CBX8
protein-codingchromobox 8, the group of Chromobox family
Gene summary
Enables histone H3K27me3 reader activity. Involved in negative regulation of transcription by RNA polymerase II. Located in chromatin and nucleoplasm. Part of PRC1 complex. Biomarker of esophagus squamous cell carcinoma and glioblastoma. [provided by Alliance of Genome Resources, Jun 2026]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~9.6 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: Unknown
Disease ID:MONDO:0005090
Submitter: Labcorp Genetics (formerly Invitae)
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to CBX8 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_020649.3. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 1 | 2 | |||
| missense | 49 | 49 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 50 | 1 | 0 | 51 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_065700.1 | 5 | MANE Select | |
| Ensembl | ENSP00000269385.4 | 5 | MANE Select | |
| Ensembl | ENSP00000405058.1 | 5 | Standard | |
| Ensembl | ENSP00000408753.2 | 4 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Signal Transduction
- Gene expression (Transcription)
- RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known
- Generic Transcription Pathway
- Oxidative Stress Induced Senescence
Biological Process
- negative regulation of transcription by RNA polymerase II
- positive regulation of cell population proliferation
- histone ubiquitination
- positive regulation of collagen biosynthetic process
- positive regulation of DNA repair
Molecular Function
- single-stranded RNA binding
- protein binding
- methylated histone binding
- ubiquitin-protein transferase activator activity
Cellular Component
- nuclear chromatin
- heterochromatin
- nucleus
- nucleoplasm
- PcG protein complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000269385
- Coding exons
- 5
- Length
- 9552
- Individuals with no LoFs
- 125737
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 6
- Defined
- 125743
- p
- 0.0000239
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.938 | 198 | 239 | 0.829 | 0.0000146 | 2444 |
| Missense (PolyPhen) | 32 | 49.729 | 0.64349 | 543 | ||
| Synonymous | -1.78 | 124 | 101 | 1.22 | 0.00000619 | 820 |
| Loss of Function | 3.84 | 1 | 19.1 | 0.0524 | 0.00000139 | 180 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000070 | 0.000062 | rare |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000030 | 0.000026 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0.00019 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Component of a Polycomb group (PcG) multiprotein PRC1- like complex, a complex class required to maintain the transcriptionally repressive state of many genes, including Hox genes, throughout development. PcG PRC1 complex acts via chromatin remodeling and modification of histones; it mediates monoubiquitination of histone H2A 'Lys-119', rendering chromatin heritably changed in its expressibility. {ECO:0000269|PubMed:21282530}.;
Recessive Scores
- pRec
- 0.175
Intolerance Scores
- LoFtool
- 0.165
- RVIS EVS
- 0
- RVIS percentile EVS
- 53.73
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.975
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |