POMC and obesity due to melanocortin 4 receptor deficiency: Furthermore, a single patient with severe early onset obesity was reported to have compound heterozygote mutations in the proprotein convertase subtilisin/kexin type 1 (PCSK1; also known as PC1) gene,44 a key component in the proteolytic processing of POMC;45 more recently, common nonsynonymous variants in PCSK1 have also been shown to confer risk of obesity.46 Indeed, biochemical experiments with N221D demonstrate that its enzyme activity is reduced by 10%,47 making it an attractive drug target going forward.