GRIA2 Gene: Glutamate Ionotropic Receptor AMPA Type Subunit 2
A critical AMPA receptor subunit involved in synaptic transmission, implicated in neurodevelopmental disorders and cancer.
Gene Information Card
| Symbol | GRIA2 |
|---|---|
| Full Name | Glutamate Ionotropic Receptor AMPA Type Subunit 2 |
| Gene Type | protein coding |
| Chromosomal Location | 4q32.1 |
| NCBI Gene ID | 2891 ncbi.nlm.nih.gov/gene/2891 |
| Ensembl ID | ENSG00000120251 |
| UniProt ID | P42262 |
| OMIM ID | 138247 |
| HGNC ID | 4572 |
| Aliases | GluA2, GluR2, GLUR2, HBGR2 |
Description
GRIA2 encodes the GluA2 (GluR2) subunit of the AMPA-type glutamate receptor, a tetrameric ligand-gated ion channel that mediates fast excitatory synaptic transmission in the central nervous system. The presence of the GluA2 subunit determines calcium permeability; receptors containing edited GluA2 are impermeable to calcium. GRIA2 undergoes RNA editing (Q/R site) critical for normal function. Alternative splicing generates flip and flop isoforms. Mutations and dysregulation are linked to neurodevelopmental disorders and various cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Neurodevelopmental disorder with hypotonia and intellectual disability | Biallelic loss-of-function mutations in GRIA2 lead to reduced AMPA receptor function, impairing synaptic transmission. | ClinVar; PMID: 31036921 |
| Intellectual disability, autosomal recessive | Homozygous missense variants affecting the ligand-binding domain disrupt receptor function. | ClinVar; PMID: 31036921 |
| Epileptic encephalopathy, early infantile | De novo gain-of-function mutations increase calcium influx, leading to neuronal hyperexcitability. | ClinVar; PMID: 31036921 |
| Colorectal cancer | GRIA2 downregulation is associated with tumor progression; loss of GluA2 promotes cell proliferation. | COSMIC; PMID: 24658143 |
| Glioblastoma | Reduced GRIA2 expression correlates with increased invasiveness and poor prognosis. | COSMIC; PMID: 24658143 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 31.2 | High |
| Cerebral cortex | 35.1 | High |
| Hippocampus | 38.4 | High |
| Cerebellum | 25.6 | High |
| Testis | 1.2 | Low |
| Liver | 0.1 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 12.5 | Moderate expression |
| U-87 MG (glioblastoma) | 8.3 | Reduced compared to normal brain |
| HCT116 (colorectal carcinoma) | 0.2 | Very low expression |
| MCF7 (breast cancer) | 0.1 | Not expressed |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1906G>A (p.Gly636Arg) | Missense | Rare (0.01%) | Gain-of-function; increased calcium permeability |
| c.2266C>T (p.Arg756Cys) | Missense | Rare (0.005%) | Loss-of-function; reduced surface expression |
| c.1576C>T (p.Arg526Ter) | Nonsense | Rare (0.001%) | Loss-of-function; truncated protein |
| c.2065A>G (p.Lys689Glu) | Missense | Rare (0.002%) | Dominant-negative; impairs tetramerization |
Mutation functional classification
Loss of Function (LOF)
Biallelic loss-of-function mutations (nonsense, frameshift, splice-site) cause neurodevelopmental disorders with intellectual disability and hypotonia.
Gain of Function (GOF)
De novo missense mutations that increase receptor activity or calcium permeability are associated with early infantile epileptic encephalopathy.
Dominant Negative (DN)
Some missense mutations impair tetramer assembly, exerting a dominant-negative effect on receptor function.
View complete mutation data：
Gene Ontology (GO)
| • ionotropic glutamate receptor activity | • AMPA glutamate receptor activity |
| • ligand-gated ion channel activity | • glutamate-gated calcium ion channel activity |
| • protein homodimerization activity | • protein heterodimerization activity |
| • plasma membrane | • postsynaptic membrane |
| • glutamatergic synapse | • chemical synaptic transmission |
| • response to glutamate | • calcium ion transport |
Pathways
• Neuroactive ligand-receptor interaction
• Glutamatergic synapse
• Long-term potentiation
• Long-term depression
• Postsynaptic signaling
Protein Summary
The GluA2 protein is a subunit of AMPA receptors, which are tetrameric ion channels that mediate fast excitatory neurotransmission. The Q/R site RNA editing is critical; unedited GluA2 (Q) allows calcium permeability, while edited (R) is calcium-impermeable. GluA2 undergoes alternative splicing (flip/flop) affecting desensitization kinetics. It interacts with various scaffolding proteins (e.g., GRIP, PICK1) for synaptic targeting and trafficking. Dysregulation of GluA2 expression or function contributes to neurological disorders and cancer.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| GRIA2 Knockout HEK293 Cell Line | EDJ-KQ1816 | Human | 2891 | Details Get a Quote |
| GRIA2 Knockout HeLa Cell Line | EDJ-KQ53420 | Human | 2891 | Details Get a Quote |
| GRIA2 Knockout A-549 Cell Line | EDJ-KQ61896 | Human | 2891 | Details Get a Quote |
| GRIA2 Knockout HCT 116 Cell Line | EDJ-KQ70377 | Human | 2891 | Details Get a Quote |
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