As shown in Fig. 2G, 4C and Supplementary Fig. 4C, the four CPP-causing MKRN3 missense mutants, which poorly ubiquitinated MBD3, only exhibited a marginal inhibitory effect on MBD3-activated GNRH1 expression when compared to that by wild-type MKRN3, suggesting a potential link between impaired MBD3 ubiquitination and weakened suppression of GnRH1 production in CPP patients. This evidence concerns the gene MKRN3 and central precocious puberty.