Type 4 Melanocortin Receptor
( MC4R )

The type 4 melanocortin receptor ( MC4R ) sits on the surface of brain cells in the hypothalamus. It is activated by a-MSH which comes from PMOC. Once a-MSH is bound, the hypothalamus decreases the sensation of feeling hungry. Defects in this receptor cause people to have increased appetites. They have no other symptoms, unlike the rest of the genetic defects.

The increased appetite shows up by one year of age. They have not only increased amount of fat, but also more lean mass and high bone densities. Their growth in height is faster in childhood. As time goes on, these symptoms seem to calm down. Adults are less hungry.

Up to 5% of people with severe obesity have mutations in both copies of this gene they received from their father and mother. 1%-2.5% of people with BMIs of more than 30 have one copy of a mutated gene. This makes MC4R mutations the most common obesity gene.

For the most part, these people are overweight. However, there are some who have this genetic defect but are not obese. This means there are other genetic and environmental factors that come into play. Additionally, a certain genetic variations called V103I and I251L seem to reduce the risk of becoming obese.

There is no current treatment for MC4R mutations. However, since most of these people have one bad and one good gene, it is possible that giving a drug that could stimulate the remaining good receptors could be a medical therapy.

The hypothalamic leptin-melanocortin system

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