PCSK1 and obesity due to melanocortin 4 receptor deficiency: We appreciate that heterozygous mutations in genes such as ALMS1, BBSs, LEPR, POMC, and PCSK1 have not been shown to be sufficient to cause the disease of obesity, except for the complete loss-of-function mutations of PCSK1 [42], but not for POMC or LEPR mutations [43].