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Gene Symbol IDH1
Synonyms HEL-216 | HEL-S-26 | IDCD | IDH | IDP | IDPC | PICD
Gene Description IDH1, isocitrate dehydrogenase (NADP(+)) 1, 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 (PMID: 23999441) and glioma (PMID: 28711227, PMID: 32186930).
NCBI Gene ID Chromosome Map Location Canonical Transcript Gene Role
3417 2 2q34 NM_005896 Oncogene (PMID: 30606230)

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Variant Impact Protein Effect Variant Description Associated with drug Resistance
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).
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, May 2024).
A410T missense no effect - predicted IDH1 A410T does not lie within any known functional domains of the Idh1 protein (UniProt.org). A410T does not lead to increased production of the oncometabolite 2HG (R(-)-2-hydroxyglutarate) in cell culture (PMID: 36222845), and therefore, is predicted to have no effect on Idh1 protein function.
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.
amp none no effect IDH1 amp indicates an increased number of copies of the IDH1 gene. However, the mechanism causing the increase is unspecified.
D279N missense unknown IDH1 D279N does not lie within any known functional domains of the Idh1 protein (UniProt.org). D279N results in cellular transformation in the context of IDH1 R132H (PMID: 36056177) and has been associated with acquired IDH1 inhibitor resistance with IDH1 R132C (PMID: 32380538; PMID: 36056177), but has not been individually characterized and therefore, its effect on Idh1 protein function is unknown (PubMed, Jan 2024).
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, May 2024).
D375Y missense unknown IDH1 D375Y does not lie within any known functional domains of the Idh1 protein (UniProt.org). D375Y has been identified in the scientific literature (PMID: 32313423), but has not been biochemically characterized and therefore, its effect on Idh1 protein function is unknown (PubMed, Oct 2024).
del deletion loss of function IDH1 del indicates a deletion of the IDH1 gene.
E17K missense unknown IDH1 E17K does not lie within any known functional domains of the Idh1 protein (UniProt.org). E17K has been identified in the sequencing studies (PMID: 27406316), but has not been biochemically characterized and therefore, its effect on Idh1 protein function is unknown (PubMed, Dec 2023).
E190K missense no effect - predicted IDH1 E190K does not lie within any known functional domains of the Idh1 protein (UniProt.org). E190K does not promote tumor formation in animal models (PMID: 27147599), and therefore, is predicted to have no effect on Idh1 protein function.
F32V missense unknown IDH1 F32V does not lie within any known functional domains of the Idh1 protein (UniProt.org). F32V has been identified in sequencing studies (PMID: 34160418, PMID: 37459200), but has not been biochemically characterized and therefore, its effect on Idh1 protein function is unknown (PubMed, Oct 2024).
G123E missense unknown IDH1 G123E lies within the active site of the Idh1 protein (PMID: 20972461). G123E has been identified in sequencing studies (PMID: 30113684, PMID: 20567020), but has not been biochemically characterized and therefore, its effect on Idh1 protein function is unknown (PubMed, May 2024).
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 results in decreased catalytic activity in an in vitro assay (PMID: 20171178), but also demonstrates catalytic activity similar to wild-type Idh1 (PMID: 21996744), and therefore, its effect on Idh1 protein function is unknown.
G131A missense unknown IDH1 G131A does not lie within any known functional domains of the Idh1 protein (UniProt.org). G131A has been associated with acquired IDH1 inhibitor resistance with IDH1 R132C (PMID: 32380538), but has not been biochemically characterized and therefore, its effect on Idh1 protein function is unknown (PubMed, Mar 2024).
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, May 2024).
G289D missense unknown IDH1 G289D does not lie within any known functional domains of the Idh1 protein (UniProt.org). G289D has been associated with acquired IDH1 inhibitor resistance (PMID: 32380538), but has not been biochemically characterized and therefore, its effect on Idh1 protein function is unknown (PubMed, Apr 2024).
G289fs frameshift loss of function - predicted IDH1 G289fs results in a change in the amino acid sequence of the Idh1 protein beginning at aa 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 (PMID: 20513808), S289fs is predicted to lead to a loss of Idh1 protein function.
G70D missense loss of function - predicted IDH1 G70D does not lie within any known functional domains of the Idh1 protein (UniProt.org). G70D results in decreased protein stability in cell culture (PMID: 21996744), and therefore, is predicted to lead to a loss of Idh1 protein function.
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, Dec 2023).
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).
G97X missense unknown IDH1 G97X indicates any Idh1 missense mutation that results in replacement of the glycine (G) at amino acid 97 by a different amino acid.
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 NADPH production comparable to wild-type Idh1 with a minor decrease in catalytic efficiency, and does not increase 2HG production at physiologically relevant conditions in in vitro assays (PMID: 21996744, PMID: 28330869), and therefore, is predicted to have no effect on Idh1 protein function.
H315D missense no effect - predicted IDH1 H315D lies within an NADP-binding region of the Idh1 protein (UniProt.org). H315D confers resistance to an IDH1 inhibitor in the presence of IDH1 R132H, but does not lead to increased production of the oncometabolite 2HG (R(-)-2-hydroxyglutarate), and results in cytokine-independent growth and erythroid differentiation similar to wild-type protein in cell culture (PMID: 36222845), and therefore, is predicted to have no effect on Idh1 protein function. Y
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, May 2024).
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, May 2024).
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 NADPH 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.
I130_G131insRCI insertion unknown IDH1 I130_G131insRCI results in the insertion of three amino acids of the Idh1 protein between amino acids 130 and 131 (UniProt.org). I130_G131insRCI has not been characterized in the scientific literature and therefore, its effect on Idh1 protein function is unknown (PubMed, Apr 2024).
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, May 2024).
I5fs frameshift loss of function - predicted IDH1 I5fs results in a change in the amino acid sequence of the Idh1 protein beginning at aa 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.
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 NADPH 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.
inact mut unknown loss of function IDH1 inact mut indicates that this variant results in a loss of function of the Idh1 protein. However, the specific amino acid change has not been identified.
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, May 2024).
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, May 2024).
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, May 2024).
L409V missense no effect - predicted IDH1 L409V does not lie within any known functional domains of the Idh1 protein (UniProt.org). L409V does not lead to increased production of the oncometabolite 2HG (R(-)-2-hydroxyglutarate) in cell culture (PMID: 36222845), and therefore, is predicted to have no effect on Idh1 protein function.
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, May 2024).
M291I missense unknown IDH1 M291I does not lie within any known functional domains of the Idh1 protein (UniProt.org). M291I has been identified in sequencing studies (PMID: 27147599), but has not been biochemically characterized and therefore, its effect on Idh1 protein function is unknown (PubMed, May 2024).
mutant unknown unknown IDH1 mutant indicates an unspecified mutation in the IDH1 gene.
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, May 2024).
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.
P33S missense unknown IDH1 P33S does not lie within any known functional domains of the Idh1 protein (UniProt.org). P33S has an associated gene expression profile that does not correlate to that of Idh1 activating mutations (PMID: 27147599), but has not been biochemically characterized, and therefore, its effect on Idh1 protein function is unknown.
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 (PMID: 20513808), Q277* is predicted to lead to a loss of Idh1 protein function.
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, May 2024).
R100* nonsense 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 (PMID: 20962861), R100* is predicted to lead to a loss of Idh1 protein function.
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, reduced isocitrate-dependent NADPH production (PMID: 21996744, PMID: 20975740), and increased production of the onco-metabolite 2HG (R(-)-2-hydroxyglutarate) in cell culture (PMID: 21996744), and therefore, is predicted to lead to a gain of Idh1 protein function.
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 a modest increase in production of 2HG (R(-)-2-hydroxyglutarate) in cell culture (PMID: 24529257, PMID: 28330869).
R100X missense unknown IDH1 R100X indicates any Idh1 missense mutation that results in replacement of the arginine (R) at amino acid 100 by a different amino acid.
R109K missense unknown IDH1 R109K lies within a substrate binding site of the Idh1 protein (UniProt.org). R109K has been identified in the scientific literature (PMID: 35639915, PMID: 24532263), but has not been biochemically characterized and therefore, its effect on Idh1 protein function is unknown (PubMed, Dec 2023).
R119P missense unknown IDH1 R119P does not lie within any known functional domains of the Idh1 protein (UniProt.org). R119P has been associated with acquired IDH1 inhibitor resistance with IDH1 R132C/L (PMID: 32380538), but has not been biochemically characterized and therefore, its effect on Idh1 protein function is unknown (PubMed, Apr 2024). Y
R119Q missense unknown IDH1 R119Q does not lie within any known functional domains of the Idh1 protein (UniProt.org). R119Q has been identified in the scientific literature (PMID: 28524162, PMID: 24376688, PMID: 36812383), but has not been biochemically characterized and therefore, its effect on Idh1 protein function is unknown (PubMed, May 2024).
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: 28419429, PMID: 23469962, PMID: 37424322), but has not been biochemically characterized and therefore, its effect on Idh1 protein function is unknown (PubMed, May 2024).
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).
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).
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).
R132I missense unknown IDH1 R132I lies within the active site of the Idh1 protein (PMID: 19228619). R132I has been identified in the scientific literature (PMID: 24403254, PMID: 31615936), but has not been biochemically characterized and therefore, its effect on Idh1 protein function is unknown (PubMed, Dec 2023).
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).
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, PMID: 20077503), but has not been biochemically characterized and therefore, its effect on Idh1 protein function is unknown (PubMed, Dec 2023).
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).
R132V missense unknown IDH1 R132V lies within the active site of the Idh1 protein (PMID: 19228619). R132V has been identified in the scientific literature (PMID: 28330869, PMID: 26189213, PMID: 18985363), but has not been biochemically characterized and therefore, its effect on Idh1 protein function is unknown (PubMed, Dec 2023).
R132X missense unknown 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 often results in conversion of alpha-ketoglutarate to the onco-metabolite 2HG (R(-)-2-hydroxyglutarate) (PMID: 19935646, PMID: 28330869, PMID: 21326614).
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: 29807833, PMID: 27149842, PMID: 33577785), but has not been biochemically characterized and therefore, its effect on Idh1 protein function is unknown (PubMed, Dec 2023).
R314H missense unknown IDH1 R314H lies within an NADP-binding region of the Idh1 protein (UniProt.org). R314H has been identified in the scientific literature (PMID: 34722261, PMID: 36355572), but has not been biochemically characterized and therefore, its effect on Idh1 protein function is unknown (PubMed, Dec 2023).
R338T missense unknown IDH1 R338T does not lie within any known functional domains of the Idh1 protein (UniProt.org). R338T has been identified in sequencing studies (PMID: 28069802), but has not been biochemically characterized and therefore, its effect on Idh1 protein function is unknown (PubMed, May 2024).
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), and therefore, is predicted to lead to a loss of Idh1 protein function.
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, May 2024).
S280F missense no effect - predicted IDH1 S280F does not lie within any known functional domains of the Idh1 protein (UniProt.org). S280F confers resistance to an IDH1 inhibitor in the presence of IDH1 R132C/H (PMID: 29950729, PMID: 32380538, PMID: 36222845), but does not lead to increased production of the oncometabolite 2HG (R(-)-2-hydroxyglutarate) in cell culture (PMID: 36222845), and therefore, is predicted to have no effect on Idh1 protein function. Y
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, May 2024).
T313I missense no effect - predicted IDH1 T313I lies within an NADP-binding region of the Idh1 protein (UniProt.org). T313I confers resistance to an IDH1 inhibitor in the presence of IDH1 R132H, but does not lead to increased production of the oncometabolite 2HG (R(-)-2-hydroxyglutarate), and results in cytokine-independent growth and erythroid differentiation similar to wild-type protein in cell culture (PMID: 36222845), and therefore, is predicted to have no effect on Idh1 protein function. Y
T325M missense unknown IDH1 T325M does not lie within any known functional domains of the Idh1 protein (UniProt.org). T325M has been identified in sequencing studies (PMID: 24325359), but has not been biochemically characterized and therefore, its effect on Idh1 protein function is unknown (PubMed, May 2024).
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.
V276M missense unknown IDH1 V276M does not lie within any known functional domains of the Idh1 protein (UniProt.org). V276M has been predicted to destabilize Idh1 by computational modeling (PMID: 36188571), but has not been biochemically characterized and therefore, its effect on Idh1 protein function is unknown.
V294M missense unknown IDH1 V294M does not lie within any known functional domains of the Idh1 protein (UniProt.org). V294M results in increased cell growth and migration (PMID: 27469031), however, demonstrates enzyme activity similar to wild-type Idh1 in culture (PMID: 21996744), and therefore, its effect on Idh1 protein function is unknown.
V386L missense unknown IDH1 V386L does not lie within any known functional domains of the Idh1 protein (UniProt.org). V386L has been identified in sequencing studies (PMID: 26960398), but has not been biochemically characterized and therefore, its effect on Idh1 protein function is unknown (PubMed, May 2024).
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).
W92R missense unknown IDH1 W92R does not lie within any known functional domains of the Idh1 protein (UniProt.org). W92R has been identified in sequencing studies (PMID: 30352278, PMID: 26645239), but has not been biochemically characterized and therefore, its effect on Idh1 protein function is unknown (PubMed, May 2024).
wild-type none no effect Wild-type IDH1 indicates that no mutation has been detected within the IDH1 gene.
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).
Y139X missense unknown IDH1 Y139X indicates any Idh1 missense mutation that results in replacement of the tyrosine (Y) at amino acid 139 by a different amino acid.
Y183C missense no effect - predicted IDH1 Y183C does not lie within any known functional domains of the Idh1 protein (UniProt.org). Y183C does not result in production of the oncometabolite 2HG in cell culture (PMID: 23063752), and therefore, is predicted to have no effect on Idh1 protein function.
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, Dec 2023).
Y285H missense unknown IDH1 Y285H does not lie within any known functional domains of the Idh1 protein (UniProt.org). Y285H has been identified in sequencing studies (PMID: 24816253), but has not been biochemically characterized and therefore, its effect on Idh1 protein function is unknown (PubMed, May 2024).