Abstract

Sex hormone-binding globulin (SHBG) controls the bioavailability of androgens, and its association has been found in a number of disorders such as hyperandrogenism, obesity, diabetes, and cancer. Many human singlenucleotide polymorphisms (SNPs) that are now recognized provide an opportunity to understand the association between genotype and phenotype. In our analysis, we found P185L (rs6258) substitution possess damaging effect on protein structure. ConSurf analysis predicted P185L is conserved and exposed in protein structure. Secondary and tertiary structure of mutated protein was predicted by PSIPRED and Swiss Modeller which were by superimposed using UCSF Chimera to predict their side-chain modification. FT site server predicted amino acid residues that are involved in ligand-binding site of SHBG protein and none of the substitution was involved in ligand-binding site. Six SNPs associated with untranslated region affect the miRNA seed region, thereby affect gene regulation. Ten SNPs associated with splice site were found to alter slicing signal by our study, hence affect the mRNA processing and resulted in faulty polypeptide. Alteration in SHBG polypeptide affects its affinity toward androgen binding and its physiological level as well. These SNPs are still uncharacterized; hence providing a baseline for validation of their association with the susceptibility of diseases and develop personalized therapeutics.

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