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GeneE
25 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
GRIA1
glutamate ionotropic receptor AMPA type subunit 1
Chromosome 5 Β· 5q33.2
NCBI Gene: 2890Ensembl: ENSG00000155511.19HGNC: HGNC:4571UniProt: A0A9L9PXG3
162PubMed Papers
22Diseases
15Drugs
8Pathogenic Variants
FUNCTIONAL ROLE
Hub GeneIon ChannelReceptorTransporter
RESEARCH IMPACT
Trending
CLINICAL
FDA Approved TargetOMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
AMPA glutamate receptor activityrecycling endosomedendritic spine membraneAMPA glutamate receptor complexintellectual developmental disorder, autosomal dominant 67epilepsymigraine disorderSeizure
✦AI Summary

GRIA1 encodes the GluA1 subunit of AMPA receptors, which are tetrameric ionotropic glutamate receptors that mediate fast excitatory neurotransmission in the central nervous system 1. These ligand-gated cation channels respond to L-glutamate and other glutamatergic agonists, converting chemical signals to electrical impulses through sodium and calcium influx. GRIA1 functions as part of heteromeric AMPA receptor complexes, with calcium permeability depending on subunit composition 1. The receptor undergoes rapid desensitization after activation and can show resensitization in the presence of specific auxiliary subunits. GRIA1 variants are associated with multiple neurological conditions. De novo mutations cause intellectual developmental disorders with features including autism spectrum disorder, seizures, and developmental epileptic encephalopathy 1. Genome-wide association studies have identified GRIA1 as a risk locus for post-traumatic stress disorder, where it functions as a synaptic modulator affecting neuronal excitability 2. Additionally, GRIA1 variants contribute to early neurological instability following ischemic stroke, potentially through excitotoxicity mechanisms 3. Polymorphisms in GRIA1 are also associated with migraine susceptibility, particularly in Asian populations 45. Beyond neurological functions, GRIA1 may play a role in bone metabolism and osteoporosis development 6.

Sources cited
1
GRIA1 encodes GluA1 subunit of AMPA receptors that mediate fast excitatory neurotransmission and cause neurodevelopmental disorders when mutated
PMID: 31300657
2
GRIA1 identified as risk locus for PTSD, functioning as synaptic modulator affecting neuronal excitability
PMID: 38637617
3
GRIA1 variants contribute to early neurological instability after ischemic stroke through excitotoxicity mechanisms
PMID: 35213696
4
GRIA1 polymorphism rs2195450 associated with migraine susceptibility in Chinese Han population
PMID: 26800698
5
Meta-analysis confirming GRIA1 rs2195450 association with migraine risk, particularly in Asian populations
PMID: 30446525
6
GRIA1 may play a role in bone metabolism and osteoporosis development
PMID: 34937502
Disease Associationsβ“˜22
intellectual developmental disorder, autosomal dominant 67Open Targets
0.73Strong
epilepsyOpen Targets
0.61Moderate
migraine disorderOpen Targets
0.61Moderate
SeizureOpen Targets
0.58Moderate
alcohol dependenceOpen Targets
0.57Moderate
Lennox-Gastaut syndromeOpen Targets
0.51Moderate
obesityOpen Targets
0.50Moderate
partial epilepsyOpen Targets
0.50Moderate
schizophreniaOpen Targets
0.43Moderate
diabetic neuropathyOpen Targets
0.42Moderate
post-traumatic stress disorderOpen Targets
0.41Moderate
intellectual developmental disorder, autosomal recessive 76Open Targets
0.41Moderate
alcohol drinkingOpen Targets
0.41Moderate
insomniaOpen Targets
0.39Weak
Parkinson diseaseOpen Targets
0.38Weak
HeadacheOpen Targets
0.37Weak
autosomal dominant non-syndromic intellectual disabilityOpen Targets
0.37Weak
autosomal recessive non-syndromic intellectual disabilityOpen Targets
0.37Weak
Intellectual disabilityOpen Targets
0.36Weak
bipolar disorderOpen Targets
0.36Weak
Intellectual developmental disorder, autosomal dominant 67UniProt
Intellectual developmental disorder, autosomal recessive 76UniProt
Pathogenic Variants8
NM_000827.4(GRIA1):c.1906G>A (p.Ala636Thr)Pathogenic
not provided|Intellectual disability|Intellectual developmental disorder, autosomal dominant 67|Intellectual developmental disorder, autosomal recessive 76;Intellectual developmental disorder, autosomal dominant 67
β˜…β˜…β˜†β˜†2025β†’ Residue 636
NM_000827.4(GRIA1):c.1129C>T (p.Arg377Ter)Pathogenic
Intellectual developmental disorder, autosomal recessive 76|not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 377
NM_000827.4(GRIA1):c.1523C>A (p.Pro508Gln)Likely pathogenic
Intellectual developmental disorder, autosomal dominant 67
β˜…β˜†β˜†β˜†2024β†’ Residue 508
NM_000827.4(GRIA1):c.2615G>C (p.Ser872Thr)Likely pathogenic
Intellectual developmental disorder, autosomal dominant 67
β˜…β˜†β˜†β˜†2023β†’ Residue 872
NM_000827.4(GRIA1):c.1538G>A (p.Gly513Glu)Likely pathogenic
Intellectual developmental disorder, autosomal dominant 67
β˜…β˜†β˜†β˜†2023β†’ Residue 513
NM_000827.4(GRIA1):c.377G>T (p.Arg126Leu)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2022β†’ Residue 126
NM_000827.4(GRIA1):c.848G>A (p.Trp283Ter)Likely pathogenic
GRIA1-related disorder
β˜†β˜†β˜†β˜†2023β†’ Residue 283
NM_000827.4(GRIA1):c.2234G>A (p.Gly745Asp)Pathogenic
Non-syndromic intellectual disability|Autism spectrum disorder|Intellectual developmental disorder, autosomal dominant 67
β˜†β˜†β˜†β˜†2022β†’ Residue 745
View on ClinVar β†—
Drug Targets15
BECAMPANELPhase II
Glutamate receptor ionotropic AMPA antagonist
epilepsy
CX1739Phase II
Glutamate receptor ionotropic AMPA positive allosteric modulator
attention deficit hyperactivity disorder
FARAMPATORPhase II
Glutamate receptor ionotropic AMPA positive allosteric modulator
depressive disorder
IRAMPANELPhase I
Glutamate receptor ionotropic AMPA antagonist
MIBAMPATORPhase II
Glutamate receptor ionotropic AMPA positive allosteric modulator
Alzheimer disease
MK-8777Phase II
Glutamate receptor ionotropic AMPA positive allosteric modulator
attention deficit hyperactivity disorder
OSAVAMPATORPhase II
Glutamate receptor ionotropic AMPA positive allosteric modulator
depressive disorder
PERAMPANELApproved
Glutamate receptor ionotropic AMPA antagonist
Seizure
PESAMPATORPhase II
Glutamate receptor ionotropic AMPA positive allosteric modulator
schizophrenia
SELURAMPANELPhase II
Glutamate receptor ionotropic AMPA antagonist
epilepsy
TALAMPANELPhase II
Glutamate receptor ionotropic, AMPA 1 antagonist
Parkinson disease
TEZAMPANELPhase II
Glutamate receptor ionotropic kainate antagonist
Pain
TEZAMPANEL ANHYDROUSPhase II
Glutamate receptor ionotropic kainate antagonist
Pain
TOPIRAMATEApproved
Glutamate receptor ionotropic AMPA antagonist
epilepsy
ZONAMPANELPhase II
Glutamate receptor ionotropic AMPA antagonist
Ischemic stroke
Related Genes
SYNDIG1Protein interaction100%GRIP2Protein interaction100%AKAP5Protein interaction100%DLG1Protein interaction100%EPB41L1Protein interaction100%EPB41L2Protein interaction100%
Tissue Expression6 tissues
Brain
100%
Lung
23%
Heart
1%
Ovary
1%
Liver
0%
Bone Marrow
0%
Gene Interaction Network
Click a node to explore
GRIA1SYNDIG1GRIP2AKAP5DLG1EPB41L1EPB41L2
PROTEIN STRUCTURE
Preparing viewer…
PDB6X5Q Β· 2.14 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.45Moderately Constrained
pLIβ“˜
1.00Intolerant
Observed/Expected LoF0.33 [0.24–0.45]
RankingsWhere GRIA1 stands among ~20K protein-coding genes
  • #2,769of 20,598
    Most Researched162 Β· top quartile
  • #570of 1,025
    FDA-Approved Drug Targets2
  • #3,037of 5,498
    Most Pathogenic Variants8
  • #2,488of 17,882
    Most Constrained (LOEUF)0.45 Β· top quartile
Genes detectedGRIA1
Sources retrieved25 papers
Response timeβ€”
πŸ“„ Sources
25β–Ό
1
Genome-wide association analyses identify 95 risk loci and provide insights into the neurobiology of post-traumatic stress disorder.
PMID: 38637617
Nat Genet Β· 2024
1.00
2
AMPA receptor GluA2 subunit defects are a cause of neurodevelopmental disorders.
PMID: 31300657
Nat Commun Β· 2019
0.90
3
Gain-of-function and loss-of-function variants in GRIA3 lead to distinct neurodevelopmental phenotypes.
PMID: 38038360
Brain Β· 2024
0.80
4
Multi-ancestry GWAS reveals excitotoxicity associated with outcome after ischaemic stroke.
PMID: 35213696
Brain Β· 2022
0.70
5
Conserved autism-associated genes tune social feeding behavior in C. elegans.
PMID: 39468047
Nat Commun Β· 2024
0.68