In-Silico Analyses of Nonsynonymous Variants in the BRCA1 Gene
BReast CAncer gene 1 ( BRCA1 )—a tumor suppressor gene plays an important role in the DNA repair mechanism. Several BRCA1 variants perturb its structure and function, including synonymous and nonsynonymous single nucleotide polymorphisms (SNPs). In the present study, we performed in-silico analyses...
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| Veröffentlicht in: | Biochemical genetics 2021-12, Vol.59 (6), p.1506-1526 |
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| creator | Arshad, Sidra Ishaque, Irfan Mumtaz, Sidra Rashid, Muhammad Usman Malkani, Naila |
| description | BReast CAncer gene 1 (
BRCA1
)—a tumor suppressor gene plays an important role in the DNA repair mechanism. Several
BRCA1
variants perturb its structure and function, including synonymous and nonsynonymous single nucleotide polymorphisms (SNPs). In the present study, we performed
in-silico
analyses of nonsynonymous SNPs (nsSNPs) of the
BRCA1
gene. In total, 122 nsSNPs were retrieved from the NCBI SNP database and
in-silico
analyses were performed using computational prediction tools: SIFT, PROVEAN, Mutation Taster, PolyPhen-2, MutPred, and ConSurf. Of these tools, SIFT, PROVEAN, and Mutation Taster predicted 61 out of 122 nsSNPs as “damaging”, based on structural homology analysis. PolyPhen-2 classified 22 nsSNPs as “probably damaging”. These nsSNPs were further analyzed by MutPred to predict basic molecular mechanisms of amino acid alteration. ConSurf analysis predicted eleven conserved amino acid residues with structural and functional consequences. We identified five amino acid residues in the RING finger domain (L22, C39, H41, C44, and C47) and two in the BRCT domain (P1771 and I1707) with the potential to deter the
BRCA1
protein function. This study provides insights into the effect of nsSNPs and amino acid substitutions in
BRCA1
. |
| doi_str_mv | 10.1007/s10528-021-10074-7 |
| format | Article |
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BRCA1
)—a tumor suppressor gene plays an important role in the DNA repair mechanism. Several
BRCA1
variants perturb its structure and function, including synonymous and nonsynonymous single nucleotide polymorphisms (SNPs). In the present study, we performed
in-silico
analyses of nonsynonymous SNPs (nsSNPs) of the
BRCA1
gene. In total, 122 nsSNPs were retrieved from the NCBI SNP database and
in-silico
analyses were performed using computational prediction tools: SIFT, PROVEAN, Mutation Taster, PolyPhen-2, MutPred, and ConSurf. Of these tools, SIFT, PROVEAN, and Mutation Taster predicted 61 out of 122 nsSNPs as “damaging”, based on structural homology analysis. PolyPhen-2 classified 22 nsSNPs as “probably damaging”. These nsSNPs were further analyzed by MutPred to predict basic molecular mechanisms of amino acid alteration. ConSurf analysis predicted eleven conserved amino acid residues with structural and functional consequences. We identified five amino acid residues in the RING finger domain (L22, C39, H41, C44, and C47) and two in the BRCT domain (P1771 and I1707) with the potential to deter the
BRCA1
protein function. This study provides insights into the effect of nsSNPs and amino acid substitutions in
BRCA1
.</description><identifier>ISSN: 0006-2928</identifier><identifier>EISSN: 1573-4927</identifier><identifier>DOI: 10.1007/s10528-021-10074-7</identifier><identifier>PMID: 33945048</identifier><language>eng</language><publisher>New York: Springer US</publisher><subject>Amino Acid Substitution ; Amino acids ; Biochemistry ; Biomedical and Life Sciences ; Biomedicine ; BRCA1 protein ; Breast cancer ; Computational Biology ; Computer applications ; DNA repair ; Domains ; Genes, BRCA1 ; Homology ; Human Genetics ; Medical Microbiology ; Molecular modelling ; Mutation ; Nucleotides ; Original Article ; Polymorphism, Single Nucleotide ; Residues ; Single-nucleotide polymorphism ; Software ; Structure-function relationships ; Tumor suppressor genes ; Tumors ; Zoology</subject><ispartof>Biochemical genetics, 2021-12, Vol.59 (6), p.1506-1526</ispartof><rights>The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2021</rights><rights>2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.</rights><rights>The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2021.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c375t-3d14c85de88776ca32ea6f4ae14c7560e36012b79262cf493d26c4b2cfa458943</citedby><cites>FETCH-LOGICAL-c375t-3d14c85de88776ca32ea6f4ae14c7560e36012b79262cf493d26c4b2cfa458943</cites><orcidid>0000-0001-6454-1525</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s10528-021-10074-7$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s10528-021-10074-7$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33945048$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Arshad, Sidra</creatorcontrib><creatorcontrib>Ishaque, Irfan</creatorcontrib><creatorcontrib>Mumtaz, Sidra</creatorcontrib><creatorcontrib>Rashid, Muhammad Usman</creatorcontrib><creatorcontrib>Malkani, Naila</creatorcontrib><title>In-Silico Analyses of Nonsynonymous Variants in the BRCA1 Gene</title><title>Biochemical genetics</title><addtitle>Biochem Genet</addtitle><addtitle>Biochem Genet</addtitle><description>BReast CAncer gene 1 (
BRCA1
)—a tumor suppressor gene plays an important role in the DNA repair mechanism. Several
BRCA1
variants perturb its structure and function, including synonymous and nonsynonymous single nucleotide polymorphisms (SNPs). In the present study, we performed
in-silico
analyses of nonsynonymous SNPs (nsSNPs) of the
BRCA1
gene. In total, 122 nsSNPs were retrieved from the NCBI SNP database and
in-silico
analyses were performed using computational prediction tools: SIFT, PROVEAN, Mutation Taster, PolyPhen-2, MutPred, and ConSurf. Of these tools, SIFT, PROVEAN, and Mutation Taster predicted 61 out of 122 nsSNPs as “damaging”, based on structural homology analysis. PolyPhen-2 classified 22 nsSNPs as “probably damaging”. These nsSNPs were further analyzed by MutPred to predict basic molecular mechanisms of amino acid alteration. ConSurf analysis predicted eleven conserved amino acid residues with structural and functional consequences. We identified five amino acid residues in the RING finger domain (L22, C39, H41, C44, and C47) and two in the BRCT domain (P1771 and I1707) with the potential to deter the
BRCA1
protein function. This study provides insights into the effect of nsSNPs and amino acid substitutions in
BRCA1
.</description><subject>Amino Acid Substitution</subject><subject>Amino acids</subject><subject>Biochemistry</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>BRCA1 protein</subject><subject>Breast cancer</subject><subject>Computational Biology</subject><subject>Computer applications</subject><subject>DNA repair</subject><subject>Domains</subject><subject>Genes, BRCA1</subject><subject>Homology</subject><subject>Human Genetics</subject><subject>Medical Microbiology</subject><subject>Molecular modelling</subject><subject>Mutation</subject><subject>Nucleotides</subject><subject>Original Article</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Residues</subject><subject>Single-nucleotide polymorphism</subject><subject>Software</subject><subject>Structure-function relationships</subject><subject>Tumor suppressor genes</subject><subject>Tumors</subject><subject>Zoology</subject><issn>0006-2928</issn><issn>1573-4927</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp9kDtPwzAUhS0EoqXwBxhQJBYWg992FqRSQamEQOK1Wq7jQKrUKXEy5N_jkAISA5N9fL97ru8B4Bijc4yQvAgYcaIgIhj2mkG5A8aYSwpZSuQuGCOEBCQpUSNwEMIqyhQxtg9GlKaMI6bG4HLh4VNRFrZKpt6UXXAhqfLkvvKh85Xv1lUbkldTF8Y3ISl80ry75OpxNsXJ3Hl3CPZyUwZ3tD0n4OXm-nl2C-8e5ovZ9A5aKnkDaYaZVTxzSkkprKHEGZEz4-Kz5AI5KhAmS5kSQWzOUpoRYdky3g3jKmV0As4G301dfbQuNHpdBOvK0ngXf6gJJ4T25j16-gddVW0dd-spJQSXQqlIkYGydRVC7XK9qYu1qTuNke7T1EO6Oqb7pZmWselka90u1y77afmOMwJ0AEIs-TdX_87-x_YTuOiB8w</recordid><startdate>20211201</startdate><enddate>20211201</enddate><creator>Arshad, Sidra</creator><creator>Ishaque, Irfan</creator><creator>Mumtaz, Sidra</creator><creator>Rashid, Muhammad Usman</creator><creator>Malkani, Naila</creator><general>Springer US</general><general>Springer Nature B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7SS</scope><scope>7TK</scope><scope>7U7</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8AO</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>RC3</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0001-6454-1525</orcidid></search><sort><creationdate>20211201</creationdate><title>In-Silico Analyses of Nonsynonymous Variants in the BRCA1 Gene</title><author>Arshad, Sidra ; Ishaque, Irfan ; Mumtaz, Sidra ; Rashid, Muhammad Usman ; Malkani, Naila</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c375t-3d14c85de88776ca32ea6f4ae14c7560e36012b79262cf493d26c4b2cfa458943</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Amino Acid Substitution</topic><topic>Amino acids</topic><topic>Biochemistry</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>BRCA1 protein</topic><topic>Breast cancer</topic><topic>Computational Biology</topic><topic>Computer applications</topic><topic>DNA repair</topic><topic>Domains</topic><topic>Genes, BRCA1</topic><topic>Homology</topic><topic>Human Genetics</topic><topic>Medical Microbiology</topic><topic>Molecular modelling</topic><topic>Mutation</topic><topic>Nucleotides</topic><topic>Original Article</topic><topic>Polymorphism, Single Nucleotide</topic><topic>Residues</topic><topic>Single-nucleotide polymorphism</topic><topic>Software</topic><topic>Structure-function relationships</topic><topic>Tumor suppressor genes</topic><topic>Tumors</topic><topic>Zoology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Arshad, Sidra</creatorcontrib><creatorcontrib>Ishaque, Irfan</creatorcontrib><creatorcontrib>Mumtaz, Sidra</creatorcontrib><creatorcontrib>Rashid, Muhammad Usman</creatorcontrib><creatorcontrib>Malkani, Naila</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Neurosciences Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Biochemical genetics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Arshad, Sidra</au><au>Ishaque, Irfan</au><au>Mumtaz, Sidra</au><au>Rashid, Muhammad Usman</au><au>Malkani, Naila</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>In-Silico Analyses of Nonsynonymous Variants in the BRCA1 Gene</atitle><jtitle>Biochemical genetics</jtitle><stitle>Biochem Genet</stitle><addtitle>Biochem Genet</addtitle><date>2021-12-01</date><risdate>2021</risdate><volume>59</volume><issue>6</issue><spage>1506</spage><epage>1526</epage><pages>1506-1526</pages><issn>0006-2928</issn><eissn>1573-4927</eissn><abstract>BReast CAncer gene 1 (
BRCA1
)—a tumor suppressor gene plays an important role in the DNA repair mechanism. Several
BRCA1
variants perturb its structure and function, including synonymous and nonsynonymous single nucleotide polymorphisms (SNPs). In the present study, we performed
in-silico
analyses of nonsynonymous SNPs (nsSNPs) of the
BRCA1
gene. In total, 122 nsSNPs were retrieved from the NCBI SNP database and
in-silico
analyses were performed using computational prediction tools: SIFT, PROVEAN, Mutation Taster, PolyPhen-2, MutPred, and ConSurf. Of these tools, SIFT, PROVEAN, and Mutation Taster predicted 61 out of 122 nsSNPs as “damaging”, based on structural homology analysis. PolyPhen-2 classified 22 nsSNPs as “probably damaging”. These nsSNPs were further analyzed by MutPred to predict basic molecular mechanisms of amino acid alteration. ConSurf analysis predicted eleven conserved amino acid residues with structural and functional consequences. We identified five amino acid residues in the RING finger domain (L22, C39, H41, C44, and C47) and two in the BRCT domain (P1771 and I1707) with the potential to deter the
BRCA1
protein function. This study provides insights into the effect of nsSNPs and amino acid substitutions in
BRCA1
.</abstract><cop>New York</cop><pub>Springer US</pub><pmid>33945048</pmid><doi>10.1007/s10528-021-10074-7</doi><tpages>21</tpages><orcidid>https://orcid.org/0000-0001-6454-1525</orcidid></addata></record> |
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| subjects | Amino Acid Substitution Amino acids Biochemistry Biomedical and Life Sciences Biomedicine BRCA1 protein Breast cancer Computational Biology Computer applications DNA repair Domains Genes, BRCA1 Homology Human Genetics Medical Microbiology Molecular modelling Mutation Nucleotides Original Article Polymorphism, Single Nucleotide Residues Single-nucleotide polymorphism Software Structure-function relationships Tumor suppressor genes Tumors Zoology |
| title | In-Silico Analyses of Nonsynonymous Variants in the BRCA1 Gene |
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