ORIGINAL RESEARCH article
Front. Bioinform.
Sec. Genomic Analysis
Volume 5 - 2025 | doi: 10.3389/fbinf.2025.1680578
This article is part of the Research TopicDecoding Genomes: Bioinformatics Pipelines for Functional InsightsView all 3 articles
Functional and Structural impacts of Oncogenic Missense Variants on Human Polo-Like Kinase 1 Protein
Provisionally accepted
Venkatraman Manickam1,2*
Gayatri Munieswaran2- 1VIT University, Vellore, India
- 2Vellore Institute of Technology, Vellore, India
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
Introduction: The polo-like kinase 1 (PLK1), a master key mitotic regulator, is frequently expressed in various types of cancers and associated with poor prognosis. The missense mutations in PLK1 may compromise its structural integrity and functional interactions, contributing to tumorigenesis. Methods: This study utilized a comprehensive computational pipeline to identify deleterious missense variants across multiple cancers. 207 non-synonymous single nucleotide polymorphisms (nsSNPs) were retrieved from cBioPortal, and 11 high-risk variants were prioritized using functional and structural prediction tools, such as SIFT, PolyPhen-2, I-mutant 2.0, and so on. Prognostic prevalence was evaluated via Kaplan-Meier survival analysis, and functional networks were explored using STRING. The structural dynamics of modeled mutations were analyzed through molecular dynamic simulations over 100 ns. Results: The kinase domain mutations such as L244F, R293C, and R293H and polo-box domain mutations such as A520T were found to cause deviations in structural stability, flexibility, solvent exposure, and compactness compared to wild-type. Further, PLK1 overexpression correlated with poor overall survival of patient outcomes in many types of cancers, including breast, liver, lung, kidney, and pancreatic cancers. Protein-protein interaction revealed PLK1's involvement in oncogenic pathways. Discussion: The study highlights the structural and functional implications of oncogenic PLK1 mutations, emphasizing their role in cancer progression. Integrating predictive and dynamic exploration approaches facilitates prioritization of variants with potential clinical relevance. Conclusion: The nsSNPs in PLK1 may perturb conformational stability and functions of the protein. Further experimental validation and discovery of novel inhibitors might develop mutation-specific interventions in precision oncology. Keywords: PLK1, nsSNPs, cancer, biomarker, molecular dynamic simulation
Keywords: plk1, nsSNPs, Cancer, biomarker, Molecular dynamic simulation
Received: 06 Aug 2025; Accepted: 20 Oct 2025.
Copyright: © 2025 Manickam and Munieswaran. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Venkatraman Manickam, venkatraman.m@vit.ac.in
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.