{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T19:05:35Z","timestamp":1770231935001,"version":"3.49.0"},"reference-count":56,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T00:00:00Z","timestamp":1770163200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010221","name":"Higher Education Commission, Pakistan","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100010221","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Bioinform."],"abstract":"\n Introduction<\/jats:title>\n Oral squamous cell carcinoma (OSCC) is a prevalent malignancy characterized by aggressive behavior, poor prognosis, and limited therapeutic options. Mutations in the NIMA-related kinase (NEK) family are increasingly implicated in tumorigenesis across various cancers. However, their contributions to OSCC pathogenesis remain largely unexplored.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n Here, we employed whole-exome sequencing (WES) of formalin-fixed paraffin-embedded (FFPE) tissue blocks from 31 OSCC tumors and 9 adjacent paired normal samples derived from patients of Khyber Pakhtunkhwa (KP), Pakistan, to systematically profile\n NEK<\/jats:italic>\n gene alterations. Subsequent\n in-silico<\/jats:italic>\n analyses were performed to evaluate the structural and functional consequences of the identified mutations.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n We identified 46 mutations overall (78.3% (36\/46) somatic, 21.7% (10\/46) germline), consisting of 82.6% (38\/46) non-synonymous single-nucleotide variants (SNVs), 10.9% (5\/46) frameshift deletions, 2.2% (1\/26) non-frameshift deletions, and 4.3% (2\/46) stop-gain mutations; notably, 10.9% (5\/46) represented novel variants (not reported previously). NEK1 displayed the highest mutation frequency, followed by\n NEK10, NEK5, NEK11, NEK2<\/jats:italic>\n , and\n NEK3<\/jats:italic>\n . ISPRED-SEQ classified 37.0% (17\/46) of mutations as residing at protein-protein interaction interfaces, indicating potential functional relevance, with several mutations including\n NEK1p.D409Y, NEK1p.N643K, NEK9 p.H174Y, NEK10 p.R275C<\/jats:italic>\n , and\n NEK10 p.E596K<\/jats:italic>\n predicted to be deleterious and destabilizing by multiple tools, occurring at conserved residues and altering structural stability via molecular dynamics simulations. Clinically,\n NEK4<\/jats:italic>\n mutations were significantly associated with tumor site (P=0.02),\n NEK9<\/jats:italic>\n with tobacco exposure (P=0.01), and\n NEK10<\/jats:italic>\n with improved overall survival (P=0.01). Mutations including\n NEK11p.E347V<\/jats:italic>\n (31\/31),\n NEK9p.R429H<\/jats:italic>\n (23\/31),\n NEK10p.L513S<\/jats:italic>\n (15\/31),\n NEK4p.P136A<\/jats:italic>\n (7\/31),\n NEK5p.K255Q<\/jats:italic>\n (6\/31) and\n NEK1 p.E650G<\/jats:italic>\n (5\/31) were found to be recurring mutations and can be validated further in large-scale studies for biomarker applicability.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n Collectively, these findings suggest\n NEK<\/jats:italic>\n mutations as candidate drivers of OSCC pathogenesis, underscoring their potential as prognostic biomarkers and therapeutic targets, particularly in tobacco-associated disease.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.3389\/fbinf.2025.1750649","type":"journal-article","created":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T06:46:06Z","timestamp":1770187566000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Mutational insights and in silico characterization of NEK family kinases in OSCC patients from the Pakistani population"],"prefix":"10.3389","volume":"5","author":[{"given":"Fouzia","family":"Nawab","sequence":"first","affiliation":[{"name":"Institute of Basic Medical Sciences, Khyber Medical University","place":["Peshawar, Pakistan"]}]},{"given":"Wafa","family":"Naeem","sequence":"additional","affiliation":[{"name":"Institute of Basic Medical Sciences, Khyber Medical University","place":["Peshawar, Pakistan"]}]},{"given":"Sadia","family":"Fatima","sequence":"additional","affiliation":[{"name":"Institute of Basic Medical Sciences, Khyber Medical University","place":["Peshawar, 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