CBX4
protein-codingchromobox 4, the group of Chromobox family
Gene summary
Enables SUMO binding activity; SUMO ligase activity; and enzyme binding activity. Involved in negative regulation of transcription by RNA polymerase II. Located in nuclear body. Part of PRC1 complex. Implicated in hepatocellular carcinoma. Biomarker of hepatocellular carcinoma. [provided by Alliance of Genome Resources, Jul 2025]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~6.3 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to CBX4 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_003655.3. 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 | 80 | 80 | ||||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 4 | 4 | ||||
| Total | 0 | 0 | 86 | 0 | 1 | 87 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_003646.2 | 5 | MANE Select | |
| Ensembl | ENSP00000269397.4 | 5 | MANE Select | |
| Ensembl | ENSP00000415348.1 | 4 | Standard | |
| Ensembl | ENSP00000415348.1 | 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
- the prc2 complex sets long-term gene silencing through modification of histone tails
- Generic Transcription Pathway
Biological Process
- negative regulation of transcription by RNA polymerase II
- chromatin organization
- protein sumoylation
- negative regulation of apoptotic process
- negative regulation of transcription, DNA-templated
Molecular Function
- chromatin binding
- transcription corepressor activity
- single-stranded RNA binding
- protein binding
- SUMO transferase activity
Cellular Component
- nucleus
- nucleoplasm
- nuclear body
- nuclear speck
- PcG protein complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000269397
- Coding exons
- 5
- Length
- 6274
- Individuals with no LoFs
- 125704
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 2
- Defined
- 125706
- p
- 0.00000796
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.22 | 261 | 383 | 0.681 | 0.0000261 | 3626 |
| Missense (PolyPhen) | 68 | 140.89 | 0.48263 | 1431 | ||
| Synonymous | 0.228 | 176 | 180 | 0.978 | 0.0000141 | 1129 |
| Loss of Function | 3.55 | 1 | 16.6 | 0.0601 | 7.13e-7 | 222 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000054 | 0.000054 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.0000089 | 0.0000088 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: E3 SUMO-protein ligase which facilitates SUMO1 conjugation by UBE2I (PubMed:12679040). Involved in the sumoylation of HNRNPK, a p53/TP53 transcriptional coactivator, hence indirectly regulates p53/TP53 transcriptional activation resulting in p21/CDKN1A expression. Monosumoylates ZNF131 (PubMed:22825850). {ECO:0000269|PubMed:12679040, ECO:0000269|PubMed:22825850}.;
Recessive Scores
- pRec
- 0.103
Intolerance Scores
- LoFtool
- 0.0942
- RVIS EVS
- 0.11
- RVIS percentile EVS
- 61.73
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.369
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |