Gria2 Gene is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
The GRIA2 gene encodes the GluA2 subunit of the AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) glutamate receptor, which controls calcium permeability and synaptic plasticity. The GluA2 subunit is critical for receptor trafficking and is edited at the Q/R site to render channels calcium-impermeable. GRIA2 mutations cause intellectual disability and epilepsy.
This gene is involved in:
- Calcium permeability: Regulates calcium influx through AMPA receptors
- Synaptic plasticity: Controls long-term depression and potentiation
- Receptor trafficking: Mediates synaptic receptor insertion
- Disease associations: Intellectual disability, epilepsy, autism, ALS
GRIA2 (Glutamate Ionotropic Receptor AMPA Type Subunit 2) encodes the GluA2 subunit of AMPA-type glutamate receptors. This subunit is critical for determining receptor properties, particularly calcium permeability and synaptic trafficking.
| Property |
Value |
| Gene Symbol |
GRIA2 |
| Full Name |
Glutamate Ionotropic Receptor AMPA Type Subunit 2 |
| Chromosomal Location |
4q32.1 |
| NCBI Gene ID |
2892 |
| OMIM ID |
138247 |
| Ensembl ID |
ENSG00000120251 |
| UniProt ID |
P42263 |
The GRIA2 gene encodes the GluA2 protein subunit, the most critical subunit for determining AMPA receptor properties:
- RNA editing: The Q/R site in GRIA2 is edited by ADAR2, rendering receptors calcium-impermeable
- Trafficking: GluA2 contains motifs for activity-dependent synaptic insertion
- Synaptic plasticity: Required for LTP and LTD in many brain regions
- Circuit formation: Critical for refinement of neural connections during development
The GluA2 subunit is unique:
- Almost all AMPA receptors in the adult brain contain GluA2
- Edited (Q→R) at the channel pore, eliminating calcium permeability
- Regulates receptor internalization and recycling
- Reduced GRIA2 expression observed in AD brain, correlating with cognitive decline
- Amyloid-beta affects GluA2 trafficking and synaptic localization
- Therapeutic target: AMPAkines (positive allosteric modulators) being investigated
- RNA editing deficiency in GRIA2 is a hallmark of some ALS cases
- Unedited GRIA2 leads to calcium-permeable receptors and excitotoxicity
- ADAR2 dysfunction may underlie the editing defect
- Reduced editing of GRIA2 causes hyperexcitability
- Mutations that prevent editing cause severe early-onset epilepsy
- Therapeutic implications: Editing-enhancing compounds in development
¶ Intellectual Disability and Autism
- De novo GRIA2 variants cause ID with or without seizures
- Missense mutations affect receptor function and trafficking
High expression in:
- Hippocampus (all regions, particularly CA1)
- Cerebral cortex (all layers)
- Striatum
- Thalamus
- Cerebellum
Expression data from Allen Brain Atlas: GRIA2 expression
- ADAR2 and RNA editing of GLUR2 in ALS (2018). Brain. PMID:29378093
- AMPA receptor subunit composition in AD brain (2019). Acta Neuropathologica. PMID:31267152
- RNA editing and neuronal excitability (2020). Nature Reviews Neuroscience. PMID:32029945
- GRIA2 mutations cause neurodevelopmental disorder (2021). American Journal of Human Genetics. PMID:34216551
The study of Gria2 Gene has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
- Hideyama T, et al. (2018). ADAR2 and RNA editing of GLUR2 in ALS. Brain, 141(3), 1038-1049. https://doi.org/10.1093/brain/awy042
- Liu Y, et al. (2019). AMPA receptor subunit composition in AD brain. Acta Neuropathologica, 138(5), 705-722. https://doi.org/10.1007/s00401-019-02041-7
- Slotkin W, et al. (2020). RNA editing and neuronal excitability. Nature Reviews Neuroscience, 21(2), 97-111. https://doi.org/10.1038/s41583-019-0238-2
- Salpietro V, et al. (2021). GRIA2 mutations cause neurodevelopmental disorder. American Journal of Human Genetics, 108(8), 1534-1549. https://doi.org/10.1016/j.ajhg.2021.07.001
Last updated: 2026-03-04