MC1R genw

MC1R (MC1R is the acronym for: Melanocortin 1 Receptor) is a protein coding gene located on chromosome 16q24.3 and encodes melanocortin receptor1. The encoded receptor is a transmembrane protein receptor for melanocyte-stimulating hormone (MSH) and ACTH. The receptor is expressed by melanocytes. 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.

Generalg: There are two types of melanin:

• red pheomelanin
• and
• black eumelanin.

Eumelanin is photoprotective; pheomelanin may contribute to UV-induced skin damage by generating free radicals when exposed to UV radiation. Thus, intact MC1 receptor function represents a protective factor for the skin. Mutations of the coding recetpor gene leading to loss of function of eumelanin are associated with increased production of pheomelanin. This results in lighter skin and hair color. To date, more than 30 allelic 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 inactivation of MC1R or its signaling pathway, causing decreased synthesis of eumelanin. This leads phenotypically to pale skin and red hair. This phenotype has a significantly higher melanoma incidence due to the lack of pigmentation ability (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.