Protein-protein interaction sites are hot spots for disease-associated nonsynonymous SNPs

Alessia David, Rozaimi Mohamad Razali, Mark N. Wass, Michael J E Sternberg

Research output: Contribution to journalArticle

84 Citations (Scopus)


Many nonsynonymous single nucleotide polymorphisms (nsSNPs) are disease causing due to effects at protein-protein interfaces. We have integrated a database of the three-dimensional (3D) structures of human protein/ protein complexes and the humsavar database of nsSNPs. We analyzed the location of nsSNPS in terms of their location in the protein core, at protein-protein interfaces, and on the surface when not at an interface. Diseasecausing nsSNPs that do not occur in the protein core are preferentially located at protein-protein interfaces rather than surface noninterface regions when compared to random segregation. The disruption of the protein-protein interaction can be explained by a range of structural effects including the loss of an electrostatic salt bridge, the destabilization due to reduction of the hydrophobic effect, the formation of a steric clash, and the introduction of a proline altering the main-chain conformation.

Original languageEnglish
Pages (from-to)359-363
Number of pages5
JournalHuman Mutation
Issue number2
Publication statusPublished - 1 Feb 2012
Externally publishedYes



  • Bioinformatics.
  • Interactome
  • Nonsynonymous snps
  • Protein structure

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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