GRIN2A

Function

N-methyl-D-aspartate (NMDA) receptors are a class of ionotropic glutamate receptors. NMDA channel has been shown to be involved in long-term potentiation, an activity-dependent increase in the efficiency of synaptic transmission thought to underlie certain kinds of memory and learning. NMDA receptor channels are heteromers composed of the key receptor subunit NMDAR1 (GRIN1) and 1 or more of the 4 NMDAR2 subunits: NMDAR2A (GRIN2A), NMDAR2B (GRIN2B), NMDAR2C (GRIN2C), and NMDAR2D (GRIN2D).

Clinical significance

Variants of the gene are associated with the protective effect of coffee on Parkinson's disease.

Mutations in GRIN2A are associated to refractory epilepsy.

Whole exome/genome sequencing has led to the discovery of an association between mutations in GRIN2A and a wide variety of neurological diseases, including epilepsy, intellectual disability, autism spectrum disorders, developmental delay, and schizophrenia.

Interactions

GRIN2A has been shown to interact with:

• DLG1
• DLG3
• DLG4
• FYN
• Interleukin 16
• PTK2B
• Src

References

References

1. (February 1998). "Localization of the human NMDAR2D receptor subunit gene (GRIN2D) to 19q13.1-qter, the NMDAR2A subunit gene to 16p13.2 (GRIN2A), and the NMDAR2C subunit gene (GRIN2C) to 17q24-q25 using somatic cell hybrid and radiation hybrid mapping panels". Genomics.
2. (July 2019). "A primate-specific short GluN2A-NMDA receptor isoform is expressed in the human brain". Molecular Brain.
3. (July 2021). "Splicing and editing of ionotropic glutamate receptors: a comprehensive analysis based on human RNA-Seq data". Cellular and Molecular Life Sciences.
4. "Entrez Gene: GRIN2A glutamate receptor, ionotropic, N-methyl D-aspartate 2A".
5. (August 2011). "Genome-wide gene-environment study identifies glutamate receptor gene GRIN2A as a Parkinson's disease modifier gene via interaction with coffee". PLOS Genetics.
6. (June 2014). "Caffeine interaction with glutamate receptor gene GRIN2A: Parkinson's disease in Swedish population". PLOS ONE.
7. (July 2014). "Whole-exome sequencing in an individual with severe global developmental delay and intractable epilepsy identifies a novel, de novo GRIN2A mutation". Epilepsia.
8. (July 2015). "Ionotropic GABA and Glutamate Receptor Mutations and Human Neurologic Diseases". Molecular Pharmacology.
9. (July 2025). "Landau-Kleffner Syndrome Can Herald the Diagnosis of GRIN2A Gene Mutation". Case Reports in Pediatrics.
10. (June 2025). "Neurodevelopmental disorder due to a frameshift mutation in the GRIN2A gene: a case report". Translational Pediatrics.
11. (November 2011). "Rare mutations in N-methyl-D-aspartate glutamate receptors in autism spectrum disorders and schizophrenia". Translational Psychiatry.
12. (November 2003). "CaMKII-dependent phosphorylation regulates SAP97/NR2A interaction". The Journal of Biological Chemistry.
13. (September 1997). "Binding of neuroligins to PSD-95". Science.
14. (June 2002). "Selectivity and promiscuity of the first and second PDZ domains of PSD-95 and synapse-associated protein 102". The Journal of Biological Chemistry.
15. (June 1997). "DAP-1, a novel protein that interacts with the guanylate kinase-like domains of hDLG and PSD-95". Genes to Cells.
16. (February 2000). "A developmental change in NMDA receptor-associated proteins at hippocampal synapses". The Journal of Neuroscience.
17. (November 2002). "Activation of NMDA receptors and L-type voltage-gated calcium channels mediates enhanced formation of Fyn-PSD95-NR2A complex after transient brain ischemia". Brain Research.
18. (September 2003). "Lithium reduced N-methyl-D-aspartate receptor subunit 2A tyrosine phosphorylation and its interactions with Src and Fyn mediated by PSD-95 in rat hippocampus following cerebral ischemia". Neuroscience Letters.
19. (January 1999). "PSD-95 promotes Fyn-mediated tyrosine phosphorylation of the N-methyl-D-aspartate receptor subunit NR2A". Proceedings of the National Academy of Sciences of the United States of America.
20. (August 1999). "The effect of transient global ischemia on the interaction of Src and Fyn with the N-methyl-D-aspartate receptor and postsynaptic densities: possible involvement of Src homology 2 domains". Journal of Cerebral Blood Flow and Metabolism.
21. (September 1999). "Neuronal interleukin-16 (NIL-16): a dual function PDZ domain protein". The Journal of Neuroscience.
22. (April 2003). "Interaction of the tyrosine kinase Pyk2 with the N-methyl-D-aspartate receptor complex via the Src homology 3 domains of PSD-95 and SAP102". The Journal of Biological Chemistry.
23. (August 2001). "NMDA receptor activation results in tyrosine phosphorylation of NMDA receptor subunit 2A(NR2A) and interaction of Pyk2 and Src with NR2A after transient cerebral ischemia and reperfusion". Brain Research.