EZH2 Gene: Enhancer of Zeste 2 Polycomb Repressive Complex 2 Subunit
A key epigenetic regulator in development and cancer, frequently mutated in lymphomas and solid tumors.
Gene Information Card
| Symbol | EZH2 |
|---|---|
| Full Name | Enhancer of zeste 2 polycomb repressive complex 2 subunit |
| Gene Type | Protein coding |
| Chromosomal Location | 7q36.1 |
| NCBI Gene ID | 2146 ncbi.nlm.nih.gov/gene/2146 |
| Ensembl ID | ENSG00000106462 |
| UniProt ID | Q15910 |
| OMIM ID | 601573 |
| HGNC ID | 3527 |
| Aliases | ENX-1, KMT6, KMT6A, WVS, WVS2 |
Description
EZH2 encodes the catalytic subunit of Polycomb Repressive Complex 2 (PRC2), which methylates histone H3 at lysine 27 (H3K27me2/me3), leading to transcriptional repression. EZH2 is essential for normal development, cell differentiation, and X-chromosome inactivation. Overexpression or gain-of-function mutations are oncogenic in various cancers, while loss-of-function mutations cause Weaver syndrome and are also seen in myeloid malignancies.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Weaver syndrome | Germline loss-of-function mutations in EZH2 cause overgrowth and intellectual disability, likely due to haploinsufficiency affecting PRC2 function. | OMIM 277590; ClinVar |
| Diffuse large B-cell lymphoma (DLBCL) | Somatic gain-of-function mutations (e.g., Y641, A677) increase H3K27me3 levels, promoting germinal center B-cell transformation. | COSMIC; PMID 20871612 |
| Follicular lymphoma | Same gain-of-function mutations as DLBCL are recurrent, driving lymphomagenesis. | COSMIC; PMID 20871612 |
| Prostate cancer | EZH2 overexpression is associated with aggressive disease and poor prognosis, promoting proliferation and invasion. | PMID 16189514 |
| Breast cancer | EZH2 overexpression correlates with poor survival, particularly in triple-negative subtypes. | PMID 16189514 |
| Myelodysplastic syndromes (MDS) / Acute myeloid leukemia (AML) | Loss-of-function mutations in EZH2 are found in myeloid malignancies, suggesting tumor suppressor role in some contexts. | COSMIC; PMID 20871612 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 22.1 | Medium |
| Bone marrow | 15.3 | Medium |
| Lymph node | 14.2 | Medium |
| Spleen | 12.8 | Medium |
| Brain | 8.5 | Low |
| Liver | 5.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| K562 (leukemia) | 18.5 | High expression; used in ENCODE studies |
| HeLa (cervical cancer) | 12.3 | Moderate expression |
| A549 (lung cancer) | 9.8 | Moderate expression |
| MCF7 (breast cancer) | 15.1 | High expression; hormone-responsive |
| HepG2 (liver cancer) | 7.4 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| Y641N | Missense (gain-of-function) | ~20% in DLBCL | Increases H3K27me3 activity; oncogenic |
| Y641F | Missense (gain-of-function) | ~10% in DLBCL | Increases H3K27me3 activity; oncogenic |
| A677G | Missense (gain-of-function) | ~5% in DLBCL | Alters substrate specificity; oncogenic |
| A687V | Missense (gain-of-function) | Rare in follicular lymphoma | Increases H3K27me3 activity |
| R690C | Missense (loss-of-function) | Rare in MDS/AML | Reduces catalytic activity; tumor suppressor |
| Q571K | Missense (loss-of-function) | Rare in Weaver syndrome | Impairs PRC2 function; developmental defects |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations (e.g., R690C, Q571K) reduce or abolish EZH2 methyltransferase activity, leading to decreased H3K27me3. In myeloid malignancies, this can promote leukemogenesis by derepressing oncogenes. In Weaver syndrome, haploinsufficiency disrupts normal development.
Gain of Function (GOF)
Gain-of-function mutations (e.g., Y641, A677) increase EZH2 catalytic activity or alter substrate specificity, leading to hypermethylation of H3K27 and silencing of tumor suppressor genes. These are oncogenic in lymphomas.
Dominant Negative (DN)
Some EZH2 mutations may act in a dominant-negative manner by forming inactive heterodimers with wild-type EZH2, reducing overall PRC2 activity. This has been observed in certain myeloid malignancies, but the exact mechanism is still under investigation.
View complete mutation data：
Gene Ontology (GO)
| • protein binding (GO:0005515) | • nucleus (GO:0005634) |
| • chromatin organization (GO:0006325) | • chromatin silencing (GO:0006342) |
| • histone-lysine N-methyltransferase activity (GO:0018024) | • histone lysine methylation (GO:0034968) |
| • regulation of transcription (GO:0042059) | • negative regulation of transcription (GO:0045892) |
| • nucleosome assembly (GO:0006334) | • nucleoplasm (GO:0005654) |
Pathways
• PRC2 methylates histone H3K27 (H3K27me2/me3)
• H3K27me3 recruits PRC1 and other repressors
• Transcriptional repression of developmental genes
• X-chromosome inactivation
• Cell cycle regulation (e.g.
• p16INK4a repression)
• Cancer pathways: DLBCL
• prostate
• breast
Protein Summary
EZH2 is a 746-amino acid protein containing a SET domain responsible for methyltransferase activity. It is the catalytic core of PRC2, which also includes EED, SUZ12, and RBBP4/7. EZH2 specifically di- and tri-methylates histone H3 at lysine 27, a mark associated with gene silencing. The protein is overexpressed in many cancers and is a target for cancer therapy (e.g., tazemetostat).
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| EZH2 Knockout HEK293 Cell Line | EDC90525 | Human | 2146 | Details Get a Quote |
| EZH2 Knockout A-549 Cell Line | EDJ-KQ20040 | Human | 2146 | Details Get a Quote |
| EZH2 Knockout HCT 116 Cell Line | EDJ-KQ20041 | Human | 2146 | Details Get a Quote |
| EZH2 Knockout HeLa Cell Line | EDJ-KQ20042 | Human | 2146 | Details Get a Quote |
