In-silico Investigation of p.Arg۲۶Pro andp.Arg۲۶Gln Missense Mutations in NANOS۲ Gene Associatedwith Azoospermia and Their Effect on Developmentand Appearance of Germ Cell Tumours

Introduction: Germ cell tumors mostly develop in cells responsiblefor producing sperm or eggs (testis or ovary), which can beeither benign or malignant. Moreover, azoospermia, the absenceof sperm in the semen, can be caused by mutations in genes relatedto male fertility, including NANOS۲. Recent research hasshown that missense mutations, p.Arg۲۶Pro and p.Arg۲۶Gln, inNANOS۲, may be associated with azoospermia and potentiallycontribute to the development and emergence of germ cell tumors.In this study, an in-silico analysis was conducted to investigatehow these missense mutations may affect the molecularmechanisms underlying tumor development in germ cells.Methods: By retrieving “rs۱۴۰۲۶۹۳۲۱” among ۱۲۸ missense variantsof the NANOS۲ gene in the National Centre of BiotechnologyInformation, the stability, hydrophobicity, function, and structureof mutant proteins were scrutinized through bioinformatic databasessuch as MUpro, HOPE, EXPASY, and PANTHER.Results: The MUpro tool predicted a “decrease in stabilityof protein structure” for both mutations (p.Arg۲۶Pro andp.Arg۲۶Gln) with confidence Scores of -۰.۰۳ and -۰.۶۱, respectively.The HOPE bioinformatic tool predicted that the firstmutation turns the protein into a “more hydrophobic” structurewhile the latter turns it into a “smaller structure,” leadingto a loss of interactions. Additionally, EXPASY predicted an“increase in hydrophobicity” in both mutations with a scoreof +۲.۹۰ and +۱.۰۰, respectively. Finally, PANTHER demonstratedthat both mutations can be “possibly damaging” with a probability of deleterious effects (Pdel) of ۰.۵.Conclusion: This in-silico study suggests that the p.Arg۲۶Proand p.Arg۲۶Gln mutations in the NANOS۲ gene are likely tohave a deleterious effect on protein function, which may contributeto the development of azoospermia and germ cell tumors.The Findings of this study provide valuable insights intothe putative role of these mutations in development and progressionof germ cell tumors, potentially leading to more effectivediagnostic and treatment options for affected individuals.

کلیدواژه ها:

Missense variant ، Bioinformatic Analysis Tool ، Tumorigenesis ، Cancer