P4HTM and obesity due to melanocortin 4 receptor deficiency: As a result, we have identified several patients with severe obesity carrying homozygous, deleterious, missense mutations in P4HTM encoding the enzyme prolyl 4-hydroxylase transmembrane (P4H-TM), an atypical member of the hypoxia inducible factors prolyl 4-hydroxylases (HIF-P4Hs), that are necessary for adaptation under reduced oxygen supply.