Isocitrate dehydrogenase 1 (NADP+), soluble (IDH1) is a gene that encodes an epigenetic modifier, a NADP(+)-dependent enzyme that catalyzes oxidative decarboxylation of isocitrate (Gene 2013). Wild type IDH1 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).
IDH1 is frequently mutated in glioma and acute myeloid leukemia, myelodysplastic syndromes, and other cancer types (Rohle et al. 2013; Walter et al. 2013). Mutations generally involve point mutations at the R132 residue of the protein, although a synonymous variant (G105G) has been found to be prognostically relevant in AML. 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).
Suggested Citation: Wheeler, S., A. Seegmiller, C. Vnencak-Jones, S. Strickland, A. Kim. 2015. IDH1. My Cancer Genome https://www.padiracinnovation.org/content/disease/acute-myeloid-leukemia/idh1/?tab=0 (Updated December 4).
Last Updated: December 4, 2015