Nonsynonymous variations of ion channel-related genes as risk factors in epilepsy

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dc.contributor.authorBiterge Süt, Burcu
dc.contributor.authorSoytürk, Hayriye
dc.date.accessioned2024-11-07T10:39:56Z
dc.date.available2024-11-07T10:39:56Z
dc.date.issued2021
dc.departmentNiğde Ömer Halisdemir Üniversitesi
dc.description.abstractRecurrent seizures are characteristic to epilepsy, which often arise due to increased electrical activity. Ligand-gated ion channels are considered as key factors in epilepsy as they regulate and maintain neuronal membrane potential via regulating ion transportation. Therefore, this study aims to identify ion channel-related single nucleotide variations that are considered as risk factors in epilepsy and determine their potential effects on pathogenicity, protein stability and structure using in silico methods. For this purpose, ion channel-related mutations linked with epilepsy were retrieved from ClinVar. Pathogenicity scores and protein stability were predicted using FATHMM-XF and MUpro, respectively. Structural alterations were determined via HOPE server. We identified 17 epilepsy-related missense mutations, 11 of which were in ion channel-related genes. Nonsynonymous substitutions of p.E177A, p.D219N, p.A322D, p.R577Q, p.E282K, p.V831M and p.R1072C were determined as pathogenic, while all mutations resulted in varying degrees of decrease in overall protein stability. Furthermore, all variants were annotated with risk for disease and introduction of distinct side chains caused differences in size, charge and hydrophobicity, as well as contact with other proteins and ligands. In conclusion, mutations in ion channel-related genes were previously identified in several genetic association studies while their functional annotations were not addressed. The results of this study provide a functional explanation to the pathogenic effects of ion channel-related gene mutations that are considered as risk factors in epilepsy. © 2021 Ondokuz Mayis Universitesi. All rights reserved.
dc.identifier.doi10.52142/omujecm.38.3.15
dc.identifier.endpage293
dc.identifier.issn1309-4483
dc.identifier.issue3
dc.identifier.scopus2-s2.0-85105338473
dc.identifier.scopusqualityQ4
dc.identifier.startpage288
dc.identifier.urihttps://doi.org/10.52142/omujecm.38.3.15
dc.identifier.urihttps://hdl.handle.net/11480/11312
dc.identifier.volume38
dc.indekslendigikaynakScopus
dc.language.isoen
dc.publisherOndokuz Mayis Universitesi
dc.relation.ispartofJournal of Experimental and Clinical Medicine (Turkey)
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/openAccess
dc.snmzKA_20241106
dc.subjectEpilepsy
dc.subjectIon channels
dc.subjectMissense mutation
dc.subjectRisk factor
dc.titleNonsynonymous variations of ion channel-related genes as risk factors in epilepsy
dc.typeArticle

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