Computational Genomic Variations of GRIN2B Associated with Autism Spectrum Disorders: An <i>In Silico</i> Approach

Genomic variations in GRIN2B have been linked to various neurodevelopmental disorders including autism spectrum disorders (ASD). Unraveling variations that modify the protein's structure and function is essential for the possible treatment of diseases. Here, we report in silico analysis of all the ASD-specific genomic variations found in GRIN2B and their roles in the pathogenesis of ASD. GRIN2B variations were collected through databases and text mining. These variants were predicted for pathogenicity scores using Varsome tools, and protein domains were predicted using InterPro. Mapping of these variants was done manually. A structural and functional analysis of GRIN2B was also conducted. The GRIN2B gene has 14 exons, and the transcripts expressed in the brain encode 1484 amino acids. Among the 379 ASD-specific variants collected, 54 had a pathogenicity score >60%. Of these, four variants, p.G459E, p.G459R, p.E657G, and p.G820R, showed pathogenic scores >80%. The homology modeling built for these variants indicated that the variants can disrupt the GRIN2B protein. The network analysis revealed that the GRIN2B protein is biologically connected. Among all the variations, 13 variations are key to consider for possible diagnostic and therapeutic approaches. Hence, the in silico analysis reveals that the most deleterious variations impair the function of GRIN2B, resulting in altered CNS development that contributes to ASD. Received: 23 April 2025 | Revised: 22 August 2025 | Accepted: 22 September 2025 Conflicts of Interest The authors declare that they have no conflicts of interest to this work. Data Availability Statement The data supporting the findings of this study are available upon request from the corresponding author. Author Contribution Statement Srushti S. Chavadapur: Methodology, Software, Validation, Formal analysis, Investigation, Resources, Data curation, Writing – original draft, Writing – review & editing, Visualization. Nallur B. Ramachandra: Conceptualization, Methodology, Validation, Resources, Supervision, Project administration.