Functional Analysis and Classification of Missense Mutations within a Critical Region of GRIN2A Open Access

Abstract

NMDA receptors (NMDARs) are a subset of ligand gated ion channels glutamate receptors which are crucial for proper neural functioning. Mutations in the genes which encode for this receptor are associated with neurological disorders such as epilepsy, developmental delay and aphasia. In this paper we evaluate the functional consequences missense mutations within a highly conserved region of the gene encoding for the GluN2A subunit (GRIN2A)  have on normal receptor functional. This region was identified by the Missense Tolerance Ratio and has a history of patent reported pathogenic variants. I catalog the spectrum of functional perturbations resulting from missense mutations in these regions in hopes of bringing clarity to the functional spectrum by defining the direction and the magnitude of these changes. Lastly, I classify these variants according to the guidelines for sequence variants interpretation laid out by the American College of Genomic Medicine.

Table of Contents

Table of Contents

Introduction and Background…………………………………..…………………………………1

Materials and Methods ...…………………………………………………………………..…….25

Results……………………………………………………………………………………………33

Discussion…………………………………………………………………………………….….49

Bibliography………………………………………………………………………………….….59

About this Honors Thesis

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School	Emory College
Department	Neuroscience and Behavioral Biology
Degree	B.S.
Submission	Honors Thesis
Language	English
Research Field	Biology, Neuroscience
Keyword	Neuroscience Genetic Disorder NMDA NMDAR GRIN2A
Committee Chair / Thesis Advisor	Stephen Traynelis, Emory University
Committee Members	Keith Easterling, Emory University Astrid Prinz, Emory University Matthew Weinschenk, Emory University

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