Disease-associated variants in PYPAF1 and NOD2 result in similar alterations of conserved sequence

Bioinformatics. 2003 Nov 22;19(17):2171-5. doi: 10.1093/bioinformatics/btg370.


Sequence variations in the gene products PYPAF1/CIAS1 and NOD2/CARD15 have been associated with several autoinflammatory diseases that, although clinically different, share a similar inflammatory pathophysiology. A multiple sequence alignment of homologous proteins demonstrates that some of the missense variants are located in highly conserved regions of the NTPase domain and possibly impair NTP-hydrolysis. Intriguingly, one of the variations, which is found identically in PYPAF1 and NOD2, is located at the same alignment position. Our findings suggest that evolutionary gene duplication can give rise to disease families because variants affect conserved sequence in a similar fashion.

Publication types

  • Comparative Study
  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autoimmune Diseases / genetics*
  • Carrier Proteins / chemistry*
  • Carrier Proteins / genetics*
  • Cattle
  • Conserved Sequence / genetics
  • Gene Expression Profiling / methods*
  • Genetic Markers / genetics
  • Genetic Predisposition to Disease / genetics
  • Genetic Variation
  • Humans
  • Inflammation / genetics
  • Intracellular Signaling Peptides and Proteins*
  • Mutation, Missense / genetics
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Nod2 Signaling Adaptor Protein
  • Sequence Alignment / methods*
  • Sequence Analysis, Protein / methods*
  • Species Specificity
  • Structure-Activity Relationship


  • Carrier Proteins
  • Genetic Markers
  • Intracellular Signaling Peptides and Proteins
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • NLRP3 protein, human
  • NOD2 protein, human
  • Nod2 Signaling Adaptor Protein