title: Red hair is the null phenotype of MC1R.
abstract: The Melanocortin-1 Receptor (MC1R) is a G-protein coupled receptor, which is responsible for production of the darker eumelanin pigment and the tanning response. The MC1R gene has many polymorphisms, some of which have been linked to variation in pigmentation phenotypes within human populations. In particular, the p.D84E, p.R151C, p.R160W and p.D294 H alleles have been strongly associated with red hair, fair skin and increased skin cancer risk. These red hair colour (RHC) variants are relatively well described and are thought to result in altered receptor function, while still retaining varying levels of signaling ability in vitro. The mouse Mc1r null phenotype is yellow fur colour, the p.R151C, p.R160W and p.D294 H alleles were able to partially rescue this phenotype, leading to the question of what the true null phenotype of MC1R would be in humans. Due to the rarity of MC1R null alleles in human populations, they have only been found in the heterozygous state until now. We report here the first case of a homozygous MC1R null individual, phenotypic analysis indicates that red hair and fair skin is found in the absence of MC1R function.
authors.affiliation: Melanogenix Group, Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland 4072, Australia.
authors.forename: Kimberley A
authors.initials: KA
authors.lastname: Beaumont
authors.forename: Sri N
authors.initials: SN
authors.lastname: Shekar
authors.forename: Anthony L
authors.initials: AL
authors.lastname: Cook
authors.forename: David L
authors.initials: DL
authors.lastname: Duffy
authors.forename: Richard A
authors.initials: RA
authors.lastname: Sturm
mesh_terms: D000483:Alleles; D000818:Animals; D002648:Child; D004252:DNA Mutational Analysis; D005260:Female; D016368:Frameshift Mutation; D006200:Hair Color / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D008297:Male; D051379:Mice; D010641:Phenotype; D010858:Pigmentation; D044102:Receptor, Melanocortin, Type 1 / Q000235:genetics*; D043562:Receptors, G-Protein-Coupled / Q000235:genetics
chemical_list: D044102:Receptor, Melanocortin, Type 1; D043562:Receptors, G-Protein-Coupled