CBX6

Chr 22

chromobox 6

NCBI Gene: 23466ENSG00000183741UniProt: O95503

Predicted to enable chromatin binding activity and methylated histone binding activity. Involved in negative regulation of transcription by RNA polymerase II. Located in nuclear body. Part of PcG protein complex. Biomarker of glioblastoma. [provided by Alliance of Genome Resources, Apr 2025]

85
ClinVar variants
20
Pathogenic / LP
0.98
pLI score· haploinsufficient
0
Active trials
Clinical Summary— CBX6
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.98). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
20 Pathogenic / Likely Pathogenic· 56 VUS of 85 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
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.
0.26LOEUF
pLI 0.976
Z-score 3.13
OE 0.00 (0.00–0.26)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

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.
2.31Z-score
OE missense 0.61 (0.54–0.69)
172 obs / 281.0 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

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.0.00 (0.00–0.26)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.61 (0.54–0.69)
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.0.95
0≤1.21.6
LoF obs/exp: 0 / 11.4Missense obs/exp: 172 / 281.0Syn Z: 0.44

ClinVar Variant Classifications

85 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic18
Likely Pathogenic2
VUS56
Likely Benign5
18
Pathogenic
2
Likely Pathogenic
56
VUS
5
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
18
0
18
Likely Pathogenic
0
0
2
0
2
VUS
0
53
3
0
56
Likely Benign
0
2
1
2
5
Benign
0
0
0
0
0
Total05524281

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

View in ClinVar →

Protein Context — Lollipop Plot

CBX6 · 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
CHROMOBOX 6; CBX6
MIM #617438 · *
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Proteasomal degradation of polycomb-group protein CBX6 confers MMP-2 expression essential for mesothelioma invasion.
Sakai K et al.·Sci Rep
2020
CBX6 induces CD8(+) T cell exhaustion and tumor development in esophageal squamous cell carcinoma through SMARCD1-mediated CCL8 secretion and lactate efflux.
Wang L et al.·Cell Biol Toxicol
2025
CBX6 overexpression contributes to tumor progression and is predictive of a poor prognosis in hepatocellular carcinoma.
Zheng H et al.·Oncotarget
2017
The predictive significance of chromobox family members in prostate cancer in humans.
Xu X et al.·Cell Oncol (Dordr)
2024
Network analysis reveals miRNA crosstalk between periodontitis and oral squamous cell carcinoma.
Li Z et al.·BMC Oral Health
2023
[Analysis of genes related to hypothyroidism during pregnancy].
Liang L et al.·Zhonghua Yi Xue Za Zhi
2019
CBXs-related prognostic gene signature correlates with immune microenvironment in gastric cancer.
Zhang YJ et al.·Aging (Albany NY)
2022
Identification and replication of the interplay of four genetic high-risk variants for urinary bladder cancer.
Selinski S et al.·Carcinogenesis
2017
Polycomb genes are associated with response to imatinib in chronic myeloid leukemia.
Crea F et al.·Epigenomics
2015
Mining database for the clinical significance and prognostic value of CBX family in skin cutaneous melanoma.
Li D et al.·J Clin Lab Anal
2020
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