Gene Variant Detail

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Gene IDH2
Variant R140W
Impact List missense
Protein Effect gain of function - predicted
Gene Variant Descriptions IDH2 R140W lies within the substrate binding region of the Idh2 protein (UniProt.org). R140W results in decreased conversion of isocitrate to alpha-ketoglutarate (alpha-KG) by Idh2, and also results in increased conversion of alpha-KG to 2HG (R(-)-2-hydroxyglutarate) in an in vitro assay (PMID: 21647154), and therefore, is predicted to lead to a gain of Idh2 protein function.
Associated Drug Resistance
Category Variants Paths

IDH2 mutant IDH2 act mut IDH2 R140W

IDH2 mutant IDH2 R140X IDH2 R140W

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Transcript NM_002168.4
gDNA chr15:g.90088703G>A
cDNA c.418C>T
Protein p.R140W
Source Database RefSeq
Genome Build GRCh38/hg38
Transcript gDNA cDNA Protein Source Database Genome Build
NM_002168.3 chr15:g.90088703G>A c.418C>T p.R140W RefSeq GRCh38/hg38
NM_002168 chr15:g.90088703G>A c.418C>T p.R140W RefSeq GRCh38/hg38
NM_002168.4 chr15:g.90088703G>A c.418C>T p.R140W RefSeq GRCh38/hg38

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
IDH2 act mut brain glioma predicted - sensitive LY3410738 Phase I Actionable In a Phase I trial, LY3410738 treatment demonstrated safety and resulted in D-2-HG inhibition in patients with IDH-mutant advanced solid tumors, and led to partial response in 1 and stable disease in 22 of 42 patients with relapsed or refractory cholangiocarcinoma and partial response in 3 and stable disease in 9 of 22 patients with glioma (Cancer Res (2023) 83 (8_Supplement): CT098; NCT04521686). detail...
IDH2 act mut cholangiocarcinoma predicted - sensitive LY3410738 Phase I Actionable In a Phase I trial, LY3410738 treatment demonstrated safety and resulted in D-2-HG inhibition in patients with IDH-mutant advanced solid tumors, and led to partial response in 1 and stable disease in 22 of 42 patients with relapsed or refractory cholangiocarcinoma and partial response in 3 and stable disease in 9 of 22 patients with glioma (Cancer Res (2023) 83 (8_Supplement): CT098; NCT04521686). detail...
IDH2 act mut acute myeloid leukemia predicted - sensitive TQB3455 Phase I Actionable In a Phase I trial, TQB3455 treatment was well tolerated in patients with acute myeloid leukemia harboring IDH2 mutations, and resulted in an objective response rate of 40.63% (13/32, 12 complete remission (CR) or CR with incomplete hematological recovery, 1 partial remission), a median duration of response of 9.17 months, and a median overall survival of 7.43 months (Blood (2022) 140 (Supplement 1): 9082-9083). detail...
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 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 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 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 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 anaplastic astrocytoma not applicable N/A Guideline Diagnostic IDH2 mutations aid in the diagnosis of grade III astrocytomas (NCCN.org). detail...
IDH2 mutant high grade glioma predicted - sensitive Vorasidenib 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 sensitive Azacitidine Guideline Actionable Vidaza (azacitidine) 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 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 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 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 oligodendroglioma predicted - sensitive Vorasidenib Phase III Actionable In a Phase III trial (INDIGO), Vorasidenib (AG-881) treatment improved progression-free survival (27.7 months vs 11.1 months; HR=0.39, p=0.000000067) and time to next intervention (not reached vs 17.8 months, HR=0.26; p=0.000000019) compared to placebo in patients with oligodendroglioma or astrocytoma harboring IDH1/2 mutations (J Clin Oncol 41, 2023 (suppl 17; abstr LBA1); NCT04164901). detail...
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 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 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 oligodendroglioma not applicable N/A Guideline Diagnostic IDH2 mutations aid in the diagnosis of oligodendrogliomas (NCCN.org). detail...
IDH2 mutant malignant 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 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 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 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 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 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 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 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 high grade 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 high grade glioma not applicable N/A Guideline Diagnostic IDH2 mutations aid in the diagnosis of gliomas (NCCN.org). detail...
IDH2 mutant malignant astrocytoma predicted - sensitive Vorasidenib Phase III Actionable In a Phase III trial (INDIGO), Vorasidenib (AG-881) treatment improved progression-free survival (27.7 months vs 11.1 months; HR=0.39, p=0.000000067) and time to next intervention (not reached vs 17.8 months; HR=0.26, p=0.000000019) compared to placebo in patients with astrocytoma or oligodendroglioma harboring IDH1/2 mutations (J Clin Oncol 41, 2023 (suppl 17; abstr LBA1); NCT04164901). detail...
IDH2 R140X acute myeloid leukemia predicted - sensitive LY3410738 Phase I Actionable In a Phase I trial, LY3410738 demonstrated safety and inhibited D-2-HG in patients with relapsed or refractory IDH-mutant acute myeloid leukemia, resulting in a composite complete remission (CRc) rate of 9% (2/23, 2 CR) in IDH inhibitor-naive patients harbor IDH2 R140 mutations (Cancer Res (2023) 83 (8_Supplement): CT026; NCT04603001). detail...
IDH2 R140X myelodysplastic syndrome predicted - sensitive Azacitidine + Enasidenib Phase II Actionable In a Phase II trial, Idhifa (enasidenib) and Vidaza (azacitidine) combination treatment was well tolerated and resulted in an overall response rate of 68% (30/46, 11 complete remission (CR), 3 partial remission, 12 marrow CR, 4 hematological improvement only) in patients with higher-risk myelodysplastic syndrome harboring IDH2 R140 or R172 mutations who were naive to hypomethylating agents, with a median overall survival of 21.3 months (J Clin Oncol 39, no. 15_suppl (May 20, 2021) 7010-7010; NCT03383575). detail...
IDH2 R140X myelodysplastic syndrome predicted - sensitive Enasidenib Phase II Actionable In a Phase II trial, Idhifa (enasidenib) treatment was well tolerated and resulted in an overall response rate of 43% (9/21, 5 complete remission (CR), 1 partial remission, 1 marrow CR, 2 hematological improvement only) in patients with higher-risk myelodysplastic syndrome harboring IDH2 R140 or R172 mutations who were refractory to or progressed on hypomethylating agents, with a median overall survival of 21.3 months (J Clin Oncol 39, no. 15_suppl (May 20, 2021) 7010-7010; NCT03383575). detail...