Abstract
The cytochrome P450 (CYP) enzymes play the central role in synthesis of endogenous substances and metabolism of xenobiotics. The substitution of single amino acid caused by non-synonymous single nucleotide polymorphism (nsSNP) will lead to the change in enzymatic activity of CYP isozymes, especially the drugmetabolizing ability. CYP-nsSNP is a specialized database focused on the effect of nsSNPs on enzymatic activity of CYPs. Its unique feature lies in providing the qualitative and quantitative description of the CYP variants in terms of enzymatic activity. In addition, the database also offers the general information about nsSNP and compounds that are involved in corresponding enzymatic reaction. The current CYP-nsSNP can be accessible at http://cypdatabase.sjtu.edu.cn/ and includes more than 300 genetic variants of 12 CYP isozymes together with about 100 compounds. In order to keep the accuracy of information within database, all experimental data were collected from the scientific literatures, and the users who conducted research to identify the novel CYP variants are encouraged to contribute their data. Therefore, CYP-nsSNP can be considered as a valuable source for experimental and computational studies of impact of genetic polymorphism on the function of CYPs.
Similar content being viewed by others
References
Ahn, C. 2007. Pharmacogenomics in drug discovery and development. Genomics Inform 5, 41–45.
Bao, L., Cui, Y. 2005. Prediction of the phenotypic effects of non-synonymous single nucleotide polymorphisms using structural and evolutionary information. Bioinformatics 21, 2185–2190.
Bromberg, Y., Rost, B. 2007. SNAP: Predict effect of non-synonymous polymorphisms on function. Nucleic Acids Res 35, 3823–3835.
Cargill, M., Altshuler, D., Ireland, J., Sklar, P., Ardlie, K., Patil, N., Lane, C., Lim, E., Kalyanaraman, N., Nemesh, J. 1999. Characterization of single-nucleotide polymorphisms in coding regions of human genes. Nat Genet 22, 231–238.
Chasman, D., Adams, R. 2001. Predicting the functional consequences of non-synonymous single nucleotide polymorphisms: Structure-based assessment of amino acid variation1. J Mol Biol 307, 683–706.
Crawford, D., Akey, D., Nickerson, D. 2005. The patterns of natural variation in human genes. Annu Rev Genomics Hum Genet 6, 287–312.
Dickinson, G., Rezaee, S., Proctor, N., Lennard, M., Tucker, G., Rostami-Hodjegan, A. 2007. Incorporating in vitro information on drug metabolism into clinical trial simulations to assess the effect of CYP2D6 polymorphism on pharmacokinetics and pharmacodynamics: dextromethorphan as a model application. J Clin Pharmacol 47, 175–186.
Halushka, M., Fan, J., Bentley, K., Hsie, L., Shen, N., Weder, A., Cooper, R., Lipshutz, R., Chakravarti, A. 1999. Patterns of single-nucleotide polymorphisms in candidate genes for blood-pressure homeostasis. Nat Genet 22, 239–247.
Ingelman-Sundberg, M., Sim, S., Gomez, A., Rodriguez-Antona, C. 2007. Influence of cytochrome P450 polymorphisms on drug therapies: pharmacogenetic, pharmacoepigenetic and clinical aspects. Pharmacol Ther 116, 496–526.
Kusama, M., Maeda, K., Chiba, K., Aoyama, A., Sugiyama, Y. 2009. Prediction of the effects of genetic polymorphism on the pharmacokinetics of CYP2C9 substrates from in vitro data. Pharm Res 26, 822–835.
Lewis, D., Ito, Y. 2010. Human CYPs involved in drug metabolism: structures, substrates and binding affinities. Expert Opin Drug Metab Toxicol 26, 1–14.
McCarthy, J., Hilfiker, R. 2000. The use of singlenucleotide polymorphism maps in pharmacogenomics. Nat Biotechnol 18, 505–508.
Nebert, D. 1997. Polymorphisms in drug-metabolizing enzymes: What is their clinical relevance and why do they exist? Am J Hum Genet 60, 265–271.
Ng, P., Henikoff, S. 2003. SIFT: Predicting amino acid changes that affect protein function. Nucleic Acids Res 31, 3812–3814.
Pelkonen, O. 2002. Human CYPs: in vivo and clinical aspects. Drug Metab Rev 34, 37–46.
Preissner, S., Kroll, K., Dunkel, M., Senger, C., Goldsobel, G., Kuzman, D., Guenther, S., Winnenburg, R., Schroeder, M., Preissner, R. 2009. SuperCYP: A comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res 38, 1–7.
Ramensky, V., Bork, P., Sunyaev, S. 2002. Human non-synonymous SNPs: Server and survey. Nucleic Acids Res 30, 3894–3900.
Shastry, B. 2009. SNPs: Impact on gene function and phenotype. Methods Mol Biol 578, 3–22.
Sim, S., Ingelman-Sundberg, M. 2006. The human cytochrome P450 Allele Nomenclature Committee Web site: Submission criteria, procedures, and objectives. Methods Mol Biol 320, 183–191.
Sim, S., Ingelman-Sundberg, M. 2010. The Human Cytochrome P450 (CYP) Allele Nomenclature website: A peer-reviewed database of CYP variants and their associated effects. Hum Genomics 4, 278–281.
Sirim, D., Wagner, F., Lisitsa, A., Pleiss, J. 2009. The Cytochrome P450 Engineering Database: Integration of biochemical properties. BMC Biochem 10, 27–30.
Sunyaev, S., Ramensky, V., Bork, P. 2000. Towards a structural basis of human non-synonymous single nucleotide polymorphisms. Trends Genet 16,198–200.
Van der Weide, J., Steijns, L. 1999. Cytochrome P450 enzyme system: genetic polymorphisms and impact on clinical pharmacology. Ann Clin Biochem 36, 722–729.
van Schaik, R. 2008. CYP450 pharmacogenetics for personalizing cancer therapy. Drug Resist Updat 11, 77–98.
Wang, L., Li, Y., Zhou, S. 2009. A bioinformatics approach for the phenotype prediction of nonsynonymous single nucleotide polymorphisms in human cytochromes P450. Drug Metab Dispos 37, 977–991.
Wang, Z., Moult, J. 2001. SNPs, protein structure, and disease. Hum Mutat 17, 263–270.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Zhang, T., Zhou, Q., Pang, Y. et al. CYP-nsSNP: A specialized database focused on effect of non-synonymous SNPs on function of CYPs. Interdiscip Sci Comput Life Sci 4, 83–89 (2012). https://doi.org/10.1007/s12539-012-0125-x
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12539-012-0125-x