title: Human pigmentation phenotype: a point mutation generates nonfunctional MSH receptor.
abstract: alpha-Melanocyte stimulating hormone (alpha-MSH) regulates skin and hair pigmentation by modulating the activity of MSH receptor (MC1R). We have identified Arg151Cys variant of human MC1R in genomic DNA isolated from a person with red hair and light skin of type I. The Arg151Cys variant of MC1R binds to radio-labelled analogue of alpha-MSH with identical affinity as wild type MC1R but can not be stimulated to produce cyclic AMP (cAMP). The mutation Arg151Cys renders human MC1R completely nonfunctional, which explains the red hair, light skin and poor tanning ability (skin type I). This is the first report ever describing a nonfunctional MC1R isolated from a human subject.
authors.affiliation: Division of Biological Research on Drug Dependence, Biomedical Centre, Uppsala, Sweden.
authors.forename: P A
authors.initials: PA
authors.lastname: Frändberg
authors.forename: M
authors.initials: M
authors.lastname: Doufexis
authors.forename: S
authors.initials: S
authors.lastname: Kapas
authors.forename: V
authors.initials: V
authors.lastname: Chhájlani
mesh_terms: D000818:Animals; D001667:Binding, Competitive; D019556:COS Cells; D003001:Cloning, Molecular; D000242:Cyclic AMP / Q000378:metabolism; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D007457:Iodine Radioisotopes / Q000378:metabolism; D010858:Pigmentation / Q000502:physiology*; D017354:Point Mutation / Q000235:genetics*; D011979:Receptors, Pituitary Hormone / Q000235:genetics* / Q000502:physiology; D017422:Sequence Analysis, DNA; D014162:Transfection / Q000235:genetics; D000521:alpha-MSH / Q000031:analogs & derivatives / Q000378:metabolism
chemical_list: D007457:Iodine Radioisotopes; D011979:Receptors, Pituitary Hormone; D000521:alpha-MSH; C027756:MSH, 4-Nle-7-Phe-alpha-; C029446:MSH receptor; D000242:Cyclic AMP