Insilico Analysis Reveal Three novel nsSNPs May effect on GM2A protein Leading to AB variant of GM2 gangliosidosis

ABSTRACT BackgroundAB variant of GM2 gangliosidosis caused as a result of mutations in GM2 activator gene (GM2A) which is regarded as neurodegenerative disorder. This study aimed to predict the possible damaging SNPs of this gene and their impact on the protein using different bioinformatics tools. MethodsSNPs retrieved from the NCBI database were analyzed using several bioinformatics tools. The different tools collectively predicted the effect of single nucleotide substitution on both structure and function of GM2 activator. ResultsThree novel mutations were found to be highly damaging to the structure and function of the GM2A gene. ConclusionFour SNPs were found to be highly damaging SNPs that affect function, structure and stability of GM2A protein, which they are: C99Y, C112F, C138S and C138R, three of them are novel SNPs (C99Y, C112F and C138S). Also 46 SNPs were predicted to affect miRNAs binding sites on 3’UTR leading to abnormal expression of the resulting protein. These SNPs should be considered as important candidates in causing AB variant of GM2 gangliosidosis and may help in diagnosis and genetic screening of the disease.