CLIC5

Chr 6AR

chloride intracellular channel 5

Also known as: DFNB102, DFNB103, MST130, MSTP130

NCBI Gene: 53405ENSG00000112782UniProt: Q9NZA1

This gene encodes a member of the chloride intracellular channel (CLIC) family of chloride ion channels. The encoded protein associates with actin-based cytoskeletal structures and may play a role in multiple processes including hair cell stereocilia formation, myoblast proliferation and glomerular podocyte and endothelial cell maintenance. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Dec 2011]

Primary Disease Associations & Inheritance

?Deafness, autosomal recessive 103MIM #616042
AR
210
ClinVar variants
15
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— CLIC5
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
15 Pathogenic / Likely Pathogenic· 91 VUS of 210 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.
1.17LOEUF
pLI 0.000
Z-score 1.06
OE 0.71 (0.45–1.17)
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.
0.54Z-score
OE missense 0.90 (0.80–1.01)
209 obs / 232.1 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.0.71 (0.45–1.17)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.90 (0.80–1.01)
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.1.07
0≤1.21.6
LoF obs/exp: 11 / 15.5Missense obs/exp: 209 / 232.1Syn Z: -0.57

ClinVar Variant Classifications

210 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic11
Likely Pathogenic4
VUS91
Likely Benign65
Benign30
Conflicting9
11
Pathogenic
4
Likely Pathogenic
91
VUS
65
Likely Benign
30
Benign
9
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
0
10
0
11
Likely Pathogenic
0
0
4
0
4
VUS
0
79
12
0
91
Likely Benign
0
8
19
38
65
Benign
0
6
21
3
30
Conflicting
—9
Total1936641210

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

View in ClinVar →

Protein Context — Lollipop Plot

CLIC5 · 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

?Deafness, autosomal recessive 103

MIM #616042

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
AAV gene therapy rescues hearing and balance in a model of CLIC5 deafness.
Hahn R et al.·EMBO Mol Med
2025Functional
Critical role of TPRN rings in the stereocilia for hearing.
Qi J et al.·Mol Ther
2024
Bi-Allelic Novel Variants in CLIC5 Identified in a Cameroonian Multiplex Family with Non-Syndromic Hearing Impairment.
Wonkam-Tingang E et al.·Genes (Basel)
2020
Identification and mutational analysis of candidate genes for juvenile myoclonic epilepsy on 6p11-p12: LRRC1, GCLC, KIAA0057 and CLIC5.
Suzuki T et al.·Epilepsy Res
2002
Progressive hearing loss and vestibular dysfunction caused by a homozygous nonsense mutation in CLIC5.
Seco CZ et al.·Eur J Hum Genet
2015
Modulation of pancreatic cancer cell sensitivity to FOLFIRINOX through microRNA-mediated regulation of DNA damage.
Carotenuto P et al.·Nat Commun
2021Meta-analysis
The c.644 G > A p.(Trp215*) founder variant in the CLIC5 gene causes progressive autosomal recessive deafness 103 (DFNB103) in Eastern Siberia.
Pshennikova VG et al.·J Hum Genet
2026
Whole Exome Sequencing of 20 Spanish Families: Candidate Genes for Non-Syndromic Pediatric Cataracts.
Rodríguez-Solana P et al.·Int J Mol Sci
2023
Genome-wide methylation profiling identifies novel methylated genes in neuroblastoma tumors.
Olsson M et al.·Epigenetics
2016
Patients with isolated oligo/hypodontia caused by RUNX2 duplication.
Molin A et al.·Am J Med Genet A
2015Case report
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