GRIA3: Glutamate Ionotropic Receptor AMPA Type Subunit 3
A key AMPA receptor subunit in glutamatergic neurotransmission, linked to neurodevelopmental disorders and intellectual disability.
Gene Information Card
| Symbol | GRIA3 |
|---|---|
| Full Name | Glutamate Ionotropic Receptor AMPA Type Subunit 3 |
| Gene Type | protein-coding |
| Chromosomal Location | Xq25 |
| NCBI Gene ID | 2892 ncbi.nlm.nih.gov/gene/2892 |
| Ensembl ID | ENSG00000125675 |
| UniProt ID | P42263 |
| OMIM ID | 305915 |
| HGNC ID | 4573 |
| Aliases | GluA3, GLUR3, GLURC, GluR-K3, AMPA-selective glutamate receptor 3 |
Description
GRIA3 encodes the GluA3 subunit of the AMPA-type ionotropic glutamate receptor, which mediates fast excitatory synaptic transmission in the central nervous system. The receptor is a tetramer of GluA1-4 subunits; GluA3-containing receptors are involved in synaptic plasticity, learning, and memory. Mutations in GRIA3 are associated with X-linked intellectual disability, autism spectrum disorder, and other neurodevelopmental conditions.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| X-linked intellectual disability | Loss-of-function mutations impair AMPA receptor trafficking or channel function, reducing glutamatergic signaling | ClinVar, OMIM #305915 |
| Autism spectrum disorder | Missense variants alter receptor gating or surface expression, disrupting synaptic homeostasis | ClinVar, NCBI GeneReviews |
| Epileptic encephalopathy | De novo gain-of-function mutations increase calcium permeability and excitotoxicity | ClinVar, literature |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain (cerebral cortex) | 12.5 | High |
| Brain (hippocampus) | 15.2 | High |
| Brain (cerebellum) | 8.3 | Medium |
| Testis | 1.2 | Low |
| Liver | 0.1 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 18.4 | Neuronal model |
| U-87 MG (glioblastoma) | 6.7 | Glial origin |
| HEK293 (embryonic kidney) | 0.3 | Low endogenous expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.2365G>A (p.Gly789Arg) | Missense | Rare | Impaired receptor trafficking; associated with intellectual disability |
| c.1915C>T (p.Arg639*) | Nonsense | Very rare | Loss of function; truncated protein |
| c.1741G>A (p.Gly581Arg) | Missense | Rare | Gain-of-function; increased calcium permeability; epileptic encephalopathy |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift variants leading to truncated or unstable GluA3 subunits, reducing AMPA receptor surface expression and synaptic transmission.
Gain of Function (GOF)
Missense variants (e.g., p.Gly581Arg) that alter channel gating or ion selectivity, increasing calcium influx and excitotoxicity.
Dominant Negative (DN)
Some missense variants may co-assemble with wild-type subunits and impair receptor trafficking or function in a dominant-negative manner.
View complete mutation data：
Gene Ontology (GO)
| • ionotropic glutamate receptor activity (GO:0004970) | • extracellular ligand-gated ion channel activity (GO:0005230) |
| • ion transmembrane transport (GO:0034220) | • chemical synaptic transmission (GO:0007268) |
| • synapse (GO:0045202) | • plasma membrane (GO:0005886) |
Pathways
• UniProt: AMPA receptor trafficking and synaptic plasticity
• Reactome: R-HSA-399719 – Trafficking of AMPA receptors
• KEGG: hsa04724 – Glutamatergic synapse
Protein Summary
The GluA3 protein (UniProt P42263) is a 894-amino acid transmembrane subunit of AMPA receptors. It contains an extracellular N-terminal domain, a ligand-binding domain, three transmembrane helices (M1, M3, M4), and a re-entrant pore loop (M2) that forms the ion channel. Alternative splicing generates flip and flop isoforms that affect desensitization kinetics. GluA3 is widely expressed in the brain, particularly in hippocampus and cortex, and is essential for normal synaptic plasticity.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| GRIA3 Knockout HEK293 Cell Line | EDJ-KQ1817 | Human | 2892 | Details Get a Quote |
| GRIA3 Knockout HeLa Cell Line | EDJ-KQ53421 | Human | 2892 | Details Get a Quote |
| GRIA3 Knockout A-549 Cell Line | EDJ-KQ61897 | Human | 2892 | Details Get a Quote |
| GRIA3 Knockout HCT 116 Cell Line | EDJ-KQ70378 | Human | 2892 | Details Get a Quote |
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