Kinase mutations in human disease: interpreting genotype-phenotype relationships

Nat Rev Genet. 2010 Jan;11(1):60-74. doi: 10.1038/nrg2707.


Protein kinases are one of the largest families of evolutionarily related proteins and comprise one of the most abundant gene families in humans. Here we survey kinase gene mutations from the perspective of human disease phenotypes and further analyse the structural features of mutant kinases, including mutational hotspots. Our evaluation of the genotype-phenotype relationship across 915 human kinase mutations - that underlie 67 single-gene diseases, mainly inherited developmental and metabolic disorders and also certain cancers - enhances our understanding of the role of kinases in development, kinase dysfunction in pathogenesis and kinases as potential targets for therapy.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • DNA Mutational Analysis
  • Disease Models, Animal
  • Genetic Diseases, Inborn / genetics*
  • Genotype
  • Germ-Line Mutation
  • Humans
  • Models, Biological
  • Models, Genetic
  • Models, Molecular
  • Multigene Family
  • Mutation*
  • Neoplasms / genetics
  • Phenotype
  • Phosphotransferases / genetics*
  • Phosphotransferases / physiology*


  • Phosphotransferases