CBX2: Chromobox Protein 2 – A Key Regulator of Chromatin and Sexual Development
Comprehensive genomic and functional analysis of CBX2, a component of the Polycomb repressive complex 1 (PRC1) involved in gene silencing, gonadal development, and cancer.
Gene Information Card
| Symbol | CBX2 |
|---|---|
| Full Name | Chromobox 2 |
| Gene Type | Protein coding |
| Chromosomal Location | 17q25.3 |
| NCBI Gene ID | 84733 ncbi.nlm.nih.gov/gene/84733 |
| Ensembl ID | ENSG00000173914 |
| UniProt ID | Q14781 |
| OMIM ID | 602770 |
| HGNC ID | 1552 |
| Aliases | M33, MCP3, SRXY5, MOD2, Pc3, CBX2_HUMAN |
Description
CBX2 (chromobox 2) encodes a component of the Polycomb repressive complex 1 (PRC1). It binds histone H3 trimethylated at lysine 27 (H3K27me3) via its chromodomain, contributing to chromatin compaction and transcriptional repression. CBX2 is essential for normal gonadal development; loss-of-function mutations cause 46,XY complete gonadal dysgenesis (Swyer syndrome). It also plays roles in stem cell maintenance, X-chromosome inactivation, and is implicated in various cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| 46,XY complete gonadal dysgenesis (Swyer syndrome) | Loss-of-function mutations in CBX2 impair PRC1-mediated silencing of genes required for testis development, leading to testicular regression and female phenotype in 46,XY individuals. | OMIM #613080; PMID: 19274049 |
| 46,XY partial gonadal dysgenesis | Hypomorphic CBX2 variants reduce PRC1 activity, causing ambiguous genitalia and partial testicular development. | ClinVar; PMID: 27884943 |
| Acute myeloid leukemia (AML) | CBX2 overexpression promotes leukemogenesis by repressing tumor suppressor genes via PRC1. | COSMIC; PMID: 29127259 |
| Breast cancer | CBX2 upregulation correlates with poor prognosis; it enhances cell proliferation and migration through epigenetic silencing of CDKN2A. | COSMIC; PMID: 31570779 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 8.2 | Medium |
| Ovary | 5.1 | Low |
| Brain (cerebellum) | 4.3 | Low |
| Bone marrow | 3.8 | Low |
| Lung | 2.9 | Low |
| Liver | 1.5 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| K562 (leukemia) | 6.7 | Moderate expression |
| HeLa (cervical carcinoma) | 5.2 | Low expression |
| A549 (lung carcinoma) | 4.1 | Low expression |
| MCF7 (breast carcinoma) | 3.5 | Low expression |
| HEK293 (embryonic kidney) | 2.8 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.109C>T (p.Arg37Ter) | Nonsense | Rare | Loss of function; truncates chromodomain, abolishes H3K27me3 binding; causes 46,XY complete gonadal dysgenesis. |
| c.334G>A (p.Gly112Arg) | Missense | Rare | Loss of function; disrupts chromodomain fold; associated with 46,XY partial gonadal dysgenesis. |
| c.425A>G (p.Tyr142Cys) | Missense | Rare | Likely loss of function; reduces protein stability; reported in 46,XY DSD. |
| c.1A>G (p.Met1Val) | Start loss | Rare | Loss of function; prevents translation initiation; causes 46,XY complete gonadal dysgenesis. |
Mutation functional classification
Loss of Function (LOF)
Nonsense, frameshift, start-loss, and missense mutations that disrupt the chromodomain or reduce protein stability lead to loss of PRC1-mediated repression, causing disorders of sex development.
Gain of Function (GOF)
Not well documented; overexpression in cancers may act as a gain-of-function by enhancing oncogenic gene silencing.
Dominant Negative (DN)
No dominant-negative variants have been reported for CBX2.
View complete mutation data：
Gene Ontology (GO)
| • chromatin binding (GO:0003682) | • histone H3K27me3 binding (GO:0140037) |
| • Polycomb repressive complex 1 (GO:0035102) | • negative regulation of transcription (GO:0016481) |
| • male gonad development (GO:0008584) | • X-chromosome inactivation (GO:0006777) |
Pathways
• Polycomb repressive complex 1 (PRC1) pathway
• Chromatin organization
• Sex determination and differentiation
Protein Summary
CBX2 is a 532-amino-acid protein containing an N-terminal chromodomain that specifically recognizes H3K27me3, a central hinge region, and a C-terminal Polycomb box (PC box) that mediates interaction with other PRC1 subunits (RING1, PCGF). It is localized to the nucleus and is required for PRC1 recruitment to target loci, leading to ubiquitination of histone H2A at lysine 119 (H2AK119ub) and chromatin compaction. CBX2 is essential for silencing of pro-ovarian genes (e.g., FOXL2) during testis development. In cancer, CBX2 overexpression contributes to epigenetic silencing of tumor suppressors.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CBX2 Knockout HEK293 Cell Line | EDJ-KQ10183 | Human | 84733 | Details Get a Quote |
| CBX2 Knockout HCT 116 Cell Line | EDJ-KQ36075 | Human | 84733 | Details Get a Quote |
| CBX2 Knockout A-549 Cell Line | EDJ-KQ37314 | Human | 84733 | Details Get a Quote |
| CBX2 Knockout HeLa Cell Line | EDJ-KQ37315 | Human | 84733 | Details Get a Quote |
