1. In-Silico analysis of missense SNPs in Human HPPD gene associated with Tyrosinemia type III and Hawkinsinuria
- Author
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Muhammad Naveed, Muhammad Zubair Mehboob, and Sana Tehreem
- Subjects
Models, Molecular ,0301 basic medicine ,In silico ,Mutation, Missense ,Single-nucleotide polymorphism ,Biology ,4-Hydroxyphenylpyruvate Dioxygenase ,Polymorphism, Single Nucleotide ,Biochemistry ,Mixed Function Oxygenases ,Conserved sequence ,03 medical and health sciences ,0302 clinical medicine ,Structural Biology ,medicine ,Humans ,Missense mutation ,Computer Simulation ,Tyrosinemia type III ,Tyrosine ,Hawkinsinuria ,Gene ,Genetics ,Binding Sites ,Tyrosinemias ,Organic Chemistry ,Computational Biology ,medicine.disease ,Computational Mathematics ,030104 developmental biology ,030220 oncology & carcinogenesis - Abstract
HPPD gene codes a dioxygenase enzyme involved in catalysis of different molecules such as tyrosine and phenylalanine by oxidizing them to produce energy. A single change in protein can trigger serious genetic disorders like Tyrosinemia type III and Hawkinsinuria. This study aims to identify the functional missense SNPs of the HPPD gene by using multiple computational tools. All deleterious missense SNPs retrieved from Ensembl and OMIM database were evaluated through six different software. Ultimately, out of 148 missense SNPs, only 27 were confirmed as diseasecausing SNPs by developing a consensus approach. These damaging SNPs were further examined to evaluate their impact on protein stability and energy including their evolutionary conservation. Native and mutated proteins structures were also designed and superimposed by I-TASSER and PyMol respectively. This work results in narrowing down missense SNPs which are still not confirmed experimentally and demands the confirmation by GWAS data. Thus, these missense SNPs could directly or indirectly destabilize the amino acid interactions causing functional deviations of protein.
- Published
- 2019