Global Journal of Medical Research, F: Diseases, Volume 22 Issue 4

© 2022. Nabaa Kamal Alshafei, Intisar Hassan Saeed & Mona Abdelrahman Mohamed Khaier. This research/review article is distributed under the terms of the Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0). You must give appropriate credit to authors and reference this article if parts of the article are reproduced in any manner. Applicable licensing terms are at https://creativecommons.org/licenses/by-nc-nd/4.0/. Computational Analysis of Possibly Pathogenic Non-Synonymous Single Nucleotide Polymorphisms Variants in HGD Gene By Nabaa Kamal Alshafei, Intisar Hassan Saeed & Mona Abdelrahman Mohamed Khaier University of Bahri Abstract- Alkaptonuria (AKU) is an autosomal recessive disorder caused by mutations in the homogentisate-1,2-dioxygenase (HGD) gene leading to the deficiency of HGD enzyme activity. The aim of this study was to use some computational bioinformatics tools to predict the most pathogenic non-synonymous mutations in the HGD gene. The data was retrieved from the SNPs database of the National Center for Biotechnology Information (dbSNPs) (Oct. 2021). The primary sequence of the protein was obtained from the UniProt database (Oct. 2021). The pathogenic effect on the protein structure and function was predicted by GeneMANIA, SIFT, Provean, Polyphen-2, I-Mutant, and Project Hope software. The human HGD gene comprises a total of 423SNPs out of that 348 were found to be synonymous, 75 were missense SNPs (nsSNPs). Analysis of the nsSNPs by SIFT predicts 35 as deleterious and 40 as tolerated ones. Using Provean only 30 were deleterious while 5 SNPs were neutral. Taking the deleterious nsSNPSs to Polyphen-2, 25 nsSNPs were damaging (22 were probably damaging and 3 were possibly damaging), while 5 were benign. Keywords: Alkaptonuria (AKU); homogentisate-1,2-dioxygenase (HGD) gene; I-Mutant; Non- synonymous Single Nucleotide Polymorphisms (nsSNPs); Project Hope, and SIFT. GJMR-F Classification: DDC Code: 724 LCC Code: NA500 ComputationalAnalysisofPossiblyPathogenicNonSynonymousSingleNucleotidePolymorphismsVariantsinHGDGene Strictly as per the compliance and regulations of: Global Journal of Medical Research: F Diseases Volume 22 Issue 4 Version 1.0 Year 2022 Type: Double Blind Peer Reviewed International Research Journal Publisher: Global Journals Online ISSN: 2249-4618 & Print ISSN: 0975-5888