Identification of common polymorphisms in the coding sequence of the human MSH receptor (MCIR) with possible biological effects

Hum Mutat. 1997;9(1):30-6. doi: 10.1002/(SICI)1098-1004(1997)9:1<30::AID-HUMU5>3.0.CO;2-T.


The extension locus has been identified in many mammalian species as a gene that determines the relative amounts of eumelanin and phaeomelanin pigments in hair and skin. In at least three species, this locus has been demonstrated to encode the melanocyte-stimulating hormone receptor (MC1-R), and functionally variant alleles have been demonstrated to cause a broad range of pigmentation phenotypes. To test for MC1-R allelic variation in man, genomic DNA was extracted from skin samples collected from patients with different skin types (I-VI), and eye and hair color. A PCR-based approach was used to amplify the full-length coding sequence of the MC1-R and the resulting products were sequenced. Two polymorphic alleles were identified with single point mutations in the coding sequence: a valine-to-methionine substitution at position 92 (V92M), and an aspartic acid-to-glutamic acid substitution at position 84 (D84E). RFLP analysis demonstrated the presence of the V92M allele in 4 out of 60 (6.6%) of individuals examined, predominantly those with blue eyes and blond hair. This polymorphism was found in both heterozygous and homozygous states in individuals with type I skin. The D84E allele was found in one individual with skin type I; this person also has the V92 M allele and thus is a compound heterozygote.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Eye Color / genetics
  • Hair Color / genetics
  • Heterozygote
  • Homozygote
  • Humans
  • Molecular Sequence Data
  • Point Mutation
  • Polymorphism, Restriction Fragment Length
  • Receptors, Pituitary Hormone / genetics*


  • Receptors, Pituitary Hormone
  • MSH receptor