Genetic analysis of a missense mutation in the NANOS۲ gene involved in Non-Obstructive Azoospermia based on in-silico pathogenicity prediction tools

According to the World Health Organization, infertility is becoming a growing issue worldwide. Infertility is reported to a↵ect ۵۰ million couples universally, and male infertility affects approximately ½ of the infertile cases. One of male infertility causes is Azoospermia which is characterized by the absence of sperm in male semen liquid. Clinically, Non-Obstructive azoospermia is considered the most severe phenotype of male infertility with spermatogenesis failure. Statistically, non-obstructive azoospermia includes ۱% of the male population and ۱۰% of infertile men. Among all causes leading to non-obstructive azoospermia, genetic anomalies play a remarkable role in ۲۵% of the cases; yet, the etiology of some cases is still unknown, which is considered as an “idiopathic” condition. The NANOS۲ gene is one of the genes associated with the disease. As a member of the transcription factor family, the NANOS۲ gene functions by binding to mRNA and also is located on chromosome ۱۹q۱۳.۳۲. In this study, a NANOS۲ variant is investigated in terms of alterations in protein structure and function. For a more specific prediction, the stability, hydrophobicity, pathogenicity and conservation of the protein is investigated through bioinformatic databases like HOPE, Mutation assessor and Mutation taster. Among all ۱۲۸ identified polymorphisms of the NANOS۲ gene listed in the National Center for Biotechnology Information/Single Nucleotide Polymorphism database (NCBI/dbSNP), a missense variant selected (rs۱۳۸۳۵۱۳۶۱), and assessed via bioinformatic tools such as HOPE, Mutation Assessor and Mutation Taster, and also studied in terms of protein stability, hydrophobicity, pathogenicity and conservation. By utilizing HOPE, Mutation Assessor, and Mutation Taster bioinformatic tools, useful information about protein pathogenicity and deleterious e↵ects of an alteration in the amino acid chain caused by a missense mutation is detected. A putative G۱۰۵S pathogenic mutation is predicted through bioinformatic databases.