Missing content? – Request curation!
Request curation for specific Genes, variants, or PubMed publications.
Have questions, comments or suggestions? - Let us know!
Email us at : email@example.com
|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|
|Transcript||gDNA||cDNA||Protein||Source Database||Genome Build|
|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|