Gene Variant Detail

Contact

Missing content? – Request curation!

Request curation for specific Genes, variants, or PubMed publications.

Have questions, comments or suggestions? - Let us know!

Email us at : ckbsupport@jax.org

Gene EZH2
Variant Y641H
Impact List missense
Protein Effect gain of function
Gene Variant Descriptions EZH2 Y641H lies within the SET domain of the Ezh2 protein (UniProt.org). Y641H confers a gain of function to the Ezh2 protein, as indicated by increased methyltransferase activity with dimethylated substrates, and increased H3K27 trimethylation in cell culture (PMID: 21078963, PMID: 26735435, PMID: 22323599).
Associated Drug Resistance

Filtering

  • Case insensitive filtering will display rows where any text in any cell matches the filter term
  • Simple literal full or partial string matches
  • Separate multiple filter terms with a spaces, order doesn't matter (a b c and c b a are equivalent )
  • Filtering will only apply to rows that are already loaded on the page, filtering has no impact on query parameters
  • Use quotes to match a longer phrase which contains spaces "mtor c1483f"

Sorting

  • Generally, the default sort order for tables is set to be first column ascending, however, specific tables may set a different default sort order.
  • Click on any column header arrows to sort by that column
  • Hold down the Shift key and click multiple columns to sort by more than one column, be sure to set ascending or descending order for a given column, before moving on to the next column.

Transcript NM_001203247.1
gDNA chr7:g.148811636A>G
cDNA c.1921T>C
Protein p.Y641H
Source Database RefSeq
Genome Build GRCh38/hg38
Transcript gDNA cDNA Protein Source Database Genome Build
NM_001203247 chr7:g.148811636A>G c.1921T>C p.Y641H RefSeq GRCh38/hg38
XM_011515889.2 chr7:g.148810375A>G c.1921T>C p.Y641H RefSeq GRCh38/hg38
XM_011515889 chr7:g.148810375A>G c.1921T>C p.Y641H RefSeq GRCh38/hg38
NM_001203247.1 chr7:g.148811636A>G c.1921T>C p.Y641H RefSeq GRCh38/hg38

Filtering

  • Case insensitive filtering will display rows where any text in any cell matches the filter term
  • Simple literal full or partial string matches
  • Separate multiple filter terms with a spaces, order doesn't matter (a b c and c b a are equivalent )
  • Filtering will only apply to rows that are already loaded on the page, filtering has no impact on query parameters
  • Use quotes to match a longer phrase which contains spaces "mtor c1483f"

Sorting

  • Generally, the default sort order for tables is set to be first column ascending, however, specific tables may set a different default sort order.
  • Click on any column header arrows to sort by that column
  • Hold down the Shift key and click multiple columns to sort by more than one column, be sure to set ascending or descending order for a given column, before moving on to the next column.

Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
EZH2 Y641H follicular lymphoma sensitive Tazemetostat FDA approved - On Companion Diagnostic Actionable In a Phase II trial that supported FDA approval, Tazverik (tazemetostat) treatment was well-tolerated, resulted in a median progression-free survival of 11.1 months, objective response in 77% (33/43), and stable disease in 23% (10/43) of patients with relapsed/refractory follicular lymphoma, who had two or more prior therapies and harbored EZH2 mutations as detected by an approved test, including EZH2 Y646H (corresponds to Y641H in the canonical isoform) (Blood (2019) 134 (Supplement_1):123; NCT01897571). detail... detail... detail...
EZH2 Y641H melanoma predicted - sensitive GSK126 Preclinical - Cell culture Actionable In a preclinical study, GSK126 inhibited H3K27 trimethylation and reversed transcriptional silencing in human melanoma cells harboring EZH2 Y641H in culture (PMID: 26936398). 26936398
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
EZH2 mutant diffuse large B-cell lymphoma sensitive MK2206 + Tazemetostat Preclinical - Cell culture Actionable In a preclinical study, Tazemetostat (EPZ-6438) and MK-2206 synergistically inhibited proliferation of diffuse large B-cell lymphoma cell lines harboring EZH2 mutations in culture (PMID: 28835384). 28835384
EZH2 mutant diffuse large B-cell lymphoma sensitive Idelalisib + Tazemetostat Preclinical - Cell culture Actionable In a preclinical study, Tazemetostat (EPZ-6438) and Zydelig (idelalisib) synergistically inhibited proliferation of diffuse large B-cell lymphoma cell lines harboring EZH2 mutations in culture (PMID: 28835384). 28835384
EZH2 mutant diffuse large B-cell lymphoma sensitive A-395 Preclinical - Cell line xenograft Actionable In a preclinical study, a diffuse large B-cell lymphoma cell line harboring an EZH2 mutation demonstrated sensitivity to A-395, showing inhibition of tumor growth, however, due to its chemical properties A-395 will not proceed to clinical development (PMID: 28135237). 28135237
EZH2 mutant diffuse large B-cell lymphoma sensitive Tazemetostat Preclinical - Cell line xenograft Actionable In a preclinical study, diffuse large B-cell lymphoma cell lines harboring EZH2 mutations demonstrated increased sensitivity to Tazemetostat (EPZ-6438) treatment-induced growth inhibition, apoptosis, and tumor inhibition compared to EZH2 wild-type cell lines (PMID: 28835384). 28835384
EZH2 mutant diffuse large B-cell lymphoma sensitive Tazemetostat + Trametinib Preclinical - Cell culture Actionable In a preclinical study, Tazemetostat (EPZ-6438) and Mekinist (trametinib) synergistically inhibited proliferation of diffuse large B-cell lymphoma cell lines harboring EZH2 mutations in culture (PMID: 28835384). 28835384
EZH2 mutant myelofibrosis not applicable N/A Guideline Prognostic EZH2 mutations are associated with inferior overall survival in patients with myelofibrosis (NCCN.org). detail...
EZH2 mutant myelodysplastic/myeloproliferative neoplasm not applicable N/A Guideline Prognostic EZH2 mutations are associated with a poor prognosis in patients with myelodysplastic/myeloproliferative neoplasm (NCCN.org). detail...
EZH2 mutant essential thrombocythemia not applicable N/A Guideline Prognostic The presence of at least one mutation in either SH2B3, IDH2, U2AF1, SRSF2, SF3B1, EZH2, TP53, or RUNX1 is associated with inferior overall survival in patients with essential thrombocythemia, EZH2 mutations are also associated with inferior leukemia-free survival (NCCN.org). detail...
EZH2 mutant myelodysplastic syndrome not applicable N/A Guideline Prognostic EZH2 mutations are associated with a poor prognosis in patients with myelodysplastic syndrome (NCCN.org). detail...
EZH2 mutant follicular lymphoma sensitive Tazemetostat Phase II Actionable In a Phase II trial, Tazverik (tazemetostat) treatment resulted in an objective response in 71% (20/28, 3 complete response, 17 partial response) and stable disease in 29% (8/28) of patients with relapsed or refractory follicular lymphoma harboring EZH2 mutations, while only resulted in object response rate in 33% (18/54, 3 complete response, 15 partial response) and stable disease in 31% (16/54) of patients with EZH2 wild-type disease (PMID: 29980507). 29980507
EZH2 mutant follicular lymphoma sensitive Tazemetostat Guideline Actionable Tazverik (tazemetostat) is included in guidelines as a second-line or subsequent therapy for patients with follicular lymphoma harboring EZH2 mutations (NCCN.org). detail...
EZH2 mutant diffuse large B-cell lymphoma sensitive Everolimus + Tazemetostat Preclinical - Cell culture Actionable In a preclinical study, Tazemetostat (EPZ-6438) and Afinitor (everolimus) synergistically inhibited proliferation of diffuse large B-cell lymphoma cell lines harboring EZH2 mutations in culture (PMID: 28835384). 28835384
EZH2 mutant diffuse large B-cell lymphoma sensitive Ibrutinib + Tazemetostat Preclinical - Cell culture Actionable In a preclinical study, Tazemetostat (EPZ-6438) and Imbruvica (ibrutinib) synergistically inhibited proliferation of diffuse large B-cell lymphoma cell lines harboring EZH2 mutations in culture (PMID: 28835384). 28835384
EZH2 mutant diffuse large B-cell lymphoma sensitive Tamatinib + Tazemetostat Preclinical - Cell culture Actionable In a preclinical study, Tazemetostat (EPZ-6438) and Tamatinib (R406) synergistically inhibited proliferation of diffuse large B-cell lymphoma cell lines harboring EZH2 mutations in culture (PMID: 28835384). 28835384
Molecular Profile Protein Effect Treatment Approaches
EZH2 Y641H gain of function EZH2 inhibitor