Moreover, given the (i) reduced Ser237 phosphorylation of the R125W mutant demonstrated in our experiments and (ii) IGF1 hypersecretion-mediated obesity in the knock-in mouse where Ser231 can no longer be phosphorylated; an attractive hypothesis is that the observed severe obesity phenotype in a subset of women with the R125W mutation may occur via a mechanism involving elevated circulating levels of IGF1. The gene discussed is IGF1; the disease is obesity due to melanocortin 4 receptor deficiency.