In-Silico Pathogenicity Prediction of a Human Missense Variant (rs۱۴۷۳۹۶۲۶۳) of NANOS۲ Gene In the Patients with Varicocele Disease

Varicoceles is defined as an abnormal, excessive dilation of the pampiniform plexus of veinswithin the scrotum. Varicocele is highly prevalent among infertile male and can result in deleteriouseffects on spermatogenesis. Recent researches illustrated that genetic mutations might play role in theonset of varicocele disease through imbalanced oxidative stress and DNA fragmentation of sperm DNA.One of the genes associated with imbalanced oxidative stress in varicocele is Nitric Oxide SynthesisFamily called NANOS (NOS) gene including: NANOS۱, NANOS۲ and NANOS۳. NANOS۲ proteinwhich is scrutinized in the current study acts as an mRNA binding protein which can regulates proteintranslation leading to germ cell differentiation into male faith. The aim of this study is to investigate agenetic variant (rs۱۴۷۳۹۶۲۶۳) of NANOS۲ gene in terms of mutant protein alterations in both structureand function in comparison with the wild type by means of bioinformatic pathogenicity prediction toolssuch as: Mupro, iMutant, HOPE, PolyPhen-۲ and Predict-SNP. The results demonstrated that themissense mutation p. ۷۳ R>C could affect protein function by changes in protein stability,hydrophobicity and conservation as well as protein structure. All in all, identifying genetic biomarkersby scrutinizing molecular mechanisms underlying varicocele might shed light into a new perspective ofvaricocele prognosis, diagnosis and treatment which leads to a better management of the disease forhealth-care professionals.

کلیدواژه ها:

Bioinformatic Tools ، NOS ، Oxidative Stress ، Point Mutation