{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T20:22:40Z","timestamp":1789503760407,"version":"build-2803163510"},"reference-count":95,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2024,2,23]],"date-time":"2024-02-23T00:00:00Z","timestamp":1708646400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Single nucleotide polymorphisms are the most common form of DNA alterations at the level of a single nucleotide in the genomic sequence. Genome-wide association studies (GWAS) were carried to identify potential risk genes or genomic regions by screening for SNPs associated with disease. Recent studies have shown that <jats:italic>SCN9A<\/jats:italic> comprises the NaV1.7 subunit, Na<jats:sup>+<\/jats:sup> channels have a gene encoding of 1988 amino acids arranged into 4 domains, all with 6 transmembrane regions, and are mainly found in dorsal root ganglion (DRG) neurons and sympathetic ganglion neurons. Multiple forms of acute hypersensitivity conditions, such as primary erythermalgia, congenital analgesia, and paroxysmal pain syndrome have been linked to polymorphisms in the <jats:italic>SCN9A<\/jats:italic> gene. Under this study, we utilized a variety of computational tools to explore out nsSNPs that are potentially damaging to heath by modifying the structure or activity of the <jats:italic>SCN9A<\/jats:italic> protein. Over 14 potentially damaging and disease-causing nsSNPs (E1889D, L1802P, F1782V, D1778N, C1370Y, V1311M, Y1248H, F1237L, M936V, I929T, V877E, D743Y, C710W, D623H) were identified by a variety of algorithms, including SNPnexus, SNAP-2, PANTHER, PhD-SNP, SNP &amp; GO, I-Mutant, and ConSurf. Homology modeling, structure validation, and protein-ligand interactions also were performed to confirm 5 notable substitutions (L1802P, F1782V, D1778N, V1311M, and M936V). Such nsSNPs may become the center of further studies into a variety of disorders brought by <jats:italic>SCN9A<\/jats:italic> dysfunction. Using <jats:italic>in-silico<\/jats:italic> strategies for assessing <jats:italic>SCN9A<\/jats:italic> genetic variations will aid in organizing large-scale investigations and developing targeted therapeutics for disorders linked to these variations.<\/jats:p>","DOI":"10.1371\/journal.pone.0297367","type":"journal-article","created":{"date-parts":[[2024,2,23]],"date-time":"2024-02-23T18:50:05Z","timestamp":1708714205000},"page":"e0297367","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":9,"title":["Identification and In-Silico study of non-synonymous functional SNPs in the human SCN9A gene"],"prefix":"10.1371","volume":"19","author":[{"given":"Sana","family":"Waheed","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kainat","family":"Ramzan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3921-8838","authenticated-orcid":true,"given":"Sibtain","family":"Ahmad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2653-402X","authenticated-orcid":true,"given":"Muhammad Saleem","family":"Khan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad","family":"Wajid","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hayat","family":"Ullah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali","family":"Umar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0473-889X","authenticated-orcid":true,"given":"Rashid","family":"Iqbal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riaz","family":"Ullah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed","family":"Bari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,2,23]]},"reference":[{"key":"pone.0297367.ref001","article-title":"Genetic polymorphisms","author":"N.R. 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