MC1R genw

The MC1R gene (MC1R is the acronym for: Melanocortin 1 Receptor) is a protein-coding gene located on chromosome 16q24.3 and encodes the specific melanocortin receptor1. The encoded receptor is a transmembrane protein receptor for melanocyte-stimulating hormone (MSH) and ACTH. The receptor is expressed by melanocytes. The binding of MSH to its receptor activates the receptor. The activated receptor triggers a complex signaling cascade(MC1R signaling pathway) that leads to the production of eumelanin (but not pheomelanin).

An important paralog of this gene is MC4R.

General: There are two types of melanin:

• red pheomelanin
• and
• black eumelanin.

Eumelanin is photoprotective; pheomelanin can contribute to UV-induced skin damage as it generates free radicals when exposed to UV radiation. The intact function of the MC1 receptor therefore represents a significant protective factor for the skin. Mutations of the coding recetpore gene, which lead to a loss of function of the eumelanin, are associated with increased production of pheomelanin. This leads to a lighter skin and hair color. To date, more than 30 allele variants have been identified that correlate with skin and hair color. This diversity proves that this gene is an important component for the phenotypic pigmentation of skin and hair.

Polymorphisms in the MC1R gene lead to the inactivation of MC1R or its signaling pathway and thus cause a reduced synthesis of eumelanin. Phenotypically, this leads to pale skin and red hair. This phenotype has a significantly higher incidence of melanoma due to the lack of pigmentation capacity (Kennedy C et al. 2001).

1. Kennedy C et al. (2001) Melanocortin 1 receptor (MC1R) gene variants are associated with an increased risk for cutaneous melanoma which is largely independent of skin type and hair color.J Invest Dermatol 117:294-300.
2. Montoya KG et al (1992) The cloning of a family of genes that encode the melanocortin receptors. Science 257:1248-1251.