Mutations in the IDH2 gene often occur at specific hotspots, most notably at the R140 and R172 residues. These mutations result in a neomorphic enzyme activity that converts α-KG into an oncometabolite known as 2-hydroxyglutarate (2-HG). Elevated levels of 2-HG can lead to epigenetic changes, disrupt cellular differentiation, and promote oncogenesis.
