Types and effects of protein variations

Hum Genet. 2015 Apr;134(4):405-21. doi: 10.1007/s00439-015-1529-6. Epub 2015 Jan 24.


Variations in proteins have very large number of diverse effects affecting sequence, structure, stability, interactions, activity, abundance and other properties. Although protein-coding exons cover just over 1 % of the human genome they harbor an disproportionately large portion of disease-causing variants. Variation ontology (VariO) has been developed for annotation and description of variation effects, mechanisms and consequences. A holistic view for variations in proteins is made available along with examples of real cases. Protein variants can be of genetic origin or emerge at protein level. Systematic names are provided for all variation types, a more detailed description can be made by explaining changes to protein function, structure and properties. Examples are provided for the effects and mechanisms, usually in relation to human diseases. In addition, the examples are selected so that protein 3D structural changes, when relevant, are included and visualized. Here, systematics is described for protein variants based on VariO. It will benefit the unequivocal description of variations and their effects and further reuse and integration of data from different sources.

MeSH terms

  • Amino Acid Sequence / genetics
  • Animals
  • Databases, Protein
  • Gene Ontology*
  • Genetic Variation*
  • Humans
  • Models, Molecular
  • Molecular Dynamics Simulation
  • Protein Folding
  • Protein Processing, Post-Translational / genetics
  • Protein Structure, Quaternary / genetics
  • Protein Structure, Secondary / genetics
  • Proteins* / chemistry
  • Proteins* / genetics
  • Proteins* / physiology
  • Structure-Activity Relationship


  • Proteins