TFE3 and Intellectual disability: Furthermore, recent works show that some gain-of-function TFE3 mutant alleles, which arise by amino acid substitutions affecting the Rag binding region of TFE3, are associated in humans with the X-linked dominant developmental syndrome with clinical manifestation of severe intellectual disability, coarse facial features, and Blaschkoid pigmentary mosaicism (Villegas et al., 2019; Diaz et al., 2020).