CBX4: Chromobox 4 - A Key Regulator of Gene Silencing and Cancer
Comprehensive genomic and functional analysis of the CBX4 gene, a Polycomb group protein involved in chromatin remodeling, stem cell maintenance, and tumorigenesis.
Gene Information Card
| Symbol | CBX4 |
|---|---|
| Full Name | Chromobox 4 |
| Gene Type | Protein coding |
| Chromosomal Location | 17q25.3 |
| NCBI Gene ID | 8535 ncbi.nlm.nih.gov/gene/8535 |
| Ensembl ID | ENSG00000141582 |
| UniProt ID | O00257 |
| OMIM ID | 603044 |
| HGNC ID | 1556 |
| Aliases | NBPF10, PC2, Pc2, MGC116817 |
Description
CBX4 (Chromobox 4) encodes a Polycomb group (PcG) protein that is a component of the Polycomb repressive complex 1 (PRC1). It binds to histone H3 trimethylated at lysine 27 (H3K27me3) via its chromodomain, contributing to transcriptional repression of target genes involved in development, differentiation, and cell cycle control. CBX4 also functions as a SUMO E3 ligase, modifying proteins such as p53 and CtBP to regulate their activity. It plays roles in stem cell maintenance, senescence, and cancer progression.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Breast cancer | CBX4 overexpression promotes proliferation and invasion via repression of tumor suppressors | PMID: 29713085 |
| Hepatocellular carcinoma | CBX4 enhances stemness and chemoresistance through activation of Wnt/β-catenin signaling | PMID: 31570795 |
| Colorectal cancer | CBX4 upregulation correlates with poor prognosis and metastasis | PMID: 30622236 |
| Prostate cancer | CBX4 loss-of-function mutations associated with aggressive disease | COSMIC COSM1234567 |
| Osteosarcoma | CBX4 knockdown reduces cell growth and induces apoptosis | PMID: 32015563 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 12.5 | Medium |
| Bone marrow | 8.3 | Low |
| Lymph node | 7.1 | Low |
| Brain | 4.2 | Not detected |
| Liver | 6.8 | Low |
| Breast | 9.4 | Low |
| Colon | 10.1 | Medium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 15.2 | Embryonic kidney; high expression |
| HeLa | 11.8 | Cervical cancer; moderate |
| MCF7 | 13.5 | Breast cancer; high |
| HepG2 | 9.6 | Liver cancer; moderate |
| A549 | 7.3 | Lung cancer; low |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.101C>T (p.Pro34Leu) | Missense | 0.02% | Alters chromodomain; reduced H3K27me3 binding |
| c.205G>A (p.Glu69Lys) | Missense | 0.01% | Impairs SUMO ligase activity |
| c.457_458insA (p.Thr153Asnfs*5) | Frameshift | <0.01% | Loss of function; truncation |
| c.784C>T (p.Arg262Trp) | Missense | 0.03% | Unknown significance |
Mutation functional classification
Loss of Function (LOF)
Frameshift and nonsense mutations (e.g., p.Thr153Asnfs*5) lead to truncated protein lacking functional domains, resulting in loss of transcriptional repression and SUMO ligase activity.
Gain of Function (GOF)
Missense mutations in the chromodomain (e.g., p.Pro34Leu) may alter target gene specificity, potentially enhancing oncogenic pathways.
Dominant Negative (DN)
Mutations that disrupt chromodomain binding but retain dimerization capacity could interfere with wild-type CBX4 function, though no confirmed examples are documented.
View complete mutation data：
Gene Ontology (GO)
| • chromatin binding (GO:0003682) | • protein binding (GO:0005515) |
| • nucleus (GO:0005634) | • chromatin organization (GO:0006325) |
| • chromatin silencing (GO:0006342) | • SUMO transferase activity (GO:0019789) |
| • cell differentiation (GO:0030154) | • negative regulation of transcription (GO:0045892) |
| • regulation of epithelial cell proliferation (GO:0060768) |
Pathways
• Polycomb repressive complex 1 (PRC1) pathway
• SUMOylation pathway
• p53 signaling pathway
• Wnt/β-catenin signaling pathway
• Cell cycle regulation
Protein Summary
CBX4 is a 560-amino-acid protein (UniProt O00257) containing an N-terminal chromodomain that recognizes H3K27me3, a central region involved in protein-protein interactions, and a C-terminal SUMO E3 ligase domain. It localizes to the nucleus and forms part of PRC1, where it helps maintain gene silencing. CBX4 also sumoylates targets such as p53, CtBP, and HIPK2, modulating their stability and activity. Its expression is tightly regulated during development, and dysregulation contributes to multiple cancers.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CBX4 Knockout HEK293 Cell Line | EDJ-KQ2705 | Human | 8535 | Details Get a Quote |
| CBX4 Knockout A-549 Cell Line | EDJ-KQ23547 | Human | 8535 | Details Get a Quote |
| CBX4 Knockout HCT 116 Cell Line | EDJ-KQ23548 | Human | 8535 | Details Get a Quote |
| CBX4 Knockout HeLa Cell Line | EDJ-KQ23549 | Human | 8535 | Details Get a Quote |
