Remarkably, several mutations on position 3.40 have been linked to dysfunctions or diseases, i.e. V5093.40A of thyrotropin receptor can cause non-autoimmune hyperthyroidism (Duprez et al., 1994 ▸), I1373.40T of melanocortin receptor 4 can cause obesity (Gu et al., 1999 ▸; Xiang et al., 2006 ▸), S1273.40F of vasopressin V2 receptor can cause nephrogenic diabetes insipidus (Erdélyi et al., 2015 ▸) and L1253.40R of rhodopsin can cause retinitis pigmentosa 4 (Dryja, 1992 ▸). Here, TSHR is linked to obesity due to melanocortin 4 receptor deficiency.