In addition to genomic alterations, elevated 2-HG inhibits hypoxia-inducible factor (HIF) prolyl hydroxylases, a group of α-ketoglutarate dependent enzymes that mediate hydroxylation of HIF-1α to target it for proteasomal degradation; IDH mutations therefore lead to increased HIF-1α and create a state of persistent pseudohypoxia that promotes tumor growth (Fig. 1) [32, 43, 44]. The gene discussed is IDH2; the disease is neoplasm.