CLIC3
protein-codingchloride intracellular channel 3, the group of Chloride intracellular channels
Gene summary
Chloride channels are a diverse group of proteins that regulate fundamental cellular processes including stabilization of cell membrane potential, transepithelial transport, maintenance of intracellular pH, and regulation of cell volume. Chloride intracellular channel 3 is a member of the p64 family and is predominantly localized in the nucleus and stimulates chloride ion channel activity. In addition, this protein may participate in cellular growth control, based on its association with ERK7, a member of the MAP kinase family. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~2.0 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to CLIC3 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_004669.3. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 0 | |||||
| missense | 39 | 39 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 40 | 0 | 0 | 40 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_004660.2 | 6 | MANE Select | |
| Ensembl | ENSP00000419378.1 | 6 | MANE Select | |
| Ensembl | ENSP00000526151.1 | 6 | Standard | |
| Ensembl | ENSP00000526151.1 | 6 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- chloride transport
- signal transduction
- regulation of ion transmembrane transport
- chloride transmembrane transport
Molecular Function
- voltage-gated ion channel activity
- chloride channel activity
- protein binding
Cellular Component
- nucleus
- cytoplasm
- nuclear body
- chloride channel complex
- extracellular exosome
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000494426
- Coding exons
- 6
- Length
- 2169
- Individuals with no LoFs
- 125265
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 20
- Defined
- 125285
- p
- 0.0000798
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.14 | 116 | 156 | 0.742 | 0.0000114 | 1496 |
| Missense (PolyPhen) | 41 | 55.466 | 0.73919 | 622 | ||
| Synonymous | 2.30 | 52 | 77.8 | 0.668 | 0.00000621 | 481 |
| Loss of Function | -0.889 | 11 | 8.25 | 1.33 | 3.93e-7 | 101 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000063 | 0.000062 | rare |
| Latino/Admixed American | 0.00031 | 0.00029 | rare |
| Ashkenazi Jewish | 0.00010 | 0.00010 | rare |
| East Asian | 0.00011 | 0.00011 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000027 | 0.000027 | rare |
| South Asian | 0.000065 | 0.000065 | rare |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Can insert into membranes and form chloride ion channels. May participate in cellular growth control. {ECO:0000269|PubMed:9880541}.;
Recessive Scores
- pRec
- 0.110
Intolerance Scores
- LoFtool
- 0.560
- RVIS EVS
- 0.04
- RVIS percentile EVS
- 56.92
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.862
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |