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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
Category Variants Paths

IDH2 mutant IDH2 act mut IDH2 R140Q

IDH2 mutant IDH2 R140X IDH2 R140Q

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Transcript NM_002168.4
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
NM_002168.4 chr15:g.90088702C>T c.419G>A p.R140Q RefSeq GRCh38/hg38

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
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 Q316E leukemia predicted - resistant Enasidenib Preclinical - Biochemical Actionable In a preclinical study, Idhifa (enasidenib) did not inhibit Idh2 activity and R-2HG production in a leukemia cell line expressing IDH2 R140Q and Q316E in culture (PMID: 36222845). 36222845
IDH2 R140Q IDH2 I319M acute myeloid leukemia resistant Enasidenib Case Reports/Case Series Actionable In a clinical case study, IDH2 I319M was identified as an acquired mutation in a patient with acute myeloid leukemia harboring IDH2 R140Q upon progression on Idhifa (enasidenib) (PMID: 36222845). 36222845
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
IDH2 R140Q IDH2 I319M leukemia predicted - resistant Enasidenib Preclinical - Biochemical Actionable In a preclinical study, Idhifa (enasidenib) did not inhibit Idh2 activity and R-2HG production in a leukemia cell line expressing IDH2 R140Q and I319M in culture (PMID: 36222845). 36222845
FLT3 exon 14 ins IDH2 R140Q acute myeloid leukemia predicted - sensitive Enasidenib + Quizartinib Preclinical Actionable In a preclinical study, the combination of Enasidenib (AG-221) and Vanflyta (quizartinib) stimulated leukemic cell differentiation and reduced leukemic cell self-renewal in an acute myeloid leukemia mouse model simultaneously expressing IDH2 R140Q and a FLT3-ITD mutation (Blood Dec 2014, 124 (21) 437). detail...
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 - 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 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 - 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
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 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
IDH1 R132C IDH1 D279N IDH2 R140Q acute myeloid leukemia predicted - resistant Ivosidenib Case Reports/Case Series Actionable In a Phase I trial, IDH1 D279N and IDH2 R140Q were identified at progression in a patient with acute myeloid leukemia harboring IDH1 R132C who previously responded to Tibsovo (ivosidenib) treatment (PMID: 32380538; NCT02074839). 32380538
IDH1 R119P IDH1 R132L IDH2 R140Q acute myeloid leukemia predicted - resistant Ivosidenib Case Reports/Case Series Actionable In a Phase I trial, IDH1 R119P and IDH2 R140Q were identified at progression in a patient with acute myeloid leukemia harboring IDH1 R132L who previously responded to Tibsovo (ivosidenib) treatment (PMID: 32380538; NCT02074839). 32380538
IDH2 R140Q IDH2 H348Q leukemia predicted - resistant Enasidenib Preclinical - Biochemical Actionable In a preclinical study, Idhifa (enasidenib) did not inhibit Idh2 activity and R-2HG production in a leukemia cell line expressing IDH2 R140Q and H348Q in culture (PMID: 36222845). 36222845
IDH1 R132L IDH2 R140Q acute myeloid leukemia predicted - resistant Ivosidenib Case Reports/Case Series Actionable In a Phase I trial, IDH2 R140Q was identified at progression in a patient with acute myeloid leukemia harboring IDH1 R132L who previously had a response of stable disease with Tibsovo (ivosidenib) treatment (PMID: 32380538; NCT02074839). 32380538
IDH1 R132C IDH2 R140Q acute myeloid leukemia predicted - resistant Ivosidenib Case Reports/Case Series Actionable In a Phase I trial, IDH2 R140Q was identified at progression in 5 patients with acute myeloid leukemia harboring IDH1 R132C who previously responded to Tibsovo (ivosidenib) treatment (PMID: 32380538; NCT02074839). 32380538
IDH1 R132H IDH2 R140Q acute myeloid leukemia predicted - resistant Ivosidenib Case Reports/Case Series Actionable In a Phase I trial, IDH2 R140Q was identified at progression in 4 patients with acute myeloid leukemia harboring IDH1 R132H who previously responded to Tibsovo (ivosidenib) treatment (PMID: 32380538; NCT02074839). 32380538
IDH2 R140Q IDH2 E343V acute myeloid leukemia predicted - resistant Enasidenib Case Reports/Case Series Actionable In a clinical case study, IDH2 E343V was identified as an acquired mutation in a patient with acute myeloid leukemia harboring IDH2 R140Q upon progression on Idhifa (enasidenib) (PMID: 36222845). 36222845
IDH2 R140Q IDH2 E343V leukemia resistant Enasidenib Preclinical - Cell line xenograft Actionable In a preclinical study, a leukemia cell line expressing IDH2 R140Q and E343V was resistant to Idhifa (enasidenib) in culture and did not reduce tumor burden in a cell line xenograft model (PMID: 36222845). 36222845
IDH2 R140Q IDH2 E343V leukemia predicted - resistant Vorasidenib Preclinical - Biochemical Actionable In a preclinical study, Vorasidenib (AG-881) did not inhibit R-2HG production in a leukemia cell line expressing IDH2 R140Q and E343V in culture (PMID: 36222845). 36222845
IDH2 R140Q IDH2 A347T leukemia resistant Enasidenib Preclinical - Cell line xenograft Actionable In a preclinical study, a leukemia cell line expressing IDH2 R140Q and A347T was resistant to Idhifa (enasidenib) in culture and did not reduce tumor burden in a cell line xenograft model (PMID: 36222845). 36222845
IDH2 R140Q IDH2 A347T acute myeloid leukemia predicted - resistant Enasidenib Case Reports/Case Series Actionable In a clinical case study, IDH2 A347T was identified as an acquired mutation in a patient with acute myeloid leukemia harboring IDH2 R140Q upon progression on Idhifa (enasidenib) (PMID: 36222845). 36222845
IDH2 R140Q IDH2 A347T leukemia predicted - resistant Vorasidenib Preclinical - Biochemical Actionable In a preclinical study, Vorasidenib (AG-881) did not inhibit R-2HG production in a leukemia cell line expressing IDH2 R140Q and A347T in culture (PMID: 36222845). 36222845
IDH2 N136S IDH2 R140Q leukemia predicted - resistant Enasidenib Preclinical - Biochemical Actionable In a preclinical study, Idhifa (enasidenib) did not inhibit Idh2 activity and R-2HG production in a leukemia cell line expressing IDH2 R140Q and N136S in culture (PMID: 36222845). 36222845
IDH2 R140Q IDH2 E345G leukemia predicted - resistant Enasidenib Preclinical - Biochemical Actionable In a preclinical study, Idhifa (enasidenib) did not inhibit Idh2 activity and R-2HG production in a leukemia cell line expressing IDH2 R140Q and E345G in culture (PMID: 36222845). 36222845
IDH2 R140Q IDH2 V351I leukemia predicted - resistant Enasidenib Preclinical - Biochemical Actionable In a preclinical study, Idhifa (enasidenib) did not inhibit Idh2 activity and R-2HG production in a leukemia cell line expressing IDH2 R140Q and V351I in culture (PMID: 36222845). 36222845
IDH2 R140Q IDH2 V351I acute myeloid leukemia predicted - resistant Enasidenib Case Reports/Case Series Actionable In a clinical case study, IDH2 V351I was identified as an acquired mutation in a patient with acute myeloid leukemia harboring IDH2 R140Q upon progression on Idhifa (enasidenib) (PMID: 36222845). 36222845
IDH2 R140Q IDH2 T352A leukemia predicted - resistant Enasidenib Preclinical - Biochemical Actionable In a preclinical study, Idhifa (enasidenib) did not inhibit Idh2 activity and R-2HG production in a leukemia cell line expressing IDH2 R140Q and T352A in culture (PMID: 36222845). 36222845
IDH2 R140Q IDH2 R353H leukemia predicted - resistant Enasidenib Preclinical - Biochemical Actionable In a preclinical study, Idhifa (enasidenib) did not inhibit Idh2 activity and R-2HG production in a leukemia cell line expressing IDH2 R140Q and R353H in culture (PMID: 36222845). 36222845
IDH2 R140Q IDH2 L449V leukemia predicted - sensitive Enasidenib Preclinical - Biochemical Actionable In a preclinical study, Idhifa (enasidenib) inhibited enzymatic activity and R-2HG production in a leukemia cell line expressing IDH2 R140Q and L449V in culture (PMID: 36222845). 36222845
IDH2 R140Q IDH2 G450S leukemia predicted - sensitive Enasidenib Preclinical - Biochemical Actionable In a preclinical study, Idhifa (enasidenib) inhibited enzymatic activity and R-2HG production in a leukemia cell line expressing IDH2 R140Q and G450S in culture (PMID: 36222845). 36222845
EML4 - ALK IDH2 R140Q lung adenocarcinoma predicted - resistant Alectinib Case Reports/Case Series Actionable In a clinical case study, IDH2 R140Q was identified at progression on Alecensa (alectinib) in a patient with non-small cell lung cancer harboring EML4-ALK (PMID: 34058070). 34058070