SET domain containing 2 (SETD2), a major H3K36me3 methyltransferase in mammalian cells, is frequently mutated in clear cell renal carcinoma, leukemia, glioma, and other cancers, and H3K36me3 catalyzed by SETD2 is involved in mRNA alternative splicing, genome stability, and DNA repair process [6–8]. The gene discussed is SETD2; the disease is leukemia.