HUMAN PIGMENTATION PHENOTYPE - A POINT MUTATION GENERATES NONFUNCTIONAL MSH RECEPTOR

alpha-Melanocyte stimulating hormone (alpha-MSH) regulates skin and ha ir pigmentation by modulating the activity of MSH receptor (MC1R), We have identified Arg151Cys variant of human MC1R in genomic DNA isolate d from a person with red hair and Light skin of type I. The Arg151Cys variant of MC1R binds to radiolabelled analogue of alpha-MSH with iden tical affinity as wild type MC1R but can not be stimulated to produce cyclic AMP (cAMP), The mutation Arg151Cys renders human MC1R completel y nonfunctional, which explains the red hair, Light skin and poor tann ing ability (skin type I). This is the first report ever describing a nonfunctional MC1R isolated from a human subject. (C) 1998 Academic Pr ess.