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Computational detection of deleterious SNPs and their effect on sequence and structural level of the VHL gene

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Abstract

In this work we have analyzed the genetic variation that can alter the expression and the function of the VHL gene using computational methods. Of 110 single nucleotide polymorphisms (SNPs), 33 were found to be nonsynonymous (nsSNPs) and 23 SNPs were found in untranslated regions. Of the 33 nsSNPs investigated, 36.3% were found to be deleterious by both SIFT and PolyPhen servers. An untranslated region (UTR) resource tool suggested that two SNPs in the 5′ UTR region and six SNPs in the 3′ UTR region might change the protein expression levels. It was found by both SIFT and PolyPhen servers that a mutation from histidine to arginine at position 115 of the native protein of the VHL gene was most deleterious. A structural analysis of this mutated protein and the native protein was performed and had a root mean square deviation (RMSD) of 2.78 Å. Based on this work, we propose that the nsSNP with a SNPid of rs5030812 is an important candidate for the cause of von Hippel–Lindau syndrome via the VHL gene.

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Acknowledgments

The authors thank the management of the Vellore Institute of Technology University for providing the facilities to carry out this work. The authors thank the reviewers for their valuable suggestions and comments.

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  1. School of Biotechnology, Chemical and Biomedical Engineering, Bioinformatics Division, Vellore Institute of Technology University, Vellore, 632014, Tamil Nadu, India

    R. Rajasekaran, C. Sudandiradoss, C. George Priya Doss, Anshuman Singh & Rao Sethumadhavan

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  1. R. Rajasekaran
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  2. C. Sudandiradoss
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Correspondence to Rao Sethumadhavan.

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Rajasekaran, R., Sudandiradoss, C., George Priya Doss, C. et al. Computational detection of deleterious SNPs and their effect on sequence and structural level of the VHL gene. Mamm Genome 19, 654–661 (2008). https://doi.org/10.1007/s00335-008-9143-8

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