Pathogenicity Prediction Assays of HumanMissense Variant (rs۱۳۸۵۷۲۵۸۱۲) in NANOS۲ GeneBased on Protein Sequence, Structure and Function

Introduction: Infertility is one of the biggest challengesworldwide, affecting ۵۰ million couples. In half of them, maleinfertility is the main reason. Among the causes of male infertility,azoospermia, which is the most severe cause of infertility,occurs due to dysfunction of the hypothalamus-pituitary, aprimary quantitative disorder in sperm, or due to obstructionof the urogenital ducts, among which ۷۰% of affected peopleare due to bilateral lack of Congenital vas deferens (CBAVD)and ۳۰% is non-obstructive azoospermia (NOA) due to primarytesticular failure. One of the single gene defects that becauseNOA is the NANOS۲ gene at chromosomal position ۱۹q۱۳.۳,which encodes a DNA-binding zinc finger that regulates RNApoly enzyme binding.Materials and Methods: We investigated the function andstructure of this type of protein by studying and checking bioinformaticsservers, PolyPhen-۲, I-mutant-۳, Expasy, PredictSNP.Results: By studying the variant V۱۳۶D (rs۱۳۸۵۷۲۵۸۱۲) in thePolyPhen-۲ prediction tool with a score of ۰.۷۱, it was predictedthat this variant could be harmful, and in I-mutant-۳, a decreasein protein stability was predicted for this species. In the Expasytool, the molecular weight of the mutant protein increased andin the Peptide۲ site, the hydrophobicity of the mutant proteinincreased with this variant by a score of ۰.۳۶. On the SIFT andPredictSNP sites. Scores of ۰.۷۹ and ۰.۶۲ were obtained.Conclusion: It was predicted that this type can cause structuraldisorder and as a result protein dysfunction.