EZH2
Chr 7ADenhancer of zeste 2 polycomb repressive complex 2 subunit
Also known as: ENX-1, ENX1, EZH2b, KMT6, KMT6A, WVS, WVS2
The protein serves as the catalytic subunit of the PRC2 complex, methylating histone H3 at lysine 27 to repress gene transcription, which is essential for embryonic development and stem cell identity. Mutations cause Weaver syndrome, characterized by overgrowth, intellectual disability, and distinctive facial features with autosomal dominant inheritance. The gene is highly constrained against loss-of-function variants (pLI ~1.0), reflecting its critical role in development.
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Among the most LoF-intolerant genes (~top 3%)
Highly missense-constrained (top ~0.1%)
This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to loss-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
EZH2 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
Registry of Patients With MPNs in Taiwan
ACTIVE NOT RECRUITINGEfficacy and Safety of the Valemetostat in Patients With Selected Solid Tumors.
RECRUITINGPrevalence Of Germline Gene Mutations In Patients With Myeloproliferative Neoplasms With Family History
NOT YET RECRUITINGMolecular Genetics Guide the Maintenance Therapy After Allogeneic Hematopoietic Stem Cell Transplantation
RECRUITINGImpact of Epigenetic Age on Clinic-biological Presentation and Prognosis in Myeloproliferative Neoplasms Epigenetic Age in Myeloproliferative Neoplasms (EpiC)
RECRUITINGReal-world Outcomes of Peripheral T-cell Lymphoma: A Multicenter Retrospective and Prospective Cohort Study
RECRUITINGTesting the Addition of Tazemetostat to the Immunotherapy Drug, Pembrolizumab (MK-3475), in Advanced Urothelial Carcinoma
ACTIVE NOT RECRUITINGA Study of Tazemetostat on Safety in Participants With Relapsed or Refractory Follicular Lymphoma With Enhancer of Zeste Homolog 2 (EZH2) Gene Mutation in Japan
ACTIVE NOT RECRUITINGTesting the Safety of the Anti-cancer Drugs Tazemetostat and Belinostat in Patients With Lymphomas That Have Resisted Treatment
ACTIVE NOT RECRUITINGA Study of Tulmimetostat DZR123 (CPI-0209) in Patients With Advanced Solid Tumors and Lymphomas
RECRUITINGA Phase 1 Study of SHR2554 in Subjects With Relapsed or Refractory Mature Lymphoid Neoplasms
ACTIVE NOT RECRUITINGTargeted Therapy Directed by Genetic Testing in Treating Pediatric Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphomas, or Histiocytic Disorders (The Pediatric MATCH Screening Trial)
ACTIVE NOT RECRUITINGExternal Resources
Links to major genomics databases and tools