare | Loss of function; premature truncation |
Mutation functional classification
Loss of Function (LOF)
Most CLIC5 mutations are loss-of-function, leading to reduced or absent protein activity, which disrupts cytoskeletal organization in kidney podocytes and inner ear hair cells.
Gain of Function (GOF)
No gain-of-function mutations have been reported for CLIC5.
Dominant Negative (DN)
No dominant-negative mutations have been described; inheritance is autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Chloride channel complex (Reactome: R-HSA-983712)
• Actin cytoskeleton regulation (Reactome: R-HSA-5663222)
• Podocyte differentiation (KEGG: hsa04530)
Protein Summary
CLIC5 is a 251-amino acid protein (isoform A) that belongs to the CLIC family. It exists as a soluble monomer in the cytoplasm and can insert into membranes to form chloride ion channels. The protein contains a conserved glutathione S-transferase (GST)-like domain and a C-terminal transmembrane domain. CLIC5 interacts with actin, ezrin, and other cytoskeletal proteins, linking ion transport to cytoskeletal dynamics. In kidney podocytes, CLIC5 is essential for maintaining the slit diaphragm and foot process architecture. In inner ear hair cells, it is required for stereocilia bundle formation and mechanotransduction.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CLIC5 Knockout HEK293 Cell Line | EDJ-KQ2787 | Human | 53405 | Details Get a Quote |
| CLIC5 Knockout HeLa Cell Line | EDJ-KQ56374 | Human | 53405 | Details Get a Quote |
| CLIC5 Knockout A-549 Cell Line | EDJ-KQ64866 | Human | 53405 | Details Get a Quote |
| CLIC5 Knockout HCT 116 Cell Line | EDJ-KQ73310 | Human | 53405 | Details Get a Quote |
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