Isocitrate dehydrogenase 2 (NADP+), mitochondrial (IDH2) is a gene that encodes an epigenetic modifier, a NADP(+)-dependent enzyme that is found in mitochondria (Gene 2013). Wild type IDH2 converts isocitrate to α-ketoglutarate, a step in the Krebs cycle, an important metabolic pathway that affects many other cellular biochemical processes (Shih et al. 2012).
IDH2 is frequently mutated in glioma, acute myeloid leukemia, and myelodysplastic syndromes (Haferlach et al. 2014; Walter et al. 2013; Yang et al. 2012). Mutations generally involve point mutations at the R140 and R172 residues of the protein. Mutations in IDH1 and IDH2 result in deleterious “gain of function”: instead of converting isocitrate to α-ketoglutarate, mutated IDH1 or IDH2 converts isocitrate to 2-hydroxyglutarate (Shih et al. 2012; Yang et al. 2012). 2-hydroxyglutarate inhibits other proteins involved in epigenetic regulation (Shih et al. 2012).