MC4R and obesity due to melanocortin 4 receptor deficiency: This contrasts with homozygous/bi-allelic carriers of LoF mutations in other genes in the leptin-melanocortin signalling pathway -LEP, LEPR, POMC, PCSK1 and MC4R-who almost inevitably develop severe obesity at an early age [[19], [20], [21], [22], [23]].