MC4R and obesity due to melanocortin 4 receptor deficiency: The majority of MC4R mutations [10], principally including missense and synonymous mutations, have demonstrated partial or complete no activity of MC4R through in vitro study [70], and this loss of function was associated with early-onset obesity in children, manifested particularly in homozygotes rather than heterozygotes, with a higher percentage of body fat mass, increased appetite and food seeking behavior during meals and hyperphagia [70].