To investigate the impacts of ICF syndrome‐associated mutations in the RD interface of the DNMT3B homodimer, we introduced H814R, D817G, V818M, and R823G mutations into a construct expressing N‐terminal tail‐truncated DNMT3B (DNMT3BΔ214, residues 215–853) that still hosts the PWWP, ADD, and MTase domains (Figure 1a). The gene discussed is DNMT3B; the disease is ICF syndrome.