GRIA4 Gene - Glutamate Ionotropic Receptor AMPA Type Subunit 4
Comprehensive genomic and functional analysis of GRIA4, a key AMPA receptor subunit involved in synaptic transmission and neurological disorders.
Gene Information Card
| Symbol | GRIA4 |
|---|---|
| Full Name | glutamate ionotropic receptor AMPA type subunit 4 |
| Gene Type | protein-coding |
| Chromosomal Location | 11q22.3 |
| NCBI Gene ID | 2893 ncbi.nlm.nih.gov/gene/2893 |
| Ensembl ID | ENSG00000152578 |
| UniProt ID | P48058 |
| OMIM ID | 138246 |
| HGNC ID | 4574 |
| Aliases | GLUR4, GLURD, GluA4, AMPA-selective glutamate receptor 4 |
Description
GRIA4 (glutamate ionotropic receptor AMPA type subunit 4) encodes the GluA4 subunit of the AMPA-type glutamate receptor, a ligand-gated ion channel that mediates fast excitatory synaptic transmission in the central nervous system. The receptor is a tetramer composed of combinations of GluA1-4 subunits. GRIA4 is highly expressed in brain regions such as the cerebellum, hippocampus, and cortex, and plays critical roles in synaptic plasticity, learning, and memory. Alternative splicing generates multiple isoforms. Variants in GRIA4 have been associated with neurodevelopmental disorders, intellectual disability, and epilepsy.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Neurodevelopmental disorder with or without seizures | Loss-of-function variants impair AMPA receptor function, disrupting glutamatergic signaling | ClinVar: pathogenic variants reported |
| Intellectual disability | Missense mutations reduce receptor trafficking or channel conductance | OMIM: 138246 |
| Epilepsy | Gain-of-function mutations increase neuronal excitability | ClinVar: de novo variants |
| Autism spectrum disorder | Rare variants alter synaptic plasticity | NCBI Gene: association studies |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Cerebellum | 45.2 | High |
| Hippocampus | 38.7 | High |
| Cerebral cortex | 32.1 | High |
| Spinal cord | 18.5 | Medium |
| Testis | 5.3 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y | 12.4 | Neuroblastoma cell line |
| U-87 MG | 8.1 | Glioblastoma cell line |
| HEK293 | 2.3 | Low endogenous expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.2365C>T (p.Arg789Trp) | Missense | Rare | Reduced channel conductance |
| c.1543G>A (p.Gly515Arg) | Missense | Rare | Impaired receptor trafficking |
| c.2020_2022del (p.Phe674del) | In-frame deletion | Rare | Loss of function |
| c.1A>G (p.Met1?) | Start loss | Rare | Loss of protein expression |
Mutation functional classification
Loss of Function (LOF)
Missense and truncating variants that reduce receptor expression, trafficking, or channel activity, associated with neurodevelopmental disorders.
Gain of Function (GOF)
Rare missense variants that increase channel open probability or calcium permeability, linked to epilepsy.
Dominant Negative (DN)
Some missense variants may interfere with tetramer assembly, reducing overall AMPA receptor function.
View complete mutation data：
Gene Ontology (GO)
| • ionotropic glutamate receptor activity (GO:0004970) | • extracellular ligand-gated ion channel activity (GO:0005230) |
| • glutamate receptor signaling pathway (GO:0007215) | • ion transmembrane transport (GO:0034220) |
| • synapse (GO:0045202) | • plasma membrane (GO:0005886) |
Pathways
• Glutamatergic synapse (KEGG: hsa04724)
• Neuroactive ligand-receptor interaction (KEGG: hsa04080)
• Long-term potentiation (KEGG: hsa04720)
Protein Summary
The GluA4 protein (UniProt P48058) is a 902-amino acid transmembrane subunit of AMPA receptors. It contains an extracellular N-terminal domain, a ligand-binding domain, three transmembrane helices (M1, M3, M4), a re-entrant pore loop (M2), and a cytoplasmic C-terminal domain. GluA4 mediates fast excitatory neurotransmission by conducting Na+ and Ca2+ ions upon glutamate binding. It is subject to alternative splicing (flip/flop isoforms) and RNA editing, which modulate receptor kinetics and trafficking.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| GRIA4 Knockout HEK293 Cell Line | EDJ-KQ1818 | Human | 2893 | Details Get a Quote |
| GRIA4 Knockout HeLa Cell Line | EDJ-KQ53422 | Human | 2893 | Details Get a Quote |
| GRIA4 Knockout A-549 Cell Line | EDJ-KQ61898 | Human | 2893 | Details Get a Quote |
| GRIA4 Knockout HCT 116 Cell Line | EDJ-KQ70379 | Human | 2893 | Details Get a Quote |
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