In-Silico Analysis of the High-Risk Missense Variants in PTH1R Gene and Association with Primary Failure of Tooth Eruption (PFE)

Primary eruption failure (PFE) is a rare condition characterized by the cessation of tooth eruption posteriorly. Due to a mutation in the PTH1R gene, this dental phenotype is distinguished by a severe posterior open bite. The current study was used to investigate and evaluate the most deleterious nsSNPs in the dbSNP-extracted PTH1R gene using a variety of computational tools, including SIFT, PolyPhen-2, PROVEAN, Condel, Meat LR, Meat SVM, SWISS-MODEL, DUET, Yassara, ConSurf, and STRING. A total of 29 nsSNPs were found to be deleterious according to the ConSurf analysis. The majority of high-risk SNP amino acid positions (79.16%) were found in conserved regions. The Duet server determined that 16 of these variants decreased protein stability. Furthermore, hydrophobic and hydrogen interaction analyses and evaluation of structural effects of the deleterious nsSNPs on PTH1R by the YASARA program and Project HOPE server revealed significant changes between the wild-type and the 16 tested mutants. According to our results, 16 deleterious variants were identified as having an impact on the structure and probably function of the PTH1R protein involved in the PFE phenotype. These findings could contribute to the development of more efficient genetic tests for detecting mutations in the PTH1R gene.