CBX2

Chr 17AR

chromobox 2

Also known as: CDCA6, M33, SRXY5

NCBI Gene: 84733ENSG00000173894UniProt: Q14781

This gene encodes a component of the polycomb multiprotein complex, which is required to maintain the transcriptionally repressive state of many genes throughout development via chromatin remodeling and modification of histones. Disruption of this gene in mice results in male-to-female gonadal sex reversal. Mutations in this gene are also associated with gonadal dysgenesis in humans. Alternatively spliced transcript variants encoding different isoforms have been noted for this gene.[provided by RefSeq, Mar 2010]

Primary Disease Associations & Inheritance

?46XY sex reversal 5MIM #613080
AR
UniProt46,XY sex reversal 5
0
Active trials
1
Pathogenic / LP
91
ClinVar variants
8
Pubs (1 yr)
-0.3
Missense Z
0.19
LOEUF· LoF intolerant
Clinical Summary— CBX2
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
1 Pathogenic / Likely Pathogenic· 74 VUS of 91 total submissions
📖
GeneReview available — CBX2
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

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.
0.19LOEUF
pLI 0.995
Z-score 3.67
OE 0.00 (0.00–0.19)
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.
-0.26Z-score
OE missense 1.04 (0.95–1.14)
345 obs / 331.6 exp
Tolerant

Tolerant to missense variation

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 (0.00–0.19)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.04 (0.95–1.14)
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.1.31
0≤1.21.6
LoF obs/exp: 0 / 15.7Missense obs/exp: 345 / 331.6Syn Z: -2.98

ClinVar Variant Classifications

91 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic1
VUS74
Likely Benign14
Benign2
1
Pathogenic
74
VUS
14
Likely Benign
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
1
0
1
Likely Pathogenic
0
0
0
0
0
VUS
0
70
3
1
74
Likely Benign
0
4
2
8
14
Benign
0
0
0
2
2
Total07461191

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

View in ClinVar →

Protein Context — Lollipop Plot

CBX2 · 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 2; CBX2
MIM #602770 · *

?46XY sex reversal 5

MIM #613080

Molecular basis of disorder known

Autosomal recessive

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Beyond EZH2: is the polycomb protein CBX2 an emerging target for anti-cancer therapy?
Jangal M et al.·Expert Opin Ther Targets
2019Review
CBX2 as a therapeutic target in colorectal cancer: insights into the altered chromatin accessibility via RUNX1-CBX2-MAP4K1 axis.
Wang B et al.·Oncogene
2025
Subcellular expression pattern and clinical significance of CBX2 and CBX7 in breast cancer subtypes.
Park S et al.·Med Mol Morphol
2024
The predictive significance of chromobox family members in prostate cancer in humans.
Xu X et al.·Cell Oncol (Dordr)
2024
Prognostic hub gene CBX2 drives a cancer stem cell-like phenotype in HCC revealed by multi-omics and multi-cohorts.
Meng Q et al.·Aging (Albany NY)
2023Cohort
CBX2 shapes chromatin accessibility promoting AML via p38 MAPK signaling pathway.
Del Gaudio N et al.·Mol Cancer
2022
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
A hypoxia-glycolysis-lactate-related gene signature for prognosis prediction in hepatocellular carcinoma.
Qin X et al.·BMC Med Genomics
2024
Loss of CBX2 causes genomic instability and Wnt activation in high grade serous ovarian carcinoma cells.
Ma Y et al.·Mol Carcinog
2023
CBX2 is a functional target of miRNA let-7a and acts as a tumor promoter in osteosarcoma.
Han Q et al.·Cancer Med
2019Functional
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
The Epigenetic Regulatory Protein CBX2 Promotes mTORC1 Signalling and Inhibits DREAM Complex Activity to Drive Breast Cancer Cell Growth
Bilton LJ et al.·Cancers (Basel)
2022
Multiomics integrative analysis reveals antagonistic roles of CBX2 and CBX7 in metabolic reprogramming of breast cancer
Iqbal MA et al.·Mol Oncol
2021
CBX2 enhances the progression and TMZ chemoresistance of glioma via EZH2-mediated epigenetic silencing of PTEN expression
Wang J et al.·Front Pharmacol
2024
Identification of hepatocellular carcinoma subtypes based on PcG-related genes and biological relevance with cancer cells
Fu Y et al.·Clin Epigenetics
2022
CBX2 in DSD: The Quirky Kid on the Block.
Hart D et al.·Sex Dev
2022
Cuproptosis-related ceRNA axis triggers cell proliferation and cell cycle through CBX2 in lung adenocarcinoma
Wu J et al.·BMC Pulm Med
2024
Correction: CBX2 as a therapeutic target in colorectal cancer: insights into the altered chromatin accessibility via RUNX1-CBX2-MAP4K1 axis.
Wang B et al.·Oncogene
2026
CBX2 Expression in Colorectal Mucosa-adenoma-adenocarcinoma Sequence.
Wang B et al.·J Coll Physicians Surg Pak
2021
Top 8 full-text resultsSearch PubTator3 ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients