Identification of deleterious single nucleotide polymorphism (SNP)s in the human TBX5 gene & prediction of their structural & functional consequences: An in silico approach

Identification of deleterious single nucleotide polymorphism (SNP)s in the human TBX5 gene & prediction of their structural & functional consequences: An in silico approach

T-box transcription factor 5 gene (TBX5) encodes the transcription factor TBX5, which plays a crucial role in the development of heart and upper limbs. Damaging single nucleotide variants in this gene alter the protein structure, disturb the functions of TBX5, and ultimately cause Holt-Oram Syndrome...

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Autores principales: A.M.U.B. Mahfuz, Md. Arif Khan, Promita Deb, Sharmin Jahan Ansary, Rownak Jahan
Formato: article
Lenguaje:EN
Publicado: Elsevier 2021
Materias:
TBX5
SNP
Mutation
Holt-oram syndrome
Congenital heart disease
Biology (General)
QH301-705.5
Biochemistry
QD415-436
Acceso en línea:https://doaj.org/article/fc252c2c71a2400e93bca9950f1e01a4
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spelling oai:doaj.org-article:fc252c2c71a2400e93bca9950f1e01a42021-12-04T04:35:22ZIdentification of deleterious single nucleotide polymorphism (SNP)s in the human TBX5 gene & prediction of their structural & functional consequences: An in silico approach2405-580810.1016/j.bbrep.2021.101179https://doaj.org/article/fc252c2c71a2400e93bca9950f1e01a42021-12-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2405580821002739https://doaj.org/toc/2405-5808T-box transcription factor 5 gene (TBX5) encodes the transcription factor TBX5, which plays a crucial role in the development of heart and upper limbs. Damaging single nucleotide variants in this gene alter the protein structure, disturb the functions of TBX5, and ultimately cause Holt-Oram Syndrome (HOS). By analyzing the available single nucleotide polymorphism information in the dbSNP database, this study was designed to identify the most deleterious TBX5 SNPs through in silico approaches and predict their structural and functional consequences.Fifty-eight missense substitutions were found damaging by sequence homology-based tools: SIFT and PROVEAN, and structure homology-based tool PolyPhen-2. Various disease association meta-predictors further scrutinized these SNPs. Additionally, conservation profile of the amino acid residues, their surface accessibility, stability, and structural integrity of the native protein upon mutations were assessed. From these analyses, finally 5 SNPs were detected as the most damaging ones: [rs1565941579 (P85S), rs1269970792 (W121R), rs772248871 (V153D), rs769113870 (E208D), and rs1318021626 (I222N)]. Analyses of stop-lost, nonsense, UTR, and splice site SNPs were also conducted.Through integrative bioinformatics analyses, this study has identified the SNPs that are deleterious to the TBX5 protein structure and have the potential to cause HOS. Further wet-lab experiments can validate these findings.A.M.U.B. MahfuzMd. Arif KhanPromita DebSharmin Jahan AnsaryRownak JahanElsevierarticleTBX5SNPMutationHolt-oram syndromeCongenital heart diseaseBiology (General)QH301-705.5BiochemistryQD415-436ENBiochemistry and Biophysics Reports, Vol 28, Iss , Pp 101179- (2021)
institution DOAJ
collection DOAJ
language EN
topic TBX5
SNP
Mutation
Holt-oram syndrome
Congenital heart disease
Biology (General)
QH301-705.5
Biochemistry
QD415-436
spellingShingle TBX5
SNP
Mutation
Holt-oram syndrome
Congenital heart disease
Biology (General)
QH301-705.5
Biochemistry
QD415-436
A.M.U.B. Mahfuz
Md. Arif Khan
Promita Deb
Sharmin Jahan Ansary
Rownak Jahan
Identification of deleterious single nucleotide polymorphism (SNP)s in the human TBX5 gene & prediction of their structural & functional consequences: An in silico approach
description T-box transcription factor 5 gene (TBX5) encodes the transcription factor TBX5, which plays a crucial role in the development of heart and upper limbs. Damaging single nucleotide variants in this gene alter the protein structure, disturb the functions of TBX5, and ultimately cause Holt-Oram Syndrome (HOS). By analyzing the available single nucleotide polymorphism information in the dbSNP database, this study was designed to identify the most deleterious TBX5 SNPs through in silico approaches and predict their structural and functional consequences.Fifty-eight missense substitutions were found damaging by sequence homology-based tools: SIFT and PROVEAN, and structure homology-based tool PolyPhen-2. Various disease association meta-predictors further scrutinized these SNPs. Additionally, conservation profile of the amino acid residues, their surface accessibility, stability, and structural integrity of the native protein upon mutations were assessed. From these analyses, finally 5 SNPs were detected as the most damaging ones: [rs1565941579 (P85S), rs1269970792 (W121R), rs772248871 (V153D), rs769113870 (E208D), and rs1318021626 (I222N)]. Analyses of stop-lost, nonsense, UTR, and splice site SNPs were also conducted.Through integrative bioinformatics analyses, this study has identified the SNPs that are deleterious to the TBX5 protein structure and have the potential to cause HOS. Further wet-lab experiments can validate these findings.
format article
author A.M.U.B. Mahfuz
Md. Arif Khan
Promita Deb
Sharmin Jahan Ansary
Rownak Jahan
author_facet A.M.U.B. Mahfuz
Md. Arif Khan
Promita Deb
Sharmin Jahan Ansary
Rownak Jahan
author_sort A.M.U.B. Mahfuz
title Identification of deleterious single nucleotide polymorphism (SNP)s in the human TBX5 gene & prediction of their structural & functional consequences: An in silico approach
title_short Identification of deleterious single nucleotide polymorphism (SNP)s in the human TBX5 gene & prediction of their structural & functional consequences: An in silico approach
title_full Identification of deleterious single nucleotide polymorphism (SNP)s in the human TBX5 gene & prediction of their structural & functional consequences: An in silico approach
title_fullStr Identification of deleterious single nucleotide polymorphism (SNP)s in the human TBX5 gene & prediction of their structural & functional consequences: An in silico approach
title_full_unstemmed Identification of deleterious single nucleotide polymorphism (SNP)s in the human TBX5 gene & prediction of their structural & functional consequences: An in silico approach
title_sort identification of deleterious single nucleotide polymorphism (snp)s in the human tbx5 gene & prediction of their structural & functional consequences: an in silico approach
publisher Elsevier
publishDate 2021
url https://doaj.org/article/fc252c2c71a2400e93bca9950f1e01a4
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AT mdarifkhan identificationofdeleterioussinglenucleotidepolymorphismsnpsinthehumantbx5geneamppredictionoftheirstructuralampfunctionalconsequencesaninsilicoapproach
AT promitadeb identificationofdeleterioussinglenucleotidepolymorphismsnpsinthehumantbx5geneamppredictionoftheirstructuralampfunctionalconsequencesaninsilicoapproach
AT sharminjahanansary identificationofdeleterioussinglenucleotidepolymorphismsnpsinthehumantbx5geneamppredictionoftheirstructuralampfunctionalconsequencesaninsilicoapproach
AT rownakjahan identificationofdeleterioussinglenucleotidepolymorphismsnpsinthehumantbx5geneamppredictionoftheirstructuralampfunctionalconsequencesaninsilicoapproach
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