CLIC3

Chr 9

chloride intracellular channel 3

NCBI Gene: 9022ENSG00000169583UniProt: O95833

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]

0
Active trials
0
Pathogenic / LP
0
ClinVar variants
4
Pubs (1 yr)
1.1
Missense Z
1.89
LOEUF
Clinical Summary— CLIC3
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.89LOEUF
pLI 0.000
Z-score -0.89
OE 1.33 (0.82–1.89)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.14Z-score
OE missense 0.74 (0.64–0.87)
116 obs / 156.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.1.33 (0.82–1.89)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.74 (0.64–0.87)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.67
0≤1.21.6
LoF obs/exp: 11 / 8.2Missense obs/exp: 116 / 156.3Syn Z: 2.30
DN
0.5870th %ile
GOF
0.75top 25%
LOF
0.3163th %ile

The highest-scoring mechanism for this gene is gain-of-function.

GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

CLIC3 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
Landmark / reviewRecent case evidence
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
In Vitro Enzymatic Studies Reveal pH and Temperature Sensitive Properties of the CLIC Proteins
Alghalayini A et al.·Biomolecules
2023
Identification of chloride intracellular channels as prognostic factors correlated with immune infiltration in hepatocellular carcinoma using bioinformatics analysis
Huang JJ et al.·Medicine (Baltimore)
2021
Identification of immune-related biomarkers in peripheral blood of schizophrenia using bioinformatic methods and machine learning algorithms
Zhu X et al.·Front Cell Neurosci
2023
The pursuit of novel head and neck cancer biomarkers - tissue and blood expression of chloride intracellular channels family.
Wojtera BP et al.·PLoS One
2025
Chloride intercellular channel 3 suppression-mediated macrophage polarization: a potential indicator of poor prognosis of hepatitis B virus-related acute-on-chronic liver failure.
Liang J et al.·Immunol Cell Biol
2022
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients