{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T21:04:58Z","timestamp":1791839098409,"version":"4.3.4"},"reference-count":43,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T00:00:00Z","timestamp":1779321600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009392","name":"Prince Sattam bin Abdulaziz University","doi-asserted-by":"publisher","award":["2025\/03\/34494"],"award-info":[{"award-number":["2025\/03\/34494"]}],"id":[{"id":"10.13039\/100009392","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      The Myelin Basic Protein (MBP) gene is essential for myelin sheath formation in the central nervous system. Coding and noncoding single-nucleotide polymorphisms (SNPs) can impair the protein structure and function, contributing to demyelinating diseases exemplified by multiple sclerosis. This study aimed to assess the impact of SNPs in the\n                      <jats:italic>MBP<\/jats:italic>\n                      gene on protein structure and function.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We employed a comprehensive approach to investigate the impact of both noncoding and coding SNPs of the\n                      <jats:italic>MBP<\/jats:italic>\n                      gene. Initially, we utilized RegulomeDB to assess the regulatory roles of SNPs located in the 3\u2032 untranslated regions (3\u2032 UTRs). Subsequently, we examined the influence of the 3\u2019 UTR SNPs on microRNA (miRNA) binding sites using PolymiRTS. Furthermore, we analyzed the functional 3\u2032 UTR SNPs using RNAfold to evaluate their impact on RNA structure. To predict deleterious nonsynonymous SNPs (nsSNPs), various bioinformatics tools, including SIFT, PolyPhen-2, PROVEAN, META-SNP, ESNPs&amp;GO, PANTHER, and AlphaMissense, were employed. Protein stability was assessed using I-Mutant2.0, MUpro, and DDMut. Structural modeling was performed with AlphaFold, and both wild-type and mutant proteins were visualized in UCSF ChimeraX. Conservation analysis was conducted using the ConSurf tool, and protein interaction networks were explored using the STRING database.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Eight noncoding SNPs were identified as potential regulatory SNPs, affecting the miRNA binding sites. Moreover, three nsSNPs, rs1971676214 (D173E), rs1242552448 (D173H), and rs772570115 (G176W), were consistently predicted to be pathogenic and to destabilize the protein structure. These variants were located in highly conserved sites and disrupted hydrogen bonds. STRING analysis revealed interactions between MBP and other myelin-related, immune, and signaling proteins, linking it to CNS and autoimmune pathways.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This study identified eight noncoding 3\u2032 UTR SNPs and three potentially pathogenic nsSNPs that may compromise gene expression and protein structure and function, respectively, offering insight into genetic mechanisms of demyelination.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0347598","type":"journal-article","created":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T17:27:51Z","timestamp":1779384471000},"page":"e0347598","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["Decoding the genetic basis of demyelination: Prediction of potential pathogenic coding and regulatory noncoding MBP SNPs in multiple sclerosis"],"prefix":"10.1371","volume":"21","author":[{"given":"Arwa Ibrahim","family":"Alwabran","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ghalia Mahfod","family":"Aldoseri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ghanem Mahfod","family":"Aldoseri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samah O.","family":"Mohager","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mobarak Mahfod","family":"Aldoseri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-6081-2615","authenticated-orcid":true,"given":"Ebtihal","family":"Kamal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,5,21]]},"reference":[{"issue":"17","key":"pone.0347598.ref001","doi-asserted-by":"crossref","first-page":"1945","DOI":"10.1007\/s00018-006-6094-7","article-title":"Myelin basic protein: a multifunctional protein","volume":"63","author":"JM Boggs","year":"2006","journal-title":"Cell Mol Life Sci"},{"issue":"7","key":"pone.0347598.ref002","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1016\/j.micron.2004.04.005","article-title":"Myelin basic protein-diverse conformational states of an intrinsically unstructured protein and its roles in myelin assembly and multiple sclerosis","volume":"35","author":"G Harauz","year":"2004","journal-title":"Micron"},{"issue":"20","key":"pone.0347598.ref003","doi-asserted-by":"crossref","first-page":"6663","DOI":"10.1523\/JNEUROSCI.5806-08.2009","article-title":"Golli myelin basic proteins regulate oligodendroglial progenitor cell migration through voltage-gated Ca2+ influx","volume":"29","author":"PM Paez","year":"2009","journal-title":"J Neurosci"},{"issue":"5","key":"pone.0347598.ref004","doi-asserted-by":"crossref","first-page":"1114","DOI":"10.1172\/JCI119622","article-title":"Recognition of the immunodominant myelin basic protein peptide by autoantibodies and HLA-DR2-restricted T cell clones from multiple sclerosis patients. 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