H3.3K36M, a mutant histone found in chondroblastoma (Behjati et al., 2013), inhibits SETD2 as well as the H3K36 mono- and di-methyltransferase NSD2, in a dominant-negative manner (i.e. in cis and in trans; Lewis et al., 2013; Lu et al., 2016; Zhang et al., 2017). The gene discussed is SETD2; the disease is chondroblastoma.