Effects of G-protein mutations on skin color

Nat Genet. 2004 Sep;36(9):961-8. doi: 10.1038/ng1412. Epub 2004 Aug 22.


A new class of dominant dark skin (Dsk) mutations discovered in a screen of approximately 30,000 mice is caused by increased dermal melanin. We identified three of four such mutations as hypermorphic alleles of Gnaq and Gna11, which encode widely expressed Galphaq subunits, act in an additive and quantitative manner, and require Ednrb. Interactions between Gq and Kit receptor tyrosine kinase signaling can mediate coordinate or independent control of skin and hair color. Our results provide a mechanism that can explain several aspects of human pigmentary variation and show how polymorphism of essential proteins and signaling pathways can affect a single physiologic system.

MeSH terms

  • Animals
  • Embryonic and Fetal Development
  • GTP-Binding Protein alpha Subunits, Gq-G11 / genetics*
  • Melanocytes
  • Mice
  • Mice, Mutant Strains
  • Molecular Sequence Data
  • Mutation, Missense*
  • Signal Transduction
  • Skin Pigmentation / genetics*


  • GTP-Binding Protein alpha Subunits, Gq-G11

Associated data

  • GENBANK/AB006541
  • GENBANK/AB006545
  • GENBANK/BC011169
  • GENBANK/J03609
  • GENBANK/L05540
  • GENBANK/P21279
  • GENBANK/U10502
  • RefSeq/NM_002067
  • RefSeq/NM_002072
  • RefSeq/NM_165920