Gene Detail

Gene Symbol IDH1
Synonyms HEL-216 | HEL-S-26 | IDCD | IDH | IDP | IDPC | PICD
Gene Description IDH1, isocitrate dehydrogenase (NADP(+)) 1, cytosolic, is an enzyme that catalyzes the conversion of isocitrate to alpha-ketoglutarate (alpha-KG), and is involved in the tricarboxylic acid cycle (PMID: 23999441, PMID: 28711227). Mutations in IDH1 are associated with aberrant conversion of alpha-KG to 2-HG, which is an oncogenic metabolite, and are recurrent in acute myeloid leukemia and glioma (PMID: 23999441, PMID: 28711227).
Entrez Id 3417
Chromosome 2
Map Location 2q34
Canonical Transcript NM_005896

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Variant Impact Protein Effect Variant Description Associated with drug Resistance
S261L missense unknown IDH1 S261L does not lie within any known functional domains of the Idh1 protein (UniProt.org). S261L has been identified in sequencing studies (PMID: 24755471), but has not been biochemically characterized and therefore, its effect on Idh1 protein function is unknown (PubMed, Mar 2018).
T325M missense unknown IDH1 T325M does not lie within any known functional domains of the Idh1 protein (UniProt.org). T325M has not been characterized and therefore, its effect on Idh1 protein function is unknown (PubMed, Mar 2018).
V294M missense no effect - predicted IDH1 V294M does not lie within any known functional domains of the Idh1 protein (UniProt.org). V294M has been demonstrated to display activity similar to wild-type Idh1 (PMID: 21996744) and therefore, is predicted to have no effect on Idh1 protein function.
R132X missense gain of function - predicted IDH1 R132X indicates any Idh1 missense mutation that results in the replacement of the arginine (R) at amino acid 132 by a different amino acid. R132 variants are hotspot mutations in Idh1, which may confer a gain of function to Idh1 resulting in conversion of alpha-ketoglutarate to the onco-metabolite 2HG (R(-)-2-hydroxyglutarate) (PMID: 19935646, PMID: 28330869, PMID: 21326614).
A134D missense loss of function IDH1 A134D does not lie within any known functional domains of the Idh1 protein (UniProt.org). A134D results in a loss of isocitrate catalytic activity in the Idh1 protein (PMID: 20702649, PMID: 21996744).
Q277* nonsense loss of function - predicted IDH1 Q277* results in a premature truncation of the Idh1 protein at amino acid 277 of 414 (UniProt.org). Due to the loss of the large domain required for formation of the active site, Q277* is predicted to lead to a loss of Idh1 protein function (PMID: 20513808).
V71I missense no effect IDH1 V71I does not lie within any known functional domains of the Idh1 protein (UniProt.org). V71I has no effect on Idh1 activity, as indicated by enzymatic activity similar to wild-type Idh1 in in vitro assays, and does not result in increased 2HG production (PMID: 21996744, PMID: 22442146).
G123E missense unknown IDH1 G123E lies within the active site of the Idh1 protein (PMID: 20972461). G123E has been identified in sequencing studies (PMID: 20567020), but has not been biochemically characterized and therefore, its effect on Idh1 protein function is unknown (PubMed, Apr 2018).
M182L missense unknown IDH1 M182L does not lie within any known functional domains of the Idh1 protein (UniProt.org). M182L has not been characterized in the scientific literature and therefore, its effect on Idh1 protein function is unknown (PubMed, Mar 2018).
amp none no effect IDH1 amp indicates an increased number of copies of the IDH1 gene. However, the mechanism causing the increase is unspecified.
G289fs frameshift loss of function - predicted IDH1 G289fs results in a change in the amino acid sequence of the Idh1 protein beginning at 289 of 414, likely resulting in premature truncation of the functional protein (UniProt.org). Due to the loss of the large domain required for formation of the active site, S289fs is predicted to lead to a loss of Idh1 protein function (PMID: 20513808).
V178I missense no effect IDH1 V178I does not lie within any known functional domains of the Idh1 protein (UniProt.org). IDH1 V178I retains wild-type Idh1 enzymatic activity, and does not increase 2HG levels in cell culture (PMID: 21996744) and therefore, has no effect on Idh1 protein function.
I112V missense unknown IDH1 I112V does not lie within any known functional domains of the Idh1 protein (UniProt.org). I112V has not been characterized in the scientific literature and therefore, its effect on Idh1 protein function is unknown (PubMed, Mar 2018).
I380F missense unknown IDH1 I380F does not lie within any known functional domains of the Idh1 protein (UniProt.org). I380F has been identified in sequencing studies (PMID: 22941189), but has not been biochemically characterized and therefore, its effect on Idh1 protein function is unknown (PubMed, Mar 2018).
H133Q missense no effect - predicted IDH1 H133Q does not lie within any known functional domains of the Idh1 protein (UniProt.org). H133Q demonstrates isocitrate-dependent NAPDH production similar to wild-type Idh1, with a small decrease in catalytic efficiency in some in vitro assays, and demonstrates low efficiency for 2HG production (PMID: 21996744, PMID: 28330869), and is therefore predicted to have no effect on Idh1 protein function.
V276M missense unknown IDH1 V276M does not lie within any known functional domains of the Idh1 protein (UniProt.org). V276M has not been characterized in the scientific literature and therefore, its effect on Idh1 protein function is unknown (PubMed, Mar 2018).
D375Y missense unknown IDH1 D375Y does not lie within any known functional domains of the Idh1 protein (UniProt.org). D375Y has not been characterized in the scientific literature and therefore, its effect on Idh1 protein function is unknown (PubMed, Mar 2018).
R222C missense unknown IDH1 R222C does not lie within any known functional domains of the Idh1 protein (UniProt.org). R222C has been identified in sequencing studies (PMID: 24755471), but has not been biochemically characterized and therefore, its effect on Idh1 protein function is unknown (PubMed, Mar 2018).
Y235C missense unknown IDH1 Y235C does not lie within any known functional domains of the Idh1 protein (UniProt.org). Y235C has been identified in sequencing studies (PMID: 24760710), but has not been biochemically characterized and therefore, its effect on Idh1 protein function is unknown (PubMed, Mar 2018).
E17K missense unknown IDH1 E17K does not lie within any known functional domains of the Idh1 protein (UniProt.org). E17K has not been characterized in the scientific literature and therefore, its effect on Idh1 protein function is unknown (PubMed, Mar 2018).
I129_I130insIRC missense unknown IDH1 I129_I130insIRC results in the insertion of three amino acids in the Idh1 protein between amino acids 129 and 130 (UniProt.org). I129_I130insIRC has not been characterized in the scientific literature and therefore, its effect on Idh1 protein function is unknown (PubMed, Mar 2018).
R132H missense gain of function IDH1 R132H lies within the active site of the Idh1 protein (PMID: 19228619). R132H results in decreased conversion of isocitrate to alpha-ketoglutarate by Idh1, but also confers a gain of function to Idh1, as indicated by increased conversion of alpha-ketoglutarate to the onco-metabolite 2HG (R(-)-2-hydroxyglutarate) in cell culture and in vitro assays, and is associated with increased 2HG levels in patient samples (PMID: 19935646, PMID: 23731180).
over exp none no effect IDH1 over exp indicates an over expression of the Idh1 protein. However, the mechanism causing the over expression is unspecified.
Y285H missense unknown IDH1 Y285H does not lie within any known functional domains of the Idh1 protein (UniProt.org). Y285H has not been characterized in the scientific literature and therefore, its effect on Idh1 protein function is unknown (PubMed, Mar 2018).
R132G missense gain of function IDH1 R132G lies within the active site of the Idh1 protein (PMID: 19228619). R132G confers a gain of function to Idh1, as indicated by production of 2-hydroxyglutarate (2HG) in patient tissue and in vitro assays (PMID: 28330869, PMID: 24529257, PMID: 19935646).
R119W missense unknown IDH1 R119W does not lie within any known functional domains of the Idh1 protein (UniProt.org). R119W has been identified in sequencing studies (PMID: 23469962), but has not been biochemically characterized in the scientific literature and therefore, its effect on Idh1 protein function is unknown (PubMed, Mar 2018).
D299H missense unknown IDH1 D299H does not lie within any known functional domains of the Idh1 protein (UniProt.org). D299H has not been characterized in the scientific literature and therefore, its effect on Idh1 protein function is unknown (PubMed, Mar 2018).
L359F missense unknown IDH1 L359F does not lie within any known functional domains of the Idh1 protein (UniProt.org). L359F has not been characterized in the scientific literature and therefore, its effect on Idh1 protein function is unknown (PubMed, Mar 2018).
P33S missense unknown IDH1 P33S does not lie within any known functional domains of the Idh1 protein (UniProt.org). P33S has not been biochemically characterized, but has an associated gene expression profile that does not correlate to that of Idh1 activating mutations (PMID: 27147599).
W92R missense unknown IDH1 W92R does not lie within any known functional domains of the Idh1 protein (UniProt.org). W92R has not been characterized in the scientific literature and therefore, its effect on Idh1 protein function is unknown (PubMed, Mar 2018).
Y139D missense gain of function IDH1 Y139D lies within a site of the Idh1 protein critical for catalysis (UniProt.org). R139D confers a gain of function to Idh1, as indicated by increased conversion of alpha-ketoglutarate to the onco-metabolite 2HG (R(-)-2-hydroxyglutarate) in cell culture and in vitro assays (PMID: 21996744m PMID: 23731180).
G221V missense unknown IDH1 G221V does not lie within any known functional domains of the Idh1 protein (UniProt.org). G221V has not been characterized in the scientific literature and therefore, its effect on Idh1 protein function is unknown (PubMed, Mar 2018).
I113V missense unknown IDH1 I113V does not lie within any known functional domains of the Idh1 protein (UniProt.org). I113V has not been characterized in the scientific literature and therefore. its effect on Idh1 protein function is unknown (PubMed, Mar 2018).
R132I missense unknown IDH1 R132I lies within the active site of the Idh1 protein (PMID: 19228619). R132I has not been characterized, and therefore, its effect on Idh1 protein function is unknown (PubMed, Oct 2018).
E190K missense no effect - predicted IDH1 E190K does not lie within any known functional domains of the Idh1 protein (UniProt.org). E190K does not confer transforming activity to the Idh1 protein as demonstrated by the lack of tumor formation in animal models (PMID: 27147599) and therefore, is predicted to have no effect on Idh1 protein function.
R338T missense unknown IDH1 R338T does not lie within any known functional domains of the Idh1 protein (UniProt.org). R338T has not been characterized in the scientific literature and therefore, its effect on Idh1 protein function is unknown (PubMed, Mar 2018).
R119Q missense unknown IDH1 R119Q does not lie within any known functional domains of the Idh1 protein (UniProt.org). R119Q has been identified in sequencing studies (PMID: 22610119, PMID: 24376688), but has not been biochemically characterized and therefore, its effect on Idh1 protein function is unknown (PubMed, Mar 2018).
I130M missense no effect - predicted IDH1 I130M does not lie within any known functional domains of the Idh1 protein (UniProt.org). I130M demonstrates isocitrate-dependent NAPDH production similar to wild-type Idh1 in in vitro assays and does not result in increased 2HG production (PMID: 21996744), and therefore, is predicted to have no effect on Idh1 protein function.
wild-type none no effect Wild-type IDH1 indicates that no mutation has been detected within the IDH1 gene.
R100A missense gain of function - predicted IDH1 R100A lies within the substrate binding region of the Idh1 protein (UniProt.org). R100A results in decreased binding and catalysis of isocitrate by Idh1 and reduced isocitrate-dependent NADPH production (PMID: 21996744, PMID: 20975740), and is predicted to confer a gain of function to Idh1, as indicated by increased production of the onco-metabolite 2HG (R(-)-2-hydroxyglutarate) in cell culture (PMID: 21996744).
Y183C missense no effect - predicted IDH1 Y183C does not lie within any known functional domains of the Idh1 protein (UniProt.org). Y183C has not been fully biochemically characterized, but does not result in production of the oncometabolite 2HG, similar to wild-type Idh1, in cell culture (PMID: 23063752) and therefore, is predicted to have no effect on Idh1 protein function.
K81N missense unknown IDH1 K81N does not lie within any known functional domains of the Idh1 protein (UniProt.org). K81N has not been characterized in the scientific literature and therefore, its effect on Idh1 protein function is unknown (PubMed, Mar 2018).
K3N missense unknown IDH1 K3N does not lie within any known functional domains of the Idh1 protein (UniProt.org). K3N has not been characterized in the scientific literature and therefore, its effect on Idh1 protein function is unknown (PubMed, Mar 2018).
R132V missense unknown IDH1 R132V lies within the active site of the Idh1 protein (PMID: 19228619). R132V has been identified in sequencing studies (PMID: 18985363), but has not been biochemically characterized and therefore, its effect on Idh1 protein function is unknown (PubMed, Oct 2018).
S280F missense unknown IDH1 S280F does not lie within any known functional domains of the Idh1 protein (UniProt.org). S280F has been associated with acquired resistance to Enasidenib when occurred in cis with IDH1 R132C in a patient, but has not been biochemically characterized and therefore, its effect on Idh1 protein function is unknown (PMID: 29950729). Y
R132P missense unknown IDH1 R132P lies within the active site of the Idh1 protein (PMID: 19228619). R132P has been identified in sequencing studies (PMID: 22520341), but has not been biochemically characterized and therefore, its effect on Idh1 protein function is unknown (PubMed, Oct 2018).
G8S missense unknown IDH1 G8S does not lie within any known functional domains of the Idh1 protein (UniProt.org). G8S has not been characterized in the scientific literature and therefore, its effect on Idh1 protein function is unknown (PubMed, Oct 2018).
Q320H missense unknown IDH1 Q320H does not lie within any known functional domains of the Idh1 protein (UniProt.org). Q320H has been identified in sequencing studies (PMID: 24121792), but has not been biochemically characterized and therefore, its effect on Idh1 protein function is unknown (PubMed, Mar 2018).
R132S missense gain of function IDH1 R132S lies within the active site of the Idh1 protein (PMID: 19228619). R132S confers a gain of function to Idh1, as indicated by increased conversion of alpha-ketoglutarate to the onco-metabolite 2HG (R(-)-2-hydroxyglutarate) in cell culture (PMID: 19935646, PMID: 21326614).
R314H missense unknown IDH1 R314H does not lie within any known functional domains of the Idh1 protein (UniProt.org). R314H has not been characterized and therefore, its effect on Idh1 protein function is unknown (PubMed, Mar 2018).
R100* deletion loss of function - predicted IDH1 R100* results in a premature truncation of the Idh1 protein at amino acid 100 of 414 (UniProt.org). Due to the loss of all known functional domains, R100* is predicted to lead to a loss of function (PMID: 20962861).
V386L missense unknown IDH1 V386L does not lie within any known functional domains of the Idh1 protein (UniProt.org). V386L has not been characterized in the scientific literature and therefore, its effect on Idh1 protein function is unknown (PubMed, Mar 2018).
R100Q missense gain of function - predicted IDH1 R100Q lies within the substrate binding region of the Idh1 protein (UniProt.org). R100Q results in a decrease in the wild-type catalytic activity of Idh1, and is also predicted to confer a gain of function to Idh1 as indicated by production of 2HG (R(-)-2-hydroxyglutarate) in cell culture; however, the level of 2HG produced is lower compared to other Idh1 mutations (PMID: 24529257, PMID: 28330869).
A179D missense unknown IDH1 A179D does not lie within any known functional domains of the Idh1 protein (UniProt.org). A179D has not been characterized in the scientific literature and therefore, its effect on Idh1 protein function is unknown (PubMed, Mar 2018).
act mut unknown gain of function IDH1 act mut indicates that this variant results in a gain of function in the Idh1 protein. However, the specific amino acid change has not been identified.
mutant unknown unknown IDH1 mutant indicates an unspecified mutation in the IDH1 gene.
G70D missense loss of function - predicted IDH1 G70D does not lie within any known functional domains of the Idh1 protein (UniProt.org). G70D is predicted to confer a loss of function to IDH1, as demonstrated by decreased protein stability in cell culture (PMID: 21996744).
I99M missense no effect - predicted IDH1 I99M does not lie within any known functional domains of the Idh1 protein (UniProt.org). I99M demonstrates isocitrate-dependent NAPDH production similar to wild-type Idh1 in in vitro assays and does not result in increased 2HG production (PMID: 21996744), and therefore, is predicted to have no effect on Idh1 protein function.
R132L missense gain of function IDH1 R132L lies within the active site of the Idh1 protein (PMID: 19228619). R132L confers a gain of function to Idh1, as indicated by increased conversion of alpha-ketoglutarate to the onco-metabolite 2HG (R(-)-2-hydroxyglutarate) in cell culture (PMID: 19935646, PMID: 21326614).
N116S missense unknown IDH1 N116S does not lie within any known functional domains of the Idh1 protein (UniProt.org). N116S has been identified in sequencing studies (PMID: 21647152), but has not been biochemically characterized and therefore, its effect on Idh1 protein function is unknown (PubMed, Mar 2018).
T162A missense unknown IDH1 T162A does not lie within any known functional domains of the Idh1 protein (UniProt.org). T162A has not been characterized in the scientific literature and therefore, its effect on Idh1 protein function is unknown (PubMed, Mar 2018).
R109K missense unknown IDH1 R109K does not lie within any known functional domains of the Idh1 protein (UniProt.org). R109K has been identified in sequencing studies (PMID: 24532263), but has not been biochemically characterized and therefore, its effect on Idh1 protein function is unknown (PubMed, Mar 2018).
I5fs frameshift loss of function - predicted IDH1 I5fs results in a change in the amino acid sequence of the Idh1 protein beginning at 5 of 414, likely resulting in premature truncation of the functional protein (UniProt.org). Due to the loss of all known functional domains (UniProt.org), I5fs is predicted to lead to a loss of Idh1 protein function.
R132C missense gain of function IDH1 R132C lies within the active site of the Idh1 protein (PMID: 19228619). R132C confers a gain of function to Idh1 as indicated by conversion of alpha-ketoglutarate to the onco-metabolite 2HG (R(-)-2-hydroxyglutarate in culture (PMID: 19935646, PMID: 26161668, PMID: 22885298).
M291I missense unknown IDH1 M291I does not lie within any known functional domains of the Idh1 protein (UniProt.org). M291I has not been characterized and therefore, its effect on Idh1 protein function is unknown (PubMed, Mar 2018).
R49C missense loss of function - predicted IDH1 R49C does not lie within any known functional domains of the Idh1 protein (UniProt.org). R49C results in decreased accumulation of Idh1 protein in cell culture (PMID: 21996744)
G97D missense gain of function IDH1 G97D lies within the substrate binding region of the Idh1 protein (UniProt.org). G97D results confers a gain of function to Idh1, as indicated by production of the onco-metabolite 2HG (R(-)-2-hydroxyglutarate) in cell culture (PMID: 21996744, PMID: 27824159, PMID: 22442146).
G123R missense unknown IDH1 G123R lies within the active site of the Idh1 protein (PMID: 20972461). The functional effect of G123R is conflicting, as it has been demonstrated to result in decreased Idh1 catalytic activity in an in vitro assay (PMID: 20171178), but has also been demonstrated to have catalytic activity similar to wild-type Idh1 (PMID: 21996744).
Molecular Profile Protein Effect Treatment Approaches
IDH1 S261L unknown
IDH1 T325M unknown
IDH1 V294M no effect - predicted
IDH1 R132X gain of function - predicted IDH Inhibitor (Pan) IDH1 Inhibitor
IDH1 A134D loss of function
IDH1 Q277* loss of function - predicted
IDH1 V71I no effect
IDH1 G123E unknown
IDH1 M182L unknown
IDH1 amp no effect
IDH1 G289fs loss of function - predicted
IDH1 V178I no effect
IDH1 I112V unknown
IDH1 I380F unknown
IDH1 H133Q no effect - predicted
IDH1 V276M unknown
IDH1 D375Y unknown
IDH1 R222C unknown
IDH1 Y235C unknown
IDH1 E17K unknown
IDH1 I129_I130insIRC unknown
IDH1 R132H gain of function IDH Inhibitor (Pan) IDH1 Inhibitor IDH1 R132H peptide vaccine PEPIDH1M vaccine
IDH1 over exp no effect
IDH1 Y285H unknown
IDH1 R132G gain of function IDH Inhibitor (Pan) IDH1 Inhibitor
IDH1 R119W unknown
IDH1 D299H unknown
IDH1 L359F unknown
IDH1 P33S unknown
IDH1 W92R unknown
IDH1 Y139D gain of function
IDH1 G221V unknown
IDH1 I113V unknown
IDH1 R132I unknown IDH Inhibitor (Pan) IDH1 Inhibitor
IDH1 E190K no effect - predicted
IDH1 R338T unknown
IDH1 R119Q unknown
IDH1 I130M no effect - predicted
IDH1 wild-type no effect
IDH1 R100A gain of function - predicted
IDH1 Y183C no effect - predicted
IDH1 K81N unknown
IDH1 K3N unknown
IDH1 R132V unknown IDH Inhibitor (Pan) IDH1 Inhibitor
IDH1 R132C IDH1 S280F
IDH1 S280F unknown
IDH1 R132P unknown IDH Inhibitor (Pan) IDH1 Inhibitor
IDH1 G8S unknown
IDH1 Q320H unknown
IDH1 R132S gain of function IDH Inhibitor (Pan) IDH1 Inhibitor
IDH1 R314H unknown
IDH1 R100* loss of function - predicted
IDH1 V386L unknown
IDH1 R100Q gain of function - predicted
IDH1 A179D unknown
IDH1 act mut gain of function
IDH1 mutant unknown
ATRX loss IDH1 mut
IDH1 G70D loss of function - predicted
IDH1 I99M no effect - predicted
IDH1 R132L gain of function IDH Inhibitor (Pan) IDH1 Inhibitor
IDH1 N116S unknown
IDH1 T162A unknown
IDH1 R109K unknown
IDH1 I5fs loss of function - predicted
IDH1 R132C gain of function IDH Inhibitor (Pan) IDH1 Inhibitor
IDH1 R132C SRC T341I
IDH1 M291I unknown
IDH1 R49C loss of function - predicted
IDH1 G97D gain of function
IDH1 G123R unknown
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
IDH1 R132X acute myeloid leukemia sensitive IDH305 Phase I Actionable In a Phase I trial, IDH305 treatment resulted in objective response in 33% (7/21) of acute myeloid leukemia patients harboring IDH1 R132 mutations, including complete remission in 3 (14%) and partial remission in 4 (19%) patients (Blood 2016 128 (22):1073). detail...
IDH1 R132H colon carcinoma sensitive Talazoparib Preclinical - Cell culture Actionable In a preclinical study, colon carcinoma cells over expressing IDH1 R132H demonstrated increased sensitivity to Talazoparib (BMN-673)-induced growth inhibition in culture (PMID: 28148839). 28148839
IDH1 R132H malignant glioma sensitive Talazoparib Preclinical - Patient cell culture Actionable In a preclinical study, patient-derived glioma cells harboring IDH1 R132H demonstrated increased sensitivity to Talazoparib (BMN-673)-induced growth inhibition in culture (PMID: 28148839). 28148839
IDH1 R132H Advanced Solid Tumor sensitive Niraparib Preclinical - Cell culture Actionable In a preclinical study, transformed cells over expressing IDH1 R132H demonstrated increased sensitivity to Zejula (niraparib)-induced growth inhibition in culture (PMID: 28148839). 28148839
IDH1 R132H malignant glioma sensitive AGI-5198 Preclinical - Cell line xenograft Actionable In a preclinical study, AGI-5198 inhibited growth of a glioma cell line harboring IDH1 R132H in culture and in xenograft models (PMID: 23558169). 23558169
IDH1 R132H malignant glioma predicted - sensitive AG-881 Preclinical - Cell line xenograft Actionable In a preclinical study, AG-881 treatment decreased brain tumor 2HG levels in an orthotopic glioma cell line xenograft model harboring IDH1 R132H (Mol Cancer Ther Jan 1 2018 (17) (1 Supp) B126). detail...
IDH1 R132H Advanced Solid Tumor sensitive Rucaparib Preclinical - Cell culture Actionable In a preclinical study, transformed cells over expressing IDH1 R132H demonstrated increased sensitivity to Rubraca (rucaparib)-induced growth inhibition in culture (PMID: 28148839). 28148839
IDH1 R132H Advanced Solid Tumor sensitive Talazoparib Preclinical - Cell culture Actionable In a preclinical study, transformed cells over expressing IDH1 R132H demonstrated increased sensitivity to Talazoparib (BMN-673)-induced growth inhibition in culture (PMID: 28148839). 28148839
IDH1 R132H colorectal cancer resistant Metformin + AGI-5198 Preclinical Actionable In a preclinical study, colorectal cancer cells harboring IDH1 R132H demonstrated increased cell proliferation when treated with a combination of Glucophage (metformin) and AGI-5198 (PMID: 26363012). 26363012
IDH1 R132H colorectal cancer resistant AGI-5198 + Radiotherapy Preclinical Actionable In a preclinical study, colorectal cancer cells expressing IDH1 R132H were resistant to radiotherapy when treated with AGI-5198 (PMID: 26363012). 26363012
IDH1 R132H Advanced Solid Tumor sensitive Cisplatin + Talazoparib Preclinical - Cell culture Actionable In a preclinical study, Talazoparib (BMN-673) and Cisplatin synergistically inhibited growth of transformed cells over expressing IDH1 R132H in culture (PMID: 28148839). 28148839
IDH1 R132H grade III astrocytoma sensitive Azacitidine Preclinical Actionable In a preclinical study, long-term treatment with Vidaza (azacitidine) resulted in increased cellular differentiation, decreased proliferation, and tumor regression in a patient-derived xenograft (PDX) model of anaplastic astrocytoma harboring IDH1 R132H (PMID: 24077805). 24077805
IDH1 R132H colorectal cancer sensitive Metformin Preclinical Actionable In a preclinical study, colorectal carcinoma cells expressing IDH1 R132H were sensitive to Glucophage (metformin), resulting in decreased cell proliferation in culture (PMID: 26363012). 26363012
IDH1 R132H oligodendroglioma sensitive Decitabine Preclinical - Pdx & cell culture Actionable In a preclinical study, Dacogen (decitabine) decreased colony formation and tumor growth in patient derived xenograft (PDX) models of patient derived oligodendroglioma cells with IDH1 R132H mutations and co-deletion of 1p and 19q (PMID: 24077826). 24077826
IDH1 R132H Advanced Solid Tumor sensitive VX-970 Preclinical - Cell culture Actionable In a preclinical study, transformed cells over expressing IDH1 R132H demonstrated increased sensitivity to VX-970-induced growth inhibition in culture (PMID: 28148839). 28148839
IDH1 R132H glioblastoma multiforme sensitive Vandetanib + Temozolomide Phase II Actionable In a Phase II trial, Caprelsa (vandetinib), in combination with Temodar (temozolomide) and radiation therapy, demonstrated a significant increase in PFS and OS in glioblastoma patients harboring IDH1 R132H compared to glioblastoma patients without IDH1 R132H (PMID: 25910950). 25910950
IDH1 R132H acute myeloid leukemia sensitive BAY1436032 Preclinical - Patient cell culture Actionable In a preclinical study, BAY1436032 decreased (R)-2-hydroxyglutarate (R-2HG) levels, and inhibited growth and increased differentiation of patient-derived acute myeloid leukemia cells harboring IDH1 R132H in culture (PMID: 28232670). 28232670
IDH1 R132H Advanced Solid Tumor sensitive Olaparib Preclinical - Cell culture Actionable In a preclinical study, transformed cells over expressing IDH1 R132H demonstrated increased sensitivity to Lynparza (olaparib)-induced growth inhibition in culture (PMID: 28148839). 28148839
IDH1 R132H malignant glioma sensitive BPTES Preclinical - Cell culture Actionable In a preclinical study, a glioma cell line expressing IDH1 R132H demonstrated increased sensitivity to growth inhibition by BPTES compared to a cell line expressing wild-type IDH1 in culture (PMID: 21045145). 21045145
IDH1 R132H Advanced Solid Tumor decreased response AGI-5198 + Talazoparib Preclinical - Cell culture Actionable In a preclinical study, AGI-5198 reverted the sensitivity of transformed cells over expressing IDH1 R132H to Talazoparib (BMN-673)-induced growth inhibition in culture (PMID: 28148839). 28148839
IDH1 R132H malignant glioma not applicable N/A Guideline Diagnostic IDH1 R132H is diagnostic and aids in the diagnosis of gliomas (NCCN.org). detail...
IDH1 R132H colon carcinoma sensitive Olaparib Preclinical - Cell culture Actionable In a preclinical study, colon carcinoma cells over expressing IDH1 R132H demonstrated increased sensitivity to Lynparza (olaparib)-induced growth inhibition in culture (PMID: 28148839). 28148839
IDH1 R132G acute myeloid leukemia sensitive BAY1436032 Preclinical - Patient cell culture Actionable In a preclinical study, BAY1436032 decreased (R)-2-hydroxyglutarate (R-2HG) levels and increased differentiation of patient-derived acute myeloid leukemia cells harboring IDH1 R132G in culture (PMID: 28232670). 28232670
IDH1 wild-type malignant glioma not applicable N/A Guideline Risk Factor IDH1 wild-type is associated with increased risk of aggressive disease in patients with grade II or III infiltrative gliomas (NCCN.org). detail...
IDH1 R132C IDH1 S280F acute myeloid leukemia resistant Enasidenib Clinical Study Actionable In a clinical study, IDH1 S280F was identified as an acquired mutation in cis with the original IDH1 R132C in a patient with acute myeloid leukemia (AML) who developed resistance to Idhifa (enasidenib) after initial response (PMID: 29950729). 29950729
IDH1 R132S intrahepatic cholangiocarcinoma sensitive Dasatinib Preclinical Actionable In a preclinical study, intrahepatic cholangiocarcinoma cells harboring IDH1 R132S demonstrated increased sensitivity to Sprycel (dasatinib) induced growth inhibition compared to IDH1 wild-type cells in culture (PMID: 27231123). 27231123
IDH1 R132S acute myeloid leukemia sensitive BAY1436032 Preclinical - Patient cell culture Actionable In a preclinical study, BAY1436032 decreased (R)-2-hydroxyglutarate (R-2HG) levels, and inhibited growth and increased differentiation of patient-derived acute myeloid leukemia cells harboring IDH1 R132S in culture (PMID: 28232670). 28232670
IDH1 R132S intrahepatic cholangiocarcinoma sensitive Saracatinib Preclinical Actionable In a preclinical study, intrahepatic cholangiocarcinoma cells harboring IDH1 R132S demonstrated increased sensitivity to Saracatinib (AZD0530) induced growth inhibition compared to IDH1 wild-type cells in culture (PMID: 27231123). 27231123
IDH1 mutant malignant glioma sensitive Ivosidenib Phase I Actionable In a Phase I trial, AG-120 demonstrated safety and preliminary efficacy in IDH1-mutant glioma patients (Neuro Oncol (2016) 18 (suppl 6): vi12). detail...
IDH1 mutant oligodendroglioma not applicable N/A Guideline Diagnostic IDH1 mutations aid in the diagnosis of oligodendrogliomas (NCCN.org). detail...
IDH1 mutant glioblastoma multiforme predicted - sensitive Bevacizumab + Lomustine Phase II Actionable In a retrospective analysis of a Phase II trial, IDH1 mutation correlated with favorable overall survival in recurrent glioblastoma patients treated with a combination of Avastin (bevacizumab) and Lomustine (PMID: 26762204). 26762204
IDH1 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
IDH1 mutant acute myeloid leukemia not applicable N/A Clinical Study Prognostic In two meta-analyses, IDH1 mutations were associated with a worse overall survival in patients with acute myeloid leukemia (PMID: 22616558, PMID: 23226625). 22616558 23226625
IDH1 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...
IDH1 mutant lung adenocarcinoma resistant Dasatinib Preclinical Actionable In a preclinical study, lung adenocarcinoma cells harboring IDH1 mutations were resistant to Sprycel (dasatinib) in culture (PMID: 27231123). 27231123
IDH1 mutant glioblastoma multiforme not applicable N/A Guideline Diagnostic IDH1 mutations aid in the diagnosis of secondary grade IV glioblastomas (NCCN.org). detail...
IDH1 mutant glioblastoma multiforme not applicable N/A Clinical Study Prognostic In multiple clinical studies, including two meta-analyses, IDH1 mutations were associated with a greater overall survival and progression-free survival in patients with glioblastoma (PMID: 23904262, PMID: 26945349, PMID: 20560678). 20560678 23904262 26945349
IDH1 mutant acute myeloid leukemia sensitive Ivosidenib FDA approved Actionable In a Phase I trial that supported FDA approval, Tibsovo (ivosidenib) treatment was well-tolerated and resulted in complete remission (CR) in 21.6% (27/125), complete remission with partial hematological recovery (CRh) in 8.8% (11/125), and overall response (OR) in 41.6% (52/125) of patients with relapsed or refractory acute myeloid leukemia harboring an IDH1 mutation, with a median duration of response of 8.2 months for CR+CRh, 9.3 months for CR, and 6.5 months for OR (PMID: 29860938; NCT02074839). detail... 29860938
IDH1 mutant astrocytoma not applicable N/A Guideline Diagnostic IDH1 mutations aid in the diagnosis of grade II and grade III astrocytomas (NCCN.org). detail...
IDH1 mutant myelofibrosis not applicable N/A Guideline Prognostic IDH1 mutations are associated with inferior leukemia-free survival in patients with myelofibrosis (NCCN.org). detail...
IDH1 mutant chondrosarcoma resistant Dasatinib Preclinical Actionable In a preclinical study, chondrosarcoma cells harboring IDH1 mutations were resistant to Sprycel (dasatinib) in culture (PMID: 27231123). 27231123
IDH1 mutant cholangiocarcinoma sensitive Ivosidenib Phase I Actionable In a Phase I trial, AG-120 treatment resulted in partial response in 6% (4/72) and stable disease in 56% (40/72) of cholangiocarcinoma patients harboring IDH1 mutations (Journal of Clinical Oncology 35, no. 15_suppl (May 2017) 4015-4015; NCT02073994). detail...
IDH1 mutant malignant glioma not applicable N/A Guideline Prognostic IDH1 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...
IDH1 mutant malignant glioma not applicable N/A Clinical Study Prognostic In multiple clinical studies, including two meta-analyses, IDH1 mutations were associated with improved overall survival and progression free survival in patients with gliomas (PMID: 23817809, PMID: 26220714, PMID: 23894344). 23894344 23817809 26220714
IDH1 mutant malignant glioma not applicable N/A Guideline Diagnostic IDH1 mutations aid in the diagnosis of gliomas (NCCN.org). detail... 23041832 19755387 19915484
IDH1 mutant grade III astrocytoma not applicable N/A Guideline Diagnostic IDH1 mutations aid in the diagnosis of grade III astrocytomas (NCCN.org). detail...
ATRX loss IDH1 mut astrocytoma not applicable N/A Guideline Diagnostic ATRX deficiency in combination with IDH mutation aids in the diagnosis of astrocytoma (NCCN.org). detail...
ATRX loss IDH1 mut malignant glioma predicted - sensitive Gemcitabine + Radiotherapy Phase I Actionable In a Phase I trial, Gemzar (gemcitabine) plus radiation therapy resulted in median overall survival of 73.5 months in 7 high-grade glioma patients with IDH mutated, non-codeleted tumors with ATRX loss (PMID: 26853339). 26853339
IDH1 R132L acute myeloid leukemia sensitive BAY1436032 Preclinical - Patient cell culture Actionable In a preclinical study, BAY1436032 decreased (R)-2-hydroxyglutarate (R-2HG) levels, and inhibited growth and increased differentiation of patient-derived acute myeloid leukemia cells harboring IDH1 R132L in culture (PMID: 28232670). 28232670
IDH1 R132C malignant glioma sensitive AGI-5198 Preclinical Actionable In a preclinical study, AGI-5198 inhibited growth and promoted differentiation in glioma cells expressing IDH1 R132C (PMID: 23558169). 23558169
IDH1 R132C malignant glioma sensitive Talazoparib Preclinical - Patient cell culture Actionable In a preclinical study, patient-derived glioma cells harboring IDH1 R132C demonstrated increased sensitivity to Talazoparib (BMN-673)-induced growth inhibition in culture (PMID: 28148839). 28148839
IDH1 R132C intrahepatic cholangiocarcinoma sensitive Dasatinib Preclinical Actionable In a preclinical study, Sprycel (dasatinib) inhibited growth of intrahepatic cholangiocarcinoma cells harboring IDH1 R132C in culture, and suppressed tumor growth in PDX models (PMID: 27231123). 27231123
IDH1 R132C sarcoma sensitive Olaparib Preclinical - Cell line xenograft Actionable In a preclinical study, Lynparza (olaparib) treatment delayed tumor growth in cell line xenograft models of sarcoma harboring IDH1 R132C (PMID: 28148839). 28148839
IDH1 R132C sarcoma decreased response AGI-5198 + Talazoparib Preclinical - Cell culture Actionable In a preclinical study, AGI-5198 reverted the sensitivity of sarcoma cells harboring IDH1 R132C to Talazoparib (BMN-673)-induced growth inhibition in culture (PMID: 28148839). 28148839
IDH1 R132C intrahepatic cholangiocarcinoma sensitive Saracatinib Preclinical Actionable In a preclinical study, intrahepatic cholangiocarcinoma cells harboring IDH1 R132C demonstrated increased sensitivity to Saracatinib (AZD0530) induced growth inhibition compared to IDH1 wild-type cells in culture (PMID: 27231123). 27231123
IDH1 R132C sarcoma decreased response AGI-5198 + Olaparib Preclinical - Cell culture Actionable In a preclinical study, AGI-5198 reverted the sensitivity of sarcoma cells harboring IDH1 R132C to Lynparza (olaparib)-induced growth inhibition in culture (PMID: 28148839). 28148839
IDH1 R132C fibrosarcoma predicted - sensitive AG-881 Preclinical - Cell line xenograft Actionable In a preclinical study, AG-881 treatment decreased tumor 2HG levels in a fibrosarcoma cell line xenograft model harboring IDH1 R132C (Mol Cancer Ther Jan 1 2018 (17) (1 Supp) B126). detail...
IDH1 R132C acute myeloid leukemia sensitive BAY1436032 Preclinical - Pdx & cell culture Actionable In a preclinical study, BAY1436032 decreased R-2HG levels and inhibited growth of primary acute myeloid leukemia (AML) cells harboring IDH1 R132C in culture, and decreased blast number and increased survival of two AML patient-derived xenograft (PDX) models, one which harbored additional alterations in FLT3, NPM1, and NRAS and one which harbored a KMT2A (MLL) alteration (PMID: 28232670). 28232670
IDH1 R132C SRC T341I intrahepatic cholangiocarcinoma resistant Dasatinib Preclinical - Cell culture Actionable In a preclinical study, intrahepatic cholangiocarcinoma cells harboring IDH1 R132S acquired resistance to Sprycel (dasatinib) after over expressing SRC T341I in culture (PMID: 27231123). 27231123