Nucleic Acids Res 31(13): 3812-3814
SIFT: predicting amino acid changes that affect protein function
Abstract
Single nucleotide polymorphism (SNP) studies and random mutagenesis projects identify amino acid substitutions in protein-coding regions. Each substitution has the potential to affect protein function. SIFT (Sorting Intolerant From Tolerant) is a program that predicts whether an amino acid substitution affects protein function so that users can prioritize substitutions for further study. We have shown that SIFT can distinguish between functionally neutral and deleterious amino acid changes in mutagenesis studies and on human polymorphisms. SIFT is available at http://blocks.fhcrc.org/sift/SIFT.html.
ACKNOWLEDGEMENTS
We thank Jorja Henikoff for advice and encouragement. This work was supported by a grant from NIH (GM29009).
REFERENCES
References
- 1. Krawczak M., Ball,E.V., Fenton,I., Stenson,P.D., Abeysinghe,S., Thomas,N. and Cooper,D.N. (2000) Human gene mutation database-a biomedical information and research resource. Hum. Mutat., 15, 45–51. [[PubMed]
- 2. Ng P.C. and Henikoff,S. (2001) Predicting deleterious amino acid substitutions. Genome Res., 11, 863–874.
- 3. Ng P.C. and Henikoff,S. (2002) Accounting for human polymorphisms predicted to affect protein function. Genome Res., 12, 436–446.
- 4. Bairoch A. and Apweiler,R. (2000) The SWISS-PROT protein sequence database and its supplement TrEMBL in 2000. Nucleic Acids Res., 28, 45–48.
- 5. Sherry S.T., Ward,M.H., Kholodov,M., Baker,J., Phan,L., Smigielski,E.M. and Sirotkin,K. (2001) dbSNP: the NCBI database of genetic variation. Nucleic Acids Res., 29, 308–311.
- 6. Sunyaev S., Ramensky,V., Koch,I., Lathe,W.,III, Kondrashov,A.S. and Bork,P. (2001) Prediction of deleterious human alleles. Hum. Mol. Genet., 10, 591–597. [[PubMed]
- 7. Chasman D. and Adams,R.M. (2001) Predicting the functional consequences of non-synonymous single nucleotide polymorphisms: structure-based assessment of amino acid variation. J. Mol. Biol., 307, 683–706. [[PubMed]
- 8. Saunders C.T. and Baker,D. (2002) Evaluation of structural and evolutionary contributions to deleterious mutation prediction. J. Mol. Biol., 322, 891–901. [[PubMed]
- 9. Wheeler D.L., Church,D.M., Lash,A.E., Leipe,D.D., Madden,T.L., Pontius,J.U., Schuler,G.D., Schriml,L.M., Tatusova,T.A., Wagner,L. and Rapp,B.A. (2002) Database resources of the National Center for Biotechnology Information: 2002 update. Nucleic Acids Res., 30, 13–16.
- 10. Leabman M.K., Huang,C.C., DeYoung,J., Carlson,E.J., Taylor,T., de la Cruz,M., Johns,S.J., Stryke,D., Kawamoto,M., Urban,T.J., et al. (2003) Natural variation in human membrane transporter genes reveals evolutionary and functional constraints. Proc. Natl Acad. Sci. USA, in press.
- 11. Schneider T.D., Stormo,G.D., Gold,L. and Ehrenfeucht,A. (1986) Information content of binding sites on nucleotide sequences. J. Mol. Biol., 188, 415–431. [[PubMed]
- 12. Pace H.C., Kercher,M.A., Lu,P., Markiewicz,P., Miller,J.H., Chang,G. and Lewis,M. (1997) Lac repressor genetic map in real space. Trends Biochem. Sci., 22, 334–339. [[PubMed]
- 13. Ramensky V., Bork,P. and Sunyaev,S. (2002) Human non-synonymous SNPs: server and survey. Nucleic Acids Res., 30, 3894–3900.

