Abstract
The current study aimed to identify and analyze missense single nucleotide polymorphisms (SNPs) that can potentially cause mandibular prognathism. After reviewing the articles, 56 genes associated with mandibular prognathism were identified and their missense SNPs were retrieved from the NCBI website. Several web-based tools including CADD, PolyPhen-2, PROVEAN, SNAP2, PANTHER, FATHMM, and PON-P2 were used to filter out harmful SNPs. Additionally, ConSurf determined the level of evolutionary conservation at positions where SNPs occur. I-Mutant2 and MUpro predicted the effect of SNPs on protein stability. Furthermore, to investigate the structural and functional changes of proteins, HOPE and LOMETS tools were utilized. Based on predictions in at least four web-based tools, the results indicated that PLXNA2-rs4844658, DUSP6-rs2279574, and FBN3-rs33967815 are harmful. These SNPs are located at positions with variable or average conservation and have the potential to reduce the stability of their respective proteins. Moreover, they may impair protein activity by causing structural and functional changes. In this study, we identified PLXNA2-rs4844658, DUSP6-rs2279574, and FBN3-rs33967815 as potential risk factors for mandibular prognathism using several web-based tools. According to the possible roles of PLXNA2, DUSP6, and FBN3 proteins in ossification pathways, we recommend that these SNPs be investigated further in experimental research. Through such studies, we hope to gain a better understanding of the molecular mechanisms involved in mandible formation.
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