Isocitrate dehydrogenase 1 R132H mutation neoantigen (IDH1 R132H)

Isocitrate dehydrogenase 1 with the R132H mutation is a mutated metabolic enzyme found predominantly in low-grade gliomas, secondary glioblastomas, and some cases of acute myeloid leukemia. The wild-type enzyme catalyzes the conversion of isocitrate to α-ketoglutarate while producing NADPH. The R132H point mutation results in a neomorphic function—conversion of α-ketoglutarate into D‑2‑hydroxyglutarate (D‑2HG), an oncometabolite that accumulates at high levels. This disrupts normal cell metabolism by inhibiting multiple α-KG–dependent dioxygenases involved in DNA/histone demethylation, leading to widespread epigenetic changes and impaired cellular differentiation. The presence of this mutation serves as both a prognostic marker—often associated with improved survival compared to wild-type—and a therapeutic target, with several small-molecule inhibitors developed specifically against it. In addition to its role in tumor metabolism, recent research suggests it may also influence immune cell recruitment within the tumor microenvironment by altering chemokine expression profiles such as CX3CL1[5].

Other names

IDH1 R132HMutant isocitrate dehydrogenase 1 (R132H)IDH1 Arg132His mutantIsocitrate dehydrogenase 1 (IDH1) R132H mutation

Inhibition of neomorphic enzymatic activity that converts α-ketoglutarate to D‑2‑hydroxyglutarate, thereby reducing oncometabolite accumulation and restoring normal epigenetic regulation and differentiation pathways[2][3]