We next proceeded to test the hypothesis that genes mutated in individuals with SMS-like features were associated with RAI1. To challenge this assumption, we first assessed if HDAC4, MBD5, and PITX3, three genes previously reported to be associated with SMS phenotypes [13, 14, 16], BRD2 and ZBTB17 (a.k.a. MIZ1), two genes encoding high-confidence RAI1 interactors we identified by two-hybrid assay (see “Methods”) and JAKMIP1, ZEB2, CASK, KMT2D, GLDC, MECP2, MAP2K2, POGZ, and KDM5C, the nine genes identified here, were part of a RAI1 functional network. This evidence concerns the gene CASK and Smith-Magenis syndrome.