Computational Analysis of High Risk Missense Variant in Human UTY Gene: A Candidate Gene of AZFa Sub-region

The human Ubiquitously transcribed tetratricopeptide repeat gene, Y-linked (UTY) gene encodes histone demethylase involved in protein-protein interactions. UTY protein evidence at protein level predicted intracellular and secreted protein. UTY is also involved in spermatogenesis process.

The high-risk non-synonymous single nucleotide polymorphism in the coding region of the UTY gene was screened by SNP database and identified missense variants were subjected to computational analysis to understand the effect on protein function, stability and structure by SIFT, PolyPhen 2, PANTHER, PROVEAN, I-Mutant 2, iPTREE-STAB, ConSurf, ModPred, SPARKS-X, QMEAN, PROCHECK, project HOPE and STRING.

A total of 151 nsSNPs variants were retrieved in UTY gene out of which one missense variant (E18D) was predicted to be damaging or deleterious using SIFT, PolyPhen 2, PANTHER and PROVEAN. Additionally, E18D variant showed less stability, high conservation and having role in post translation modification using i-Mutant 2 and iPTREE-STAB, ConSurf and ModPred, respectively. The predicted 3D model of UTY using SPARKS-X with z-score of 15.16 was generated and validated via QMEAN (Z-score of 0.472) and PROCHECK which plots Ramachandran plot (85.3% residues in most favored regions, 12.3% in additionally allowed regions, 2.0% in generously allowed regions and 4.0% were in disallowed regions) and it indicates a good quality model. STRING showed that UTY interacts with ten different proteins.

This study revealed that SNP data available on database was deduced to find out the most damaging nsSNPs i.e. rs3212293 (E18D). Therefore, it provides useful information about functional SNPs for future prospects concerning infertility in men.