SETD2 and cancer: Notably, while H3K36me2-generating enzymes like NSD2 and NSD3 promote oncogenesis when mutated or overexpressed (e.g., Kuo et al., 2011; Hudlebusch et al., 2011; Jaffe et al., 2013; Aytes et al., 2018; Yuan et al., 2021; Sengupta et al., 2021), SETD2 is a potent tumor suppressor frequently mutated in clear cell renal cell carcinoma (ccRCC) (Duns et al., 2010; Dalgliesh et al., 2010) and several other cancers.