GRIA2

Summary

GRIA2 (glutamate ionotropic receptor AMPA type subunit 2, HGNC:4572) is a protein-coding gene on chromosome 4q32.1, encoding Glutamate receptor 2 (P42262). 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. This gene product belongs to a family of glutamate receptors that are sensitive to alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA), and function as ligand-activated cation channels. These channels are assembled from 4 related subunits, GRIA1-4. The subunit encoded by this gene (GRIA2) is subject to RNA editing (CAG->CGG; Q->R) within the second transmembrane domain, which is thought to render the channel impermeable to Ca(2+). Human and animal studies suggest that pre-mRNA editing is essential for brain function, and defective GRIA2 RNA editing at the Q/R site may be relevant to amyotrophic lateral sclerosis (ALS) etiology. Alternative splicing, resulting in transcript variants encoding different isoforms, (including the flip and flop isoforms that vary in their signal transduction properties), has been noted for this gene.

Source: NCBI Gene 2891 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neurodevelopmental disorder with language impairment and behavioral abnormalities (Definitive, ClinGen)
• GWAS associations: 1
• Clinical variants (ClinVar): 237 total — 12 pathogenic, 30 likely-pathogenic
• Phenotypes (HPO): 25
• Druggable target: yes — 6 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001083619

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4572
Approved symbol	GRIA2
Name	glutamate ionotropic receptor AMPA type subunit 2
Location	4q32.1
Locus type	gene with protein product
Status	Approved
Aliases	GluA2, GLURB, GluR-K2, GluR-B, GluR-2
Ensembl gene	ENSG00000120251
Ensembl biotype	protein_coding
OMIM	138247
Entrez	2891

Gene structure

Transcript identifiers

Ensembl transcripts: 39 — 22 protein_coding, 10 nonsense_mediated_decay, 5 retained_intron, 2 protein_coding_CDS_not_defined

ENST00000264426, ENST00000296526, ENST00000323661, ENST00000393815, ENST00000471736, ENST00000503437, ENST00000503980, ENST00000504801, ENST00000505888, ENST00000506284, ENST00000507898, ENST00000509417, ENST00000510854, ENST00000512774, ENST00000645636, ENST00000703717, ENST00000703718, ENST00000703719, ENST00000703750, ENST00000703751, ENST00000703752, ENST00000703753, ENST00000703754, ENST00000703755, ENST00000703756, ENST00000703757, ENST00000703758, ENST00000703759, ENST00000703760, ENST00000703761, ENST00000703762, ENST00000703763, ENST00000703764, ENST00000703765, ENST00000703766, ENST00000703767, ENST00000703768, ENST00000703769, ENST00000703770

RefSeq mRNA: 5 — MANE Select: NM_001083619 NM_000826, NM_001083619, NM_001083620, NM_001379000, NM_001379001

CCDS: CCDS3797, CCDS43274, CCDS43275, CCDS93659

Canonical transcript exons

ENST00000264426 — 16 exons

Exon	Start	End
ENSE00002450850	157334010	157334120
ENSE00002484343	157335671	157335877
ENSE00003467039	157362799	157363047
ENSE00003485442	157321438	157321599
ENSE00003518638	157359896	157360143
ENSE00003524693	157312679	157312875
ENSE00003534977	157336377	157336747
ENSE00003553449	157361010	157361124
ENSE00003573388	157317658	157317711
ENSE00003578829	157333249	157333353
ENSE00003638947	157332819	157332986
ENSE00003670666	157341264	157341462
ENSE00003691974	157303552	157303791
ENSE00003989795	157363435	157366075
ENSE00003989820	157220728	157221130
ENSE00003989848	157221667	157221807

Expression profiles

Bgee: expression breadth ubiquitous, 212 present calls, max score 99.82.

FANTOM5 (CAGE): breadth broad, TPM avg 10.7708 / max 2253.5174, expressed in 200 samples.

FANTOM5 promoters (11 alternative TSS)

Promoter ID	TPM avg	Samples expressed
50246	4.0335	153
50245	3.1718	135
50242	2.1338	133
50244	0.7147	104
50241	0.3211	96
50249	0.1025	60
50247	0.0858	46
50252	0.0753	13
50248	0.0690	45
50243	0.0372	23

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
frontal pole	UBERON:0002795	99.82	gold quality
Brodmann (1909) area 23	UBERON:0013554	99.79	gold quality
middle temporal gyrus	UBERON:0002771	99.77	gold quality
Brodmann (1909) area 10	UBERON:0013541	99.76	gold quality
CA1 field of hippocampus	UBERON:0003881	99.56	gold quality
orbitofrontal cortex	UBERON:0004167	99.52	gold quality
parietal lobe	UBERON:0001872	99.50	gold quality
postcentral gyrus	UBERON:0002581	99.49	gold quality
cerebellar vermis	UBERON:0004720	99.49	gold quality
entorhinal cortex	UBERON:0002728	99.46	gold quality
Brodmann (1909) area 46	UBERON:0006483	99.43	gold quality
superior frontal gyrus	UBERON:0002661	99.41	gold quality
paraflocculus	UBERON:0005351	99.11	gold quality
occipital lobe	UBERON:0002021	99.01	gold quality
middle frontal gyrus	UBERON:0002702	98.96	gold quality
primary visual cortex	UBERON:0002436	98.83	gold quality
endothelial cell	CL:0000115	98.57	gold quality
cortical plate	UBERON:0005343	98.50	gold quality
lateral globus pallidus	UBERON:0002476	98.41	gold quality
corpus callosum	UBERON:0002336	98.25	gold quality
right hemisphere of cerebellum	UBERON:0014890	98.10	gold quality
ventral tegmental area	UBERON:0002691	97.98	gold quality
frontal cortex	UBERON:0001870	97.95	gold quality
Brodmann (1909) area 9	UBERON:0013540	97.95	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	97.60	gold quality
cerebral cortex	UBERON:0000956	97.59	gold quality
prefrontal cortex	UBERON:0000451	97.56	gold quality
cerebellum	UBERON:0002037	97.54	gold quality
superior vestibular nucleus	UBERON:0007227	97.54	gold quality
cerebellar cortex	UBERON:0002129	97.47	gold quality

Single-cell (SCXA)

Detected in 9 experiment(s), a significant marker in 9.

Experiment	Marker?	Max mean expression
E-GEOD-75140	yes	1692.08
E-MTAB-10485	yes	449.71
E-HCAD-5	yes	56.04
E-HCAD-35	yes	30.94
E-MTAB-7316	yes	30.73
E-GEOD-84465	yes	27.25
E-GEOD-137537	yes	16.46
E-GEOD-93593	yes	16.11
E-ANND-3	yes	6.21

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ESR1, HR, MECP2, NCOA2, NRF1, REST, SP1, SP3, SP4

miRNA regulators (miRDB)

243 targeting GRIA2, 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-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-3925-3P	100.00	69.95	1237
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-188-3P	100.00	68.76	1240
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-4775	99.98	75.00	6394

Literature-anchored findings (GeneRIF, showing 40)

• Post-transcriptional editing of this subunit at the Q/R/N site controls calcium permeability (PMID:11860506)
• Flip and flop splice variants of AMPA receptor subunits in the spinal cord of amyotrophic lateral sclerosis. (PMID:12125045)
• role of interaction with N-ethylmaleimide-sensitive factor in regulation of AMPA receptors by brain-derived neurotrophic factor (PMID:12130635)
• Low levels of GluR2 mRNA in motoneurons of ALS did not differ from the control group, implying that selective reduction of the GluR2 subunit cannot be a mechanism of AMPA receptor-mediated neurotoxicity in ALS (PMID:12694394)
• the Q/R site of GluRs editing is regulated in a regional manner and the GluR2 Q/R site editing is critically regulated by ADAR2 in human brain (PMID:12859334)
• GluR2, a subunit of a ligand-gated cation channel, is up-regulated in leiomyomata relative to myometrium by 15- to 30-fold at the protein and mRNA level and is localized in endothelial cells (PMID:14630051)
• There is a defect in the editing of the mRNA encoding the GluR2 subunit of glutamate AMPA receptors in the spinal motor neurons of individuals affected by amyotrophic lateral sclerosis (PMID:14985749)
• R/G editing status: the relative amount of edited GLUR2 mRNA was increased in epileptic hippocampi, whereas no changes were found in neocortical tissues. (PMID:15006707)
• Control of GLUR2 translation was mediated by a sequence containing a 34-42 nucleotide imperfect GU repeat predicted to form secondary structure in vivo. This translation suppression domain is included in some rat and human GluR2 transcripts in vivo (PMID:15071096)
• 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)
• GluR2 was localized to the perikarya and proximal dendrites of BLA neurons; dense labeling was also present over the pyramidal cell layer of hippocampal subfields CA1 and CA3 (PMID:16045445)
• Circumstance data have indicated that the GluR2 subunits dictate Ca2+/Zn2+ permeability of AMPA receptor channels and gate injurious Ca2+/Zn2+ signals in vulnerable neurons. (PMID:16215279)
• Laser capture microdissection combined with quantitative PCR was used to examine the expression of AMPA (GRIA1-4) and NMDA (GRIN1, 2A and 2B) subunit mRNA levels in Layer II/III and Layer V pyramidal cells (PMID:17942280)
• Of the three AMPA genes analyzed here, only GRIA3 seems to be involved in the pathogenesis of schizophrenia, but only in females. (PMID:18163426)
• utilized reverse-transcription polymerase chain reaction and BbvI digestion to demonstrate that neural progenitor cells contain Q/R-unedited GluR2, and differentiated cells contain Q/R-edited GluR2 subunits (PMID:18403631)
• the GluR4 subunit exhibits a different correlation between receptor activation and ligand-binding domain cleft closure than does GluR2 (PMID:19102704)
• These findings indicate that the absence of the GluR2 subunit favours malignancy in gliomas (PMID:19558602)
• This dimeric structure provides a mechanism for how the ATDs can drive receptor assembly and subtype-restricted composition. (PMID:19651138)
• [review] The importance of mGlu2/3 glutamate receptors during normal central nervous system development is likely to play an important mechanistic role in the neurodevelopmental hypothesis of schizophrenia. (PMID:19933774)
• We conclude that polymorphisms in the GluR2 gene (GRIA2) are not a major contributory factor in the pathogenesis of ALS. (PMID:20409611)
• Transsynaptic signaling mediated by the extracellular domain of GluR2 regulates the stability of presynaptic terminals. (PMID:21173224)
• Data show that CALM influences the cell surface level of the AMPA receptor subunit GluR2. (PMID:21221849)
• Gain-of-function glutamate receptor interacting protein 1 variants alter GluA2 recycling and surface distribution in patients with autism (PMID:21383172)
• The balance of expression of nerve growth factor (NGF) and that of its receptors shifts toward cell death mechanisms during the progression of Alzheimer disease. (PMID:21397006)
• New insights in endosomal dynamics and AMPA receptor trafficking (PMID:21843653)
• AMPA receptor regulation during synaptic plasticity in hippocampus and neocortex (PMID:21856433)
• the GluR2 gene is embedded into an open chromatin configuration in glioma cells and expression of GluR2 is controlled by REST and Sp1 (PMID:21948504)
• Did not observed significant association between GRIA2 polymorphisms and clinical improvement in patients with Major depressive disorder.But rs4302506 and rs4403097 single nucleotide polymorphisms could be associated with age of onset of the disease. (PMID:22057216)
• significant association GRIA2 polymorphisms was found with the diagnosis of schizophrenia. (PMID:22094384)
• SNPs within GRIA2 may not be associated with the development and treatment outcomes in BD (PMID:22122651)
• ADAR2 expression level reflects editing activity at the GluA2 Q/R site; although the edited GluA2 pre-mRNA is readily spliced, the unedited GluA2 pre-mRNA is also spliced and transported to the cytoplasm when ADAR2 expression is low. (PMID:22366356)
• We demonstrated that the expression of GRIA2 among the differentially expressed genes provides better prognosis of patients with advanced serous papillary ovarian adenocarcinoma. (PMID:22644307)
• 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)
• The ionotrophic glutamate receptors AMPA2 and AMPA3 were decreased in hippocampus in patient with multiple sclerosis. (PMID:23595422)
• The data potentially suggest a lack of epistatic interaction between GRIA2 and GRIA4 variants regarding clinical outcomes in patients with major depressive disorder. (PMID:23613500)
• 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)
• GRIA2 is a useful marker for distinguishing solitary fibrous tumour from most mimics (PMID:24456377)
• Statistical analysis showed no association between migraine and the GRIA2 and GRIA4 polymorphisms investigated. (PMID:24512576)
• analysis of changes in receptor kinetics with the R628E charge-inverting mutation in the “linker” region of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor (PMID:24550387)

Cross-species orthologs

43 orthologs

Organism	Symbol	Gene ID
danio_rerio	gria2b	ENSDARG00000052765
danio_rerio	gria2a	ENSDARG00000070173
mus_musculus	Gria2	ENSMUSG00000033981
rattus_norvegicus	Gria2	ENSRNOG00000054204
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), GRIA3 (ENSG00000125675), GRIK4 (ENSG00000149403), GRID2 (ENSG00000152208), GRIA4 (ENSG00000152578), GRIA1 (ENSG00000155511), GRIN2C (ENSG00000161509), GRIK3 (ENSG00000163873), GRIK2 (ENSG00000164418), GRIK1 (ENSG00000171189), GRIN1 (ENSG00000176884), GRID1 (ENSG00000182771), GRIN2A (ENSG00000183454), GRIN3A (ENSG00000198785), GRIN2B (ENSG00000273079)

Protein

Protein identifiers

Glutamate receptor 2 — P42262 (reviewed: P42262)

Alternative names: AMPA-selective glutamate receptor 2, GluR-B, GluR-K2, Glutamate receptor ionotropic, AMPA 2

All UniProt accessions (26): A0A994J3U8, A0A994J3V2, A0A994J3V5, A0A994J404, A0A994J413, A0A994J418, A0A994J422, A0A994J425, A0A994J4F1, A0A994J4G8, A0A994J4H3, A0A994J6J5, A0A994J6J8, A0A994J6K1, A0A994J6Y1, A0A994J6Y8, A0A994J6Z1, A0A994J6Z5, P42262, A0A994J6Z8, D6R9Z0, D6RBV7, D6RDX5, D6RFM6, F8W7L6, H0Y972

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 and plays an important role in fast excitatory synaptic transmission. 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 CACNG4 or CACNG7 or CACNG8, shows resensitization which is characterized by a delayed accumulation of current flux upon continued application of L-glutamate. Through complex formation with NSG1, GRIP1 and STX12 controls the intracellular fate of AMPAR and the endosomal sorting of the GRIA2 subunit toward recycling and membrane targeting.

Subunit / interactions. Homotetramer or heterotetramer of pore-forming glutamate receptor subunits. Tetramers may be formed by the dimerization of dimers. May interact with MPP4. Forms a ternary complex with GRIP1 and CSPG4. Interacts with ATAD1 in an ATP-dependent manner. ATAD1-catalyzed ATP hydrolysis disrupts binding to ATAD1 and to GRIP1 and leads to AMPAR complex disassembly. Interacts with GRIP1 and GRIP2. Interacts with NSF via its C-terminus. Isoform 1, but not isoform 3, interacts with PICK1. Interacts with CACNG2. Interacts with GRIA1 and SYNDIG1. Part of a complex containing GRIA2, NSF and NAPA and/or NAPB. Interacts with SNX27 (via PDZ domain); the interaction is required for recycling to the plasma membrane when endocytosed and prevent degradation in lysosomes. Interacts with LRFN1. Found in a complex with GRIA1, GRIA3, GRIA4, CNIH2, CNIH3, CACNG2, CACNG3, CACNG4, CACNG5, CACNG7 and CACNG8. Interacts with CACNG5. Interacts with OLFM2. Interacts with AP4B1, AP4E1 and AP4M1; probably indirect it mediates the somatodendritic localization of GRIA2 in neurons. Forms a complex with GRIP1, NSG1 and STX12; controls the intracellular fate of AMPAR and the endosomal sorting of the GRIA2 subunit toward recycling and membrane targeting. Interacts with IQSEC1; the interaction is required for ARF6 activation. Interacts (heterotetramer form) with CNIH2 and CNIH3; this interaction promotes expression at the plasma membrane and extensively modulates their gating properties by slowing deactivation and desensitization kinetics.

Subcellular location. Cell membrane. Postsynaptic cell membrane. Postsynaptic density membrane.

Post-translational modifications. Palmitoylated. Depalmitoylated upon L-glutamate stimulation. Cys-610 palmitoylation leads to Golgi retention and decreased cell surface expression. In contrast, Cys-836 palmitoylation does not affect cell surface expression but regulates stimulation-dependent endocytosis. Ubiquitinated by RNF167, leading to its degradation. Phosphorylation at Tyr-876 is required for interaction with IQSEC1 and ARF6 activation, which in turn triggers AMPAR internalization for persistent synaptic depression. N-glycosylated.

Disease relevance. Neurodevelopmental disorder with language impairment and behavioral abnormalities (NEDLIB) [MIM:618917] A neurodevelopmental disorder characterized by global developmental delay, impaired intellectual development, poor or absent speech, and behavioral abnormalities, such as autism spectrum disorder, repetitive behaviors, and hyperactivity. Some patients develop seizures and manifest developmental regression. The disease is caused by variants affecting the gene represented in this entry. The genetic variation producing the missense variant p.Q607E, associated with NEDLIB, is predicted to deeply affect RNA editing. In a physiological context, the adenosine (A) residue of the original glutamine (Q) codon CAG is post-transcriptionaly edited to inosine (I) by ADAR2, leading to a codon recognized by the ribosome as arginine (R). The glutamate (E) codon GAG, resulting from the genetic variation, is predicted to be edited 90% less than the normal CAG codon. If edited, the codon GIG would be translated as p.Q607G.

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. GRIA2 subfamily.

Isoforms (4)

UniProt ID	Names	Canonical?
P42262-1	Flop	yes
P42262-2	Flip
P42262-3	3, Long
P42262-4	4

RefSeq proteins (5): NP_000817, NP_001077088, NP_001077089, NP_001365929, NP_001365930 (=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), 2 shown:

• Ca(2+)(in) = Ca(2+)(out) (RHEA:29671)
• Na(+)(in) = Na(+)(out) (RHEA:34963)

UniProt features (123 total): strand 32, helix 25, sequence variant 19, turn 7, binding site 6, modified residue 6, topological domain 5, glycosylation site 4, sequence conflict 4, transmembrane region 3, splice variant 3, lipid moiety-binding region 2, disulfide bond 2, intramembrane region 2, signal peptide 1, chain 1, region of interest 1

Structure

Experimental structures (PDB)

16 structures.

PDB	Method	Resolution (Å)
5ZG2	X-RAY DIFFRACTION	1.25
5ZG1	X-RAY DIFFRACTION	1.32
7F3O	X-RAY DIFFRACTION	1.44
5YBF	X-RAY DIFFRACTION	1.5
5YBG	X-RAY DIFFRACTION	1.52
5ZG0	X-RAY DIFFRACTION	1.58
5ZG3	X-RAY DIFFRACTION	1.65
3RN8	X-RAY DIFFRACTION	1.7
5H8S	X-RAY DIFFRACTION	1.7
8I0B	X-RAY DIFFRACTION	1.73
3RNN	X-RAY DIFFRACTION	1.75
2WJW	X-RAY DIFFRACTION	1.8
2XHD	X-RAY DIFFRACTION	1.8
3UA8	X-RAY DIFFRACTION	1.9
3R7X	X-RAY DIFFRACTION	2.1
2WJX	X-RAY DIFFRACTION	4.1

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P42262-F1	85.24	0.62

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): 499; 501; 506; 675; 676; 726

Post-translational modifications (8): 683, 717, 860, 863, 876, 880, 610, 836

Disulfide bonds (2): 78–330, 739–794

Glycosylation sites (4): 256, 370, 406, 413

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-399710	Activation 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-9022699	MECP2 regulates neuronal receptors and channels
R-HSA-9620244	Long-term potentiation

MSigDB gene sets: 344 (showing top): TAATAAT_MIR126, MODY_HIPPOCAMPUS_POSTNATAL, BENPORATH_ES_WITH_H3K27ME3, chr4q32, MODULE_274, GOMF_GLUTAMATE_GATED_RECEPTOR_ACTIVITY, GOCC_CELL_SURFACE, TACAATC_MIR508, MOTAMED_RESPONSE_TO_ANDROGEN_UP, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_CELL_CELL_SIGNALING, MODULE_66, GTGCCTT_MIR506, CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_1, RAMALHO_STEMNESS_DN

GO Biological Process (10): ionotropic glutamate receptor signaling pathway (GO:0035235), synaptic transmission, glutamatergic (GO:0035249), modulation of chemical synaptic transmission (GO:0050804), monoatomic ion transport (GO:0006811), signal transduction (GO:0007165), cell surface receptor signaling pathway (GO:0007166), chemical synaptic transmission (GO:0007268), monoatomic ion transmembrane transport (GO:0034220), regulation of postsynaptic membrane potential (GO:0060078), monoatomic cation transmembrane transport (GO:0098655)

GO Molecular Function (10): amyloid-beta binding (GO:0001540), glutamate-gated receptor activity (GO:0004970), AMPA glutamate receptor activity (GO:0004971), ligand-gated monoatomic cation channel activity (GO:0099094), transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential (GO:1904315), monoatomic ion channel activity (GO:0005216), protein binding (GO:0005515), ligand-gated monoatomic ion channel activity (GO:0015276), transmitter-gated monoatomic ion channel activity (GO:0022824), signaling receptor activity (GO:0038023)

GO Cellular Component (16): plasma membrane (GO:0005886), external side of plasma membrane (GO:0009897), postsynaptic density (GO:0014069), dendrite (GO:0030425), endocytic vesicle membrane (GO:0030666), asymmetric synapse (GO:0032279), AMPA glutamate receptor complex (GO:0032281), neuronal cell body (GO:0043025), dendritic spine (GO:0043197), excitatory synapse (GO:0060076), postsynapse (GO:0098794), postsynaptic density membrane (GO:0098839), postsynaptic endocytic zone (GO:0098843), membrane (GO:0016020), synapse (GO:0045202), postsynaptic membrane (GO:0045211)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Glutamate binding, activation of AMPA receptors and synaptic plasticity	1
Trafficking of AMPA receptors	1
Activation of NMDA receptors and postsynaptic events	1
Transcriptional Regulation by MECP2	1
Post NMDA receptor activation events	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
postsynapse	3
cellular anatomical structure	3
glutamate-gated receptor activity	2
chemical synaptic transmission	2
transmitter-gated monoatomic ion channel activity	2
postsynaptic density	2
synapse	2
glutamate receptor signaling pathway	1
ligand-gated ion channel signaling pathway	1
regulation of trans-synaptic signaling	1
transport	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
signal transduction	1
anterograde trans-synaptic signaling	1
monoatomic ion transport	1
transmembrane transport	1
regulation of membrane potential	1
monoatomic cation transport	1
monoatomic ion transmembrane transport	1
peptide binding	1
dicarboxylic acid transmembrane transporter activity	1
glutamate receptor activity	1
amino acid transmembrane transporter activity	1
ionotropic glutamate receptor signaling pathway	1
monoatomic cation channel activity	1
ligand-gated monoatomic ion channel activity	1
regulation of postsynaptic membrane potential	1
monoatomic ion transmembrane transporter activity	1
channel activity	1
binding	1
monoatomic ion channel activity	1
ligand-gated channel activity	1
extracellular ligand-gated monoatomic ion channel activity	1
transmitter-gated channel activity	1
molecular transducer activity	1
membrane	1

Protein interactions and networks

STRING

3332 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GRIA2	PICK1	Q9NRD5	999
GRIA2	GRIP1	Q9Y3R0	997
GRIA2	GRIA4	P48058	982
GRIA2	GRIA1	P42261	982
GRIA2	GRIA3	P42263	982
GRIA2	CDH2	P19022	981
GRIA2	CACNG2	Q9Y698	886
GRIA2	DLG4	P78352	880
GRIA2	GRIP2	Q9C0E4	865
GRIA2	CACNG8	Q8WXS5	853
GRIA2	ADARB1	P78555	819
GRIA2	GRM7	Q14831	816
GRIA2	GRM5	P41594	801
GRIA2	GSR	P00390	793
GRIA2	SLC17A7	Q9P2U7	787

IntAct

106 interactions, top by confidence:

A	B	Type	Score
Pick1	GRIA2	psi-mi:“MI:0407”(direct interaction)	0.560
NSF	GRIA2	psi-mi:“MI:0407”(direct interaction)	0.540
GRIA2	NSF	psi-mi:“MI:0915”(physical association)	0.540
NUFIP1	PDE2A	psi-mi:“MI:0914”(association)	0.530
GRIA2	Grip1	psi-mi:“MI:0407”(direct interaction)	0.440
GRIA2	PARD3B	psi-mi:“MI:0407”(direct interaction)	0.440
MAST2	GRIA2	psi-mi:“MI:0407”(direct interaction)	0.440
GRIA2	MAST1	psi-mi:“MI:0407”(direct interaction)	0.440
GRIA2	HTRA1	psi-mi:“MI:0407”(direct interaction)	0.440
TIAM2	GRIA2	psi-mi:“MI:0407”(direct interaction)	0.440
GRIA2	DLG3	psi-mi:“MI:0407”(direct interaction)	0.440
GRIA2	GORASP2	psi-mi:“MI:0407”(direct interaction)	0.440
GRIA2	LNX1	psi-mi:“MI:0407”(direct interaction)	0.440
GRIA2	DLG1	psi-mi:“MI:0407”(direct interaction)	0.440
APBA3	GRIA2	psi-mi:“MI:0407”(direct interaction)	0.440
GRIA2	MAGI2	psi-mi:“MI:0407”(direct interaction)	0.440
GRIA2	APBA2	psi-mi:“MI:0407”(direct interaction)	0.440
GRIA2	GRID2IP	psi-mi:“MI:0407”(direct interaction)	0.440
GRIA2	MPP2	psi-mi:“MI:0407”(direct interaction)	0.440
GRIA2	PDZD7	psi-mi:“MI:0407”(direct interaction)	0.440
GRIA2	RAPGEF6	psi-mi:“MI:0407”(direct interaction)	0.440
GRIA2	LIN7C	psi-mi:“MI:0407”(direct interaction)	0.440
GRIA2	PDZRN4	psi-mi:“MI:0407”(direct interaction)	0.440
NHERF4	GRIA2	psi-mi:“MI:0407”(direct interaction)	0.440
GRIA2	PATJ	psi-mi:“MI:0407”(direct interaction)	0.440
GRIA2	DLG4	psi-mi:“MI:0407”(direct interaction)	0.440
GRIA2	IL16	psi-mi:“MI:0407”(direct interaction)	0.440
GRIA2	ARHGAP21	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (109): GRIA2 (Affinity Capture-MS), GRIA2 (Affinity Capture-MS), GRIA2 (Affinity Capture-MS), GRIA2 (Affinity Capture-MS), ATP5F1 (Affinity Capture-MS), NDUFV3 (Affinity Capture-MS), NCOA4 (Affinity Capture-MS), KCNAB2 (Affinity Capture-MS), POM121 (Affinity Capture-MS), TXNL4A (Affinity Capture-MS), ECD (Affinity Capture-MS), TRMT6 (Affinity Capture-MS), TSPYL2 (Affinity Capture-MS), DPP9 (Affinity Capture-MS), GRIP1 (Affinity Capture-Western)

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: A0A1L8F5J9, B3LZ39, B3P2E5, B4GF83, B4I414, B4JHV0, B4KD90, B4LZB5, B4MU83, B4PVB0, B4QWW7, P19491, P23819, P34299, P35438, P35439, P42262, P54952, Q05586, Q10914, Q21415, Q24418, Q296F7, Q38PU7, Q5R1P0, A0A2R8QF68, A7XY94, B1AS29, E9NA96, P19439, P19490, P19492, P19493, P20262, P22756, P23818, P26591, P35436, P39086, P39087

SIGNOR signaling

12 interactions.

A	Effect	B	Mechanism
PRKCA	unknown	GRIA2	phosphorylation
SHANK3	“up-regulates quantity”	GRIA2	binding
“glutamic acid”	“up-regulates activity”	GRIA2	“chemical activation”
GRIA2	up-regulates	Excitatory_synaptic_transmission
IQSEC2	“up-regulates quantity”	GRIA2	relocalization
GRIA2	“up-regulates quantity”	calcium(2+)	relocalization
PTPN5	“down-regulates activity”	GRIA2	dephosphorylation
MECP2	“down-regulates quantity by repression”	GRIA2	“transcriptional regulation”
PICK1	“up-regulates activity”	GRIA2	binding
GRIA2	up-regulates	Synaptic_plasticity

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 76 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Trafficking of GluR2-containing AMPA receptors	5	70.0×	7e-07
Assembly and cell surface presentation of NMDA receptors	6	31.7×	2e-06
Neurexins and neuroligins	7	28.7×	7e-07

GO biological processes:

GO term	Partners	Fold	FDR
establishment or maintenance of epithelial cell apical/basal polarity	6	49.1×	1e-06
receptor clustering	5	44.0×	2e-05
regulation of postsynaptic membrane neurotransmitter receptor levels	5	34.9×	5e-05
cell-cell adhesion	6	8.6×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	12
Likely pathogenic	30
Uncertain significance	149
Likely benign	25
Benign	9

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1174085	NM_001083619.3(GRIA2):c.258del (p.Val85_Tyr86insTer)	Pathogenic
1685861	NM_001083619.3(GRIA2):c.1927G>A (p.Ala643Thr)	Pathogenic
1698825	NM_001083619.3(GRIA2):c.506del (p.Ala169fs)	Pathogenic
1701007	NM_001083619.3(GRIA2):c.2375G>A (p.Gly792Glu)	Pathogenic
1708230	NM_001083619.3(GRIA2):c.699C>A (p.Tyr233Ter)	Pathogenic
1803979	NM_001083619.3(GRIA2):c.1589_1619dup (p.Asp540delinsGluValGlnThrArgSerValPheLeuSerTer)	Pathogenic
2501002	NM_001083619.3(GRIA2):c.1940T>C (p.Val647Ala)	Pathogenic
2920713	NM_001083619.3(GRIA2):c.2263dup (p.Ile755fs)	Pathogenic
3903361	NM_001083619.3(GRIA2):c.2012dup (p.Leu671fs)	Pathogenic
4088182	NM_001083619.3(GRIA2):c.1915G>A (p.Ala639Thr)	Pathogenic
4813763	NM_001083619.3(GRIA2):c.2076G>A (p.Trp692Ter)	Pathogenic
929842	NM_001083619.3(GRIA2):c.1939G>C (p.Val647Leu)	Pathogenic
1012507	NM_001083619.3(GRIA2):c.967C>T (p.Arg323Ter)	Likely pathogenic
1064411	NM_001083619.3(GRIA2):c.2363G>T (p.Trp788Leu)	Likely pathogenic
1064412	NM_001083619.3(GRIA2):c.2375G>T (p.Gly792Val)	Likely pathogenic
1064413	NM_001083619.3(GRIA2):c.1819C>G (p.Gln607Glu)	Likely pathogenic
1064414	NM_001083619.3(GRIA2):c.1937C>A (p.Thr646Asn)	Likely pathogenic
1064415	NM_001083619.3(GRIA2):c.1932C>A (p.Phe644Leu)	Likely pathogenic
1064417	NM_001083619.3(GRIA2):c.2435A>G (p.Asn812Ser)	Likely pathogenic
1064418	NM_001083619.3(GRIA2):c.2420C>T (p.Ala807Val)	Likely pathogenic
1320197	NM_001083619.3(GRIA2):c.1958_1960delinsTCTACAGCAC (p.Pro653fs)	Likely pathogenic
1679184	NM_001083619.3(GRIA2):c.1589A>T (p.Lys530Met)	Likely pathogenic
1700091	NM_001083619.3(GRIA2):c.2296G>A (p.Ala766Thr)	Likely pathogenic
1700092	NM_001083619.3(GRIA2):c.1710C>A (p.Tyr570Ter)	Likely pathogenic
2501001	NM_001083619.3(GRIA2):c.1859G>A (p.Arg620His)	Likely pathogenic
2576545	NM_001083619.3(GRIA2):c.830G>A (p.Trp277Ter)	Likely pathogenic
2584383	NM_001083619.3(GRIA2):c.2188A>T (p.Asn730Tyr)	Likely pathogenic
2584460	NM_001083619.3(GRIA2):c.1916C>G (p.Ala639Gly)	Likely pathogenic
2683746	NM_001083619.3(GRIA2):c.1883T>C (p.Phe628Ser)	Likely pathogenic
2692488	NM_001083619.3(GRIA2):c.1667G>A (p.Gly556Glu)	Likely pathogenic

SpliceAI

3801 predictions. Top by Δscore:

Variant	Effect	Δscore
4:157221665:AGGG:A	acceptor_gain	1.0000
4:157221666:GGGG:G	acceptor_gain	1.0000
4:157221803:TGCTT:T	donor_gain	1.0000
4:157221804:GCTT:G	donor_gain	1.0000
4:157221804:GCTTG:G	donor_gain	1.0000
4:157221805:CTT:C	donor_gain	1.0000
4:157221808:G:GG	donor_gain	1.0000
4:157303542:A:AG	acceptor_gain	1.0000
4:157303543:T:G	acceptor_gain	1.0000
4:157303550:A:AG	acceptor_gain	1.0000
4:157303550:AGTCT:A	acceptor_gain	1.0000
4:157303551:G:GA	acceptor_gain	1.0000
4:157303551:GT:G	acceptor_gain	1.0000
4:157303551:GTC:G	acceptor_gain	1.0000
4:157303551:GTCT:G	acceptor_gain	1.0000
4:157303551:GTCTG:G	acceptor_gain	1.0000
4:157303789:GAG:G	donor_gain	1.0000
4:157303790:AGG:A	donor_loss	1.0000
4:157303791:GGTA:G	donor_loss	1.0000
4:157303792:G:C	donor_loss	1.0000
4:157303792:G:GG	donor_gain	1.0000
4:157303793:T:A	donor_loss	1.0000
4:157310160:G:T	donor_gain	1.0000
4:157312677:A:AC	acceptor_loss	1.0000
4:157312677:A:AG	acceptor_gain	1.0000
4:157312678:G:GG	acceptor_gain	1.0000
4:157312678:GGC:G	acceptor_gain	1.0000
4:157312678:GGCT:G	acceptor_gain	1.0000
4:157312678:GGCTT:G	acceptor_gain	1.0000
4:157312819:G:GT	donor_gain	1.0000

AlphaMissense

5826 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:157221130:G:T	G30W	1.000
4:157221667:G:A	G30E	1.000
4:157221669:G:T	G31W	1.000
4:157221673:T:C	L32P	1.000
4:157221676:T:C	F33S	1.000
4:157221676:T:G	F33C	1.000
4:157221717:G:T	G47W	1.000
4:157221789:T:C	F71L	1.000
4:157221790:T:G	F71C	1.000
4:157221791:C:A	F71L	1.000
4:157221791:C:G	F71L	1.000
4:157303554:T:A	C78S	1.000
4:157303554:T:C	C78R	1.000
4:157303555:G:A	C78Y	1.000
4:157303555:G:C	C78S	1.000
4:157303555:G:T	C78F	1.000
4:157303556:C:G	C78W	1.000
4:157303582:C:A	A87D	1.000
4:157303590:G:A	G90R	1.000
4:157303590:G:C	G90R	1.000
4:157303591:G:A	G90E	1.000
4:157303633:G:A	C104Y	1.000
4:157303634:C:G	C104W	1.000
4:157303642:T:C	L107P	1.000
4:157303755:T:A	W145R	1.000
4:157303755:T:C	W145R	1.000
4:157312691:T:C	L161P	1.000
4:157312703:T:C	L165P	1.000
4:157321487:T:A	V257D	1.000
4:157321493:G:A	G259E	1.000

dbSNP variants (sampled 300 via entrez): RS1000055297 (4:157339399 T>G), RS1000062138 (4:157304508 T>C), RS1000073527 (4:157325931 A>G), RS1000090272 (4:157349941 A>G,T), RS1000090689 (4:157259735 C>G), RS1000097505 (4:157218566 T>G), RS1000114683 (4:157247246 A>G,T), RS1000157317 (4:157341885 GA>G), RS1000161472 (4:157297071 A>G), RS1000180902 (4:157343136 A>G), RS1000185202 (4:157254852 A>G), RS1000209669 (4:157335316 G>A,T), RS1000230288 (4:157356267 G>C), RS1000258568 (4:157349076 C>CTT), RS1000309963 (4:157253954 T>A)

Disease associations

OMIM: gene MIM:138247 | disease phenotypes: MIM:618917

GenCC curated gene-disease

Disease	Classification	Inheritance
neurodevelopmental disorder with language impairment and behavioral abnormalities	Definitive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
neurodevelopmental disorder with language impairment and behavioral abnormalities	Definitive	AD

Mondo (2): neurodevelopmental disorder with language impairment and behavioral abnormalities (MONDO:0030060), neurodevelopmental disorder (MONDO:0700092)

Orphanet (0):

HPO phenotypes

25 total (25 of 25 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000028	Cryptorchidism
HP:0000253	Progressive microcephaly
HP:0000722	Compulsive behaviors
HP:0000729	Autistic behavior
HP:0000733	Motor stereotypy
HP:0000750	Delayed speech and language development
HP:0001249	Intellectual disability
HP:0001257	Spasticity
HP:0001263	Global developmental delay
HP:0001272	Cerebellar atrophy
HP:0001332	Dystonia
HP:0001344	Absent speech
HP:0001762	Talipes equinovarus
HP:0002059	Cerebral atrophy
HP:0002066	Gait ataxia
HP:0002069	Bilateral tonic-clonic seizure
HP:0002072	Chorea
HP:0002373	Febrile seizure (within the age range of 3 months to 6 years)
HP:0002540	Inability to walk
HP:0007359	Focal-onset seizure
HP:0012171	Stereotypical hand wringing
HP:0020221	Clonic seizure
HP:0032792	Tonic seizure
HP:0100716	Self-injurious behavior

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST009615_7	Triglyceride levels x loop diuretics use interaction	2.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004530	triglyceride measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D065886	Neurodevelopmental Disorders	F03.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (4): CHEMBL2096670 (PROTEIN COMPLEX GROUP), CHEMBL3883291 (PROTEIN COMPLEX), CHEMBL3883294 (PROTEIN COMPLEX), CHEMBL4016 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

6 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 951,988 (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
CHEMBL61593	CYCLOTHIAZIDE	4	4,410
CHEMBL575060	GLUTAMIC ACID	3	929,756
CHEMBL14935	TEZAMPANEL ANHYDROUS	2	106
CHEMBL39664	SELFOTEL	2	2,588
CHEMBL275040	KAINIC ACID	2	15,084
CHEMBL1214399	GSK-729327	1	44

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: lgic — Ionotropic glutamate receptors

Most potent curated ligand interactions (4 total), top 4:

Ligand	Action	Affinity	Parameter
talampanel	Antagonist	7.82	pKi
LY404187	Positive	6.82	pEC50
LY392098	Positive	6.66	pEC50
cyclothiazide	Positive	5.65	pEC50

Binding affinities (BindingDB)

4 measured of 9 human assays (9 total across all organisms); most potent 4 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
LY-302679	KI	820 nM
LY-293558	KI	3200 nM
LY 457691	KI	5500 nM
LY-458545	KI	8300 nM

ChEMBL bioactivities

506 potent at pChembl≥5 of 675 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.90	EC50	1.259	nM	CHEMBL4218628
8.85	EC50	1.4	nM	CHEMBL4218628
8.70	EC50	1.995	nM	CHEMBL4091984
8.70	EC50	2	nM	CHEMBL4091984
8.52	Ki	3	nM	CHEMBL3088070
8.41	Ki	3.89	nM	CHEMBL370038
8.40	Ki	4	nM	CHEMBL12696
8.40	Ki	4	nM	CHEMBL84142
8.40	Ki	4	nM	CHEMBL82375
8.30	Ki	5	nM	CHEMBL13076
8.30	Ki	5	nM	CHEMBL273675
8.15	Ki	7	nM	CHEMBL309831
7.87	EC50	13.4	nM	CHEMBL4202524
7.84	EC50	14.45	nM	CHEMBL4202524
7.82	Ki	15	nM	CHEMBL12510
7.80	Ki	16	nM	CHEMBL188018
7.78	Ki	16.7	nM	CHEMBL331696
7.78	Ki	16.8	nM	(S)-AMPA
7.77	Ki	17	nM	(R,S)-AMPA
7.72	Ki	19	nM	CHEMBL90251
7.72	IC50	19	nM	(R,S)-AMPA
7.71	Ki	19.3	nM	CHEMBL331644
7.70	Ki	20	nM	CHEMBL5192550
7.70	Ki	20	nM	CHEMBL310503
7.66	Ki	22	nM	CHEMBL116565
7.66	Ki	22	nM	CHEMBL293613
7.64	IC50	23	nM	(R,S)-AMPA
7.60	Ki	25.1	nM	CHEMBL123132
7.52	IC50	30	nM	CHEMBL94859
7.50	EC50	32	nM	CHEMBL215090
7.44	EC50	36	nM	CHEMBL384271
7.40	IC50	40	nM	(R,S)-AMPA
7.38	EC50	42	nM	CHEMBL384402
7.34	EC50	46.13	nM	CHEMBL4062524
7.33	EC50	47	nM	CHEMBL214833
7.32	EC50	48	nM	CHEMBL3800556
7.31	Ki	49	nM	CHEMBL12989
7.30	EC50	50	nM	CHEMBL4062524
7.28	Ki	53.1	nM	CHEMBL121388
7.28	IC50	52	nM	NBQX
7.27	Ki	54	nM	CHEMBL79348
7.26	EC50	55	nM	CHEMBL384402
7.24	EC50	57	nM	CHEMBL215090
7.24	Ki	57	nM	CHEMBL5199485
7.22	Ki	60	nM	CHEMBL79454
7.20	IC50	63	nM	CHEMBL293206
7.18	Ki	66	nM	CHEMBL5209014
7.18	Ki	66	nM	CHEMBL314248
7.17	Ki	68	nM	CHEMBL93649
7.16	Ki	70	nM	NBQX

PubChem BioAssay actives

438 with measured affinity, of 1108 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
4-cyclopropyl-6-[2-(4-cyclopropyl-1,1-dioxo-2,3-dihydro-1lambda6,2,4-benzothiadiazin-6-yl)ethyl]-2,3-dihydro-1lambda6,2,4-benzothiadiazine 1,1-dioxide	1380931: Positive allosteric modulation of GluA2Q flop isoform (unknown origin) expressed in HEK293 cells assessed as increase in L-glutamate induced calcium flux after 1 hr by fluo-4AM dye-based fluorescence assay	ec50	0.0013	uM
4-cyclopropyl-7-(3-methoxyphenoxy)-2,3-dihydro-1lambda6,2,4-benzothiadiazine 1,1-dioxide	1478393: Positive allosteric modulation of GluA2 (Q) flop isoform (unknown origin) expressed in HEK293 cells assessed as potentiation of glutamate-evoked calcium flux by fluo-4/AM dye-based fluorescence assay	ec50	0.0020	uM
(3S,4aS,6S,8aR)-6-[5-(4-chlorophenyl)-2-(2H-tetrazol-5-yl)phenoxy]-1,2,3,4,4a,5,6,7,8,8a-decahydroisoquinoline-3-carboxylic acid;hydrochloride	1054527: Displacement of [3H]AMPA from homomeric recombinant GluA2 receptor (unknown origin)	ki	0.0030	uM
(2S)-2-amino-3-[5-(2-methyltetrazol-5-yl)-3-oxo-1,2-oxazol-4-yl]propanoic acid	239016: Binding affinity for ionotropic Glutamate receptor AMPA 2 expressed in Sf9 cells	ki	0.0039	uM
4-methyl-6-[2-(4-methyl-1,1-dioxo-2,3-dihydro-1lambda6,2,4-benzothiadiazin-6-yl)ethyl]-2,3-dihydro-1lambda6,2,4-benzothiadiazine 1,1-dioxide	1380931: Positive allosteric modulation of GluA2Q flop isoform (unknown origin) expressed in HEK293 cells assessed as increase in L-glutamate induced calcium flux after 1 hr by fluo-4AM dye-based fluorescence assay	ec50	0.0134	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
(2S)-2-amino-3-(6-chloro-3,5-dioxo-1,2,4-triazin-2-yl)propanoic acid	92962: Displacement of [3H]AMPA from human Ionotropic glutamate receptor AMPA 2 expressed in HEK293 cells	ki	0.0167	uM
(2S)-2-amino-3-(5-methyl-3-oxo-1,2-oxazol-4-yl)propanoic acid	239016: Binding affinity for ionotropic Glutamate receptor AMPA 2 expressed in Sf9 cells	ki	0.0168	uM
2-amino-3-(5-methyl-3-oxo-1,2-oxazol-4-yl)propanoic acid	93098: Binding affinity of compound was determined towards cloned Ionotropic glutamate receptor AMPA 2 (GluR2) expressed in Sf 9 insect cells	ki	0.0170	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
(2S)-2-amino-3-(6-bromo-3,5-dioxo-1,2,4-triazin-2-yl)propanoic acid	92962: Displacement of [3H]AMPA from human Ionotropic glutamate receptor AMPA 2 expressed in HEK293 cells	ki	0.0193	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
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
(2S)-2-amino-3-(5-fluoro-2,4-dioxopyrimidin-1-yl)propanoic acid	92962: Displacement of [3H]AMPA from human Ionotropic glutamate receptor AMPA 2 expressed in HEK293 cells	ki	0.0251	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
4-cyano-5-ethyl-1-methyl-3-[4-(2-methylsulfanylphenyl)phenyl]pyrrole-2-carboxylic acid	270307: Activity at human recombinant iGluR2 flop expressed in HEK293 cells measured as change in intracellular calcium ion concentration in presence of glutamate by FLIPR assay	ec50	0.0320	uM
4-cyano-3-[4-(2-ethoxyphenyl)phenyl]-5-ethyl-1-methylpyrrole-2-carboxylic acid	270307: Activity at human recombinant iGluR2 flop expressed in HEK293 cells measured as change in intracellular calcium ion concentration in presence of glutamate by FLIPR assay	ec50	0.0360	uM
3-[4-(2-chlorophenyl)phenyl]-4-cyano-5-ethyl-1-methylpyrrole-2-carboxylic acid	270304: Activity at human recombinant iGluR2 flip expressed in HEK293 cells measured as change in intracellular calcium ion concentration in presence of glutamate by FLIPR assay	ec50	0.0420	uM
4-cyclopropyl-7-(3-methylphenoxy)-2,3-dihydro-1lambda6,2,4-benzothiadiazine 1,1-dioxide	1478393: Positive allosteric modulation of GluA2 (Q) flop isoform (unknown origin) expressed in HEK293 cells assessed as potentiation of glutamate-evoked calcium flux by fluo-4/AM dye-based fluorescence assay	ec50	0.0461	uM
3-(4-tert-butylphenyl)-4-cyano-5-ethylthiophene-2-carboxylic acid	270083: Activity against human GLUR2 flip expressed in HEK293 cells assessed as glutamate-stimulated calcium influx by FLIPR assay	ec50	0.0470	uM
7-[[5-chloro-3-(trifluoromethyl)pyrazol-1-yl]methyl]-3-[(1R,2R)-2-(hydroxymethyl)cyclopropyl]-2-methyl-[1,3]thiazolo[3,2-a]pyrimidin-5-one	1296120: Positive allosteric modulation of human GluA2 AMPAR flop isomer expressed in Dox-inducible cells measured every 5 mins by BD calcium indicator dye based-fluorescence analysis in presence of glutamate	ec50	0.0480	uM
(2S)-2-amino-3-(5-chloro-2,4-dioxopyrimidin-1-yl)propanoic acid	92962: Displacement of [3H]AMPA from human Ionotropic glutamate receptor AMPA 2 expressed in HEK293 cells	ki	0.0531	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
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
12-imidazol-1-yl-11-(trifluoromethyl)-2,5,8,13-tetrazatricyclo[7.4.0.02,6]trideca-1(9),3,5,10,12-pentaen-7-one	1859112: Displacement of [3H]AMPA from AMPA receptor (unknown origin)	ki	0.0660	uM
1-(2-ethoxycarbonyl-7-nitro-4-oxo-5H-[1,2,4]triazolo[1,5-a]quinoxalin-8-yl)pyrrole-3-carboxylic acid	1859112: Displacement of [3H]AMPA from AMPA receptor (unknown origin)	ki	0.0680	uM
4-cyano-3-[4-(2-cyanophenyl)phenyl]-5-ethyl-1-methylpyrrole-2-carboxylic acid	270307: Activity at human recombinant iGluR2 flop expressed in HEK293 cells measured as change in intracellular calcium ion concentration in presence of glutamate by FLIPR assay	ec50	0.0730	uM
cis-(1R,2R)-2-[7-[[5-chloro-3-(trifluoromethyl)pyrazol-1-yl]methyl]-2-methyl-5-oxo-[1,3]thiazolo[3,2-a]pyrimidin-3-yl]cyclopropane-1-carbonitrile	1296120: Positive allosteric modulation of human GluA2 AMPAR flop isomer expressed in Dox-inducible cells measured every 5 mins by BD calcium indicator dye based-fluorescence analysis in presence of glutamate	ec50	0.0730	uM
7,8-dichloro-4-oxo-5H-[1,2,4]triazolo[1,5-a]quinoxaline-2-carboxylic acid	1859124: Displacement of [3H]glycine from AMPA receptor (unknown origin)	ki	0.0740	uM
3-(4-tert-butylphenyl)-4-cyano-5-(trifluoromethyl)thiophene-2-carboxylic acid	270083: Activity against human GLUR2 flip expressed in HEK293 cells assessed as glutamate-stimulated calcium influx by FLIPR assay	ec50	0.0780	uM
2-amino-3-[5-(2-ethyltetrazol-5-yl)-3-oxo-1,2-oxazol-4-yl]propanoic acid	239016: Binding affinity for ionotropic Glutamate receptor AMPA 2 expressed in Sf9 cells	ki	0.0802	uM
6-imidazol-1-yl-7-nitro-1,4-dihydroquinoxaline-2,3-dione	1859112: Displacement of [3H]AMPA from AMPA receptor (unknown origin)	ki	0.0840	uM
2-amino-3-[3-oxo-5-(1,3-thiazol-2-yl)-1,2-oxazol-4-yl]propanoic acid	92806: In vitro binding affinity against Ionotropic glutamate receptor AMPA using [3H]AMPA as radioligand	ic50	0.0940	uM
3-(4-tert-butylphenyl)-4-cyano-5-methylsulfanylthiophene-2-carboxylic acid	270083: Activity against human GLUR2 flip expressed in HEK293 cells assessed as glutamate-stimulated calcium influx by FLIPR assay	ec50	0.0970	uM
N-[(2S)-5-[[3,5-bis(trifluoromethyl)pyrazol-1-yl]methyl]-2,3-dihydro-1H-inden-2-yl]propane-2-sulfonamide	551164: Modulatory activity at GluA2 receptor LBD	ec50	0.1000	uM
N-[5-[[4-(hydroxymethyl)-3-(trifluoromethyl)pyrazol-1-yl]methyl]-2,3-dihydro-1H-inden-1-yl]propane-2-sulfonamide	551164: Modulatory activity at GluA2 receptor LBD	ec50	0.1000	uM
N-[(3S,4R)-4-[4-(3-acetylphenyl)phenyl]oxolan-3-yl]propane-2-sulfonamide	539271: Positive modulation of human GluA2 flip receptor by FLIPR assay	ec50	0.1000	uM
(2S)-2-amino-3-(5-bromo-2,4-dioxopyrimidin-1-yl)propanoic acid	92962: Displacement of [3H]AMPA from human Ionotropic glutamate receptor AMPA 2 expressed in HEK293 cells	ki	0.1010	uM
(2S)-2-amino-3-(6-iodo-3,5-dioxo-1,2,4-triazin-2-yl)propanoic acid	92962: Displacement of [3H]AMPA from human Ionotropic glutamate receptor AMPA 2 expressed in HEK293 cells	ki	0.1010	uM
4-cyano-5-ethyl-1-methyl-3-(4-phenylphenyl)pyrrole-2-carboxylic acid	270304: Activity at human recombinant iGluR2 flip expressed in HEK293 cells measured as change in intracellular calcium ion concentration in presence of glutamate by FLIPR assay	ec50	0.1030	uM
3-oxo-4,5,6,7-tetrahydro-[1,2]oxazolo[5,4-c]pyridine-7-carboxylic acid	541698: Displacement of [3H]AMPA from GluA2-S1S2 receptor	ki	0.1080	uM
4-cyano-5-ethyl-3-[4-(2-fluorophenyl)phenyl]-1-methylpyrrole-2-carboxylic acid	270304: Activity at human recombinant iGluR2 flip expressed in HEK293 cells measured as change in intracellular calcium ion concentration in presence of glutamate by FLIPR assay	ec50	0.1110	uM
(2S)-2-amino-3-(5-nitro-2,4-dioxopyrimidin-1-yl)propanoic acid	92962: Displacement of [3H]AMPA from human Ionotropic glutamate receptor AMPA 2 expressed in HEK293 cells	ki	0.1150	uM
2-amino-3-(3-hydroxy-5-methyltriazol-4-yl)propanoic acid	2071188: Binding affinity to AMPA receptor (unknown origin)	ic50	0.1300	uM
2-[(6-ethyl-7-nitro-2,3-dioxo-1,4-dihydroquinoxalin-5-yl)methyl-methylamino]acetic acid	1859112: Displacement of [3H]AMPA from AMPA receptor (unknown origin)	ic50	0.1400	uM
6-imidazol-1-yl-7-nitro-1,4-dihydropyrido[2,3-b]pyrazine-2,3-dione	1859112: Displacement of [3H]AMPA from AMPA receptor (unknown origin)	ki	0.1400	uM
ethyl 2-[(6-ethyl-7-nitro-2,3-dioxo-1,4-dihydroquinoxalin-5-yl)methyl-methylamino]acetate	1866051: Antagonist activity at AMPA receptor (unknown origin)	ic50	0.1400	uM
8-chloro-9-(3-formylpyrrol-1-yl)-5-oxo-6H-pyrazolo[1,5-c]quinazoline-2-carboxylic acid	1871553: Binding affinity to AMPA (unknown origin)	ki	0.1400	uM
8-chloro-5-oxo-9-(1,2,4-triazol-4-yl)-6H-pyrazolo[1,5-c]quinazoline-2-carboxylic acid	1859112: Displacement of [3H]AMPA from AMPA receptor (unknown origin)	ki	0.1400	uM
7-chloro-4-oxo-8-(1,2,4-triazol-4-yl)-5H-[1,2,4]triazolo[1,5-a]quinoxaline-2-carboxylic acid	1859112: Displacement of [3H]AMPA from AMPA receptor (unknown origin)	ki	0.1400	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
trichostatin A	affects cotreatment, increases expression, affects expression, decreases reaction	4
Valproic Acid	affects expression, increases expression	4
Nickel	affects expression, decreases expression, decreases reaction	3
bisphenol A	decreases expression, decreases methylation	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	2
Ascorbic Acid	increases expression, affects binding, affects cotreatment	2
Benzo(a)pyrene	increases methylation, affects reaction, decreases expression	2
Dronabinol	affects cotreatment, decreases expression, decreases response to substance	2
6,7-dimethoxy-2-(pyrrolidin-1-yl)-N-(5-(pyrrolidin-1-yl)pentyl)quinazolin-4-amine	increases expression	1
ascorbate-2-phosphate	increases expression, affects binding, affects cotreatment	1
arsenite	increases methylation	1
4-(2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)-1-propenyl)benzoic acid	affects cotreatment, increases expression	1
azoxystrobin	decreases expression	1
CGP 52608	affects binding, increases reaction	1
deguelin	decreases expression	1
4-chloro-N-((4-(1,1-dimethylethyl)phenyl)methyl)-3-ethyl-1-methyl-1H-pyrazole-5-carboxamide	decreases expression	1
Chir 99021	affects cotreatment, increases expression, affects binding	1
pyrimidifen	decreases expression	1
thifluzamide	decreases expression	1
pyrachlostrobin	decreases expression	1
dorsomorphin	increases expression, affects cotreatment	1
XAV939	affects binding, affects cotreatment, increases expression	1
LDN 193189	affects cotreatment, increases expression	1
picoxystrobin	decreases expression	1
3-(4-pyridyl)-1H-indole	affects cotreatment, increases expression	1
theaflavin-3,3’-digallate	affects expression	1
Vorinostat	affects cotreatment, increases expression	1
Cyclic AMP	affects cotreatment, increases expression	1
Antimycin A	decreases expression	1
Cannabidiol	affects cotreatment, decreases expression, decreases response to substance	1

ChEMBL screening assays

192 unique, capped per target: 163 binding, 25 functional, 4 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5114182	Binding	Displacement of [3H]AMPA from AMPA receptor (unknown origin)	Functionalized quinoxalinones as privileged structures with broad-ranging pharmacological activities. — Eur J Med Chem
CHEMBL702514	Functional	Compound was evaluated to potentiate response of AMPA-activated current in Xenopus oocytes expressing Ionotropic glutamate receptor AMPA	Enantioselective synthesis of a pyrrolo-benzothiadiazine derivative S 18986, a new AMPA receptor positive modulator — Bioorg Med Chem Lett
CHEMBL3871162	ADMET	Positive allosteric modulation of human GluA2 receptor flip isoform assessed as increase in glutamate-induced calcium flux measured at time interval of 5 mins in presence of saturating glycine by calcium dye-based fluorescence assay	GluN2A-Selective Pyridopyrimidinone Series of NMDAR Positive Allosteric Modulators with an Improved in Vivo Profile. — ACS Med Chem Lett

Cellosaurus cell lines

2 cell lines: 1 induced pluripotent stem cell, 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_C0F7	SJTUXHi002-A	Induced pluripotent stem cell	Male
CVCL_D1SV	Abcam U-87MG GRIA2 KO	Cancer cell line	Male

Clinical trials (associated diseases)

202 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,
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
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT00503191	PHASE1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	PHASE1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT01783041	PHASE2/PHASE3	COMPLETED	Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
NCT05767385	PHASE2/PHASE3	RECRUITING	Fetal Cerebrovascular Autoregulation in Congenital Heart Disease and Association With Neonatal Neurobehavior
NCT05675098	EARLY_PHASE1	NOT_YET_RECRUITING	Central Nervous System Stimulants and Physical Function in Children With Cerebral Palsy
NCT00783783	Not specified	COMPLETED	CYP2D6 Pharmacogenetics in Risperidone-Treated Children
NCT01778504	Not specified	RECRUITING	Studying Childhood-onset Behavioral, Psychiatric, and Developmental Disorders
NCT01850784	Not specified	UNKNOWN	High Energy Formula Feeding in Infants With Congenital Heart Disease
NCT01922791	Not specified	COMPLETED	Nutrition and Pregnancy Intervention Study
NCT01942525	Not specified	UNKNOWN	Influence of Intrauterine Growth Restriction on Amplitude-integrated EEG in Preterm Infants
NCT02003170	Not specified	COMPLETED	Etiology and Early Diagnosis of Neurodevelopmental Disorders
NCT02118649	Not specified	ACTIVE_NOT_RECRUITING	Enhancing Behavior and Brain Response to Visual Targets Using a Computer Game
NCT02557191	Not specified	TERMINATED	Biomarkers, Neurodevelopment and Preterm Infants
NCT02690675	Not specified	COMPLETED	Iron Supplement Effect on Child Development
NCT02694003	Not specified	COMPLETED	Better Nights, Better Days for Children With Neurodevelopment Disorders
NCT02792894	Not specified	COMPLETED	Family Networks (FaNs) for Children With Developmental Disorders and Delays
NCT02871674	Not specified	UNKNOWN	Good Night Project: Behavioural Sleep Interventions for Children With ADHD: A Randomised Controlled Trial
NCT02887157	Not specified	COMPLETED	Analyzing Retinal Microanatomy in ROP
NCT02898298	Not specified	COMPLETED	Positive Emotion Regulation Training in Children, Adolescents and Young Adults With and Without Developmental Disorder
NCT02912780	Not specified	UNKNOWN	Introduction of Microsystems in a Level 3 Neonatal Intensive Care Unit
NCT03023293	Not specified	COMPLETED	n-3 PUFAs, Irisin and Maternal Glucose Metabolism From Pregnancy to Postpartum
NCT03023644	Not specified	COMPLETED	Improving Neurodevelopmental Outcomes in Children With Congenital Heart Disease: An Intervention Study
NCT03032991	Not specified	UNKNOWN	Early Biomarkers of Neurodevelopment in Offspring of Diabetic Mothers
NCT03088189	Not specified	TERMINATED	Effect of Parental Peri-conceptional Vitamin B12 Supplementation on Infant Neurocognitive Development in Offspring
NCT03096028	Not specified	COMPLETED	Developmental Origins of Mental Health Disorders
NCT03148782	Not specified	COMPLETED	Brain Plasticity Underlying Acquisition of New Organizational Skills in Children-R61 Phase
NCT03172104	Not specified	COMPLETED	Neurobehavioural Development of Infants Born <30 Weeks Gestational Age Between Birth and Five Years of Age
NCT03222375	Not specified	RECRUITING	SQUED™ Series 28.1 Home-use and Treatment of Autowave Reverberator of Autism
NCT03229928	Not specified	COMPLETED	Clinical Testing of a Real-Time Behavior Measurement Tool: Measuring Outcomes for CHAnge
NCT03232489	Not specified	UNKNOWN	Study for the Evaluation of the Feasibility of Applying Advanced MRI Scanning in Pediatric Clinical Practice