MC4R and obesity due to melanocortin 4 receptor deficiency: Second, human mutations affecting either a dibasic cleavage site [16] or a conserved tyrosine residue of β-MSH important for MC4R binding [17], [18] are strongly associated with obesity, suggesting that β-MSH is of direct clinical relevance and that its loss cannot be compensated by either α-MSH and/or d-α-MSH.