Histone H2A and H2B cumulatively have 15 non-canonical histone variants, out of which 11 are H2A variants—H2A.X, H2A.Z.1, H2A.Z.2.1, H2A.Z.2.2, H2A.Bbd, H2A.J, H2A.B, TH2A, H2A.P, macroH2A.1.1, macroH2A.2, and macroH2A1.2, and four are H2B variants—H2BE, H2B.S.M, TH2B, and H2B.W (Oberdoerffer and Miller, 2022), which are often dysregulated in cancers (Figure 4A). Here, H2BC21 is linked to cancer.