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Gene | IDH2 |
Variant | R172K |
Impact List | missense |
Protein Effect | gain of function |
Gene Variant Descriptions | 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). |
Associated Drug Resistance | |
Category Variants Paths |
IDH2 mutant IDH2 act mut IDH2 R172K IDH2 mutant IDH2 R172X IDH2 R172K |
Transcript | NM_002168.4 |
gDNA | chr15:g.90088606C>T |
cDNA | c.515G>A |
Protein | p.R172K |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
NM_002168 | chr15:g.90088606C>T | c.515G>A | p.R172K | RefSeq | GRCh38/hg38 |
NM_002168.4 | chr15:g.90088606C>T | c.515G>A | p.R172K | RefSeq | GRCh38/hg38 |
NM_002168.3 | chr15:g.90088606C>T | c.515G>A | p.R172K | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
IDH2 R172K | glioblastoma | predicted - sensitive | Enasidenib | Preclinical - Biochemical | 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 R172K | acute myeloid leukemia | sensitive | Enasidenib | FDA approved - On Companion Diagnostic | Actionable | In a Phase I/II trial that supported FDA approval, Idhifa (enasidenib) treatment resulted in an overall response rate of 40.3% (71/176) with a median response duration of 5.8 months, complete remission in 19.3% (34/176), and stable disease in 48.3% (85/176) of acute myeloid leukemia patients harboring IDH2 mutations (PMID: 28588020; NCT01915498) and IDH2 R172K is on the companion diagnostic. | detail... detail... 28588020 |
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 - Biochemical | 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 | acute myeloid leukemia | predicted - sensitive | Enasidenib + Venetoclax | Phase Ib/II | Actionable | In a Phase Ib/II trial, Idhifa (enasidenib) plus Venclexta (venetoclax) was well tolerated and demonstrated activity in relapsed or refractory acute myeloid leukemia patients harboring IDH2 R140Q (15/27) or IDH2 R172K/W (12/27), resulting in an overall response rate (ORR) of 70% (16/23), with complete remission (CR) in 57% (13/23) of evaluable patients, and an ORR of 83% (10/12) and a CR rate of 67% (8/12) in patients harboring IDH2 R172K or IDH2 R172W (Blood (2023) 142 (Supplement 1): 159; NCT04092179). | detail... |
IDH2 R172K | Advanced Solid Tumor | predicted - sensitive | HMPL-306 | Preclinical - Biochemical | Actionable | In a preclinical study, HMPL-306 inhibited the enzymatic activity of IDH2 R172K in a fluorescence-based assay (Cancer Res (2023) 83 (7_Supplement): 543). | detail... |
IDH2 R172K | hematologic cancer | predicted - sensitive | SH1573 | Preclinical - Biochemical | Actionable | In a preclinical study, SH1573 inhibited the activity of IDH2 R172K in an in vitro assay (PMID: 34221866). | 34221866 |
IDH2 R172K | acute myeloid leukemia | predicted - sensitive | TQB3455 | Case Reports/Case Series | Actionable | In a Phase I trial, TQB3455 treatment was well tolerated in patients with acute myeloid leukemia harboring IDH2 mutations, and resulted in an objective response rate (ORR) of 40.63% (13/32, 12 complete remission (CR) or CR with incomplete hematological recovery, 1 partial remission), with an ORR of 66.67%, and a CR rate of 41.67% in patients harboring IDH2 R172K (n=14) (Blood (2022) 140 (Supplement 1): 9082-9083). | detail... |
IDH2 R172K | high grade glioma | sensitive | TQ05310 | Preclinical - Cell culture | Actionable | In a preclinical study, TQ05310 treatment decreased 2-HG levels and increased differentiation in a glioma cell line expressing IDH2 R172K in culture (PMID: 31361380). | 31361380 |
IDH2 R172K | acute myeloid leukemia | sensitive | TQ05310 | Preclinical - Cell culture | Actionable | In a preclinical study, TQ05310 treatment decreased 2-HG levels and increased differentiation in an acute myeloid leukemia cell line expressing IDH2 R172K in culture (PMID: 31361380). | 31361380 |