Single-gene disorders: what role could moonlighting enzymes play?

Am J Hum Genet. 2005 Jun;76(6):911-24. doi: 10.1086/430799. Epub 2005 Apr 22.


Single-gene disorders with "simple" Mendelian inheritance do not always imply that there will be an easy prediction of the phenotype from the genotype, which has been shown for a number of metabolic disorders. We propose that moonlighting enzymes (i.e., metabolic enzymes with additional functional activities) could contribute to the complexity of such disorders. The lack of knowledge about the additional functional activities of proteins could result in a lack of correlation between genotype and phenotype. In this review, we highlight some notable and recent examples of moonlighting enzymes and their possible contributions to human disease. Because knowledge and cataloging of the moonlighting activities of proteins are essential for the study of cellular function and human physiology, we also review recently reported and recommended methods for the discovery of moonlighting activities.

Publication types

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

MeSH terms

  • Animals
  • Apoptosis
  • Gene Expression Regulation
  • Genetic Diseases, Inborn / enzymology*
  • Genetic Diseases, Inborn / metabolism*
  • Humans
  • Molecular Biology / methods
  • Multienzyme Complexes / chemistry
  • Multienzyme Complexes / genetics*
  • Multienzyme Complexes / metabolism*
  • Proteins / chemistry
  • Proteins / genetics*
  • Proteins / metabolism
  • Signal Transduction
  • Structure-Activity Relationship
  • Transcription, Genetic


  • Multienzyme Complexes
  • Proteins