Bioinformatic analysis of GRIN2B gene and GluN2B protein mutations in autism spectrum disorder (ASD) disease

چکیده مقاله

Introduction: Autism spectrum disorder (ASD) consists of a genetically heterogenous group of neurobehavioral disorders characterized by impairment in three behavioral domains including communication, social interaction, and stereotypic repetitive behaviors [1]. Many of the genetic defects associated with ASD encode proteins that are relevant at the neuronal synapse or that are involved in activity-dependent changes in neurons, including regulatory proteins such as transcription factors. Transcriptional and splicing dysregulation or alterations in epigenetic mechanisms such as DNA methylation or histone acetylation and modification may play a role[2]. GRIN2B is one of the genes that impact on this disease.The GRIN2B gene provides instructions for making a protein called GluN2B. This protein is found in nerve cells (neurons) in the brain, primarily during development before birth[3]. Methods: In this study, GluN2B protein information was collected through NCBI, Uniprot and PDB databases. Also, reported mutations for GRIN2B gene, which is effective in ASD, were obtained through NCBI and Uniprot databases. Then, by using SIFT and Polyphen sites, the effect of these mutations on the disease was investigated separately, and common mutations were extracted and analyzed in the form of a statistical chart. Eventually, we used NCBI to diagnosis where the most regions had mutation. Result: According to PDB database, GluN2B receptor is a membrane protein and has 2 chains B and D and its sequence length is 862 amino acids. Based on SIFT, we found 24 single nucleoutide polymorphism (SNP) with score between 0_0.05 that was deleterious and had pathogenicity records in UniProt and ClinVar databases and and by analyzing the data by polyphen we got the damage rate in replacing amino acids witheachother. The results showed that most of them were malignant and only 4 benign samples were found. Conclusion: In this research, we analyzed GRIN2B gene mutations and their pathogenicity. The detailed analysis of our study’s findings highlighted the significance of variation at the Thr685, Arg682, Asn615, and Ser526 positions involved in posttranslational modifications directly or indirectly, which may be at the root of thedestabilization of the GluN2B and, as a result, the occurrence of the disease. were identified as pathogenic, with the potential to inflict significant functional and stability impacts on the proteins[4].