DNMT3B and immune system disorder: DNMT3B mutations associated with the FF interface, which mediates the interaction between DNMT3B and either another DNMT3B (in a homotetramer) or DNMT3L (in a heterotetramer), have been found in patients with immunodeficiency, centromeric instability, and facial anomalies (ICF) syndrome (L664P, L664T, R670Q) (Fig. 3a) [27, 82].