First comprehensive in silico analysis of the functional and structural consequences of SNPs in human GalNAc-T1 gene.
GalNAc-T1, a key candidate of GalNac-transferases genes family that is involved in mucin-type O-linked glycosylation pathway, is expressed in most biological tissues and cell types. Despite the reported association of GalNAc-T1 gene mutations with human disease susceptibility, the comprehensive computational analysis of coding, noncoding and regulatory SNPs, and their functional impacts on protein level, still remains unknown. Therefore, sequence- and structure-based computational tools were employed to screen the entire listed coding SNPs of GalNAc-T1 gene in order to identify and characterize them. Our concordant in silico analysis by SIFT, PolyPhen-2, PANTHER-cSNP, and SNPeffect tools, identified the potential nsSNPs (S143P, G258V, and Y414D variants) from 18 nsSNPs of GalNAc-T1. Additionally, 2 regulatory SNPs (rs72964406 and #x26; rs34304568) were also identified in GalNAc-T1 by using FastSNP tool. Using multiple computational approaches, we have systematically classified the functional mutations in regulatory and coding regions that can modify expression and function of GalNAc-T1 enzyme. These genetic variants can further assist in better understanding the wide range of disease susceptibility associated with the mucin-based cell signalling and pathogenic binding, and may help to develop novel therapeutic elements for associated diseases.
Human Genetics Research Centre, Division of Biomedical Sciences (BMS), Saint George's University of London (SGUL), London, UK ; Princess Al-Jawhara Al-Ibrahim Center of Excellence in Research of Hereditary Disorders, King Abdulaziz University, Jeddah, Saudi Arabia.
Hussein Sheikh Ali
HS
Mohamoud
Princess Al-Jawhara Al-Ibrahim Center of Excellence in Research of Hereditary Disorders, King Abdulaziz University, Jeddah, Saudi Arabia.
Muhammad Ramzan Manwar
MR
Hussain
Princess Al-Jawhara Al-Ibrahim Center of Excellence in Research of Hereditary Disorders, King Abdulaziz University, Jeddah, Saudi Arabia ; Department of Genetic Medicine, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia.
Ashraf A
AA
El-Harouni
Princess Al-Jawhara Al-Ibrahim Center of Excellence in Research of Hereditary Disorders, King Abdulaziz University, Jeddah, Saudi Arabia ; Department of Genetic Medicine, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia.
Noor Ahmad
NA
Shaik
Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan.
Zaheer Ulhaq
ZU
Qasmi
Institute of Biological Sciences and Centre of Research for Computational Sciences and Informatics for Biology, Bioindustry, Environment, Agriculture and Healthcare (CRYSTAL, UM), University of Malaya, Kuala Lumpur, Malaysia.
Amir Feisal
AF
Merican
Faculty of Medicine, King Abdulaziz University, Rabigh, Saudi Arabia.
Mukhtiar
M
Baig
Department of Biological Sciences, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia.
Yasir
Y
Anwar
Princess Al-Jawhara Al-Ibrahim Center of Excellence in Research of Hereditary Disorders, King Abdulaziz University, Jeddah, Saudi Arabia.
Hani
H
Asfour
Princess Al-Jawhara Al-Ibrahim Center of Excellence in Research of Hereditary Disorders, King Abdulaziz University, Jeddah, Saudi Arabia.
Nabeel
N
Bondagji
Princess Al-Jawhara Al-Ibrahim Center of Excellence in Research of Hereditary Disorders, King Abdulaziz University, Jeddah, Saudi Arabia ; Department of Genetic Medicine, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia.
Jumana Yousuf
JY
Al-Aama
D000465:Algorithms; D000595:Amino Acid Sequence; D001499:Bayes Theorem; D001665:Binding Sites; D019295:Computational Biology / Q000379:methods; D003198:Computer Simulation; D017124:Conserved Sequence; D057225:Data Mining / Q000379:methods; D004198:Disease Susceptibility; D019143:Evolution, Molecular; D006801:Humans; D006860:Hydrogen Bonding; D008024:Ligands; D008958:Models, Molecular; D008968:Molecular Conformation; D008969:Molecular Sequence Data; D009154:Mutation; D017350:N-Acetylgalactosaminyltransferases / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011485:Protein Binding; D025941:Protein Interaction Mapping; D017386:Sequence Homology, Amino Acid; D012984:Software; D055672:Static Electricity; D000097763:Polypeptide N-acetylgalactosaminyltransferase
D008024:Ligands; D017350:N-Acetylgalactosaminyltransferases; D000097763:Polypeptide N-acetylgalactosaminyltransferase