GRIA1

Summary

GRIA1 (glutamate ionotropic receptor AMPA type subunit 1, HGNC:4571) is a protein-coding gene on chromosome 5q33.2, encoding Glutamate receptor 1 (P42261). Ionotropic glutamate receptor that functions as a ligand-gated cation channel, gated by L-glutamate and glutamatergic agonists such as alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), quisqualic acid, and kainic acid.

Glutamate receptors are the predominant excitatory neurotransmitter receptors in the mammalian brain and are activated in a variety of normal neurophysiologic processes. These receptors are heteromeric protein complexes with multiple subunits, each possessing transmembrane regions, and all arranged to form a ligand-gated ion channel. The classification of glutamate receptors is based on their activation by different pharmacologic agonists. This gene belongs to a family of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptors. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 2890 — RefSeq curated summary.

At a glance

• Gene–disease (curated): intellectual developmental disorder, autosomal dominant 67 (Strong, GenCC) — +2 more curated relationships
• GWAS associations: 30
• Clinical variants (ClinVar): 239 total — 1 pathogenic, 5 likely-pathogenic
• Phenotypes (HPO): 33
• Druggable target: yes — 6 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_000827

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4571
Approved symbol	GRIA1
Name	glutamate ionotropic receptor AMPA type subunit 1
Location	5q33.2
Locus type	gene with protein product
Status	Approved
Aliases	GluA1, GLURA
Ensembl gene	ENSG00000155511
Ensembl biotype	protein_coding
OMIM	138248
Entrez	2890

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 10 protein_coding, 4 protein_coding_CDS_not_defined, 2 retained_intron

ENST00000285900, ENST00000340592, ENST00000448073, ENST00000474198, ENST00000481559, ENST00000492291, ENST00000517469, ENST00000518142, ENST00000518783, ENST00000518862, ENST00000520353, ENST00000520966, ENST00000521843, ENST00000706733, ENST00000706734, ENST00000706767

RefSeq mRNA: 10 — MANE Select: NM_000827 NM_000827, NM_001114183, NM_001258019, NM_001258020, NM_001258021, NM_001258022, NM_001258023, NM_001364165, NM_001364166, NM_001364167

CCDS: CCDS4322, CCDS47318, CCDS58986, CCDS58987, CCDS58988, CCDS58989

Canonical transcript exons

ENST00000285900 — 16 exons

Exon	Start	End
ENSE00003694807	153705697	153706067
ENSE00003695213	153770168	153770415
ENSE00003695369	153493928	153494065
ENSE00003695809	153802356	153802490
ENSE00003696290	153650330	153650514
ENSE00003698810	153698044	153698154
ENSE00003698951	153698867	153699073
ENSE00003699550	153655819	153655872
ENSE00003699608	153676994	153677161
ENSE00003699928	153674500	153674661
ENSE00003700907	153686225	153686329
ENSE00003701272	153646928	153647167
ENSE00003701861	153764434	153764632
ENSE00003996776	153811025	153813869
ENSE00003996780	153794621	153794735
ENSE00003996920	153490670	153490970

Expression profiles

Bgee: expression breadth ubiquitous, 194 present calls, max score 96.31.

FANTOM5 (CAGE): breadth broad, TPM avg 6.3021 / max 918.6313, expressed in 368 samples.

FANTOM5 promoters (11 alternative TSS)

Promoter ID	TPM avg	Samples expressed
59706	3.0205	270
59704	0.9871	159
59707	0.7199	115
59708	0.6491	134
59705	0.2634	83
59703	0.2322	92
59709	0.1635	76
59710	0.1394	47
59715	0.0541	21
203758	0.0515	32

Top tissues by expression

289 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
CA1 field of hippocampus	UBERON:0003881	96.31	gold quality
cortical plate	UBERON:0005343	96.31	gold quality
cranial nerve II	UBERON:0000941	94.43	gold quality
middle temporal gyrus	UBERON:0002771	93.71	gold quality
Ammon’s horn	UBERON:0001954	92.90	gold quality
ganglionic eminence	UBERON:0004023	92.35	gold quality
paraflocculus	UBERON:0005351	91.99	gold quality
ventricular zone	UBERON:0003053	91.86	gold quality
right hemisphere of cerebellum	UBERON:0014890	91.80	gold quality
entorhinal cortex	UBERON:0002728	91.50	gold quality
prefrontal cortex	UBERON:0000451	91.47	gold quality
Brodmann (1909) area 46	UBERON:0006483	91.42	gold quality
Brodmann (1909) area 23	UBERON:0013554	91.34	gold quality
orbitofrontal cortex	UBERON:0004167	91.29	gold quality
amygdala	UBERON:0001876	90.94	gold quality
temporal lobe	UBERON:0001871	90.64	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	90.47	gold quality
nucleus accumbens	UBERON:0001882	90.45	gold quality
cerebellar cortex	UBERON:0002129	90.45	gold quality
cerebellar hemisphere	UBERON:0002245	90.39	gold quality
Brodmann (1909) area 9	UBERON:0013540	90.37	gold quality
cerebral cortex	UBERON:0000956	90.25	gold quality
cerebellum	UBERON:0002037	90.11	gold quality
cingulate cortex	UBERON:0003027	89.69	gold quality
anterior cingulate cortex	UBERON:0009835	89.52	gold quality
telencephalon	UBERON:0001893	89.38	gold quality
neocortex	UBERON:0001950	89.20	gold quality
frontal cortex	UBERON:0001870	89.14	gold quality
caudate nucleus	UBERON:0001873	88.93	gold quality
right frontal lobe	UBERON:0002810	88.90	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-GEOD-93593	yes	624.41
E-HCAD-35	yes	90.51
E-HCAD-25	yes	45.79
E-ANND-3	yes	6.01
E-HCAD-30	no	1081.46

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ASCL1, HES1, REST, RORA, SP1, SP3, SP4, TCF3

miRNA regulators (miRDB)

108 targeting GRIA1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-6740-5P	100.00	65.64	932
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-12133	99.92	71.82	2006
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-1271-5P	99.91	71.99	1972
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-6857-5P	99.87	65.32	985
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-137-3P	99.87	74.74	2401
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-548AC	99.84	70.77	4351

Literature-anchored findings (GeneRIF, showing 40)

• Modeling of the pore domain of the GLUR1 channel: homology with K+ channel and binding of channel blockers (PMID:11916847)
• Flip and flop splice variants of AMPA receptor subunits in the spinal cord of amyotrophic lateral sclerosis. (PMID:12125045)
• a short sequence present in the N-terminal domain has a role in controlling anterograde trafficking of ionotropic glutamate receptors (PMID:12368290)
• kinetics for the opening of the GluR1Qflip channel (PMID:14610080)
• This study investigated whether the AMPA receptor subunit content (GluR1, GluR2, GluR2/3) within “vulnerable” vs. “resistant” sectors of the hippocampus is quantitatively altered with increasing Alzheimer Disease neuropathology (PMID:15144856)
• cell loss and up-regulation of glutamate receptor subunits appear early in temporal lobe epilepsy and contribute to the synaptic plasticity that may facilitate the subsequent sprouting of mossy fiber collaterals (PMID:15145077)
• According to receptor simulations, most differences can be explained if the C-terminal domain is assumed to stabilize the ligand-bound closed and open states. (PMID:15866042)
• Data indicate that GRIA1 may be involved in susceptibility to DSM-IV-TR schizophrenia. (PMID:16526023)
• Results indicate that CTZ and TCM target deactivation and agonist potency independently of desensitization, most likely by modifying agonist dissociation (koff). (PMID:17208968)
• the Q/R site modulates the interaction of stargazin with the transmembrane domains of AMPA receptors via an allosteric mechanism and that this modulation leads to the observed differences in the electrophysiological properties of the receptor (PMID:17483093)
• biochemical study of GLUR1 L497Y AMPA receptor (PMID:17545169)
• AKAP79 provides a mechanism to overcome limitations in kinase abundance thereby ensuring faithful signal propagation and efficient modification of AMPA receptor-mediated responses (PMID:18305116)
• These results suggest that AMPA receptors are abundantly expressed in high-grade gliomas and gene silencing of the GluR1 AMPA receptor subunit results in abrogation of AMPA-mediated signaling and tumor growth. (PMID:18317690)
• combined analysis of all 60 families continued to support evidence for association of GRIA1 with psychotic BP; however, individual SNPs could not be replicated across datasets (PMID:18484081)
• Overexpression of GluR1 positively correlated with glioma cell adhesion to type I and type IV collagen (PMID:18957620)
• Attenuated AMPA receptor expression allows glioblastoma cell survival in glutamate-rich environment (PMID:19536293)
• the intracellularly located CTD of GLUR1 is the origin of TARP-specific functional modulation and not merely a facilitator of trafficking (PMID:19773551)
• Data show that S-nitrosylation of stargazin increases binding to the AMPAR subunit GluR1, causing increased surface expression of the AMPAR. (PMID:19805317)
• Increase in GluR1 trafficking by leptin is associated with an increase in phosphatidylinositol 3,4,5-triphosphate (PtdIns(3,4,5)P3) levels. (PMID:20237279)
• Two variants in the regulative regions of GRIA1 (rs2195450) and GRIA3 (rs3761555) genes resulted strongly associated with MA (P = 0.00002 and P = 0.0001, respectively), but not associated with MO. (PMID:20579352)
• single-nucleotide polymorphisms annotated to GRIA1 were also significantly associated with allergy to asparaginase (PMID:20592726)
• Findings reveal the ligand-binding domain as the critical quality control target in AMPAR biogenesis. (PMID:20837486)
• In transgenic Caenorhabditis elegans, glutamate receptor 1 is required for nose-touch avoidance behavior. (PMID:21037582)
• These results do not support a significant role of GRIA1 or CLINT1 in the development of schizophrenia in the German population. (PMID:21116212)
• by favoring apoCaM binding to AKAP79, KN-62 and KN-93 derail the ability of AKAP79 to efficiently recruit PKC for regulation of GluA1. Thus, AKAP79 endows PKC with a pharmacological profile that overlaps with CaMKII. (PMID:21156788)
• These results provide critical new insights into the agonist dependence of both AMPA receptor activation and desensitization and the mechanism of the effects of stargazin on responses of partial agonists. (PMID:21697386)
• New insights in endosomal dynamics and AMPA receptor trafficking (PMID:21843653)
• analysis of how the AMPA receptor is activated by partial agonists (PMID:21846932)
• AMPA receptor regulation during synaptic plasticity in hippocampus and neocortex (PMID:21856433)
• Did not observed any significant association between GRIA1 polymorphisms and clinical improvement in patients with Major depressive disorder. (PMID:22057216)
• No significant association GRIA1 polymorphisms was found with the diagnosis of schizophrenia. (PMID:22094384)
• SNPs within GRIA1 may not be associated with the development and treatment outcomes in BD (PMID:22122651)
• These results suggest that GRIA1 polymorphism may have influence upon the risk of developing schizophrenia. (PMID:23053966)
• Glioblastoma brain tumor initiating cells express high concentrations of functional calcium-permeable AMPA receptors, raising the possibility that glutamate secretion in the GBM tumor microenvironment may stimulate brain tumor derived cancer stem cells. (PMID:23110111)
• human hippocampal samples from neonatal seizure autopsy cases also showed an increase in GluR1 S831 and S845. (PMID:23223299)
• Studies indicate that AMPAR trafficking is a key mechanism that drives nascent synapse development, and is the main determinant of both Hebbian and homeostatic plasticity in mature synapses. (PMID:23475111)
• Inhibition of CREB function is associated with a specific reduction of AMPA receptor subunit GluA1. (PMID:23504989)
• This study failed to replicate previously reported association between GRIA1 rs548294 and migraine without aura, either as single marker or when analyzed in haplotype combination with rs2195450. (PMID:24030684)
• the levels were comparable for complexes containing GluR2, GluR3 and GluR4 as well as 5-HT1A. Moreover, the levels of complexes containing muscarinic AChR M1, NR1 and GluR1 were significantly increased in male patients with AD. (PMID:24292102)
• insight into the structure and function of the C-terminal domain of GluA1, which controls AMPA receptor function and trafficking during synaptic plasticity in the central nervous system. (PMID:24452473)

Cross-species orthologs

43 orthologs

Organism	Symbol	Gene ID
danio_rerio	gria1a	ENSDARG00000021352
danio_rerio	gria1b	ENSDARG00000032714
mus_musculus	Gria1	ENSMUSG00000020524
rattus_norvegicus	Gria1	ENSRNOG00000045816
drosophila_melanogaster	GluRIA	FBGN0004619
drosophila_melanogaster	GluRIIA	FBGN0004620
drosophila_melanogaster	GluRIIB	FBGN0020429
drosophila_melanogaster	clumsy	FBGN0026255
drosophila_melanogaster	GluRIID	FBGN0028422
drosophila_melanogaster	Ir7b	FBGN0029965
drosophila_melanogaster	Ir7c	FBGN0029966
drosophila_melanogaster	Ir7g	FBGN0029968
drosophila_melanogaster	Ir25a	FBGN0031634
drosophila_melanogaster	Ir60a	FBGN0034994
drosophila_melanogaster	Ir64a	FBGN0035604
drosophila_melanogaster	Ir68a	FBGN0036150
drosophila_melanogaster	Ir68b	FBGN0036250
drosophila_melanogaster	Ir75a	FBGN0036757
drosophila_melanogaster	Ir75d	FBGN0036829
drosophila_melanogaster	Ir76b	FBGN0036937
drosophila_melanogaster	Ir84a	FBGN0037501
drosophila_melanogaster	Ir85a	FBGN0037630
drosophila_melanogaster	Ir92a	FBGN0038789
drosophila_melanogaster	Grik	FBGN0038840
drosophila_melanogaster	Ekar	FBGN0039916
drosophila_melanogaster	CG11155	FBGN0039927
drosophila_melanogaster	Ir41a	FBGN0040849
drosophila_melanogaster	GluRIIC	FBGN0046113
drosophila_melanogaster	GluRIIE	FBGN0051201
drosophila_melanogaster	Nmdar2	FBGN0053513
drosophila_melanogaster	Ir7e	FBGN0259189
drosophila_melanogaster	Ir94d	FBGN0259193
drosophila_melanogaster	Ir93a	FBGN0259215
drosophila_melanogaster	Ir40a	FBGN0259683
drosophila_melanogaster	Ir76a	FBGN0260874
drosophila_melanogaster	Ir75c	FBGN0261401
drosophila_melanogaster	Ir75b	FBGN0261402
drosophila_melanogaster	GluRIB	FBGN0264000
caenorhabditis_elegans		WBGENE00001612
caenorhabditis_elegans	glr-3	WBGENE00001614
caenorhabditis_elegans		WBGENE00001618
caenorhabditis_elegans		WBGENE00003775
caenorhabditis_elegans		WBGENE00012190

Paralogs (17): GRIN2D (ENSG00000105464), GRIK5 (ENSG00000105737), GRIN3B (ENSG00000116032), GRIA2 (ENSG00000120251), GRIA3 (ENSG00000125675), GRIK4 (ENSG00000149403), GRID2 (ENSG00000152208), GRIA4 (ENSG00000152578), GRIN2C (ENSG00000161509), GRIK3 (ENSG00000163873), GRIK2 (ENSG00000164418), GRIK1 (ENSG00000171189), GRIN1 (ENSG00000176884), GRID1 (ENSG00000182771), GRIN2A (ENSG00000183454), GRIN3A (ENSG00000198785), GRIN2B (ENSG00000273079)

Protein

Protein identifiers

Glutamate receptor 1 — P42261 (reviewed: P42261)

Alternative names: AMPA-selective glutamate receptor 1, GluR-A, GluR-K1, Glutamate receptor ionotropic, AMPA 1

All UniProt accessions (5): P42261, A0A9L9PXA5, A0A9L9PXG3, A0A9L9PXX0, A0A9L9PYA4

UniProt curated annotations — full annotation on UniProt →

Function. Ionotropic glutamate receptor that functions as a ligand-gated cation channel, gated by L-glutamate and glutamatergic agonists such as alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), quisqualic acid, and kainic acid. L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system. Binding of the excitatory neurotransmitter L-glutamate induces a conformation change, leading to the opening of the cation channel, and thereby converts the chemical signal to an electrical impulse upon entry of monovalent and divalent cations such as sodium and calcium. The receptor then desensitizes rapidly and enters in a transient inactive state, characterized by the presence of bound agonist. In the presence of CACNG2 or CACNG4 or CACNG7 or CACNG8, shows resensitization which is characterized by a delayed accumulation of current flux upon continued application of L-glutamate. Resensitization is blocked by CNIH2 through interaction with CACNG8 in the CACNG8-containing AMPA receptors complex. Calcium (Ca(2+)) permeability depends on subunits composition and, heteromeric channels containing edited GRIA2 subunit are calcium-impermeable. Also permeable to other divalents cations such as strontium(2+) and magnesium(2+) and monovalent cations such as potassium(1+) and lithium(1+).

Subunit / interactions. Homotetramer or heterotetramer of pore-forming glutamate receptor subunits; heteromeric assembly can be the result of both receptor subtype and flip or flop form and according the composition, one partner can be dominant with respect to the fast desensitizing current component, whereas the other can determine the steady-state component. Tetramers may be formed by the dimerization of dimers. Found in a complex with GRIA2, GRIA3, GRIA4, CNIH2, CNIH3, CACNG2, CACNG3, CACNG4, CACNG5, CACNG7 and CACNG8. Interacts with HIP1 and RASGRF2. Interacts with SYNDIG1 and GRIA2. Interacts with DLG1 (via C-terminus). Interacts with LRFN1. Interacts with PRKG2. Interacts with CNIH2 and CACNG2. Interacts with CACNG5; this interaction modulates the gating. Interacts (via C-terminus) with PDLIM4 (via LIM domain); this interaction as well as the interaction of PDLIM4 with alpha-actinin is required for their colocalization in early endosomes. Interacts with SNX27 (via PDZ domain); the interaction is required for recycling to the plasma membrane when endocytosed and prevent degradation in lysosomes. Interacts (via PDZ-binding motif) with SHANK3 (via PDZ domain). Interacts with CACNG3; associates GRIA1 with the adapter protein complex 4 (AP-4) to target GRIA1 to the somatodendritic compartment of neurons. Interacts with CACNG2; this interaction mediates traffick to the plasma membrane and modulation of desensitization. Interacts with CNIH2 and CNIH3; this interaction promotes expression at the plasma membrane and extensively modulates their gating properties by slowing deactivation and desensitization kinetics. Found in a complex with GRIA2, GRIA3, GRIA4, DLG4, CACNG8 and CNIH2.

Subcellular location. Cell membrane. Endoplasmic reticulum membrane. Postsynaptic cell membrane. Postsynaptic density membrane. Cell projection. Dendrite. Dendritic spine. Early endosome membrane. Recycling endosome membrane. Presynapse. Synapse.

Tissue specificity. Widely expressed in brain.

Post-translational modifications. Palmitoylated. Depalmitoylated by CPT1C and upon L-glutamate stimulation. ZDHHC3/GODZ specifically palmitoylates Cys-603, which leads to Golgi retention and decreased cell surface expression. In contrast, Cys-829 palmitoylation does not affect cell surface expression but regulates stimulation-dependent endocytosis. Phosphorylated at Ser-645. Phosphorylated at Ser-710 by PKC. Phosphorylated at Ser-849 by PKC, PKA and CAMK2. Phosphorylated at Ser-863 by PKC, PKA and PRKG2. Phosphorylation of Ser-863 is reduced by induction of long-term depression and increased by induction of long-term potentiation.

Disease relevance. Intellectual developmental disorder, autosomal dominant 67 (MRD67) [MIM:619927] An autosomal dominant disorder characterized by global development delay and impaired intellectual development apparent from infancy or early childhood. Additional features may include behavioral abnormalities, and language and sleeping difficulties. The disease is caused by variants affecting the gene represented in this entry. Intellectual developmental disorder, autosomal recessive 76 (MRT76) [MIM:619931] An autosomal recessive disorder characterized by global developmental delay, severely impaired intellectual development, absent speech, seizures, sleep disturbances, and feeding difficulties. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The M4 transmembrane segment mediates tetramerization and is required for cell surface expression.

Miscellaneous. The postsynaptic actions of L-glutamate are mediated by a variety of receptors that are named according to their selective agonists. This receptor binds AMPA (quisqualate) > L-glutamate > kainate.

Similarity. Belongs to the glutamate-gated ion channel (TC 1.A.10.1) family. GRIA1 subfamily.

Isoforms (6)

UniProt ID	Names	Canonical?
P42261-1	Flop	yes
P42261-2	Flip
P42261-3	3
P42261-4	4
P42261-5	5
P42261-6	6

RefSeq proteins (10): NP_000818, NP_001107655, NP_001244948, NP_001244949, NP_001244950, NP_001244951, NP_001244952, NP_001351094, NP_001351095, NP_001351096 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001320	Iontro_rcpt_C	Domain
IPR001508	Iono_Glu_rcpt_met	Family
IPR001828	ANF_lig-bd_rcpt	Domain
IPR015683	Ionotropic_Glu_rcpt	Family
IPR019594	Glu/Gly-bd	Domain
IPR028082	Peripla_BP_I	Homologous_superfamily

Pfam: PF00060, PF01094, PF10613

Catalyzed reactions (Rhea), 6 shown:

• K(+)(in) = K(+)(out) (RHEA:29463)
• Ca(2+)(in) = Ca(2+)(out) (RHEA:29671)
• Mg(2+)(in) = Mg(2+)(out) (RHEA:29827)
• Na(+)(in) = Na(+)(out) (RHEA:34963)
• Li(+)(in) = Li(+)(out) (RHEA:78551)
• Sr(2+)(in) = Sr(2+)(out) (RHEA:78679)

UniProt features (54 total): sequence variant 10, binding site 6, glycosylation site 6, topological domain 5, sequence conflict 5, modified residue 4, splice variant 4, transmembrane region 3, lipid moiety-binding region 2, disulfide bond 2, intramembrane region 2, signal peptide 1, chain 1, region of interest 1, short sequence motif 1, helix 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
6X5Q	X-RAY DIFFRACTION	2.14

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P42261-F1	81.77	0.48

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (6): 492; 494; 499; 668; 669; 719

Post-translational modifications (6): 645, 710, 849, 863, 603, 829

Disulfide bonds (2): 75–323, 732–787

Glycosylation sites (6): 63, 249, 257, 363, 401, 406

Function

Pathways and Gene Ontology

Reactome pathways

8 pathways

ID	Pathway
R-HSA-204005	COPII-mediated vesicle transport
R-HSA-399710	Activation of AMPA receptors
R-HSA-399719	Trafficking of AMPA receptors
R-HSA-416993	Trafficking of GluR2-containing AMPA receptors
R-HSA-438066	Unblocking of NMDA receptors, glutamate binding and activation
R-HSA-5694530	Cargo concentration in the ER
R-HSA-8849932	Synaptic adhesion-like molecules
R-HSA-9620244	Long-term potentiation

MSigDB gene sets: 447 (showing top): GSE45365_NK_CELL_VS_CD11B_DC_UP, GOBP_SPINAL_CORD_DEVELOPMENT, GOBP_MEMORY, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_RESPONSE_TO_ETHANOL, MODY_HIPPOCAMPUS_POSTNATAL, GOBP_COGNITION, GOBP_BEHAVIOR, GOBP_RESPONSE_TO_ELECTRICAL_STIMULUS, GOBP_RESPONSE_TO_ESTRADIOL, GOBP_RESPONSE_TO_COCAINE, GOMF_GLUTAMATE_GATED_RECEPTOR_ACTIVITY, GOBP_RESPONSE_TO_AMINE, GOBP_RESPONSE_TO_ACID_CHEMICAL, GOBP_SYNAPSE_ASSEMBLY

GO Biological Process (50): regulation of receptor recycling (GO:0001919), signal transduction (GO:0007165), chemical synaptic transmission (GO:0007268), synapse assembly (GO:0007416), long-term memory (GO:0007616), response to xenobiotic stimulus (GO:0009410), response to sucrose (GO:0009744), response to lithium ion (GO:0010226), positive regulation of gene expression (GO:0010628), neuronal action potential (GO:0019228), spinal cord development (GO:0021510), cerebral cortex development (GO:0021987), receptor internalization (GO:0031623), response to nutrient levels (GO:0031667), response to estradiol (GO:0032355), regulation of monoatomic ion transmembrane transport (GO:0034765), synaptic transmission, glutamatergic (GO:0035249), response to cocaine (GO:0042220), response to morphine (GO:0043278), response to ethanol (GO:0045471), positive regulation of membrane potential (GO:0045838), response to arsenic-containing substance (GO:0046685), behavioral response to pain (GO:0048266), modulation of chemical synaptic transmission (GO:0050804), response to electrical stimulus (GO:0051602), long-term synaptic potentiation (GO:0060291), long-term synaptic depression (GO:0060292), response to fungicide (GO:0060992), cellular response to ammonium ion (GO:0071242), cellular response to dsRNA (GO:0071359), cellular response to peptide hormone stimulus (GO:0071375), cellular response to amine stimulus (GO:0071418), positive regulation of locomotion involved in locomotory behavior (GO:0090326), cellular response to L-glutamate (GO:1905232), cellular response to brain-derived neurotrophic factor stimulus (GO:1990416), conditioned place preference (GO:1990708), response to psychosocial stress (GO:1990911), positive regulation of excitatory postsynaptic potential (GO:2000463), monoatomic ion transport (GO:0006811), response to toxic substance (GO:0009636)

GO Molecular Function (25): amyloid-beta binding (GO:0001540), G-protein alpha-subunit binding (GO:0001965), AMPA glutamate receptor activity (GO:0004971), adenylate cyclase binding (GO:0008179), immunoglobulin binding (GO:0019865), protein kinase binding (GO:0019901), glutamate-gated calcium ion channel activity (GO:0022849), PDZ domain binding (GO:0030165), small GTPase binding (GO:0031267), myosin V binding (GO:0031489), G-protein beta-subunit binding (GO:0031681), beta-2 adrenergic receptor binding (GO:0031698), glutamate receptor binding (GO:0035254), identical protein binding (GO:0042802), protein kinase A binding (GO:0051018), peptide hormone receptor binding (GO:0051428), scaffold protein binding (GO:0097110), ligand-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential (GO:0099507), transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential (GO:1904315), glutamate-gated receptor activity (GO:0004970), monoatomic ion channel activity (GO:0005216), protein binding (GO:0005515), ligand-gated monoatomic ion channel activity (GO:0015276), protein domain specific binding (GO:0019904), signaling receptor activity (GO:0038023)

GO Cellular Component (50): endoplasmic reticulum membrane (GO:0005789), cytosol (GO:0005829), plasma membrane (GO:0005886), cell-cell junction (GO:0005911), external side of plasma membrane (GO:0009897), cell surface (GO:0009986), ER to Golgi transport vesicle membrane (GO:0012507), postsynaptic density (GO:0014069), dendrite (GO:0030425), endocytic vesicle membrane (GO:0030666), synaptic vesicle membrane (GO:0030672), neuromuscular junction (GO:0031594), early endosome membrane (GO:0031901), AMPA glutamate receptor complex (GO:0032281), dendritic spine membrane (GO:0032591), neuronal cell body membrane (GO:0032809), endoplasmic reticulum-Golgi intermediate compartment membrane (GO:0033116), neuronal cell body (GO:0043025), dendritic spine (GO:0043197), dendritic shaft (GO:0043198), axonal spine (GO:0044308), neuron spine (GO:0044309), postsynaptic membrane (GO:0045211), presynaptic active zone membrane (GO:0048787), recycling endosome (GO:0055037), recycling endosome membrane (GO:0055038), excitatory synapse (GO:0060076), synaptic membrane (GO:0097060), presynapse (GO:0098793), postsynaptic density membrane (GO:0098839), glutamatergic synapse (GO:0098978), postsynaptic density, intracellular component (GO:0099092), perisynaptic space (GO:0099544), proximal dendrite (GO:1990635), endosome (GO:0005768), early endosome (GO:0005769), endoplasmic reticulum (GO:0005783), synaptic vesicle (GO:0008021), ionotropic glutamate receptor complex (GO:0008328), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
ER to Golgi Anterograde Transport	2
Glutamate binding, activation of AMPA receptors and synaptic plasticity	2
Trafficking of AMPA receptors	1
Activation of NMDA receptors and postsynaptic events	1
Protein-protein interactions at synapses	1
Post NMDA receptor activation events	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein binding	5
cellular anatomical structure	3
anatomical structure development	2
response to oxygen-containing compound	2
glutamate-gated receptor activity	2
transmitter-gated monoatomic ion channel activity	2
bounding membrane of organelle	2
dendrite	2
receptor recycling	1
regulation of signaling	1
regulation of macromolecule metabolic process	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
anterograde trans-synaptic signaling	1
nervous system development	1
cell junction assembly	1
synapse organization	1
memory	1
response to chemical	1
response to disaccharide	1
response to metal ion	1
gene expression	1
regulation of gene expression	1
positive regulation of macromolecule biosynthetic process	1
action potential	1
transmission of nerve impulse	1
central nervous system development	1
pallium development	1
receptor-mediated endocytosis	1
response to stimulus	1
response to lipid	1
monoatomic ion transmembrane transport	1
regulation of transmembrane transport	1
regulation of monoatomic ion transport	1
chemical synaptic transmission	1
response to alkaloid	1
response to isoquinoline alkaloid	1

Protein interactions and networks

STRING

3360 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GRIA1	DLG1	Q12959	995
GRIA1	EPB41L1	Q9H4G0	991
GRIA1	CACNG2	Q9Y698	990
GRIA1	GRIA4	P48058	983
GRIA1	GRIA3	P42263	983
GRIA1	GRIA2	P42262	982
GRIA1	DLG4	P78352	982
GRIA1	GRM2	Q14416	965
GRIA1	SHISA9	B4DS77	946
GRIA1	GRM5	P41594	901
GRIA1	CNIH1	O95406	899
GRIA1	CAMK2A	Q9UQM7	891
GRIA1	CACNG8	Q8WXS5	882
GRIA1	HOMER1	Q86YM7	873
GRIA1	GRIP1	Q9Y3R0	869

IntAct

20 interactions, top by confidence:

A	B	Type	Score
GRIA1	ZNF232	psi-mi:“MI:0915”(physical association)	0.560
GRIA1	BECN1	psi-mi:“MI:0915”(physical association)	0.560
GRIA1	RAB11B	psi-mi:“MI:0915”(physical association)	0.560
GRIA1	KLF15	psi-mi:“MI:0915”(physical association)	0.560
GRIA1	ASCL4	psi-mi:“MI:0915”(physical association)	0.560
PPP1CA	GRIA1	psi-mi:“MI:0203”(dephosphorylation reaction)	0.440
PRKACA	GRIA1	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
GRIA1	CXCR2	psi-mi:“MI:0915”(physical association)	0.400
GRIA1	GAPDHS	psi-mi:“MI:0914”(association)	0.350

BioGRID (63): GRIA1 (Biochemical Activity), GRIA1 (FRET), GRIA1 (Biochemical Activity), GRIA1 (Reconstituted Complex), GRIA1 (Synthetic Lethality), EPB41L1 (Reconstituted Complex), GRID2 (Affinity Capture-Western), GRIA1 (Affinity Capture-Western), GRIA1 (Affinity Capture-Western), GRIA1 (FRET), GRIA1 (Affinity Capture-Western), GRIA1 (Affinity Capture-Western), GRIA2 (Affinity Capture-Western), GRIA1 (Biochemical Activity), GRIA1 (Biochemical Activity)

ESM2 similar proteins: A0A2R8QF68, B1AS29, P19439, P19490, P19491, P19492, P19493, P20262, P22756, P23818, P23819, P26591, P31422, P34299, P39086, P39087, P42260, P42261, P42262, P42263, P42264, P48058, Q01812, Q03445, Q13002, Q13003, Q14832, Q16099, Q16478, Q1ZZH1, Q21415, Q38PU2, Q38PU3, Q38PU4, Q38PU5, Q38PU6, Q38PU7, Q38PU8, Q5IS46, Q5R4M0

Diamond homologs: A0A2R8QF68, A7XY94, B1AS29, E9NA96, P19439, P19490, P19491, P19492, P19493, P20262, P22756, P23818, P23819, P26591, P34299, P35436, P39086, P39087, P42260, P42261, P42262, P42263, P42264, P48058, Q00959, Q01812, Q03445, Q10914, Q12879, Q13002, Q13003, Q16099, Q16478, Q21415, Q38PU2, Q38PU3, Q38PU4, Q38PU5, Q38PU6, Q38PU7

SIGNOR signaling

14 interactions.

A	Effect	B	Mechanism
PRKCA	unknown	GRIA1	phosphorylation
PRKACA	“up-regulates activity”	GRIA1	phosphorylation
SHANK3	“up-regulates quantity”	GRIA1	binding
GRIA1	up-regulates	Excitatory_synaptic_transmission
“glutamic acid”	“up-regulates activity”	GRIA1	“chemical activation”
IQSEC2	“up-regulates quantity”	GRIA1	relocalization
GRIA1	“up-regulates quantity”	calcium(2+)	relocalization
PRKG2	“up-regulates activity”	GRIA1	phosphorylation
NEDD4	“down-regulates quantity”	GRIA1	ubiquitination
NPTX1	“up-regulates activity”	GRIA1	binding
CAMK2G	“up-regulates activity”	GRIA1	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

239 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	5
Uncertain significance	162
Likely benign	49
Benign	7

Top pathogenic / likely-pathogenic (6)

Variant ID	HGVS	Classification
1693467	NM_000827.4(GRIA1):c.1129C>T (p.Arg377Ter)	Pathogenic
1676545	NM_000827.4(GRIA1):c.1523C>A (p.Pro508Gln)	Likely pathogenic
2024127	NM_000827.4(GRIA1):c.377G>T (p.Arg126Leu)	Likely pathogenic
2500992	NM_000827.4(GRIA1):c.1538G>A (p.Gly513Glu)	Likely pathogenic
2500998	NM_000827.4(GRIA1):c.2615G>C (p.Ser872Thr)	Likely pathogenic
3037836	NM_000827.4(GRIA1):c.848G>A (p.Trp283Ter)	Likely pathogenic

SpliceAI

3889 predictions. Top by Δscore:

Variant	Effect	Δscore
5:153494061:TAGAT:T	donor_gain	1.0000
5:153494063:GAT:G	donor_gain	1.0000
5:153494064:AT:A	donor_gain	1.0000
5:153494064:ATGT:A	donor_loss	1.0000
5:153494065:TG:T	donor_loss	1.0000
5:153494066:G:GA	donor_loss	1.0000
5:153494066:G:GG	donor_gain	1.0000
5:153494067:TAA:T	donor_loss	1.0000
5:153646926:A:AG	acceptor_gain	1.0000
5:153646926:AGTCT:A	acceptor_gain	1.0000
5:153646927:G:GA	acceptor_gain	1.0000
5:153646927:GT:G	acceptor_gain	1.0000
5:153646927:GTC:G	acceptor_gain	1.0000
5:153646927:GTCT:G	acceptor_gain	1.0000
5:153646927:GTCTG:G	acceptor_gain	1.0000
5:153647164:CGGG:C	donor_gain	1.0000
5:153647165:GGG:G	donor_gain	1.0000
5:153647165:GGGG:G	donor_gain	1.0000
5:153647166:GG:G	donor_gain	1.0000
5:153647166:GGG:G	donor_gain	1.0000
5:153647167:GG:G	donor_gain	1.0000
5:153647168:G:GC	donor_loss	1.0000
5:153647168:G:GG	donor_gain	1.0000
5:153647169:TAAG:T	donor_loss	1.0000
5:153650313:A:AG	acceptor_gain	1.0000
5:153650314:C:G	acceptor_gain	1.0000
5:153650317:A:AG	acceptor_gain	1.0000
5:153650317:ATCT:A	acceptor_gain	1.0000
5:153650318:T:G	acceptor_gain	1.0000
5:153650320:T:A	acceptor_gain	1.0000

AlphaMissense

5992 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:153490970:G:T	G28W	1.000
5:153646930:T:A	C75S	1.000
5:153646930:T:C	C75R	1.000
5:153646931:G:A	C75Y	1.000
5:153646931:G:C	C75S	1.000
5:153646932:T:G	C75W	1.000
5:153646966:G:A	G87R	1.000
5:153646966:G:C	G87R	1.000
5:153646966:G:T	G87W	1.000
5:153646967:G:A	G87E	1.000
5:153647009:G:A	C101Y	1.000
5:153647010:T:G	C101W	1.000
5:153647018:T:C	L104P	1.000
5:153647068:T:C	F121L	1.000
5:153647070:T:A	F121L	1.000
5:153647070:T:G	F121L	1.000
5:153650342:T:C	L158P	1.000
5:153677007:T:C	L292P	1.000
5:153677018:G:T	G296W	1.000
5:153677039:G:C	A303P	1.000
5:153677052:T:C	L307P	1.000
5:153677099:T:A	C323S	1.000
5:153677099:T:C	C323R	1.000
5:153677100:G:A	C323Y	1.000
5:153677100:G:C	C323S	1.000
5:153677101:T:G	C323W	1.000
5:153677123:T:A	W331R	1.000
5:153677123:T:C	W331R	1.000
5:153677125:G:C	W331C	1.000
5:153677125:G:T	W331C	1.000

dbSNP variants (sampled 300 via entrez): RS1000003670 (5:153489958 G>A,C), RS1000013448 (5:153705516 C>A,G), RS1000024777 (5:153748999 G>A), RS1000033985 (5:153655882 G>A), RS1000035375 (5:153621129 T>C), RS1000051018 (5:153662024 C>A), RS1000069727 (5:153790736 C>T), RS1000078626 (5:153702041 C>T), RS1000078746 (5:153659106 C>T), RS1000099295 (5:153618827 G>A), RS1000103327 (5:153490242 T>G), RS1000107833 (5:153808747 A>G), RS1000121470 (5:153576105 A>G), RS1000128593 (5:153742475 A>G), RS1000137288 (5:153650000 G>C)

Disease associations

OMIM: gene MIM:138248 | disease phenotypes: MIM:619927, MIM:619931, MIM:156200

GenCC curated gene-disease

Disease	Classification	Inheritance
intellectual developmental disorder, autosomal dominant 67	Strong	Autosomal dominant
complex neurodevelopmental disorder	Strong	Autosomal dominant
intellectual developmental disorder, autosomal recessive 76	Limited	Autosomal recessive

ClinGen Gene-Disease Validity (2)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
complex neurodevelopmental disorder	Moderate	AD
complex neurodevelopmental disorder	Limited	AR

Mondo (8): neurodevelopmental disorder (MONDO:0700092), intellectual developmental disorder, autosomal dominant 67 (MONDO:0030964), intellectual developmental disorder, autosomal recessive 76 (MONDO:0030968), autism spectrum disorder (MONDO:0005258), intellectual disability (MONDO:0001071), intellectual disability, autosomal dominant 1 (MONDO:0007974), non-syndromic intellectual disability (MONDO:0000509), complex neurodevelopmental disorder (MONDO:0100038)

Orphanet (3): 2q23.1 microdeletion syndrome (Orphanet:228402), NON RARE IN EUROPE: Autism (Orphanet:106), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

33 total (30 of 33 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000483	Astigmatism
HP:0000506	Telecanthus
HP:0000722	Compulsive behaviors
HP:0000729	Autistic behavior
HP:0000750	Delayed speech and language development
HP:0000752	Hyperactivity
HP:0000821	Hypothyroidism
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001260	Dysarthria
HP:0001263	Global developmental delay
HP:0001270	Motor delay
HP:0001344	Absent speech
HP:0002020	Gastroesophageal reflux
HP:0002194	Delayed gross motor development
HP:0002205	Recurrent respiratory infections
HP:0002360	Sleep disturbance
HP:0003593	Infantile onset
HP:0007018	Attention deficit hyperactivity disorder
HP:0007302	Bipolar affective disorder
HP:0010465	Precocious puberty in females
HP:0010862	Delayed fine motor development
HP:0010864	Severe intellectual disability
HP:0011182	Interictal epileptiform activity
HP:0011327	Posterior plagiocephaly
HP:0011968	Feeding difficulties
HP:0012450	Chronic constipation
HP:0012471	Thick vermilion border

GWAS associations

30 associations (top):

Study	Trait	p-value
GCST000327_1	Anthropometric traits	9.000000e-06
GCST000715_1	Asparaginase hypersensitivity in acute lymphoblastic leukemia	4.000000e-07
GCST001099_33	Sudden cardiac arrest	3.000000e-10
GCST001166_3	Aging (time to event)	7.000000e-06
GCST001762_431	Obesity-related traits	8.000000e-06
GCST002149_10	Schizophrenia	3.000000e-09
GCST002539_61	Schizophrenia	1.000000e-10
GCST002820_8	Survival in microsatellite instability low/stable colorectal cancer	8.000000e-06
GCST002985_5	Middle childhood and early adolescence aggressive behavior	5.000000e-06
GCST003263_48	Post bronchodilator FEV1 in COPD	3.000000e-06
GCST004946_114	Schizophrenia	1.000000e-09
GCST004946_41	Schizophrenia	4.000000e-08
GCST005830_111	Hand grip strength	4.000000e-11
GCST006103_18	Interleukin-6 levels	5.000000e-06
GCST007201_247	Schizophrenia	1.000000e-09
GCST007201_284	Schizophrenia	5.000000e-09
GCST007201_303	Schizophrenia	3.000000e-07
GCST007201_58	Schizophrenia	6.000000e-09
GCST007201_59	Schizophrenia	6.000000e-07
GCST007325_191	General risk tolerance (MTAG)	2.000000e-08
GCST007325_253	General risk tolerance (MTAG)	2.000000e-09
GCST007565_181	Morning person	6.000000e-14
GCST007565_4	Morning person	2.000000e-17
GCST007565_5	Morning person	2.000000e-18
GCST007565_72	Morning person	7.000000e-18
GCST007565_9	Morning person	4.000000e-18
GCST007576_29	Chronotype	2.000000e-18
GCST010242_156	HDL cholesterol levels	7.000000e-12
GCST010988_345	Adult body size	2.000000e-09
GCST012033_11	Sleep (1/3-day periodicity)	5.000000e-10

EFO canonical traits (12, from GWAS)

EFO ID	Trait name
EFO:0004302	anthropometric measurement
EFO:0004881	asparaginase hypersensitivity
EFO:0004278	sudden cardiac arrest
EFO:0022597	aging
EFO:0000638	overall survival
EFO:0007054	microsatellite instability measurement
EFO:0004314	forced expiratory volume
EFO:0006941	grip strength measurement
EFO:0004810	interleukin-6 measurement
EFO:0008579	risk-taking behaviour
EFO:0008328	chronotype measurement
EFO:0004612	high density lipoprotein cholesterol measurement

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D065886	Neurodevelopmental Disorders	F03.625
C566947	Mental Retardation, Autosomal Dominant 1 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (5): CHEMBL2009 (SINGLE PROTEIN), CHEMBL2096670 (PROTEIN COMPLEX GROUP), CHEMBL3883294 (PROTEIN COMPLEX), CHEMBL4296110 (PROTEIN COMPLEX), CHEMBL4296111 (PROTEIN COMPLEX)

Molecules with ChEMBL bioactivity

6 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 953,502 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1214124	PERAMPANEL	4	1,558
CHEMBL61593	CYCLOTHIAZIDE	4	4,410
CHEMBL575060	GLUTAMIC ACID	3	929,756
CHEMBL14935	TEZAMPANEL ANHYDROUS	2	106
CHEMBL275040	KAINIC ACID	2	15,084
CHEMBL39664	SELFOTEL	2	2,588

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs4958381	Toxicity	3	asparaginase	Acute lymphoblastic leukemia

PharmGKB variants

6 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs1994862	GRIA1		0.00	0
rs4958381	GRIA1	3	1.75	1	asparaginase
rs4958351	GRIA1		0.00	0
rs548294	GRIA1		0.00	0
rs2195450	GRIA1		0.00	0
rs6890057	GRIA1		0.00	0

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: lgic — Ionotropic glutamate receptors

Most potent curated ligand interactions (3 total), top 3:

Ligand	Action	Affinity	Parameter
LY392098	Positive	5.75	pEC50
LY404187	Positive	5.25	pEC50
cyclothiazide	Positive	4.72	pEC50

ChEMBL bioactivities

597 potent at pChembl≥5 of 678 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.30	IC50	0.05	nM	CHEMBL6019202
10.22	IC50	0.06	nM	CHEMBL5767381
10.22	IC50	0.06	nM	CHEMBL6041259
10.22	IC50	0.06	nM	CHEMBL5922169
10.10	IC50	0.08	nM	CHEMBL4522808
10.10	IC50	0.08	nM	CHEMBL5881588
10.10	IC50	0.08	nM	CHEMBL5942693
10.00	IC50	0.1	nM	CHEMBL4522808
10.00	IC50	0.1	nM	CHEMBL5769276
9.89	IC50	0.13	nM	CHEMBL5801723
9.89	IC50	0.13	nM	CHEMBL5849167
9.89	IC50	0.13	nM	CHEMBL5962844
9.80	IC50	0.16	nM	CHEMBL5827339
9.80	IC50	0.16	nM	CHEMBL6040712
9.80	IC50	0.16	nM	CHEMBL4581775
9.80	IC50	0.16	nM	CHEMBL5976032
9.80	IC50	0.16	nM	CHEMBL5861166
9.80	IC50	0.16	nM	CHEMBL5893567
9.70	IC50	0.1995	nM	CHEMBL4211865
9.70	IC50	0.1995	nM	CHEMBL4436028
9.70	IC50	0.2	nM	CHEMBL5741015
9.70	IC50	0.2	nM	CHEMBL5799670
9.70	IC50	0.2	nM	CHEMBL5968644
9.70	IC50	0.2	nM	CHEMBL4443161
9.70	IC50	0.2	nM	CHEMBL4436028
9.70	IC50	0.2	nM	CHEMBL5762623
9.70	IC50	0.2	nM	CHEMBL5923830
9.70	IC50	0.2	nM	CHEMBL4582925
9.60	IC50	0.2512	nM	CHEMBL4581775
9.60	IC50	0.25	nM	CHEMBL6011439
9.60	IC50	0.25	nM	CHEMBL5848546
9.49	IC50	0.32	nM	CHEMBL5747700
9.49	IC50	0.32	nM	CHEMBL4466359
9.49	IC50	0.32	nM	CHEMBL5769947
9.49	IC50	0.32	nM	CHEMBL6016209
9.49	IC50	0.32	nM	CHEMBL5820816
9.49	IC50	0.32	nM	CHEMBL6024024
9.49	IC50	0.32	nM	CHEMBL5824495
9.49	IC50	0.32	nM	CHEMBL6053236
9.49	IC50	0.32	nM	CHEMBL5918983
9.40	IC50	0.3981	nM	CHEMBL4522625
9.40	IC50	0.3981	nM	CHEMBL4466359
9.40	IC50	0.4	nM	CHEMBL6017626
9.40	IC50	0.4	nM	CHEMBL4522625
9.40	IC50	0.4	nM	CHEMBL5996019
9.40	IC50	0.4	nM	CHEMBL5862659
9.40	IC50	0.4	nM	CHEMBL5990023
9.40	IC50	0.4	nM	CHEMBL6031241
9.40	IC50	0.4	nM	CHEMBL6023541
9.30	IC50	0.5012	nM	CHEMBL4454257

PubChem BioAssay actives

282 with measured affinity, of 585 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
5-[2-(4-fluorophenyl)-8-(4-fluoropiperidin-1-yl)imidazo[1,2-a]pyrazin-3-yl]-1,3-dihydroindol-2-one	1542530: Negative allosteric modulation of recombinant human GluA1 flop isoform/TARPgamma2 expressed in HEK293 cells assessed as inhibition of glutamate-induced calcium flux at 100 uM by calcium 5/6 dye based FLIPR assay	ic50	0.0001	uM
5-[2-chloro-6-(trifluoromethoxy)phenyl]-7-methyl-1,3-dihydroindol-2-one	1385854: Modulation of recombinant human GluA1 flop isoform/TARPgamma8 expressed in HEK293F cells assessed as blockade of glutamate-induced calcium flux by calcium 5/6 dye based FLIPR assay	ic50	0.0002	uM
5-[2-(4-fluorophenyl)-7-(4-hydroxypiperidin-1-yl)pyrazolo[1,5-c]pyrimidin-3-yl]-1,3-dihydroindol-2-one	1542530: Negative allosteric modulation of recombinant human GluA1 flop isoform/TARPgamma2 expressed in HEK293 cells assessed as inhibition of glutamate-induced calcium flux at 100 uM by calcium 5/6 dye based FLIPR assay	ic50	0.0002	uM
5-[7-(4-acetylpiperazin-1-yl)-2-(4-fluorophenyl)pyrazolo[1,5-c]pyrimidin-3-yl]-1,3-dihydroindol-2-one	1542530: Negative allosteric modulation of recombinant human GluA1 flop isoform/TARPgamma2 expressed in HEK293 cells assessed as inhibition of glutamate-induced calcium flux at 100 uM by calcium 5/6 dye based FLIPR assay	ic50	0.0003	uM
5-[2-(4-fluorophenyl)-8-(4-hydroxypiperidin-1-yl)imidazo[1,2-a]pyrazin-3-yl]-1,3-dihydroindol-2-one	1542530: Negative allosteric modulation of recombinant human GluA1 flop isoform/TARPgamma2 expressed in HEK293 cells assessed as inhibition of glutamate-induced calcium flux at 100 uM by calcium 5/6 dye based FLIPR assay	ic50	0.0004	uM
5-[8-(4-acetylpiperazin-1-yl)-2-(4-fluorophenyl)imidazo[1,2-a]pyrazin-3-yl]-1,3-dihydroindol-2-one	1542530: Negative allosteric modulation of recombinant human GluA1 flop isoform/TARPgamma2 expressed in HEK293 cells assessed as inhibition of glutamate-induced calcium flux at 100 uM by calcium 5/6 dye based FLIPR assay	ic50	0.0004	uM
5-[2-(4-fluorophenyl)-7-morpholin-4-ylpyrazolo[1,5-c]pyrimidin-3-yl]-1,3-dihydroindol-2-one	1542530: Negative allosteric modulation of recombinant human GluA1 flop isoform/TARPgamma2 expressed in HEK293 cells assessed as inhibition of glutamate-induced calcium flux at 100 uM by calcium 5/6 dye based FLIPR assay	ic50	0.0005	uM
5-[2-(4-fluorophenyl)-8-morpholin-4-ylimidazo[1,2-a]pyrazin-3-yl]-1,3-dihydroindol-2-one	1542530: Negative allosteric modulation of recombinant human GluA1 flop isoform/TARPgamma2 expressed in HEK293 cells assessed as inhibition of glutamate-induced calcium flux at 100 uM by calcium 5/6 dye based FLIPR assay	ic50	0.0005	uM
5-[2-(4-fluorophenyl)-8-(3-oxopiperazin-1-yl)imidazo[1,2-a]pyrazin-3-yl]-1,3-dihydroindol-2-one	1542530: Negative allosteric modulation of recombinant human GluA1 flop isoform/TARPgamma2 expressed in HEK293 cells assessed as inhibition of glutamate-induced calcium flux at 100 uM by calcium 5/6 dye based FLIPR assay	ic50	0.0005	uM
4-[2-(4-fluorophenyl)-3-(1H-indazol-5-yl)imidazo[1,2-a]pyrazin-8-yl]morpholine	1542530: Negative allosteric modulation of recombinant human GluA1 flop isoform/TARPgamma2 expressed in HEK293 cells assessed as inhibition of glutamate-induced calcium flux at 100 uM by calcium 5/6 dye based FLIPR assay	ic50	0.0006	uM
5-[3-chloro-5-(trifluoromethoxy)-4-pyridinyl]-7-methyl-1,3-dihydroindol-2-one	1385854: Modulation of recombinant human GluA1 flop isoform/TARPgamma8 expressed in HEK293F cells assessed as blockade of glutamate-induced calcium flux by calcium 5/6 dye based FLIPR assay	ic50	0.0025	uM
5-[2-chloro-6-(trifluoromethoxy)phenyl]-7-fluoro-1,3-dihydroindol-2-one	1385854: Modulation of recombinant human GluA1 flop isoform/TARPgamma8 expressed in HEK293F cells assessed as blockade of glutamate-induced calcium flux by calcium 5/6 dye based FLIPR assay	ic50	0.0025	uM
6-[2-chloro-6-(trifluoromethoxy)phenyl]-3H-1,3-benzothiazol-2-one	1385854: Modulation of recombinant human GluA1 flop isoform/TARPgamma8 expressed in HEK293F cells assessed as blockade of glutamate-induced calcium flux by calcium 5/6 dye based FLIPR assay	ic50	0.0025	uM
N-[1-[5-(6-aminohexylamino)pentylamino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]butanamide	75670: Inhibition of the (-80 mV) current elicited by 100 uM glutamate by simultaneous co-application in xenopus oocytes injected with GluR1 flop RNA.	ki	0.0033	uM
5-[2-(4-fluorophenyl)-7-(4-fluoropiperidin-1-yl)pyrazolo[1,5-c]pyrimidin-3-yl]-1,3-dihydroindol-2-one	1542530: Negative allosteric modulation of recombinant human GluA1 flop isoform/TARPgamma2 expressed in HEK293 cells assessed as inhibition of glutamate-induced calcium flux at 100 uM by calcium 5/6 dye based FLIPR assay	ic50	0.0050	uM
5-[2-(4-fluorophenyl)-7-(3-oxopiperazin-1-yl)pyrazolo[1,5-c]pyrimidin-3-yl]-1,3-dihydroindol-2-one	1542530: Negative allosteric modulation of recombinant human GluA1 flop isoform/TARPgamma2 expressed in HEK293 cells assessed as inhibition of glutamate-induced calcium flux at 100 uM by calcium 5/6 dye based FLIPR assay	ic50	0.0050	uM
(2S)-2-amino-3-[5-(2-methyltetrazol-5-yl)-3-oxo-1,2-oxazol-4-yl]propanoic acid	239015: Binding affinity for ionotropic Glutamate receptor AMPA 1 expressed in Sf9 cells	ki	0.0052	uM
5-(2-chloro-6-cyclopropylphenyl)-1,3-dihydrobenzimidazol-2-one	1385854: Modulation of recombinant human GluA1 flop isoform/TARPgamma8 expressed in HEK293F cells assessed as blockade of glutamate-induced calcium flux by calcium 5/6 dye based FLIPR assay	ic50	0.0063	uM
(2S)-2-amino-3-(6-chloro-3,5-dioxo-1,2,4-triazin-2-yl)propanoic acid	92951: Displacement of [3H]AMPA from human Ionotropic glutamate receptor AMPA 1 expressed in HEK293 cells	ki	0.0071	uM
5-[3-chloro-5-(difluoromethoxy)-4-pyridinyl]-7-methyl-1,3-dihydroindol-2-one	1385854: Modulation of recombinant human GluA1 flop isoform/TARPgamma8 expressed in HEK293F cells assessed as blockade of glutamate-induced calcium flux by calcium 5/6 dye based FLIPR assay	ic50	0.0079	uM
5-[2-chloro-6-(trifluoromethoxy)phenyl]-1,3-dihydrobenzimidazol-2-one	1385854: Modulation of recombinant human GluA1 flop isoform/TARPgamma8 expressed in HEK293F cells assessed as blockade of glutamate-induced calcium flux by calcium 5/6 dye based FLIPR assay	ic50	0.0100	uM
2-[3-chloro-2-(2-oxo-1,3-dihydrobenzimidazol-5-yl)phenyl]acetonitrile	1385854: Modulation of recombinant human GluA1 flop isoform/TARPgamma8 expressed in HEK293F cells assessed as blockade of glutamate-induced calcium flux by calcium 5/6 dye based FLIPR assay	ic50	0.0100	uM
4-[2-(4-chlorophenyl)-8-morpholin-4-ylimidazo[1,2-a]pyrazin-3-yl]phenol	1542530: Negative allosteric modulation of recombinant human GluA1 flop isoform/TARPgamma2 expressed in HEK293 cells assessed as inhibition of glutamate-induced calcium flux at 100 uM by calcium 5/6 dye based FLIPR assay	ic50	0.0100	uM
4-[2-(4-fluorophenyl)-8-morpholin-4-ylimidazo[1,2-a]pyrazin-3-yl]phenol	1542530: Negative allosteric modulation of recombinant human GluA1 flop isoform/TARPgamma2 expressed in HEK293 cells assessed as inhibition of glutamate-induced calcium flux at 100 uM by calcium 5/6 dye based FLIPR assay	ic50	0.0126	uM
(2S)-2-amino-3-(5-fluoro-2,4-dioxopyrimidin-1-yl)propanoic acid	92951: Displacement of [3H]AMPA from human Ionotropic glutamate receptor AMPA 1 expressed in HEK293 cells	ki	0.0147	uM
5-[2-chloro-6-(trifluoromethoxy)phenyl]-1,3-dihydroindol-2-one	1385854: Modulation of recombinant human GluA1 flop isoform/TARPgamma8 expressed in HEK293F cells assessed as blockade of glutamate-induced calcium flux by calcium 5/6 dye based FLIPR assay	ic50	0.0158	uM
7-[4-[(4-carboxyphenyl)carbamoyloxymethyl]imidazol-1-yl]-3-oxo-6-(trifluoromethyl)-4H-quinoxaline-2-carboxylic acid	1859131: Binding affinity to AMPA receptor (unknown origin)	ki	0.0160	uM
8-(3-carboxypyrrol-1-yl)-7-nitro-4-oxo-5H-[1,2,4]triazolo[1,5-a]quinoxaline-2-carboxylic acid	1859112: Displacement of [3H]AMPA from AMPA receptor (unknown origin)	ki	0.0190	uM
2-amino-3-(5-methyl-3-oxo-1,2-oxazol-4-yl)propanoic acid	92807: Inhibition of the binding of radioligand [3H]AMPA in the presence at high-affinity AMPA receptor sites.	ic50	0.0190	uM
3-ethyl-12-imidazol-1-yl-11-nitro-2,5,8,13-tetrazatricyclo[7.4.0.02,6]trideca-1(13),3,5,9,11-pentaen-7-one	1859112: Displacement of [3H]AMPA from AMPA receptor (unknown origin)	ki	0.0200	uM
(2S)-2-amino-3-(5-methyl-3-oxo-1,2-oxazol-4-yl)propanoic acid	239015: Binding affinity for ionotropic Glutamate receptor AMPA 1 expressed in Sf9 cells	ki	0.0219	uM
7-[4-[(4-carboxyphenyl)carbamoyloxymethyl]imidazol-1-yl]-6-nitro-3-oxo-4H-quinoxaline-2-carboxylic acid	1859131: Binding affinity to AMPA receptor (unknown origin)	ki	0.0220	uM
6-[2-ethoxyethyl-(4-pyridin-2-yl-1,3-thiazol-2-yl)amino]-3H-1,3-benzothiazol-2-one	1309746: Antagonist activity at human iGluA1 receptor flop isoform expressed in CHO-S cells coexpressing TARP gamma-8 and human EAAT3 assessed as inhibition of glutamate-induced increase in intracellular calcium levels after 2 mins followed by cyclothiazide/glutamate addition by fluo-4 AM dye based fluorescence imaging plate reader method	ic50	0.0220	uM
(2S)-2-amino-3-(6-bromo-3,5-dioxo-1,2,4-triazin-2-yl)propanoic acid	92951: Displacement of [3H]AMPA from human Ionotropic glutamate receptor AMPA 1 expressed in HEK293 cells	ki	0.0290	uM
2-amino-3-[5-(2-methyltetrazol-5-yl)-3-oxo-1,2-oxazol-4-yl]propanoic acid	92806: In vitro binding affinity against Ionotropic glutamate receptor AMPA using [3H]AMPA as radioligand	ic50	0.0300	uM
N-[1-[4-(7-aminoheptylamino)butylamino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]butanamide	75670: Inhibition of the (-80 mV) current elicited by 100 uM glutamate by simultaneous co-application in xenopus oocytes injected with GluR1 flop RNA.	ki	0.0380	uM
(2S)-N-[5-[3-[4-(3-aminopropylamino)butylamino]propanoylamino]pentyl]-2-[[2-(2,4-dihydroxyphenyl)acetyl]amino]butanediamide	477264: Inhibition of recombinant GluA1 receptor flop isoform expressed in Xenopus oocytes assessed as inhibition of 300 uM kainate-induced current by patch clamp electrophysiological assay	ic50	0.0400	uM
5-(2-chloro-6-methylphenyl)-1,3-dihydrobenzimidazol-2-one	1385854: Modulation of recombinant human GluA1 flop isoform/TARPgamma8 expressed in HEK293F cells assessed as blockade of glutamate-induced calcium flux by calcium 5/6 dye based FLIPR assay	ic50	0.0501	uM
5-(2,6-dichlorophenyl)-1,3-dihydrobenzimidazol-2-one	1385854: Modulation of recombinant human GluA1 flop isoform/TARPgamma8 expressed in HEK293F cells assessed as blockade of glutamate-induced calcium flux by calcium 5/6 dye based FLIPR assay	ic50	0.0501	uM
6-[(1S)-1-(1-pyridin-2-ylpyrazol-3-yl)ethyl]-3H-1,3-benzothiazol-2-one	1309746: Antagonist activity at human iGluA1 receptor flop isoform expressed in CHO-S cells coexpressing TARP gamma-8 and human EAAT3 assessed as inhibition of glutamate-induced increase in intracellular calcium levels after 2 mins followed by cyclothiazide/glutamate addition by fluo-4 AM dye based fluorescence imaging plate reader method	ic50	0.0509	uM
6-[(1S)-1-[1-(5-fluoro-2-pyridinyl)pyrazol-3-yl]ethyl]-3H-1,3-benzothiazol-2-one	1309746: Antagonist activity at human iGluA1 receptor flop isoform expressed in CHO-S cells coexpressing TARP gamma-8 and human EAAT3 assessed as inhibition of glutamate-induced increase in intracellular calcium levels after 2 mins followed by cyclothiazide/glutamate addition by fluo-4 AM dye based fluorescence imaging plate reader method	ic50	0.0536	uM
N-(1H-indazol-5-yl)-N-[(1-methylpyrazol-3-yl)methyl]-4-pyridin-2-yl-1,3-thiazol-2-amine	1309746: Antagonist activity at human iGluA1 receptor flop isoform expressed in CHO-S cells coexpressing TARP gamma-8 and human EAAT3 assessed as inhibition of glutamate-induced increase in intracellular calcium levels after 2 mins followed by cyclothiazide/glutamate addition by fluo-4 AM dye based fluorescence imaging plate reader method	ic50	0.0539	uM
12-imidazol-1-yl-11-nitro-2,5,8,13-tetrazatricyclo[7.4.0.02,6]trideca-1(13),3,5,9,11-pentaen-7-one	1859112: Displacement of [3H]AMPA from AMPA receptor (unknown origin)	ki	0.0570	uM
6-[(1S)-1-[1-[5-(2-hydroxyethyl)-2-pyridinyl]pyrazol-3-yl]ethyl]-3H-1,3-benzothiazol-2-one	1309746: Antagonist activity at human iGluA1 receptor flop isoform expressed in CHO-S cells coexpressing TARP gamma-8 and human EAAT3 assessed as inhibition of glutamate-induced increase in intracellular calcium levels after 2 mins followed by cyclothiazide/glutamate addition by fluo-4 AM dye based fluorescence imaging plate reader method	ic50	0.0616	uM
9-methyl-6-nitro-4,7,8,10-tetrahydro-1H-pyrido[3,4-f]quinoxaline-2,3-dione	1859112: Displacement of [3H]AMPA from AMPA receptor (unknown origin)	ic50	0.0630	uM
4-[2-(4-fluorophenyl)-8-morpholin-4-ylimidazo[1,2-a]pyrazin-3-yl]aniline	1542530: Negative allosteric modulation of recombinant human GluA1 flop isoform/TARPgamma2 expressed in HEK293 cells assessed as inhibition of glutamate-induced calcium flux at 100 uM by calcium 5/6 dye based FLIPR assay	ic50	0.0631	uM
N-[1-[8-(3-aminopropylamino)octylamino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]pyridine-4-carboxamide	75670: Inhibition of the (-80 mV) current elicited by 100 uM glutamate by simultaneous co-application in xenopus oocytes injected with GluR1 flop RNA.	ki	0.0640	uM
N-[1-[8-(3-aminopropylamino)octylamino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]butanamide	75670: Inhibition of the (-80 mV) current elicited by 100 uM glutamate by simultaneous co-application in xenopus oocytes injected with GluR1 flop RNA.	ki	0.0650	uM
(2S)-2-amino-3-(5-chloro-2,4-dioxopyrimidin-1-yl)propanoic acid	92951: Displacement of [3H]AMPA from human Ionotropic glutamate receptor AMPA 1 expressed in HEK293 cells	ki	0.0650	uM
6-[(1S)-1-[1-[5-(2-hydroxyethoxy)-2-pyridinyl]pyrazol-3-yl]ethyl]-3H-1,3-benzothiazol-2-one	1309746: Antagonist activity at human iGluA1 receptor flop isoform expressed in CHO-S cells coexpressing TARP gamma-8 and human EAAT3 assessed as inhibition of glutamate-induced increase in intracellular calcium levels after 2 mins followed by cyclothiazide/glutamate addition by fluo-4 AM dye based fluorescence imaging plate reader method	ic50	0.0653	uM

CTD chemical–gene interactions

33 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression, decreases methylation, increases expression	5
trichostatin A	affects cotreatment, decreases expression, increases expression	3
entinostat	decreases expression, affects cotreatment	2
Benzo(a)pyrene	decreases expression, decreases methylation, increases methylation, affects reaction	2
Estradiol	increases expression, affects cotreatment, decreases expression, decreases reaction, increases reaction	2
Progesterone	decreases reaction, increases reaction, increases expression, affects cotreatment, decreases expression	2
methylmercuric chloride	decreases expression	1
bisphenol A	affects methylation	1
sodium arsenite	affects methylation	1
maleic acid	increases expression	1
CGP 52608	affects binding, increases reaction	1
corosolic acid	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
2,2’,4,4’,5-brominated diphenyl ether	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
Rimonabant	decreases expression, decreases reaction	1
Vorinostat	decreases expression	1
Panobinostat	affects cotreatment, decreases expression	1
Atrazine	increases expression	1
Diethylhexyl Phthalate	decreases expression	1
Doxorubicin	increases expression	1
Lead	affects splicing	1
Rifampin	decreases expression	1
Sodium Fluoride	decreases expression	1
Dronabinol	decreases expression, decreases reaction	1
Tretinoin	decreases expression	1
8-Bromo Cyclic Adenosine Monophosphate	affects cotreatment, decreases expression, decreases reaction, increases reaction	1
Citalopram	affects response to substance	1
Mifepristone	decreases expression	1

ChEMBL screening assays

168 unique, capped per target: 127 binding, 39 functional, 2 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1029771	Functional	Agonist activity at cyclothiazide-desensitized human flip iGluR1 expressed in CHO-K1 cells by whole cell patch-clamp method	1H-cyclopentapyrimidine-2,4(1H,3H)-dione-related ionotropic glutamate receptors ligands. structure-activity relationships and identification of potent and Selective iGluR5 modulators. — J Med Chem
CHEMBL1072470	Binding	Binding affinity to S1S2 domain of GluA2 receptor expressed in Escherichia coli by crystallography	Piracetam defines a new binding site for allosteric modulators of alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptors. — J Med Chem
CHEMBL4339687	ADMET	Negative allosteric modulation of recombinant human GluA1 flop isoform/TARPgamma2 expressed in HEK293 cells assessed as inhibition of glutamate-induced calcium flux by calcium 5/6 dye based FLIPR assay	Discovery of Imidazo[1,2-a]pyrazines and Pyrazolo[1,5-c]pyrimidines as TARP γ-8 Selective AMPAR Negative Modulators. — ACS Med Chem Lett

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_D1SU	Abcam U-87MG GRIA1 KO	Cancer cell line	Male

Clinical trials (associated diseases)

302 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT00391261	PHASE4	COMPLETED	An Open-label Trial of Metformin for Weight Control of Pediatric Patients on Antipsychotic Medications.
NCT01028820	PHASE4	COMPLETED	FMRI Brain Activation of Aripiprazole Treatment in Autism Spectrum Disorders
NCT01333865	PHASE4	COMPLETED	A Study of Memantine Hydrochloride (Namenda®) for Cognitive and Behavioral Impairment in Adults With Autism Spectrum Disorders
NCT01337700	PHASE4	COMPLETED	Milnacipran in Autism and the Functional Locus Coeruleus and Noradrenergic Model of Autism
NCT01695200	PHASE4	COMPLETED	Omega-3 Fatty Acids in Autism Spectrum Disorders
NCT02096952	PHASE4	COMPLETED	Methylphenidate ER Liquid Formulation in Adults With ASD and ADHD
NCT02235467	PHASE4	COMPLETED	Multisite Study: Parental Training Using Video Modelling to Develop Social Skills in Children With Autism
NCT02940574	PHASE4	COMPLETED	Neural and Behavioral Effects of Oxytocin in Autism Spectrum Disorders
NCT03333629	PHASE4	COMPLETED	Promoting Positive Outcomes for Individuals With ASD: Linking Early Detection, Treatment, and Long-term Outcomes
NCT03337646	PHASE4	COMPLETED	Evaluation of the Effect and Safety of Lisdexamfetamine in Children Aged 6-12 With ADHD and Autism
NCT03538431	PHASE4	COMPLETED	Improving Driving in Young People With Autism Spectrum Disorders
NCT03757585	PHASE4	COMPLETED	Natural Treatments for the Management of Emotional Dysregulation in Youth With Non-verbal Learning Disability (NVLD) and/or Autism Spectrum Disorders (ASD)
NCT04903353	PHASE4	COMPLETED	Pragmatic Trial Comparing Weight Gain in Children With Autism Taking Risperidone Versus Aripiprazole
NCT05063656	PHASE4	COMPLETED	Biomarker-Driven Pharmacological Treatment of Adolescents With Autism Spectrum Disorder With Gabapentin
NCT05146245	PHASE4	UNKNOWN	Safety and Pharmacokinetics of Antipsychotics in Children 2: Studying TDM in an RCT
NCT05916339	PHASE4	RECRUITING	AWARE: Management of ADHD in Autism Spectrum Disorder
NCT05954052	PHASE4	TERMINATED	A Study of Glutathione in Children With Autism Spectrum Disorder
NCT06853665	PHASE4	RECRUITING	The TEAM Study - Treatment Efficacy for Autism/Attention Using Mixed Amphetamine
NCT07054697	PHASE4	COMPLETED	Pilot-RCT With Individualized Homeopathic Treatment in the Children With Autism Spectrum Disorder
NCT07161804	PHASE4	COMPLETED	Pilot RCT Using Homeopathic Medicines in ASD
NCT07439042	PHASE4	NOT_YET_RECRUITING	Buspirone for Anxiety in Autistic Youth
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT01302964	PHASE3	COMPLETED	Mirtazapine Treatment of Anxiety in Children and Adolescents With Pervasive Developmental Disorders
NCT01706523	PHASE3	TERMINATED	Open Label Extension Study of STX209 (Arbaclofen) in Autism Spectrum Disorders
NCT01825798	PHASE3	COMPLETED	Treatment of Overweight Induced by Antipsychotic Medication in Young People With Autism Spectrum Disorders (ASD)
NCT01972074	PHASE3	COMPLETED	Behavioral and Neural Response to Memantine in Adolescents With Autism Spectrum Disorder
NCT02985749	PHASE3	COMPLETED	A Study of Oxytocin for the Treatment of Social Impairment in Individuals With High Functioning Autism Spectrum Disorder
NCT03197922	PHASE3	COMPLETED	Treatment of Encopresis in Children With Autism Spectrum Disorders
NCT03504917	PHASE3	TERMINATED	A Study of Balovaptan in Adults With Autism Spectrum Disorder With a 2-Year Open-Label Extension
NCT03553875	PHASE3	TERMINATED	Memantine for the Treatment of Social Deficits in Youth With Disorders of Impaired Social Interactions
NCT03640156	PHASE3	COMPLETED	Modulating Socially Adaptive Mirror System Functioning in Autism by Oxytocin
NCT03715153	PHASE3	TERMINATED	Efficacy and Safety of Bumetanide Oral Liquid Formulation in Children Aged From 2 to Less Than 7 Years Old With Autism Spectrum Disorder.
NCT03715166	PHASE3	TERMINATED	Efficacy and Safety of Bumetanide Oral Liquid Formulation in Children and Adolescents Aged From 7 to Less Than 18 Years Old With Autism Spectrum Disorder
NCT04233502	PHASE3	WITHDRAWN	Efficacy and Safety of Slenyto for Insomnia in Children With ASD
NCT04578756	PHASE3	COMPLETED	Open-Label, Flexible-dose Study to Evaluate the Long-Term Safety and Tolerability of Cariprazine in the Treatment of Pediatric Participants With Schizophrenia, Bipolar I Disorder, or Autism Spectrum Disorder