Gene

EZH2

enhancer of zeste 2 polycomb repressive complex 2 subunit

Explore in graph →CI-GENE-00001160HGNC:3527 ENSG00000106462 NCBI 2146 CIViC Cancer geneApproved

Curated evidence

Clinical evidence (63)

CIViC items involving this gene, grouped by molecular profile and therapy, with native levels and directions. 50 items per page.

civicCuratedShowing 51–63 of 63 evidence items · levels, directions and significance as curated at the source; each row links to its CIViC record.

Therapy	Cancer	Type	Level	Direction · significance	Rating (1–5)	Status	Evidence	Source
EZH2 Y646N5
(functional)	—UNRESOLVED	Functional	D	Supports Loss Of Function	3	accepted

Cohorts

Alteration frequency by cohort (90)

Frequency = cases affected / cases profiled within one cohort. Cohorts are never pooled.

cbioportalObserved90 cohort rows (showing 40, sorted by frequency) · frequency = affected / profiled, as published by each cohort; cohorts are not pooled. Hover a row badge for its release.

Cohort	Mapped cancer	Alteration	Affected (n)	Profiled (n)	Frequency (%)	Rank in cohort	Source
Endometrial Cancer (MSK, 2018) ucec_msk_2018	Endometrial Carcinoma	Ssm	3

Literature

Linked publications (18)

25 per page, newest first.

pubmedPublishedShowing 1–18 of 18 publications · bibliographic data as recorded by PubMed; abstracts are not reproduced.

Tazemetostat for patients with relapsed or refractory follicular lymphoma: an open-label, single-arm, multicentre, phase 2 trial.
· Lancet Oncol · 2020 · PMID 33035457 · validated civic_curation pubmed
Tazemetostat, an EZH2 inhibitor, in relapsed or refractory B-cell non-Hodgkin lymphoma and advanced solid tumours: a first-in-human, open-label, phase 1 study.
· Lancet Oncol · 2018 · PMID 29650362 · validated civic_curation pubmed
Somatic mutations altering EZH2 (Tyr641) in follicular and diffuse large B-cell lymphomas of germinal-center origin.
· Nat Genet · 2010 · PMID 20081860 · validated civic_curation pubmed
An EZH2 polymorphism is associated with clinical outcome in metastatic colorectal cancer patients.
· Ann Oncol · 2012 · PMID 21926398 · validated

EZH2 Y646S3
(functional)	—UNRESOLVED	Functional	D	Supports Gain Of Function	4	submitted	EID7218 EZH2 (enhancer of zeste homolog 2) is a critical enzymatic subunit of the polycomb repressive complex 2 (PRC2), which trimethylates histone H3 (H3K27) to mediate gene repression. Somatic mutations, ov… (full text at CIViC) PMID 24469040 · Sahasrabuddhe et al., 2015 · Open in CIViC	civic
〃	—UNRESOLVED	Functional	D	Supports Gain Of Function	3	accepted	EID9522 Whole-cell lysates from frozen GCB-derived lymphoma sections with EZH2 Y641H showed a higher level of H3K27me3 (histone H3 Lys-27–specific trimethylation) compared with those from tumor with wild-type… (full text at CIViC) PMID 21190999 · Yap et al., 2011 · Open in CIViC	civic
〃	—UNRESOLVED	Functional	D	Supports Gain Of Function	3	submitted	EID11051 Authors of this study identified and detailed the role of USP47, a novel deubiquitinase (DUB), that stabilizes mutated EZH2 in cancers and prevents the protein’s degradation by ubiquitination. Degrada… (full text at CIViC) PMID 35034955 · Yang et al., 2022 · Open in CIViC	civic

EZH2 Y646S3

(functional)

—UNRESOLVED

Functional

Supports Gain Of Function

submitted

EID7218

EZH2 (enhancer of zeste homolog 2) is a critical enzymatic subunit of the polycomb repressive complex 2 (PRC2), which trimethylates histone H3 (H3K27) to mediate gene repression. Somatic mutations, ov… (full text at CIViC)

PMID 24469040 · Sahasrabuddhe et al., 2015 · Open in CIViC

civic

〃

—UNRESOLVED

Functional

Supports Gain Of Function

accepted

EID9522

Whole-cell lysates from frozen GCB-derived lymphoma sections with EZH2 Y641H showed a higher level of H3K27me3 (histone H3 Lys-27–specific trimethylation) compared with those from tumor with wild-type… (full text at CIViC)

PMID 21190999 · Yap et al., 2011 · Open in CIViC

civic

〃

—UNRESOLVED

Functional

Supports Gain Of Function

submitted

EID11051

Authors of this study identified and detailed the role of USP47, a novel deubiquitinase (DUB), that stabilizes mutated EZH2 in cancers and prevents the protein’s degradation by ubiquitination. Degrada… (full text at CIViC)

PMID 35034955 · Yang et al., 2022 · Open in CIViC

civic

EZH2 A682G + EZH2 A692V + EZH2 Y646C + EZH2 Y646F + EZH2 Y646H + EZH2 Y646N + EZH2 Y646S4
(oncogenic)	Follicular Lymphoma	Oncogenic	B	Supports Oncogenicity	4	accepted	EID11111 In this large cohort study, 366 patients with follicular lymphoma (FL) were recruited to investigate the incidence and distribution of EZH2 mutations. NGS and Sanger detected EZH2 positive mutations i… (full text at CIViC) PMID 24052547 · Bödör et al., 2013 · Open in CIViC	civic
Tazemetostat	B-Cell Non-Hodgkin Lymphoma	Predictive	A	Supports Sensitivity Response	2	accepted	EID11220 In a multicentre, open-label, phase 1 trial, tazemetostat was evaluated in 64 adult patients (≥18 years) with relapsed or refractory B-cell non-Hodgkin lymphoma (n=21) or advanced solid tumours (n=43)… (full text at CIViC) PMID 29650362 · Italiano et al., 2018 · Open in CIViC	civic
〃	Follicular Lymphoma	Predictive	B	Supports Sensitivity Response	4	accepted	EID11109 In this study, Koji Izutsu et al. conducted a multicenter, open-label phase II clinical trial to evaluate the efficacy and safety of the EZH2 inhibitor tazemetostat in Japanese patients with relapsed … (full text at CIViC) PMID 34159682 · Izutsu et al., 2021 · Open in CIViC	civic
〃	Diffuse Large B-Cell LymphomaCURATED_BROADER	Predictive	B	Supports Sensitivity Response	3	accepted	EID11110 This phase II study evaluated the efficacy and safety of the EZH2 inhibitor tazemetostat in Japanese adults with relapsed or refractory B-cell non-Hodgkin lymphoma harboring EZH2-activating mutations … (full text at CIViC) PMID 34159682 · Izutsu et al., 2021 · Open in CIViC	civic

EZH2 A682G + EZH2 A692V + EZH2 Y646C + EZH2 Y646F + EZH2 Y646H + EZH2 Y646N + EZH2 Y646S4

(oncogenic)

Follicular Lymphoma

Oncogenic

Supports Oncogenicity

accepted

EID11111

In this large cohort study, 366 patients with follicular lymphoma (FL) were recruited to investigate the incidence and distribution of EZH2 mutations. NGS and Sanger detected EZH2 positive mutations i… (full text at CIViC)

PMID 24052547 · Bödör et al., 2013 · Open in CIViC

civic

Tazemetostat

B-Cell Non-Hodgkin Lymphoma

Predictive

Supports Sensitivity Response

accepted

EID11220

In a multicentre, open-label, phase 1 trial, tazemetostat was evaluated in 64 adult patients (≥18 years) with relapsed or refractory B-cell non-Hodgkin lymphoma (n=21) or advanced solid tumours (n=43)… (full text at CIViC)

PMID 29650362 · Italiano et al., 2018 · Open in CIViC

civic

〃

Follicular Lymphoma

Predictive

Supports Sensitivity Response

accepted

EID11109

In this study, Koji Izutsu et al. conducted a multicenter, open-label phase II clinical trial to evaluate the efficacy and safety of the EZH2 inhibitor tazemetostat in Japanese patients with relapsed … (full text at CIViC)

PMID 34159682 · Izutsu et al., 2021 · Open in CIViC

civic

〃

Diffuse Large B-Cell LymphomaCURATED_BROADER

Predictive

Supports Sensitivity Response

accepted

EID11110

This phase II study evaluated the efficacy and safety of the EZH2 inhibitor tazemetostat in Japanese adults with relapsed or refractory B-cell non-Hodgkin lymphoma harboring EZH2-activating mutations … (full text at CIViC)

PMID 34159682 · Izutsu et al., 2021 · Open in CIViC

civic

EZH2 Y731D1
(functional)	—UNRESOLVED	Functional	D	Supports Loss Of Function	2	submitted	EID9867 EZH2 mutations were identified in a screen of 614 patients with myeloid malignancies. Several mutations in the highly conserved CXC-SET domains were expressed in Sf9 insect cells along with polycomb r… (full text at CIViC) PMID 20601953 · Ernst et al., 2010 · Open in CIViC	civic

EZH2 Y731D1

(functional)

—UNRESOLVED

Functional

Supports Loss Of Function

submitted

EID9867

EZH2 mutations were identified in a screen of 614 patients with myeloid malignancies. Several mutations in the highly conserved CXC-SET domains were expressed in Sf9 insect cells along with polycomb r… (full text at CIViC)

PMID 20601953 · Ernst et al., 2010 · Open in CIViC

civic