Impact of highly deleterious non-synonymous polymorphisms on GRIN2A protein's structure and function

GRIN2A is a gene that encodes NMDA receptors found in the central nervous system and plays a pivotal role in excitatory synaptic transmission, plasticity and excitotoxicity in the mammalian central nervous system. Changes in this gene have been associated with a spectrum of neurodevelopmental disorders such as epilepsy. Previous studies on GRIN2A suggest that non-synonymous single nucleotide polymorphisms (nsSNPs) can alter the protein's structure and function. To gain a better understanding of the impact of potentially deleterious variants of GRIN2A, a range of bioinformatics tools were employed in this study. Out of 1320 nsSNPs retrieved from the NCBI database, initially 16 were predicted as deleterious by 9 tools. Further assessment of their domain association, conservation profile, homology models, interatomic interaction, and Molecular Dynamic Simulation revealed that the variant I463S is likely to be the most deleterious for the structure and function of the protein. Despite the limitations of computational algorithms, our analyses have provided insights that can be a valuable resource for further in vitro and in vivo research on GRIN2A-associated diseases.

Automated summary

GRIN2A is a gene encoding NMDA receptors in the central nervous system, playing a crucial role in synaptic transmission, plasticity, and excitotoxicity. Variants in this gene, particularly the I463S variant, are predicted to have deleterious effects on protein structure and function. Bioinformatics tools were used to assess the impact of these variants, providing valuable insights for future research on GRIN2A-related diseases.