Computational analysis unravels novel destructive single nucleotide polymorphisms in the non-synonymous region of human caveolin gene

Nitin Chitranshi, Yogita Dheer, Roshana Vander Wall, Veer Gupta, Mojdeh Abbasi, Stuart L. Graham, Vivek Gupta

Research output: Contribution to journalArticleResearchpeer-review

Abstract

The caveolin (Cav) family of proteins comprises key constituents of caveolar structures in cell membranes, which are involved in receptor-independent endocytosis and cellular signalling pathways. Three isoforms of caveolin viz. cav-1, cav-2 and cav-3 encoded by CAV1, CAV2 and CAV3 genes respectively, have been reported to be expressed in various tissues. Genetic polymorphism in CAV has been identified as associated with the development of pathological changes in the cardiovascular system, chronic kidney disease as well as neurodegenerative diseases of the brain and retina such as Alzheimer's disease, Parkinson's disease and glaucoma. In this study, we investigate and characterise various polymorphisms associated with CAV1, CAV2 and CAV3 by using a combination of in silico algorithms such as SIFT, Polyphen 2.0, I-Mutant, PROVEAN, PANTHER, SNP&Go, PhD-SNP, MutPred and SNPEffects. Three-dimensional comparative modelling was performed using Phyre2 server, ab initio modelling, using the I-TASSER and RaptorX program. The predicted models were evaluated using Ramachandran plot to establish the accuracy of the models generated. The resulting mutant and wild type proteins obtained were energy minimized in Swiss Deep Viewer and evaluated. The study has identified two of the non-synonymous single nucleotide polymorphism (nsSNP) in CAV3 gene that may have a damaging effect on the protein stability. The surface residues in the wild type and mutant forms highlight different accessible surface area (ASA) of amino acid residues in the corresponding proteins. Our analysis predicted that none of the known nsSNPs have a negative effect on the CAV1 and CAV2 protein structures. Phylogenetic analysis using ConSurf further identified that most of the disease-associated nsSNPs were within the conserved regions in human cav3.

LanguageEnglish
Pages142-157
Number of pages16
JournalGene Reports
Volume6
DOIs
Publication statusPublished - 1 Mar 2017

Fingerprint

Caveolins
Single Nucleotide Polymorphism
Cell Membrane Structures
Genes
Protein Stability
Genetic Polymorphisms
Mutant Proteins
Cardiovascular System
Endocytosis
Chronic Renal Insufficiency
Neurodegenerative Diseases
Glaucoma
Computer Simulation
Parkinson Disease
Retina
Alzheimer Disease
Protein Isoforms
Proteins
Amino Acids
Brain

Keywords

  • Caveolin
  • Homology modelling
  • Mutation
  • SNP

Cite this

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title = "Computational analysis unravels novel destructive single nucleotide polymorphisms in the non-synonymous region of human caveolin gene",
abstract = "The caveolin (Cav) family of proteins comprises key constituents of caveolar structures in cell membranes, which are involved in receptor-independent endocytosis and cellular signalling pathways. Three isoforms of caveolin viz. cav-1, cav-2 and cav-3 encoded by CAV1, CAV2 and CAV3 genes respectively, have been reported to be expressed in various tissues. Genetic polymorphism in CAV has been identified as associated with the development of pathological changes in the cardiovascular system, chronic kidney disease as well as neurodegenerative diseases of the brain and retina such as Alzheimer's disease, Parkinson's disease and glaucoma. In this study, we investigate and characterise various polymorphisms associated with CAV1, CAV2 and CAV3 by using a combination of in silico algorithms such as SIFT, Polyphen 2.0, I-Mutant, PROVEAN, PANTHER, SNP&Go, PhD-SNP, MutPred and SNPEffects. Three-dimensional comparative modelling was performed using Phyre2 server, ab initio modelling, using the I-TASSER and RaptorX program. The predicted models were evaluated using Ramachandran plot to establish the accuracy of the models generated. The resulting mutant and wild type proteins obtained were energy minimized in Swiss Deep Viewer and evaluated. The study has identified two of the non-synonymous single nucleotide polymorphism (nsSNP) in CAV3 gene that may have a damaging effect on the protein stability. The surface residues in the wild type and mutant forms highlight different accessible surface area (ASA) of amino acid residues in the corresponding proteins. Our analysis predicted that none of the known nsSNPs have a negative effect on the CAV1 and CAV2 protein structures. Phylogenetic analysis using ConSurf further identified that most of the disease-associated nsSNPs were within the conserved regions in human cav3.",
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Computational analysis unravels novel destructive single nucleotide polymorphisms in the non-synonymous region of human caveolin gene. / Chitranshi, Nitin; Dheer, Yogita; Wall, Roshana Vander; Gupta, Veer; Abbasi, Mojdeh; Graham, Stuart L.; Gupta, Vivek.

In: Gene Reports, Vol. 6, 01.03.2017, p. 142-157.

Research output: Contribution to journalArticleResearchpeer-review

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