Human MC1R Gene Controls Hair Color and Skin Color

 
The human MC1R gene encodes melanocortin 1 receptor, a protein found in the membranes of melanocytes. The human gene is orthologous to genes in other mammals that give rise to red coat color. For example, red hair in cattle, mice, guinea pig and horses (chestnut) are all due to variants in this gene.

It is thought that the receptor regulates production of the red melanin known as pheomelanin by stimulating cAMP production in response to the hormone α-MSH (melanocyte-stimulating hormone). Mutations in the gene show reduced levels of cAMP production in response to hormone and this may increase the amount of pheomelanin and reduce the levels of the brown form of melanin (eumelanin). Individuals carrying the variant gene will have fair skin containing pheomelanin as well as red hair and freckles. All three phenotyoes are due to the same variant, as is sensitivity to sunlight [OMIM 155555].

It is often thought that the red hair/fair skin/freckles phenotype is recessive but genotypes of people with these characters are often heterozygous, suggesting that it is inappropriate overproduction of pheomelanin, rather than underproduction of eumelanin, that is mainly responsible for the traits. (Gain-of-function mutations are often dominant.)

The gene (MC1R) is located on chromosome 16 at q24.3 [EntreGene="4157]. The gene is unusual because it does not contain introns and it has large 5ʹ and 3ʹ untranslated regions (UTRs).

There are over 30 known variants of this gene segregating in the human population. The variant responsible for red hair in the British population is a substitution of histidine for aspartate at amino acid 294 (D219H). This single amino acid substitution seems to account for all of the traits associated with red hair.