SETD2 and nonpapillary renal cell carcinoma: Notably, while H3K36me2-generating enzymes like NSD2 and NSD3 promote oncogenesis when mutated or overexpressed (e.g. (12–17)), SETD2 is a potent tumor suppressor frequently mutated in clear cell renal cell carcinoma (ccRCC) (9, 18) and several other cancers.