CBX3

Chr 7

chromobox 3

Also known as: HECH, HP1-GAMMA, HP1Hs-gamma, HP1gamma

NCBI Gene: 11335ENSG00000122565UniProt: Q13185

At the nuclear envelope, the nuclear lamina and heterochromatin are adjacent to the inner nuclear membrane. The protein encoded by this gene binds DNA and is a component of heterochromatin. This protein also can bind lamin B receptor, an integral membrane protein found in the inner nuclear membrane. The dual binding functions of the encoded protein may explain the association of heterochromatin with the inner nuclear membrane. This protein binds histone H3 tails methylated at Lys-9 sites. This protein is also recruited to sites of ultraviolet-induced DNA damage and double-strand breaks. Two transcript variants encoding the same protein but differing in the 5' UTR, have been found for this gene.[provided by RefSeq, Mar 2011]

46
ClinVar variants
31
Pathogenic / LP
0.41
pLI score
0
Active trials
Clinical Summary— CBX3
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.21) despite low pLI — interpret in context.
📋
ClinVar Variants
31 Pathogenic / Likely Pathogenic· 15 VUS of 46 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.
0.67LOEUF
pLI 0.410
Z-score 2.24
OE 0.21 (0.09–0.67)
Tolerant

Typical tolerance to LoF variation

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.
1.93Z-score
OE missense 0.42 (0.32–0.55)
37 obs / 87.9 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.0.21 (0.09–0.67)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.42 (0.32–0.55)
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.1.36
0≤1.21.6
LoF obs/exp: 2 / 9.4Missense obs/exp: 37 / 87.9Syn Z: -1.52

ClinVar Variant Classifications

46 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic27
Likely Pathogenic4
VUS15
27
Pathogenic
4
Likely Pathogenic
15
VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
27
0
27
Likely Pathogenic
0
0
4
0
4
VUS
0
8
7
0
15
Likely Benign
0
0
0
0
0
Benign
0
0
0
0
0
Total0838046

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

View in ClinVar →

Protein Context — Lollipop Plot

CBX3 · 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 3; CBX3
MIM #604477 · *
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Fusion of Tumor Cells with Lipid-Associated Macrophages Drives Metastatic Progression of Breast Cancer.
Cheng Y et al.·Cancer Res
2026
CBX3 confers ferroptosis resistance during blood-borne metastasis.
Wu C et al.·J Hematol Oncol
2026
Integrating Bulk RNA and Single-Cell RNA Sequencing Identifies and Validates Lactylation-Related Signatures for Intervertebral Disc Degeneration.
Shi Y et al.·J Cell Mol Med
2024
SETDB1 recruits CBX3 to regulate the SIRT4/PTEN axis, inhibiting autophagy and promoting ischemia-reperfusion-induced kidney injury.
Liu YF et al.·FASEB J
2025
CBX3/HP1γ promotes tumor proliferation and predicts poor survival in hepatocellular carcinoma.
Zhong X et al.·Aging (Albany NY)
2019
The predictive significance of chromobox family members in prostate cancer in humans.
Xu X et al.·Cell Oncol (Dordr)
2024
CBX3 promotes glioma U87 cell proliferation and predicts an unfavorable prognosis.
Zhao SP et al.·J Neurooncol
2019
CBX3 predicts an unfavorable prognosis and promotes tumorigenesis in osteosarcoma.
Ma C et al.·Mol Med Rep
2019
Integrated bioinformatics investigation and experimental validation reveals the clinical and biological significance of chromobox family in breast cancer.
Ge X et al.·Sci Rep
2025
The inner nuclear membrane protein LEMD3 organizes the 3D chromatin architecture to maintain vascular smooth muscle cell identity.
Li W et al.·Nat Commun
2025
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