CLIC6

Chr 21

CLIC family member 6

Also known as: CLIC1L

NCBI Gene: 54102 ENSG00000159212 UniProt: Q96NY7 OMIM: 615321

This gene encodes a member of the chloride intracellular channel family of proteins. The gene is part of a large triplicated region found on chromosomes 1, 6, and 21. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Nov 2015]

OMIM Research

OMIM ResearchGenerating clinical summary…

GOFmechanismLOEUF 1.10

Clinical Summary— CLIC6

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

1 unique Pathogenic / Likely Pathogenic· 137 VUS of 174 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.10LOEUF

pLI 0.000

Z-score 1.30

OE 0.63 (0.38–1.10)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.68Z-score

OE missense 0.88 (0.79–0.98)

220 obs / 250.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.63 (0.38–1.10)

0≤0.351.4

Missense OE?0.88 (0.79–0.98)

0≤0.61.4

Synonymous OE?1.04

0≤1.21.6

LoF obs/exp: 9 / 14.3Missense obs/exp: 220 / 250.3Syn Z: -0.34

This gene — mechanism propensity

0.5674th %ile

GOF

0.6930th %ile

LOF

0.3550th %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

174 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic1

VUS137

Likely Benign21

Benign10

Pathogenic

137

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	1	0	1
Likely Pathogenic	0	0	0	0
VUS	137	0	0	137
Likely Benign	10	0	11	21
Benign	7	0	3	10
Total	154	1	14	169

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

View in ClinVar →

61 pathogenic / likely-pathogenic (of 71) ClinVar copy-number / structural variants overlap CLIC6 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →