In Silico Functional and Structural Analysis of Non-synonymous Single Nucleotide Polymorphisms (nsSNPs) in Human Paired Box 4 Gene
In human genome, members of Paired box (PAX) transcription factor family are highly sequence-specific DNA-binding proteins. Among PAX gene family members, PAX4 gene has significant role in growth, proliferation, differentiation, and insulin secretion of pancreatic β-cells. Single nucleotide polymorp...
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| creator | Kamal, Md. Mostafa Islam, Md. Numan Rabby, Md. Golam Zahid, Md. Ashrafuzzaman Hasan, Md. Mahmudul |
| description | In human genome, members of Paired box (PAX) transcription factor family are highly sequence-specific DNA-binding proteins. Among
PAX
gene family members,
PAX4
gene has significant role in growth, proliferation, differentiation, and insulin secretion of pancreatic β-cells. Single nucleotide polymorphisms (SNPs) in
PAX4
gene progress in the pathogenesis of various human diseases. Hence, the molecular mechanism of how these SNPs in
PAX4
gene significantly progress diseases pathogenesis needs to be elucidated. For the reason, a series of bioinformatic analyzes were done to identify the SNPs of
PAX4
gene that contribute in diseases pathogenesis. From the analyzes, 4145 SNPs (rsIDs) in
PAX4
gene were obtained, where, 362 missense (8.73%), 169 synonymous (4.08%), and 2323 intron variants (56.04%). The rest SNPs were unspecified. Among the 362 missense variants, 118 nsSNPs were found as deleterious in SIFT analysis. Among those, 25 nsSNPs were most probably damaging and 23 were deleterious as observed in PolyPhen-2 and PROVEAN analyzes, respectively. Following all analyzes, 14 nsSNPs (rs149708455, rs115887120, rs147279315, rs35155575, rs370095957, rs373939873, rs145468905, rs121917718, rs2233580, rs3824004, rs372751660, rs369459316, rs375472849, rs372497946) were common and observed as deleterious, probably damaging, affective and diseases associated. Following structural analyzes, 11 nsSNPs guided proteins were found as most unstable and highly conserved. Among these, R20W, R39Q, R45Q, R60H, G65D, and A223D mutated proteins were highly harmful. Hence, the results from above-mentioned integrated comprehensive bioinformatic analyzes guide how different nsSNPs in
PAX4
gene alter structural and functional characteristics of the protein that might progress diseases pathogenesis in human including type 2 diabetes. |
| doi_str_mv | 10.1007/s10528-023-10589-1 |
| format | Article |
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PAX
gene family members,
PAX4
gene has significant role in growth, proliferation, differentiation, and insulin secretion of pancreatic β-cells. Single nucleotide polymorphisms (SNPs) in
PAX4
gene progress in the pathogenesis of various human diseases. Hence, the molecular mechanism of how these SNPs in
PAX4
gene significantly progress diseases pathogenesis needs to be elucidated. For the reason, a series of bioinformatic analyzes were done to identify the SNPs of
PAX4
gene that contribute in diseases pathogenesis. From the analyzes, 4145 SNPs (rsIDs) in
PAX4
gene were obtained, where, 362 missense (8.73%), 169 synonymous (4.08%), and 2323 intron variants (56.04%). The rest SNPs were unspecified. Among the 362 missense variants, 118 nsSNPs were found as deleterious in SIFT analysis. Among those, 25 nsSNPs were most probably damaging and 23 were deleterious as observed in PolyPhen-2 and PROVEAN analyzes, respectively. Following all analyzes, 14 nsSNPs (rs149708455, rs115887120, rs147279315, rs35155575, rs370095957, rs373939873, rs145468905, rs121917718, rs2233580, rs3824004, rs372751660, rs369459316, rs375472849, rs372497946) were common and observed as deleterious, probably damaging, affective and diseases associated. Following structural analyzes, 11 nsSNPs guided proteins were found as most unstable and highly conserved. Among these, R20W, R39Q, R45Q, R60H, G65D, and A223D mutated proteins were highly harmful. Hence, the results from above-mentioned integrated comprehensive bioinformatic analyzes guide how different nsSNPs in
PAX4
gene alter structural and functional characteristics of the protein that might progress diseases pathogenesis in human including type 2 diabetes.</description><identifier>ISSN: 0006-2928</identifier><identifier>ISSN: 1573-4927</identifier><identifier>EISSN: 1573-4927</identifier><identifier>DOI: 10.1007/s10528-023-10589-1</identifier><identifier>PMID: 38062275</identifier><language>eng</language><publisher>New York: Springer US</publisher><subject>Beta cells ; Biochemistry ; Biomedical and Life Sciences ; Biomedicine ; Cell differentiation ; Cell proliferation ; Computational Biology - methods ; Computer Simulation ; Diabetes mellitus (non-insulin dependent) ; DNA-binding protein ; Genetic Predisposition to Disease ; Homeodomain Proteins - genetics ; Human Genetics ; Humans ; Insulin secretion ; Medical Microbiology ; Molecular modelling ; Mutation, Missense ; Nucleotide sequence ; Nucleotides ; Original Article ; Paired Box Transcription Factors - genetics ; Pathogenesis ; Pax gene ; Polymorphism, Single Nucleotide ; Proteins ; Single-nucleotide polymorphism ; Structural analysis ; Structure-function relationships ; Zoology</subject><ispartof>Biochemical genetics, 2024-08, Vol.62 (4), p.2975-2998</ispartof><rights>The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.</rights><rights>2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c375t-b4fca8cf471c613dc1a4ee4f5b91aac2a0baf538d0c39ff7d73cfef149f627463</citedby><cites>FETCH-LOGICAL-c375t-b4fca8cf471c613dc1a4ee4f5b91aac2a0baf538d0c39ff7d73cfef149f627463</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s10528-023-10589-1$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s10528-023-10589-1$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>315,781,785,27929,27930,41493,42562,51324</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38062275$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kamal, Md. Mostafa</creatorcontrib><creatorcontrib>Islam, Md. Numan</creatorcontrib><creatorcontrib>Rabby, Md. Golam</creatorcontrib><creatorcontrib>Zahid, Md. Ashrafuzzaman</creatorcontrib><creatorcontrib>Hasan, Md. Mahmudul</creatorcontrib><title>In Silico Functional and Structural Analysis of Non-synonymous Single Nucleotide Polymorphisms (nsSNPs) in Human Paired Box 4 Gene</title><title>Biochemical genetics</title><addtitle>Biochem Genet</addtitle><addtitle>Biochem Genet</addtitle><description>In human genome, members of Paired box (PAX) transcription factor family are highly sequence-specific DNA-binding proteins. Among
PAX
gene family members,
PAX4
gene has significant role in growth, proliferation, differentiation, and insulin secretion of pancreatic β-cells. Single nucleotide polymorphisms (SNPs) in
PAX4
gene progress in the pathogenesis of various human diseases. Hence, the molecular mechanism of how these SNPs in
PAX4
gene significantly progress diseases pathogenesis needs to be elucidated. For the reason, a series of bioinformatic analyzes were done to identify the SNPs of
PAX4
gene that contribute in diseases pathogenesis. From the analyzes, 4145 SNPs (rsIDs) in
PAX4
gene were obtained, where, 362 missense (8.73%), 169 synonymous (4.08%), and 2323 intron variants (56.04%). The rest SNPs were unspecified. Among the 362 missense variants, 118 nsSNPs were found as deleterious in SIFT analysis. Among those, 25 nsSNPs were most probably damaging and 23 were deleterious as observed in PolyPhen-2 and PROVEAN analyzes, respectively. Following all analyzes, 14 nsSNPs (rs149708455, rs115887120, rs147279315, rs35155575, rs370095957, rs373939873, rs145468905, rs121917718, rs2233580, rs3824004, rs372751660, rs369459316, rs375472849, rs372497946) were common and observed as deleterious, probably damaging, affective and diseases associated. Following structural analyzes, 11 nsSNPs guided proteins were found as most unstable and highly conserved. Among these, R20W, R39Q, R45Q, R60H, G65D, and A223D mutated proteins were highly harmful. Hence, the results from above-mentioned integrated comprehensive bioinformatic analyzes guide how different nsSNPs in
PAX4
gene alter structural and functional characteristics of the protein that might progress diseases pathogenesis in human including type 2 diabetes.</description><subject>Beta cells</subject><subject>Biochemistry</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Cell differentiation</subject><subject>Cell proliferation</subject><subject>Computational Biology - methods</subject><subject>Computer Simulation</subject><subject>Diabetes mellitus (non-insulin dependent)</subject><subject>DNA-binding protein</subject><subject>Genetic Predisposition to Disease</subject><subject>Homeodomain Proteins - genetics</subject><subject>Human Genetics</subject><subject>Humans</subject><subject>Insulin secretion</subject><subject>Medical Microbiology</subject><subject>Molecular modelling</subject><subject>Mutation, Missense</subject><subject>Nucleotide sequence</subject><subject>Nucleotides</subject><subject>Original Article</subject><subject>Paired Box Transcription Factors - genetics</subject><subject>Pathogenesis</subject><subject>Pax gene</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Proteins</subject><subject>Single-nucleotide polymorphism</subject><subject>Structural analysis</subject><subject>Structure-function relationships</subject><subject>Zoology</subject><issn>0006-2928</issn><issn>1573-4927</issn><issn>1573-4927</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kUuPFCEUhYnROO3oH3BhSNyMC5RXFcVynDiPZNJ20romNAUjkypouUVib_3loj1q4sIVXO53Drn3IPSS0beMUvUOGO34QCgXpN0GTdgjtGKdEkRqrh6jFaW0J1zz4QQ9A7hvpaZSPkUnYqA956pboe83CW_jFF3GlzW5JeZkJ2zTiLdLqW6ppZXn7e0AEXAOeJ0TgUPK6TDnCk2b7iaP19VNPi9x9HiTp9Yq-y8RZsBnCbbrDbzBMeHrOtuENzYWP-L3-RuW-Mon_xw9CXYC_-LhPEWfLz98urgmtx-vbi7Ob4kTqlvITgZnBxekYq5nYnTMSu9l6HaaWeu4pTsbOjGM1AkdghqVcMEHJnXouZK9OEVnR999yV-rh8XMEZyfJpt8G8VwTbnuOVOioa__Qe9zLW0LYAQdetYophvFj5QrGaD4YPYlzrYcDKPmZ0LmmJBpCZlfCRnWRK8erOtu9uMfye9IGiCOALRWuvPl79__sf0BzMWc0g</recordid><startdate>202408</startdate><enddate>202408</enddate><creator>Kamal, Md. Mostafa</creator><creator>Islam, Md. Numan</creator><creator>Rabby, Md. Golam</creator><creator>Zahid, Md. Ashrafuzzaman</creator><creator>Hasan, Md. Mahmudul</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>7SS</scope><scope>7TK</scope><scope>7U7</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>K9.</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>202408</creationdate><title>In Silico Functional and Structural Analysis of Non-synonymous Single Nucleotide Polymorphisms (nsSNPs) in Human Paired Box 4 Gene</title><author>Kamal, Md. Mostafa ; Islam, Md. Numan ; Rabby, Md. Golam ; Zahid, Md. Ashrafuzzaman ; Hasan, Md. Mahmudul</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c375t-b4fca8cf471c613dc1a4ee4f5b91aac2a0baf538d0c39ff7d73cfef149f627463</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Beta cells</topic><topic>Biochemistry</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Cell differentiation</topic><topic>Cell proliferation</topic><topic>Computational Biology - methods</topic><topic>Computer Simulation</topic><topic>Diabetes mellitus (non-insulin dependent)</topic><topic>DNA-binding protein</topic><topic>Genetic Predisposition to Disease</topic><topic>Homeodomain Proteins - genetics</topic><topic>Human Genetics</topic><topic>Humans</topic><topic>Insulin secretion</topic><topic>Medical Microbiology</topic><topic>Molecular modelling</topic><topic>Mutation, Missense</topic><topic>Nucleotide sequence</topic><topic>Nucleotides</topic><topic>Original Article</topic><topic>Paired Box Transcription Factors - genetics</topic><topic>Pathogenesis</topic><topic>Pax gene</topic><topic>Polymorphism, Single Nucleotide</topic><topic>Proteins</topic><topic>Single-nucleotide polymorphism</topic><topic>Structural analysis</topic><topic>Structure-function relationships</topic><topic>Zoology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kamal, Md. Mostafa</creatorcontrib><creatorcontrib>Islam, Md. Numan</creatorcontrib><creatorcontrib>Rabby, Md. Golam</creatorcontrib><creatorcontrib>Zahid, Md. Ashrafuzzaman</creatorcontrib><creatorcontrib>Hasan, Md. Mahmudul</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Neurosciences Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</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>Kamal, Md. Mostafa</au><au>Islam, Md. Numan</au><au>Rabby, Md. Golam</au><au>Zahid, Md. Ashrafuzzaman</au><au>Hasan, Md. Mahmudul</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>In Silico Functional and Structural Analysis of Non-synonymous Single Nucleotide Polymorphisms (nsSNPs) in Human Paired Box 4 Gene</atitle><jtitle>Biochemical genetics</jtitle><stitle>Biochem Genet</stitle><addtitle>Biochem Genet</addtitle><date>2024-08</date><risdate>2024</risdate><volume>62</volume><issue>4</issue><spage>2975</spage><epage>2998</epage><pages>2975-2998</pages><issn>0006-2928</issn><issn>1573-4927</issn><eissn>1573-4927</eissn><abstract>In human genome, members of Paired box (PAX) transcription factor family are highly sequence-specific DNA-binding proteins. Among
PAX
gene family members,
PAX4
gene has significant role in growth, proliferation, differentiation, and insulin secretion of pancreatic β-cells. Single nucleotide polymorphisms (SNPs) in
PAX4
gene progress in the pathogenesis of various human diseases. Hence, the molecular mechanism of how these SNPs in
PAX4
gene significantly progress diseases pathogenesis needs to be elucidated. For the reason, a series of bioinformatic analyzes were done to identify the SNPs of
PAX4
gene that contribute in diseases pathogenesis. From the analyzes, 4145 SNPs (rsIDs) in
PAX4
gene were obtained, where, 362 missense (8.73%), 169 synonymous (4.08%), and 2323 intron variants (56.04%). The rest SNPs were unspecified. Among the 362 missense variants, 118 nsSNPs were found as deleterious in SIFT analysis. Among those, 25 nsSNPs were most probably damaging and 23 were deleterious as observed in PolyPhen-2 and PROVEAN analyzes, respectively. Following all analyzes, 14 nsSNPs (rs149708455, rs115887120, rs147279315, rs35155575, rs370095957, rs373939873, rs145468905, rs121917718, rs2233580, rs3824004, rs372751660, rs369459316, rs375472849, rs372497946) were common and observed as deleterious, probably damaging, affective and diseases associated. Following structural analyzes, 11 nsSNPs guided proteins were found as most unstable and highly conserved. Among these, R20W, R39Q, R45Q, R60H, G65D, and A223D mutated proteins were highly harmful. Hence, the results from above-mentioned integrated comprehensive bioinformatic analyzes guide how different nsSNPs in
PAX4
gene alter structural and functional characteristics of the protein that might progress diseases pathogenesis in human including type 2 diabetes.</abstract><cop>New York</cop><pub>Springer US</pub><pmid>38062275</pmid><doi>10.1007/s10528-023-10589-1</doi><tpages>24</tpages></addata></record> |
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| subjects | Beta cells Biochemistry Biomedical and Life Sciences Biomedicine Cell differentiation Cell proliferation Computational Biology - methods Computer Simulation Diabetes mellitus (non-insulin dependent) DNA-binding protein Genetic Predisposition to Disease Homeodomain Proteins - genetics Human Genetics Humans Insulin secretion Medical Microbiology Molecular modelling Mutation, Missense Nucleotide sequence Nucleotides Original Article Paired Box Transcription Factors - genetics Pathogenesis Pax gene Polymorphism, Single Nucleotide Proteins Single-nucleotide polymorphism Structural analysis Structure-function relationships Zoology |
| title | In Silico Functional and Structural Analysis of Non-synonymous Single Nucleotide Polymorphisms (nsSNPs) in Human Paired Box 4 Gene |
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