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

Area of Science:

• Neuroscience
• Genetics
• Computational Biology

Background:

• The GRIN2A gene encodes NMDA receptors, vital for central nervous system function, synaptic transmission, and plasticity.
• Alterations in GRIN2A are linked to neurodevelopmental disorders, including epilepsy.
• Non-synonymous single nucleotide polymorphisms (nsSNPs) in GRIN2A can potentially affect protein structure and function.

Purpose of the Study:

• To identify and characterize potentially deleterious nsSNPs in the GRIN2A gene.
• To assess the impact of these variants on GRIN2A protein structure and function using bioinformatics tools.

Main Methods:

• Retrieved 1320 nsSNPs from the NCBI database.
• Utilized multiple bioinformatics tools to predict deleterious variants.
• Performed domain association, conservation profiling, homology modeling, interatomic interaction analysis, and Molecular Dynamic Simulation for further assessment.

Main Results:

• Initially, 16 out of 1320 nsSNPs were predicted as deleterious by nine different tools.
• The GRIN2A variant I463S was identified as the most likely to be deleterious to protein structure and function based on comprehensive analysis.

Conclusions:

• Bioinformatics analysis provides valuable insights into the functional impact of GRIN2A variants.
• The identified I463S variant warrants further in vitro and in vivo investigation for its role in GRIN2A-associated diseases.