CLIC1

Chr 6

chloride intracellular channel 1

Also known as: CL1C1, CLCNL1, G6, NCC27

NCBI Gene: 1192ENSG00000213719UniProt: O00299

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 1 is a member of the p64 family; the protein localizes principally to the cell nucleus and exhibits both nuclear and plasma membrane chloride ion channel activity. [provided by RefSeq, Jul 2008]

37
ClinVar variants
7
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— CLIC1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
7 Pathogenic / Likely Pathogenic· 26 VUS of 37 total submissions

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.
1.26LOEUF
pLI 0.000
Z-score 0.97
OE 0.67 (0.38–1.26)
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.
1.43Z-score
OE missense 0.65 (0.54–0.77)
83 obs / 128.6 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.0.67 (0.38–1.26)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.65 (0.54–0.77)
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.0.87
0≤1.21.6
LoF obs/exp: 7 / 10.4Missense obs/exp: 83 / 128.6Syn Z: 0.75

ClinVar Variant Classifications

37 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic5
Likely Pathogenic2
VUS26
Likely Benign4
5
Pathogenic
2
Likely Pathogenic
26
VUS
4
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
5
0
5
Likely Pathogenic
0
0
2
0
2
VUS
0
22
4
0
26
Likely Benign
0
4
0
0
4
Benign
0
0
0
0
0
Total02611037

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

CLIC1 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
A CLIC1 network coordinates matrix stiffness and the Warburg effect to promote tumor growth in pancreatic cancer.
Zheng JH et al.·Cell Rep
2024
The CLIC1-PKM2 axis orchestrates glycolytic metabolism to accelerate gastric cancer progression.
Yang J et al.·J Transl Med
2025
Comprehensive analysis of clinical prognosis and CLIC1 immune invasion in lung adenocarcinoma.
Chen Z et al.·Medicine (Baltimore)
2022
CLIC1 Drives Angiogenesis in Hepatocellular Carcinoma by Modulating VEGFA.
Wei X et al.·Technol Cancer Res Treat
2022
The chloride intracellular channel 1 (CLIC1) is essential for microglial morphodynamics and neuroinflammation.
Rifat A et al.·Sci Adv
2025
CLIC1 regulates cellular oxidative stress and gastric cancer progress by enhancing ACOX1 ubiquitination.
Li C et al.·Int J Biol Macromol
2025
The expression and clinical significance of CLIC1 and HSP27 in lung adenocarcinoma.
Wang W et al.·Tumour Biol
2011
CLIC1-mediated autophagy confers resistance to DDP in gastric cancer.
Nong ZL et al.·Anticancer Drugs
2024
Genetic associations in ankylosing spondylitis: circulating proteins as drug targets and biomarkers.
Zhang Y et al.·Front Immunol
2024
CLIC1 overexpression is associated with poor prognosis in pancreatic ductal adenocarcinomas.
Jia N et al.·J Cancer Res Ther
2016
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools