Gene Detail

Gene Symbol IDH2
Synonyms D2HGA2 | ICD-M | IDH | IDHM | IDP | IDPM | mNADP-IDH
Gene Description IDH2, isocitrate dehydrogenase (NADP(+)) 2, mitochondrial, is an enzyme that catalyzes the conversion of isocitrate to alpha-ketoglutarate (alpha-KG), and is involved in the tricarboxylic acid cycle (PMID: 28711227, PMID: 28980701). Mutations in IDH2 are associated with aberrant conversion of alpha-KG to 2-HG, which is an oncogenic metabolite, and are recurrent in acute myeloid leukemia and subtypes of glioma (PMID: 27621679, PMID: 19228619, PMID: 23999441).
Entrez Id 3418
Chromosome 15
Map Location 15q26.1
Canonical Transcript NM_002168

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Variant Impact Protein Effect Variant Description Associated with drug Resistance
R159H missense unknown IDH2 R159H does not lie within any known functional domains of the Idh2 protein (UniProt.org). R159H has not been characterized in the scientific literature and therefore, its effect on Idh2 protein function is unknown (PubMed, Feb 2018).
R172M missense gain of function IDH2 R172M lies within the active site of the Idh2 protein (PMID: 19228619). R172M confers a gain of function to the Idh2 protein as indicated by increased production of 2HG (R(-)-2-hydroxyglutarate) in cultured cells (PMID: 21326614, PMID: 27577048).
R172X missense gain of function - predicted IDH2 R172X indicates any Idh2 missense mutation that results in the replacement of the arginine (R) at amino acid 172 by a different amino acid. R172 variants are hotspot mutations in Idh2, which may confer a gain of function to Idh2 resulting in conversion of alpha-ketoglutarate to the onco-metabolite 2HG (R(-)-2-hydroxyglutarate) (PMID: 28711227, PMID: 21326614).
F394V missense loss of function - predicted IDH2 F394V does not lie within any known functional domains of the Idh2 protein (UniProt.org). F394V results in decreased cellular accumulation of Idh2 protein in culture (PMID: 21996744), and therefore is predicted to lead to a loss of Idh2 protein function.
A47V missense unknown IDH2 A47V does not lie within any known functional domains of the Idh2 protein (UniProt.org). A47V has not been biochemically characterized, but has an associated gene expression profile that does not correlate to that of Idh2 activating mutations (PMID: 27147599).
A410S missense unknown IDH2 A410S does not lie within any known functional domains of the Idh2 protein (UniProt.org). A410S has not been characterized in the scientific literature and therefore, its effect on Idh2 protein function is unknown (PubMed, Feb 2018).
L143M missense unknown IDH2 L143M does not lie within any known functional domains of the Idh2 protein (UniProt.org). L143M has not been characterized in the scientific literature and therefore, its effect on Idh2 protein function is unknown (PubMed, Feb 2018).
Q316E missense no effect - predicted IDH2 Q316E does not lie within any known functional domains of the Idh2 protein (UniPort.org). Q316E demonstrates dimerization ability and does not lead to increased production of 2HG in culture similar to wild-type Idh2, however, is associated with resistance to Enasidenib when occurring in cis or trans with IDH2 R140Q (PMID: 29950729). Y
R377C missense unknown IDH2 R377C does not lie within any known functional domains of the Idh2 protein (UniProt.org). R377C has been identified in sequencing studies (PMID: 24755471), but has not been biochemically characterized and therefore, its effect on Idh2 protein function is unknown (PubMed, Feb 2018).
H348Q missense unknown IDH2 H348Q does not lie within any known functional domains of the Idh2 protein (UniProt.org). H348Q has not been characterized in the scientific literature and therefore, its effect on Idh2 protein function is unknown (PubMed, Feb 2018).
E68K missense unknown IDH2 E68K does not lie within any known functional domains of the Idh2 protein (UniProt.org). E68K has not been characterized in the scientific literature and therefore, its effect on Idh2 protein function is unknown (PubMed, Feb 2018).
I319M missense no effect - predicted IDH2 I319M does not lie within any known functional domains of the Idh2 protein (UniPort.org). I319M demonstrates dimerization ability and does not lead to increased production of 2HG in culture similar to wild-type Idh2, however, is associated with resistance to Enasidenib when occurring in cis or trans with IDH2 R140Q (PMID: 29950729). Y
G260W missense unknown IDH2 G260W does not lie within any known functional domains of the Idh2 protein (UniProt.org). G260W has not been characterized in the scientific literature and therefore, its effect on Idh2 protein function is unknown (PubMed, Feb 2018).
E208* nonsense loss of function - predicted IDH2 E208* results in a premature truncation of the Idh2 protein at amino acid 208 of 452 (UniProt.org). Due to the loss of sites critical for catalysis, E208* is predicted to lead to a loss of Idh2 protein function (UniProt.org).
W375* nonsense unknown IDH2 W375* results in a premature truncation of the Idh2 protein at amino acid 375 of 452 (UniProt.org). W375* has not been characterized in the scientific literature and therefore, its effect on Idh2 protein function is unknown (PubMed, Feb 2018).
I441T missense unknown IDH2 I441T does not lie within any known functional domains of the Idh2 protein (UniProt.org). I441T has been identified in sequencing studies (PMID: 22810696), but has not been biochemically characterized and therefore, its effect on Idh2 protein function is unknown (PubMed, Mar 2018).
V294M missense no effect - predicted IDH2 V294M does not lie within any known functional domains of the Idh2 protein (UniProt.org). V294M demonstrates isocitrate-dependent NAPDH production similar to wild-type Idh2 in in vitro assays and does not result in increased 2HG production (PMID: 21996744), and therefore, is predicted to have no effect on Idh2 protein function.
G421S missense unknown IDH2 G421S does not lie within any known functional domains of the Idh2 protein (UniProt.org). G421S has not been characterized in the scientific literature and therefore, its effect on Idh2 protein function is unknown (PubMed, Feb 2018).
R140W missense gain of function - predicted 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 confer a gain of function to Idh2.
G145fs frameshift loss of function - predicted IDH2 G145fs results in a change in the amino acid sequence of the Idh2 protein beginning at aa 145 of 452, likely resulting in premature truncation of the functional protein (UniProt.org). Due to the loss of sites critical for catalysis, G145fs is predicted to lead to a loss of Idh2 protein function (UniProt.org).
R140G missense unknown IDH2 R140G lies within the substrate binding region of the Idh2 protein (UniProt.org). R140G has been identified in sequencing studies (PMID: 27276561), but has not been biochemically characterized and therefore, its effect on Idh2 protein function is unknown (PubMed, Feb 2018).
P158L missense unknown IDH2 P158L does not lie within any known functional domains of the Idh2 protein (UniProt.org). P158L has been identified in sequencing studies (PMID: 25495392), but has not been biochemically characterized and therefore, its effect on Idh2 protein function is unknown (PubMed, Feb 2018).
E268D missense unknown IDH2 E268D does not lie within any known functional domains of the Idh2 protein (UniProt.org). E268D has not been biochemically characterized, but has an associated gene expression profile that does not correlate to that of Idh2 activating mutations (PMID: 27147599).
D76fs frameshift loss of function - predicted IDH2 D76fs result in a change in the amino acid sequence of the Idh2 protein beginning at aa 76 of 452, likely resulting in premature truncation of the functional protein (UniProt.org). Due to the loss of the substrate binding region and sites critical for catalysis (UniProt.org), D76fs is predicted to lead to a loss of Idh2 protein function.
K48N missense unknown IDH2 K48N does not lie within any known functional domains of the Idh2 protein (UniProt.org). K48N has been identified in sequencing studies (PMID: 24121792), but has not been biochemically characterized and therefore, its effect on Idh2 protein function is unknown (PubMed, Feb 2018).
R140X missense gain of function - predicted IDH2 R140X indicates any Idh2 missense mutation that results in the replacement of the arginine (R) at amino acid 140 by a different amino acid. R140 variants are hotspot mutations in Idh2, which may confer a gain of function to the Idh2 protein resulting in conversion of alpha-ketoglutarate to the onco-metabolite 2HG (R(-)-2-hydroxyglutarate) (PMID: 23071358, PMID: 27621679).
R140Q missense gain of function 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).
G201D missense unknown IDH2 G201D does not lie within any known functional domains of the Idh2 protein (UniProt.org). G201D has not been characterized in the scientific literature and therefore, its effect on Idh2 protein function is unknown (PubMed, Feb 2018).
amp none no effect IDH2 amp indicates an increased number of copies of the Idh2 gene. However, the mechanism causing the increase is unspecified.
R353fs frameshift unknown IDH2 R353fs results in a change in the amino acid sequence of the Idh2 protein beginning at aa 353 of 452, likely resulting in premature truncation of the functional protein (UniProt.org). R353fs has not been characterized in the scientific literature and therefore, its effect on Idh2 protein function is unknown (PubMed, Feb 2018).
F394I missense loss of function - predicted IDH2 F394I does not lie within any known functional domains of the Idh2 protein (UniProt.org). F394I results in decreased cellular accumulation of Idh2 protein in culture (PMID: 21996744), and therefore is predicted to lead to a loss of Idh2 protein function.
G137E missense unknown IDH2 G137E lies within the substrate binding region of the Idh2 protein (UniProt.org). G137E has not been biochemically characterized, but has an associated gene expression profile that does not correlate to that of Idh2 activating mutations (PMID: 27147599).
wild-type none no effect Wild-type IDH2 indicates that no mutation has been detected within the IDH2 gene.
A416V missense unknown IDH2 A416V does not lie within any known functional domains of the Idh2 protein (UniProt.org). A416V has not been biochemically characterized, but has an associated gene expression profile that does not correlate to that of Idh2 activating mutations (PMID: 27147599).
G190D missense unknown IDH2 G190D does not lie within any known functional domains of the Idh2 protein (UniProt.org). G190D has not been characterized in the scientific literature and therefore, its effect on Idh2 protein function is unknown (PubMed, Feb 2018).
T146fs frameshift loss of function - predicted IDH2 T146fs results in a change in the amino acid sequence of the Idh2 protein beginning at aa 146 of 452, likely resulting in premature truncation of the functional protein (UniProt.org). Due to the loss of sites critical for catalysis (UniProt.org), T146fs is predicted to lead to a loss of Idh2 protein function.
Q322K missense unknown IDH2 Q322K does not lie within any known functional domains of the Idh2 protein (UniProt.org). Q322K has not been characterized in the scientific literature and therefore, its effect on Idh2 protein function is unknown (PubMed, Feb 2018).
R140K missense unknown IDH2 R140K lies within the substrate binding region of the Idh2 protein (UniProt.org). R140K has not been characterized in the scientific literature and therefore, it effect on Idh2 protein function is unknown (PubMed, Feb 2018).
R172G missense gain of function IDH2 R172G lies within the active site of the Idh2 protein (PMID: 19228619). R172G results in decreased Idh2 enzymatic activity as indicated by reduced production of NADPH in culture (PMID: 21326614, PMID: 19228619), and confers a gain of function to Idh2 as indicated by production of 2HG (R(-)-2-hydroxyglutarate), and leads to activation of HIF-1-alpha signaling and nuclear accumulation of beta-catenin in cell culture (PMID: 22309944, PMID: 21326614).
A101P missense unknown IDH2 A101P does not lie within any known functional domains of the Idh2 protein (UniProt.org). A101P has not been characterized in the scientific literature and therefore, its effect on Idh2 protein function is unknown (PubMed, Feb 2018).
R172W missense unknown IDH2 R172W lies within the active site of the Idh2 protein (PMID: 19228619). R172W has been identified in sequencing studies (PMID: 22180306, PMID: 25836588), but has not been biochemically characterized and therefore, its effect on Idh2 protein function is unknown (PubMed, Mar 2018).
A416fs frameshift unknown IDH2 A416fs results in a change in the amino acid sequence of the Idh2 protein beginning at aa 416 of 452, likely resulting in a premature truncation of the functional protein (UniProt.org). A416fs has not been characterized in the scientific literature and therefore, its effect on Idh2 protein function is unknown (PubMed, Feb 2018).
act mut unknown gain of function IDH2 act mut indicates that this variant results in a gain of function in the Idh2 protein. However, the specific amino acid change has not been identified.
P162S missense unknown IDH2 P162S does not lie within any known functional domains of the Idh2 protein (UniProt.org). P162S has been identified in the scientific literature (PMID: 25495392, PMID: 26068201), but has not been biochemically characterized and therefore, its effect on Idh2 protein function is unknown (PubMed, Feb 2018).
R140S missense unknown IDH2 R140S lies within the substrate binding region of the Idh2 protein (UniProt.org). R140S has not been characterized in the scientific literature and therefore, it effect on Idh2 protein function is unknown (PubMed, Feb 2018).
R172S missense gain of function IDH2 R172S lies within the active site of the Idh2 protein (PMID: 19228619). R172S confers a gain of function to the Idh2 protein as demonstrated by accumulation 2HG (R(-)-2-hydroxyglutarate), and leads to increased migration in cultured cells (PMID: 23264629, PMID: 27913435).
over exp none no effect IDH2 over exp indicates an over expression of the Idh2 protein. However, the mechanism causing the over expression is unspecified.
E226K missense unknown IDH2 E226K does not lie within any known functional domains of the Idh2 protein (UniProt.org). E226K has been identified in sequencing studies (PMID: 24030381), but has not been biochemically characterized and therefore, its effect on Idh2 protein function is unknown (PubMed, Nov 2018).
R140M missense unknown IDH2 R140M lies within the substrate binding region of the Idh2 protein (UniProt.org). R140M has not been characterized in the scientific literature and therefore, it effect on Idh2 protein function is unknown (PubMed, Feb 2018).
I228L missense unknown IDH2 I228L does not lie within any known functional domains of the Idh2 protein (UniProt.org). I228L has not been characterized in the scientific literature and therefore, its effect on Idh2 protein function is unknown (PubMed, Feb 2018).
Q359H missense unknown IDH2 Q359H does not lie within any known functional domains of the Idh2 protein (UniProt.org). Q359H has not been characterized in the scientific literature and therefore, its effect on Idh2 protein function is unknown (PubMed, Feb 2018).
P158T missense unknown IDH2 P158T does not lie within any known functional domains of the Idh2 protein (UniProt.org). P158T has been identified in sequencing studies (PMID: 21356389), but has not been biochemically characterized and therefore, its effect on Idh2 protein function is unknown (PubMed, Feb 2018).
A370T missense unknown IDH2 A370T does not lie within any known functional domains of the Idh2 protein (UniProt.org). A370T has not been characterized in the scientific literature and therefore, its effect on Idh2 protein function is unknown (PubMed, Feb 2018).
I139F missense unknown IDH2 I139F lies within the substrate binding region of the Idh2 protein (UniProt.org). I139F has not been biochemically characterized, but has an associated gene expression profile that does not correlate to that of Idh2 activating mutations (PMID: 27147599).
R140L missense unknown IDH2 R140L lies within the substrate binding of the Idh2 protein (UniProt.org). R140L has been identified in the scientific literature (PMID: 21596855, PMID: 25836588, PMID: 24344212), but has not been biochemically characterized and therefore, its effect on Idh2 protein function is unknown.
R172T missense unknown IDH2 R172T lies within the active site of the Idh2 protein (PMID: 19228619). R172T has been identified in sequencing studies (PMID: 23485734, PMID: 22215888), but has not been biochemically characterized and therefore, its effect on Idh2 protein function is unknown (PubMed, Feb 2018).
K133R missense unknown IDH2 K133R does not lie within any known functional domains of the Idh2 protein (UniProt.org). K133R has not been characterized in the scientific literature and therefore, its effect on Idh2 protein function is unknown (PubMed, Feb 2018).
G171D missense unknown IDH2 G171D does not lie within any known functional domains of the Idh2 protein (UniProt.org). G171D has been identified in sequencing studies (PMID: 21356389), but has not been biochemically characterized and therefore, its effect on Idh2 protein function is unknown (PubMed, Feb 2018).
R172K missense gain of function IDH2 R172K lies within the active site of the Idh2 protein (PMID: 19228619). R172K confers a gain of function to Idh2, as indicated by the increased conversion of alpha-ketoglutarate to the onco-metabolite 2HG (R(-)-2-hydroxyglutarate) in cell culture (PMID: 20171147, PMID: 21326614).
mutant unknown unknown IDH2 mutant indicates an unspecified mutation in the IDH2 gene.
T331M missense unknown IDH2 T331M does not lie within any known functional domains of the Idh2 protein (UniProt.org). T331M has not been biochemically characterized, but has an associated gene expression profile that does not correlate to that of Idh2 activating mutations (PMID: 27147599).
D83V missense unknown IDH2 D83V does not lie within any known functional domains of the Idh2 protein (UniProt.org). D83V has not been characterized in the scientific literature and therefore, its effect on Idh2 protein function is unknown (PubMed, Feb 2018).
M248T missense unknown IDH2 M248T does not lie within any known functional domains of the Idh2 protein (UniProt.org). M248T has been identified in sequencing studies (PMID: 22895193), but has not been biochemically characterized and therefore, its effect on Idh2 protein function is unknown (PubMed, Feb 2018).
K280N missense unknown IDH2 K280N does not lie within any known functional domains of the Idh2 protein (UniProt.org). K280N has not been characterized in the scientific literature and therefore, its effect on Idh2 protein function is unknown (PubMed, Feb 2018).
G144R missense unknown IDH2 G144R does not lie within any known functional domains of the Idh2 protein (UniProt.org). G144R has not been characterized in the scientific literature and therefore, its effect on Idh2 protein function is unknown (PubMed, Feb 2018).
H358R missense unknown IDH2 H358R does not lie within any known functional domains of the Idh2 protein (UniProt.org). H358R has not been characterized in the scientific literature and therefore, its effect on Idh2 protein function is unknown (PubMed, Feb 2018).
S301L missense unknown IDH2 S301L does not lie within any known functional domains of the Idh2 protein (UniProt.org). S301L has not been characterized in the scientific literature and therefore, its effect on Idh2 protein function is unknown (PubMed, Feb 2018).
W244* nonsense loss of function - predicted IDH2 W244* results in a premature truncation of the Idh2 protein at amino acid 244 of 452 (UniProt.org). Due to the loss of a site critical for catalysis (UniProt.org), W244* is predicted to lead to a loss of Idh2 protein function.
K130del deletion unknown IDH2 K130del results in the deletion of an amino acid in the Idh2 protein at amino acid 130 (UniProt.org). K130del has not been characterized in the scientific literature and therefore, its effect on Idh2 protein function is unknown (PubMed, Feb 2018).
T435M missense unknown IDH2 T435M does not lie within any known functional domains of the Idh2 protein (UniProt.org). T435M has not been characterized in the scientific literature and therefore, its effect on Idh2 protein function is unknown (PubMed, Feb 2018).
Molecular Profile Protein Effect Treatment Approaches
IDH2 R159H unknown
IDH2 R172M gain of function IDH Inhibitor (Pan) IDH2 Inhibitor
IDH2 R172X gain of function - predicted IDH Inhibitor (Pan) IDH2 Inhibitor
IDH2 F394V loss of function - predicted
IDH2 A47V unknown
IDH2 A410S unknown
IDH2 L143M unknown
IDH2 R140Q IDH2 Q316E
IDH2 Q316E no effect - predicted
IDH2 R377C unknown
IDH2 H348Q unknown
IDH2 E68K unknown
IDH2 I319M no effect - predicted
IDH2 R140Q IDH2 I139M
IDH2 G260W unknown
IDH2 E208* loss of function - predicted
IDH2 W375* unknown
IDH2 I441T unknown
IDH2 V294M no effect - predicted
IDH2 G421S unknown
IDH2 R140W FLT3 Y599_D600insSTDNEYFYVDFREYEY
IDH2 R140W gain of function - predicted IDH Inhibitor (Pan) IDH2 Inhibitor
IDH2 G145fs loss of function - predicted
IDH2 R140G unknown
IDH2 P158L unknown
IDH2 E268D unknown
IDH2 D76fs loss of function - predicted
IDH2 K48N unknown
IDH2 R140X gain of function - predicted IDH Inhibitor (Pan) IDH2 Inhibitor
IDH2 R140Q gain of function IDH Inhibitor (Pan) IDH2 Inhibitor
IDH2 G201D unknown
IDH2 amp no effect
IDH2 R353fs unknown
IDH2 F394I loss of function - predicted
IDH2 G137E unknown
IDH2 wild-type no effect
IDH2 A416V unknown
IDH2 G190D unknown
IDH2 T146fs loss of function - predicted
IDH2 Q322K unknown
IDH2 R140K unknown
IDH2 R172G gain of function IDH Inhibitor (Pan) IDH2 Inhibitor
IDH2 A101P unknown
IDH2 R172W unknown
IDH2 A416fs unknown
IDH2 act mut gain of function IDH Inhibitor (Pan) IDH2 Inhibitor
IDH2 P162S unknown
IDH2 R140S unknown
IDH2 R172S gain of function IDH Inhibitor (Pan) IDH2 Inhibitor
IDH2 over exp no effect
IDH2 E226K unknown
IDH2 R140M unknown
IDH2 I228L unknown
IDH2 Q359H unknown
IDH2 P158T unknown
IDH2 A370T unknown
IDH2 I139F unknown
IDH2 R140L unknown
IDH2 R172T unknown
IDH2 K133R unknown
IDH2 G171D unknown
IDH2 R172K KRAS G12D
IDH2 R172K gain of function IDH Inhibitor (Pan) IDH2 Inhibitor
IDH2 mutant unknown
ATRX loss IDH2 mut
IDH2 T331M unknown
IDH2 D83V unknown
IDH2 M248T unknown
IDH2 K280N unknown
IDH2 G144R unknown
IDH2 H358R unknown
IDH2 S301L unknown
IDH2 W244* loss of function - predicted
IDH2 K130del unknown
IDH2 T435M unknown
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
IDH2 R172X myelodysplastic syndrome not applicable N/A Guideline Prognostic IDH2 R172X is associated with a poor prognosis in patients with myelodysplastic syndrome (NCCN.org). detail...
IDH2 R140Q IDH2 Q316E acute myeloid leukemia resistant Enasidenib Clinical Study 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, 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 I139M acute myeloid leukemia resistant Enasidenib Clinical Study 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, 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 R140W FLT3 Y599_D600insSTDNEYFYVDFREYEY acute myeloid leukemia predicted - sensitive Enasidenib + Quizartinib Preclinical Actionable In a preclinical study, the combination of Enasidenib (AG-221) and Quizartinib (AC220) 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...
IDH2 D76fs acute myeloid leukemia sensitive Venetoclax Phase II Actionable In a Phase II trial, an acute myeloid leukemia patient harboring IDH2 D76fs demonstrated sensitivity to treatment with Venclexta (venetoclax), achieving a complete response with incomplete blood count recovery after 24 weeks (PMID: 27520294). 27520294
IDH2 R140Q glioblastoma multiforme 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 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 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 wild-type malignant glioma not applicable N/A Guideline Risk Factor IDH2 wild-type is associated with increased risk of aggressive disease in patients with grade II or III infiltrative gliomas (NCCN.org). detail...
IDH2 R172K KRAS G12D intrahepatic cholangiocarcinoma sensitive Saracatinib Preclinical Actionable In a preclinical study, intrahepatic cholangiocarcinoma cells harboring IDH2 R172K and KRAS G12D demonstrated increased sensitivity to Saracatinib (AZD0530) induced growth inhibition in culture (PMID: 27231123). 27231123
IDH2 R172K KRAS G12D intrahepatic cholangiocarcinoma sensitive Dasatinib Preclinical Actionable In a preclinical study, intrahepatic cholangiocarcinoma cells harboring IDH2 R172K and KRAS G12D demonstrated increased sensitivity to Sprycel (dasatinib) induced growth inhibition in culture and in xenograft models (PMID: 27231123). 27231123
IDH2 R172K acute myeloid leukemia sensitive Enasidenib Preclinical - Patient cell culture Actionable In a preclinical study, Enasidenib (AG-221) decreased 2-hydroxyglutarate (2HG) levels and induced differentiation of leukemic blasts from acute myeloid leukemia (AML) patients harboring IDH2 R172K in culture (PMID: 28193778). 28193778
IDH2 R172K colorectal cancer predicted - sensitive Enasidenib Preclinical - Cell culture Actionable In a preclinical study, Enasidenib (AG-221) decreased 2-hydroxyglutarate (2HG) levels in a colorectal carcinoma cell line expressing IDH2 R172K in culture (PMID: 28193778). 28193778
IDH2 R172K glioblastoma multiforme predicted - sensitive Enasidenib Preclinical - Cell culture Actionable In a preclinical study, Enasidenib (AG-221) decreased 2-hydroxyglutarate (2HG) levels in a glioblastoma cell line expressing IDH2 R172K in culture (PMID: 28193778). 28193778
IDH2 mutant acute myeloid leukemia predicted - 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 oligodendroglioma not applicable N/A Guideline Diagnostic IDH2 mutations aid in the diagnosis of oligodendrogliomas (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 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 grade III astrocytoma not applicable N/A Guideline Diagnostic IDH2 mutations aid in the diagnosis of grade III astrocytomas (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 essential thrombocythemia not applicable N/A Guideline Prognostic The presence of at least one mutation in either SH2B3, IDH2, U2AF1, SF3B1, EZH2, or TP53 is associated with inferior overall survival in patients with essential thrombocythemia (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 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 Enasidenib FDA approved 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). 28588020
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 glioblastoma multiforme no benefit N/A Guideline Diagnostic IDH2 mutations aid in the diagnosis of secondary grade IV glioblastomas (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...
ATRX loss IDH2 mut astrocytoma not applicable N/A Guideline Diagnostic ATRX deficiency in combination with IDH mutation aids in the diagnosis of astrocytoma (NCCN.org). detail...