Most of the mutations occur de novo, and missense mutations that cause Rett syndrome are concentrated in two discrete clusters coinciding with interaction sites for partner macromolecules: the methyl-CpG binding domain (MBD), involved in DNA binding (Nan et al., 1993) and the NCoR/SMRT interaction domain (Lyst et al., 2013; Tillotson et al., 2017). Here, NCOR2 is linked to Rett syndrome.