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Gene IDH2
Variant R140Q
Impact List missense
Protein Effect gain of function
Gene Variant Descriptions IDH2 R140Q lies within the substrate binding region of the Idh2 protein (UniProt.org). R140Q confers a gain of function to Idh2, enabling conversion of alpha-ketoglutarate to the onco-metabolite 2HG (R(-)-2-hydroxyglutarate), results in increased 2HG levels in patient samples, and is transforming in cell culture (PMID: 20171147, PMID: 23558173).
Associated Drug Resistance

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Transcript NM_002168.3
gDNA chr15:g.90088702C>T
cDNA c.419G>A
Protein p.R140Q
Source Database RefSeq
Genome Build GRCh38/hg38
Transcript gDNA cDNA Protein Source Database Genome Build
NM_002168 chr15:g.90088702C>T c.419G>A p.R140Q RefSeq GRCh38/hg38
NM_002168.3 chr15:g.90088702C>T c.419G>A p.R140Q RefSeq GRCh38/hg38

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  • Simple literal full or partial string matches
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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
IDH2 R140Q myelodysplastic syndrome not applicable N/A Guideline Prognostic IDH2 R140Q is associated with a poor prognosis in patients with myelodysplastic syndrome (NCCN.org). detail...
IDH2 R140Q malignant glioma predicted - sensitive AG-881 Preclinical - Cell line xenograft Actionable In a preclinical study, AG-881 treatment decreased tumor 2HG levels in a glioma cell line xenograft model harboring IDH2 R140Q (Mol Cancer Ther Jan 1 2018 (17) (1 Supp) B126). detail...
IDH2 R140Q glioblastoma predicted - sensitive Enasidenib Preclinical - Cell line xenograft Actionable In a preclinical study, Enasidenib (AG-221) decreased 2-hydroxyglutarate (2HG) levels in a glioblastoma cell line expressing IDH2 R140Q in culture and in xenograft models (PMID: 28193778). 28193778
IDH2 R140Q acute myeloid leukemia sensitive AGI-6780 Preclinical Actionable In a preclinical study, treatment with AGI-6780 resulted in the differentiation of erythroleukemia and AML cell lines expressing IDH2 R140Q (PMID: 23558173). 23558173
IDH2 R140Q acute myeloid leukemia sensitive Enasidenib FDA approved - On Companion Diagnostic Actionable In a Phase I/II trial that supported FDA approval, Idhifa (enasidenib) treatment resulted in an overall response rate of 40.3% (71/176) with a median response duration of 5.8 months, complete remission in 19.3% (34/176), and stable disease in 48.3% (85/176) of acute myeloid leukemia patients harboring IDH2 mutations (PMID: 28588020; NCT01915498) and IDH2 R140Q is on the companion diagnostic. detail... detail... 28588020
IDH2 R140Q acute myeloid leukemia sensitive Enasidenib Preclinical - Pdx & cell culture Actionable In a preclinical study, Enasidenib (AG-221) treatment reduced 2-hydroxyglutarate (2HG) levels and induced differentiation of leukemic blasts from acute myeloid leukemia (AML) patients harboring IDH2 R140Q in culture, and decreased 2HG levels and blast percentage and improved survival relative to Cytosar-U (cytarabine) treatment in IDH2 R140Q-mutant primary AML xenograft models (PMID: 28193778). 28193778
IDH2 R140Q IDH2 Q316E acute myeloid leukemia resistant Enasidenib Case Reports/Case Series Actionable In a clinical study, IDH2 Q316E was identified as an acquired mutation in trans with the original IDH2 R140Q in a patient with acute myeloid leukemia (AML), who developed resistance to Idhifa (enasidenib) after initial response, and coexpression of IDH2 Q316E in trans or in cis with IDH2 R140Q conferred resistance to Idhifa (enasidenib) in culture and in animal models of AML, supporting a mechanism of variants cooperating to confer resistance (PMID: 29950729). 29950729
IDH2 R140Q IDH2 I319M acute myeloid leukemia resistant Enasidenib Case Reports/Case Series Actionable In a clinical study, IDH2 I319M was identified as an acquired mutation in trans with the original IDH2 R140Q in a patient with acute myeloid leukemia (AML), who developed resistance to Idhifa (enasidenib) after initial response, and coexpression of IDH2 I319M in trans or in cis with IDH2 R140Q conferred resistance to Idhifa (enasidenib) in culture, supporting a mechanism of variants cooperating to confer resistance (PMID: 29950729). 29950729
FLT3 exon 14 ins IDH2 R140Q acute myeloid leukemia predicted - resistant Sorafenib Preclinical Actionable In a preclinical study, Nexavar (sorafenib) failed to inhibit growth of cells isolated from a transgenic mouse model of acute myeloid leukemia harboring a FLT3-ITD mutation and IDH2 R140Q in culture (PMID: 33268594). 33268594
FLT3 exon 14 ins IDH2 R140Q acute myeloid leukemia predicted - sensitive Gilteritinib Preclinical - Cell culture Actionable In a preclinical study, high dosage Xospata (gilteritinib) treatment resulted in reduced viability and colony formation of cells isolated from a transgenic mouse model of acute myeloid leukemia harboring a FLT3-ITD mutation and IDH2 R140Q in culture (PMID: 33268594). 33268594
FLT3 exon 14 ins IDH2 R140Q acute myeloid leukemia predicted - sensitive Dubermatinib Preclinical Actionable In a preclinical study, Dubermatinib (TP-0903) treatment inhibited growth and colony formation of cells isolated from a transgenic mouse model of acute myeloid leukemia harboring a FLT3-ITD mutation and IDH2 R140Q in culture, and increased survival in mouse models (PMID: 33268594). 33268594
FLT3 exon 14 ins IDH2 R140Q acute myeloid leukemia predicted - sensitive Crenolanib Preclinical - Cell culture Actionable In a preclinical study, high dosage Crenolanib (CP-868596) treatment resulted in reduced viability of cells isolated from a transgenic mouse model of acute myeloid leukemia harboring a FLT3-ITD mutation and IDH2 R140Q in culture (PMID: 33268594). 33268594
FLT3 exon 14 ins IDH2 R140Q acute myeloid leukemia predicted - resistant Quizartinib Preclinical Actionable In a preclinical study, Vanflyta (Quizartinib) failed to inhibit growth of cells isolated from a transgenic mouse model of acute myeloid leukemia harboring a FLT3-ITD mutation and IDH2 R140Q in culture (PMID: 33268594). 33268594
FLT3 exon 14 ins IDH2 R140Q acute myeloid leukemia predicted - resistant Midostaurin Preclinical Actionable In a preclinical study, Rydapt (midostaurin) failed to inhibit growth of cells isolated from a transgenic mouse model of acute myeloid leukemia harboring a FLT3-ITD mutation and IDH2 R140Q in culture (PMID: 33268594). 33268594
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
IDH2 mutant acute myeloid leukemia predicted - sensitive Venetoclax Phase II Actionable In a Phase II trial, 33% (4/12) of acute myeloid leukemia patients harboring either IDH1 or IDH2 mutations responded to treatment with Venclexta (venetoclax), demonstrating a complete response or complete response with incomplete blood count recovery (PMID: 27520294). 27520294
IDH2 mutant glioblastoma not applicable N/A Guideline Diagnostic IDH2 mutations aid in the diagnosis of secondary grade IV glioblastomas (NCCN.org). detail...
IDH2 mutant acute myeloid leukemia sensitive Azacitidine + Venetoclax Guideline Actionable Venclexta (venetoclax) in combination with Vidaza (azacitidine) is included in guidelines for adult patients with acute myeloid leukemia harboring an IDH2 mutation (NCCN.org). detail...
IDH2 mutant hematologic cancer sensitive Enasidenib Phase I Actionable In a Phase I study, Enasidenib (AG-221) demonstrated safety and efficacy in patients with hematological cancer harboring IDH2 mutations and included 8 CR, 1 CRp, 3 CRi, and 8 PR (ASH Meeting, Dec 2014, abstract #115). detail...
IDH2 mutant grade III astrocytoma not applicable N/A Guideline Diagnostic IDH2 mutations aid in the diagnosis of grade III astrocytomas (NCCN.org). detail...
IDH2 mutant acute myeloid leukemia sensitive Cytarabine + Venetoclax Guideline Actionable Venclexta (venetoclax) in combination with Cytosar-U (cytarabine) is included in guidelines for adult patients with acute myeloid leukemia harboring an IDH2 mutation (NCCN.org). detail...
IDH2 mutant acute myeloid leukemia sensitive Cytarabine + Venetoclax Phase Ib/II Actionable In a Phase I/II trial, Venclexta (venetoclax) in combination with low-dose cytarabine resulted in complete remission or complete remission with incomplete count recovery in 72% (13/18) of patients with acute myeloid leukemia harboring IDH1 or IDH2 mutations who were ineligible for intensive chemotherapy (ASH Annual Meeting, Dec 2018, Abstract 284; NCT02287233). detail...
IDH2 mutant acute myeloid leukemia predicted - sensitive Daunorubicin + Talazoparib Preclinical - Patient cell culture Actionable In a preclinical study, the combination therapy of Talzenna (talazoparib) and Cerubidine (daunoruibicin) resulted in an additive effect in cells from a patient with acute myeloid leukemia harboring an IDH2 mutation, demonstrating decreased colony formation in culture (PMID: 29339439). 29339439
IDH2 mutant acute myeloid leukemia sensitive Decitabine + Venetoclax Guideline Actionable Venclexta (venetoclax) in combination with Dacogen (decitabine) is included in guidelines for adult patients with acute myeloid leukemia harboring an IDH2 mutation (NCCN.org). detail...
IDH2 mutant acute myeloid leukemia predicted - sensitive Daunorubicin + Olaparib Preclinical - Patient cell culture Actionable In a preclinical study, the combination therapy of Lynparza (olaparib) and Cerubidine (daunoruibicin) resulted in an additive effect in cells from a patient with acute myeloid leukemia harboring an IDH2 mutation, demonstrating decreased colony formation in culture (PMID: 29339439). 29339439
IDH2 mutant malignant glioma predicted - sensitive AG-881 Case Reports/Case Series Actionable In a Phase I trial, Vorasidenib (AG-881) treatment resulted in an objective response in 13.6% (3/21, 1 partial response, 2 minor response) and stable disease in 77.3% (17/21) of patients with recurrent or progressive non-enhancing glioma harboring mutations in IDH1 (n=20) or IDH2 (n=1), with 60.5% of the patients remained progression-free and alive at 24 months (J Clin Oncol 38: 2020 (suppl; abstr 2504); NCT02481154). detail...
IDH2 mutant acute myeloid leukemia predicted - sensitive Olaparib Preclinical - Patient cell culture Actionable In a preclinical study, cells from a patient with acute myeloid leukemia harboring an IDH2 mutation were sensitive to treatment with Lynparza (olaparib) in culture, demonstrating decreased colony formation (PMID: 29339439). 29339439
IDH2 mutant acute myeloid leukemia predicted - sensitive Talazoparib Preclinical - Patient cell culture Actionable In a preclinical study, cells from a patient with acute myeloid leukemia harboring an IDH2 mutation were sensitive to treatment with Talzenna (talazoparib) in culture, demonstrating decreased colony formation (PMID: 29339439). 29339439
IDH2 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 (NCCN.org). detail...
IDH2 mutant astrocytoma not applicable N/A Guideline Diagnostic IDH2 mutations aid in the diagnosis of grade II and grade III astrocytomas (NCCN.org). detail...
IDH2 mutant malignant glioma not applicable N/A Guideline Prognostic IDH2 mutations are associated with a favorable prognosis in patients with glioma, and are associated with a survival benefit for patients treated with radiation or alkylator therapy (NCCN.org). detail...
IDH2 mutant malignant glioma not applicable N/A Guideline Diagnostic IDH2 mutations aid in the diagnosis of gliomas (NCCN.org). detail...
IDH2 mutant myelofibrosis not applicable N/A Guideline Diagnostic IDH2 mutations aid in the diagnosis of primary myelofibrosis in the absence of JAK2, CALR, or MPL mutations (NCCN.org). detail...
IDH2 mutant myelofibrosis not applicable N/A Guideline Prognostic IDH2 mutations are associated with inferior leukemia-free survival in patients with myelofibrosis (NCCN.org). detail...
IDH2 mutant acute myeloid leukemia sensitive Decitabine Guideline Actionable Dacogen (decitabine) is included in guidelines for adult patients with acute myeloid leukemia harboring an IDH2 mutation (NCCN.org). detail...
IDH2 mutant polycythemia vera not applicable N/A Guideline Prognostic IDH2 mutations are associated with inferior overall survival and leukemia-free survival in patients with polycythemia vera (NCCN.org). detail...
IDH2 mutant acute myeloid leukemia sensitive Enasidenib Guideline Actionable Idhifa (enasidenib) is included in guidelines for patients with relapsed or refractory acute myeloid leukemia harboring an IDH2 mutation (NCCN.org). detail...
IDH2 mutant acute myeloid leukemia sensitive Enasidenib FDA approved - Has Companion Diagnostic Actionable In a Phase I/II trial that supported FDA approval, Idhifa (enasidenib) treatment resulted in an overall response rate of 40.3% (71/176) with a median response duration of 5.8 months, complete remission in 19.3% (34/176), and stable disease in 48.3% (85/176) of acute myeloid leukemia patients harboring IDH2 mutations (R140Q/L/G/W, R172K/M/G/S/W) (PMID: 28588020; NCT01915498). 28588020 detail... detail...
IDH2 mutant oligodendroglioma not applicable N/A Guideline Diagnostic IDH2 mutations aid in the diagnosis of oligodendrogliomas (NCCN.org). detail...
IDH2 mutant angioimmunoblastic T-cell lymphoma not applicable N/A Guideline Diagnostic IDH2 mutations aid in the diagnosis of angioimmunoblastic T-cell lymphoma (NCCN.org). detail...
IDH2 mutant acute myeloid leukemia sensitive Azacitidine Guideline Actionable Vidaza (azacitidine) is included in guidelines for adult patients with acute myeloid leukemia harboring an IDH2 mutation (NCCN.org). detail...