GRIN3A

Summary

GRIN3A (glutamate ionotropic receptor NMDA type subunit 3A, HGNC:16767) is a protein-coding gene on chromosome 9q31.1, encoding Glutamate receptor ionotropic, NMDA 3A (Q8TCU5). Component of a non-conventional N-methyl-D-aspartate (NMDA) receptors (NMDARs) that function as heterotetrameric, ligand-gated cation channels with low calcium permeability and low voltage-dependent block by Mg(2+).

This gene encodes a subunit of the N-methyl-D-aspartate (NMDA) receptors, which belong to the superfamily of glutamate-regulated ion channels, and function in physiological and pathological processes in the central nervous system. This subunit shows greater than 90% identity to the corresponding subunit in rat. Studies in the knockout mouse deficient in this subunit suggest that this gene may be involved in the development of synaptic elements by modulating NMDA receptor activity.

Source: NCBI Gene 116443 — RefSeq curated summary.

At a glance

• GWAS associations: 16
• Clinical variants (ClinVar): 190 total
• Druggable target: yes — 22 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_133445

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16767
Approved symbol	GRIN3A
Name	glutamate ionotropic receptor NMDA type subunit 3A
Location	9q31.1
Locus type	gene with protein product
Status	Approved
Aliases	GluN3A
Ensembl gene	ENSG00000198785
Ensembl biotype	protein_coding
OMIM	606650
Entrez	116443

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 1 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000361820, ENST00000479772

RefSeq mRNA: 1 — MANE Select: NM_133445 NM_133445

CCDS: CCDS6758

Canonical transcript exons

ENST00000361820 — 9 exons

Exon	Start	End
ENSE00001148109	101628256	101628401
ENSE00001162926	101569352	101573513
ENSE00001162934	101737281	101738647
ENSE00001265013	101579196	101579360
ENSE00001265036	101613376	101613527
ENSE00001265038	101623318	101623433
ENSE00001265046	101670060	101671107
ENSE00001265051	101686596	101687200
ENSE00001265089	101577768	101577844

Expression profiles

Bgee: expression breadth ubiquitous, 149 present calls, max score 77.76.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.7939 / max 220.4610, expressed in 121 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
101766	0.7304	119
101765	0.0635	31

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
Brodmann (1909) area 46	UBERON:0006483	77.76	gold quality
middle temporal gyrus	UBERON:0002771	76.93	silver quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	76.14	gold quality
Brodmann (1909) area 23	UBERON:0013554	75.63	silver quality
prefrontal cortex	UBERON:0000451	74.42	gold quality
substantia nigra pars compacta	UBERON:0001965	73.07	silver quality
frontal cortex	UBERON:0001870	70.23	gold quality
entorhinal cortex	UBERON:0002728	70.12	silver quality
dorsolateral prefrontal cortex	UBERON:0009834	69.72	gold quality
anterior cingulate cortex	UBERON:0009835	69.50	gold quality
neocortex	UBERON:0001950	69.45	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	69.42	gold quality
superior frontal gyrus	UBERON:0002661	68.90	gold quality
cerebral cortex	UBERON:0000956	68.14	gold quality
substantia nigra pars reticulata	UBERON:0001966	68.12	silver quality
Brodmann (1909) area 9	UBERON:0013540	67.53	gold quality
hypothalamus	UBERON:0001898	67.34	gold quality
temporal lobe	UBERON:0001871	65.72	gold quality
primary visual cortex	UBERON:0002436	64.93	gold quality
endothelial cell	CL:0000115	64.87	gold quality
occipital lobe	UBERON:0002021	64.47	gold quality
midbrain	UBERON:0001891	64.34	gold quality
right frontal lobe	UBERON:0002810	64.32	gold quality
substantia nigra	UBERON:0002038	64.13	gold quality
parietal lobe	UBERON:0001872	63.83	silver quality
postcentral gyrus	UBERON:0002581	63.64	silver quality
amygdala	UBERON:0001876	62.10	gold quality
monocyte	CL:0000576	61.78	gold quality
leukocyte	CL:0000738	61.76	gold quality
pons	UBERON:0000988	61.69	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.03

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CTCF, NRF1

miRNA regulators (miRDB)

189 targeting GRIN3A, 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-4673	100.00	66.64	1490
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-3605-5P	99.96	67.12	932

Literature-anchored findings (GeneRIF, showing 35)

• NR3A is highly expressed in the developing human neocortex (PMID:14684485)
• NR3 NMDA receptors induce plasticity in NR1 with respect to subunit assembly and ligand binding/channel coupling that is unique among ligand-gated ion channel subunits. (PMID:17047094)
• Individuals carrying Val/Val genotype showed significantly reduced frontal P300 amplitudes compared with Met/Met subjects. (PMID:17214563)
• This review summarizes recent research regarding the functional roles of the N-methyl-D-aspartate (NMDA) receptor subunit NR3A in dendrite spine formation, plasticity and synaptogenesis, and sensory processing in the spinal cord [review]. (PMID:17617428)
• NR3A was found in the cerebral cortex, subcortical forebrain, midbrain and hindbrain. Very low levels of NR3A could be detected in homogenized adult human spinal cord, limited to ventral motoneurons. (PMID:17997397)
• a case-control association study of common nucleotide variants of the GRIN3A gene with susceptibility to schizophrenia; findings did not show any difference in allele and genotype frequency of each polymorphism between patients and controls (PMID:18075478)
• NR3A levels are low during gestation, surge soon after birth, and decline progressively through adolescence and into adulthood (PMID:18296432)
• NMDA receptor protein subunit NR3A overexpressed in transgenic mice protects them from neuronal damage due to cerebral ischemia. (PMID:19386922)
• significant lower protein and mRNA levels of the N-methyl-D-aspartate receptors, NR-1 and hr-3a in frontal corte in bipolar disorder. (PMID:19488045)
• This study indicated that rare mutations in the GRIN3A gene may contribute to the pathogenesis of schizophrenia in certain patients. (PMID:19665356)
• These observations suggest that the genetic variation of the NR3A subunit of the NMDA receptor may be a risk factor for Alzheimer’s dis pathogenesis (PMID:20016182)
• Results indicate that GRIN3A is significantly associated with nicotine dependence. (PMID:20084518)
• In a human embryonic brain cDNA library mTOR-activating GTPase Rheb is screened as an interacting protein of the NMDAR subunit NR3A. (PMID:21135540)
• Data show that that all seven currently known NMDAR subunits (NR1, NR2A, NR2B, NR2C, NR2D, NR3A and NR3B) are expressed in astrocytes, but at different levels. (PMID:21152063)
• NR3a, by maintaining low intracellular calcium levels, protects the function of the principal cells to reabsorb water and thereby increase medullary osmolality (PMID:21429969)
• reductions of toxic calpain activation might be linked to inhibition by GluN3A of pathological extrasynaptic NMDAR activity. (PMID:22801082)
• Vasoactive intestinal polypeptipe and GRIN3A SNPs may be associated with cerebral palsy at age 2 in children born preterm. (PMID:22914463)
• the GRIN3A R480G variant showed the strongest association with schizophrenia. (PMID:23237318)
• These findings reveal an early pathogenic role of GluN3A dysregulation in Huntington’s disease. (PMID:23852340)
• Our results suggest that a polymorphism of the GRIN3A gene may play a role in KD pathogenesis. (PMID:24278430)
• It modulates episodic memory. (PMID:24332987)
• This review highlights GluN3A properties and addresses its role in neurophysiology and associated pathologies–{REVIEW} (PMID:24386575)
• Isolated GluN1/GluN3A receptors integrated into lipid bilayers responded to addition of either glycine or d-serine, but not glutamate, with a approximately 1 nm reduction in height of the extracellular domain (PMID:25017909)
• the genetic variations of NR3A subunit of NMDA receptor may be a predisposing factor to delirium among the Polish population of cardiac surgery patients (PMID:25041634)
• The rare variants in GRIN3A were significantly associated with smoking status. (PMID:25450229)
• Single nucleotide polymorphism in GRIN3A is associated with osteonecrosis in children with acute lymphoblastic leukemia. (PMID:26265699)
• Results suggest that GRIN3A rs17189632 and GRIN3B rs2240158 may contribute to the susceptibility of heroin addiction. (PMID:27542340)
• discuss current evidence for emerging roles for GluN3NMDARs in the physiology and pathology of the CNS. (PMID:27558536)
• Increased expression levels of MAPT and GRIN3A may lead to the abnormal pathologic condition of nerve tissue in macrodactyly and, to a certain extent, may have potential applications in nerve regeneration. (PMID:27840953)
• GRIN3A locus was associated with thyroid antibodies levels in females. (PMID:29678681)
• Demonstration of critical role of GRIN3A in nicotine dependence through both genetic association and molecular functional studies. (PMID:30741440)
• Structural features in the glycine-binding sites of the GluN1 and GluN3A subunits regulate the surface delivery of NMDA receptors. (PMID:31444392)
• Pathogenesis of sporadic Alzheimer’s disease by deficiency of NMDA receptor subunit GluN3A. (PMID:34151525)
• Correlations between GRIN2B and GRIN3A gene polymorphisms and postpartum depressive symptoms in Chinese parturients undergoing cesarean section: A prospective cohort study. (PMID:36898314)
• Excitatory GluN1/GluN3A glycine receptors (eGlyRs) in brain signaling. (PMID:37248111)

Cross-species orthologs

41 orthologs

Organism	Symbol	Gene ID
mus_musculus	Grin3a	ENSMUSG00000039579
rattus_norvegicus	Grin3a	ENSRNOG00000005723
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), GRIA1 (ENSG00000155511), GRIN2C (ENSG00000161509), GRIK3 (ENSG00000163873), GRIK2 (ENSG00000164418), GRIK1 (ENSG00000171189), GRIN1 (ENSG00000176884), GRID1 (ENSG00000182771), GRIN2A (ENSG00000183454), GRIN2B (ENSG00000273079)

Protein

Protein identifiers

Glutamate receptor ionotropic, NMDA 3A — Q8TCU5 (reviewed: Q8TCU5)

Alternative names: N-methyl-D-aspartate receptor subtype 3A, NMDAR-L

All UniProt accessions (1): Q8TCU5

UniProt curated annotations — full annotation on UniProt →

Function. Component of a non-conventional N-methyl-D-aspartate (NMDA) receptors (NMDARs) that function as heterotetrameric, ligand-gated cation channels with low calcium permeability and low voltage-dependent block by Mg(2+). During the development of neural circuits, participates in the synaptic refinement period, restricting spine maturation and growth. Forms glutamatergic receptor complexes with GluN1 and GluN2 subunits which are activated by glycine binding to the GluN1 and GluN3 subunits and L-glutamate binding to GluN2 subunits. Forms excitatory glycinergic receptor complexes with GluN1 alone which are activated by glycine binding to the GluN1 and GluN3 subunits. GluN3A subunit also binds D-serine. Each GluN3 subunit confers differential attributes to channel properties, including activation, deactivation and desensitization kinetics, pH sensitivity, Ca2(+) permeability, and binding to allosteric modulators. By competing with GIT1 interaction with ARHGEF7/beta-PIX, may reduce GIT1/ARHGEF7-regulated local activation of RAC1, hence affecting signaling and limiting the maturation and growth of inactive synapses.

Subunit / interactions. Heterotetramer. Forms heterotetrameric channels composed of two GluN1/zeta subunits (GRIN1), and two identical GluN3 subunits (GRIN3A or GRIN3B) (in vitro). Can also form heterotetrameric channels that contain at least two GluN1 subunits and at least a combination of one GluN2 and one GluN3 subunits (in vitro). Does not form functional homomeric channels. Found in a complex with GRIN1, GRIN2A or GRIN2B and PPP2CB. Probably interacts with PPP2CB. No complex with PPP2CB is detected when NMDARs are stimulated by NMDA. Interacts (via C-terminus) with GIT1, but not with GRIA1/GluA1, nor with synaptophysin/SYP; this interaction competes with GIT1 interaction with ARHGEF7/beta-PIX.

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

Post-translational modifications. N-glycosylated.

Similarity. Belongs to the glutamate-gated ion channel (TC 1.A.10.1) family. NR3A/GRIN3A subfamily.

RefSeq proteins (1): NP_597702* (*=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 (64 total): sequence variant 22, binding site 10, glycosylation site 10, topological domain 5, region of interest 3, transmembrane region 3, disulfide bond 3, sequence conflict 3, signal peptide 1, chain 1, coiled-coil region 1, compositionally biased region 1, intramembrane region 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
8UUE	ELECTRON MICROSCOPY	3.96
8USX	ELECTRON MICROSCOPY	4.1
8USW	ELECTRON MICROSCOPY	4.23

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8TCU5-F1	73.24	0.26

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 (10): 631; 633; 633; 638; 638; 801; 801; 802; 845; 845

Disulfide bonds (3): 537–575, 543–576, 859–913

Glycosylation sites (10): 145, 264, 275, 285, 296, 426, 439, 549, 565, 886

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-9609736	Assembly and cell surface presentation of NMDA receptors

MSigDB gene sets: 190 (showing top): GOBP_DENDRITE_DEVELOPMENT, GOBP_NEGATIVE_REGULATION_OF_DENDRITIC_SPINE_DEVELOPMENT, GOBP_RESPONSE_TO_ETHANOL, BENPORATH_ES_WITH_H3K27ME3, GOMF_GLUTAMATE_GATED_RECEPTOR_ACTIVITY, GOBP_DENDRITIC_SPINE_DEVELOPMENT, GOBP_NEUROGENESIS, EFC_Q6, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_CELL_CELL_SIGNALING, GTGCCTT_MIR506, GOBP_STARTLE_RESPONSE, CAGCAGG_MIR370, GOBP_REGULATION_OF_SYNAPTIC_PLASTICITY, GOBP_REGULATION_OF_POSTSYNAPTIC_MEMBRANE_POTENTIAL

GO Biological Process (17): calcium ion transport (GO:0006816), dendrite development (GO:0016358), ionotropic glutamate receptor signaling pathway (GO:0035235), synaptic transmission, glutamatergic (GO:0035249), response to ethanol (GO:0045471), regulation of synaptic plasticity (GO:0048167), rhythmic process (GO:0048511), modulation of chemical synaptic transmission (GO:0050804), prepulse inhibition (GO:0060134), negative regulation of dendritic spine development (GO:0061000), monoatomic cation transmembrane transport (GO:0098655), presynaptic modulation of chemical synaptic transmission (GO:0099171), monoatomic ion transport (GO:0006811), monoatomic ion transmembrane transport (GO:0034220), neuron development (GO:0048666), regulation of postsynaptic membrane potential (GO:0060078), calcium ion transmembrane transport (GO:0070588)

GO Molecular Function (15): NMDA glutamate receptor activity (GO:0004972), calcium channel activity (GO:0005262), glutamate receptor activity (GO:0008066), glycine binding (GO:0016594), identical protein binding (GO:0042802), protein phosphatase 2A binding (GO:0051721), serine binding (GO:0070905), glycine-gated cation channel activity (GO:0160212), 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), transmitter-gated monoatomic ion channel activity (GO:0022824), signaling receptor activity (GO:0038023)

GO Cellular Component (16): endoplasmic reticulum membrane (GO:0005789), plasma membrane (GO:0005886), membrane (GO:0016020), NMDA selective glutamate receptor complex (GO:0017146), neuron projection (GO:0043005), neuronal cell body (GO:0043025), synapse (GO:0045202), postsynaptic membrane (GO:0045211), presynapse (GO:0098793), postsynaptic density membrane (GO:0098839), neurotransmitter receptor complex (GO:0098878), glutamatergic synapse (GO:0098978), cytoplasm (GO:0005737), postsynaptic density (GO:0014069), monoatomic ion channel complex (GO:0034702), organelle (GO:0043226)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Activation of NMDA receptors and postsynaptic events	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
transmitter-gated monoatomic ion channel activity	3
glutamate-gated receptor activity	2
chemical synaptic transmission	2
modulation of chemical synaptic transmission	2
amino acid binding	2
carboxylic acid binding	2
cation binding	2
synapse	2
metal ion transport	1
neuron projection development	1
anatomical structure development	1
glutamate receptor signaling pathway	1
ligand-gated ion channel signaling pathway	1
response to alcohol	1
regulation of biological quality	1
biological_process	1
regulation of trans-synaptic signaling	1
startle response	1
negative regulation of response to external stimulus	1
negative regulation of developmental process	1
dendritic spine development	1
regulation of dendritic spine development	1
monoatomic cation transport	1
monoatomic ion transmembrane transport	1
presynapse	1
transport	1
monoatomic ion transport	1
transmembrane transport	1
neuron differentiation	1
cell development	1
regulation of membrane potential	1
calcium ion transport	1
monoatomic cation transmembrane transport	1
voltage-gated monoatomic ion channel activity	1
monoatomic cation channel activity	1
calcium ion transmembrane transporter activity	1
transmembrane signaling receptor activity	1
glutamate binding	1
protein binding	1

Protein interactions and networks

STRING

1384 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GRIN3A	GRIN1	P35437	991
GRIN3A	GRIN2D	O15399	988
GRIN3A	GRIN2A	Q12879	988
GRIN3A	GRIN2B	Q13224	987
GRIN3A	GRIN2C	Q14957	986
GRIN3A	GRIN3B	O60391	981
GRIN3A	GRM5	P41594	683
GRIN3A	GRM3	Q14832	680
GRIN3A	GRM7	Q14831	663
GRIN3A	GRM4	Q14833	661
GRIN3A	DLG4	P78352	646
GRIN3A	GRM2	Q14416	621
GRIN3A	KCND2	Q9NZV8	615
GRIN3A	GRM8	O00222	615
GRIN3A	BDNF	P23560	588

IntAct

3 interactions, top by confidence:

A	B	Type	Score
GRIN3B	DAPK3	psi-mi:“MI:0914”(association)	0.350
KLHL22	TRAV18	psi-mi:“MI:0914”(association)	0.350

BioGRID (12): GRIN3A (Affinity Capture-Western), PPP2R4 (Two-hybrid), GRIN3A (Affinity Capture-Western), GRIN3A (Affinity Capture-MS), GRIN1 (Affinity Capture-Western), GRIN2A (Affinity Capture-Western), GRIN2B (Affinity Capture-Western), GRIN3A (Positive Genetic), GRIN3A (Affinity Capture-MS), GRIN3A (Cross-Linking-MS (XL-MS)), GRIN3A (Affinity Capture-MS), GRIN3A (Affinity Capture-MS)

ESM2 similar proteins: A1A5B4, A2A259, A2AIR5, E9PTA2, F6RG56, H2Q5A1, O35245, O62826, O70212, O94759, P02715, P04758, P09690, P11230, P13536, P23979, P25109, P35563, P37088, Q04671, Q13507, Q13563, Q4GZT3, Q60HE8, Q6IVV8, Q7Z403, Q86V40, Q8BWC0, Q8MIQ9, Q8R4F0, Q8TCT7, Q8TCU5, Q8TDD5, Q91YD4, Q96BD0, Q99J21, Q9EQJ0, Q9GZU1, Q9HA82, Q9JJH7

Diamond homologs: A0A1L8F5J9, A2AIR5, O15399, O60391, Q8TCU5, Q8VHN2, Q91ZU9, Q9R1M7, A7XY94, B1AS29, B7ZSK1, P0AEM9, P0AEN0, P19491, P19492, P19493, P23819, P34299, P35436, P39086, P42262, P42263, P42264, P48058, Q00959, Q00960, Q00961, Q01097, Q01098, Q01812, Q03391, Q12879, Q13003, Q13224, Q14957, Q16099, Q38PU2, Q38PU4, Q38PU5, Q38PU7

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	175
Likely benign	8
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

2515 predictions. Top by Δscore:

Variant	Effect	Δscore
9:101573183:A:AC	donor_gain	1.0000
9:101573184:C:CC	donor_gain	1.0000
9:101573184:CAAGT:C	donor_gain	1.0000
9:101623312:TAATA:T	donor_loss	1.0000
9:101623314:ATACC:A	donor_loss	1.0000
9:101623315:TACCT:T	donor_loss	1.0000
9:101623316:ACC:A	donor_loss	1.0000
9:101623317:C:CG	donor_loss	1.0000
9:101623432:TCCT:T	acceptor_loss	1.0000
9:101623434:CT:C	acceptor_loss	1.0000
9:101623435:T:G	acceptor_loss	1.0000
9:101623447:C:CT	acceptor_gain	1.0000
9:101623448:A:T	acceptor_gain	1.0000
9:101628254:A:AC	donor_gain	1.0000
9:101628255:C:CC	donor_gain	1.0000
9:101628255:CTT:C	donor_gain	1.0000
9:101628397:TGTAA:T	acceptor_gain	1.0000
9:101628398:GTAA:G	acceptor_gain	1.0000
9:101628399:TAA:T	acceptor_gain	1.0000
9:101628399:TAAC:T	acceptor_loss	1.0000
9:101628402:C:CC	acceptor_gain	1.0000
9:101628402:C:T	acceptor_loss	1.0000
9:101628403:T:G	acceptor_loss	1.0000
9:101628404:A:C	acceptor_gain	1.0000
9:101687201:C:CC	acceptor_gain	1.0000
9:101573197:T:TA	donor_gain	0.9900
9:101573209:C:CA	donor_gain	0.9900
9:101573513:CCTAG:C	acceptor_loss	0.9900
9:101573514:C:CC	acceptor_gain	0.9900
9:101573514:C:G	acceptor_loss	0.9900

AlphaMissense

7358 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:101613421:C:A	W907C	0.999
9:101613421:C:G	W907C	0.999
9:101613423:A:G	W907R	0.999
9:101613423:A:T	W907R	0.999
9:101623386:A:G	L849P	0.999
9:101623398:T:A	D845V	0.999
9:101623407:A:G	F842S	0.999
9:101623410:G:T	A841D	0.999
9:101628400:A:G	L785S	0.999
9:101670167:A:G	W749R	0.999
9:101670167:A:T	W749R	0.999
9:101670480:G:C	F644L	0.999
9:101670480:G:T	F644L	0.999
9:101670482:A:G	F644L	0.999
9:101670664:A:G	L583P	0.999
9:101670679:C:T	G578E	0.999
9:101670684:G:C	C576W	0.999
9:101670783:A:C	C543W	0.999
9:101670784:C:G	C543S	0.999
9:101670785:A:G	C543R	0.999
9:101670785:A:T	C543S	0.999
9:101670978:C:A	W478C	0.999
9:101670978:C:G	W478C	0.999
9:101670980:A:G	W478R	0.999
9:101670980:A:T	W478R	0.999
9:101737314:G:C	S222R	0.999
9:101737314:G:T	S222R	0.999
9:101737316:T:G	S222R	0.999
9:101613512:A:G	L877P	0.998
9:101613515:C:T	G876D	0.998

dbSNP variants (sampled 300 via entrez): RS1000026283 (9:101636028 A>G), RS1000027248 (9:101591544 C>A), RS1000040816 (9:101685365 T>C,G), RS1000044664 (9:101595713 G>T), RS1000053068 (9:101700789 C>A,T), RS1000070912 (9:101641801 A>AAC), RS1000078093 (9:101719616 G>A,T), RS1000079271 (9:101592007 C>G,T), RS1000089405 (9:101635362 T>G), RS1000103157 (9:101700538 G>A), RS1000108680 (9:101724303 C>T), RS1000123845 (9:101657551 C>T), RS1000136244 (9:101617868 A>G), RS1000159872 (9:101636832 C>T), RS1000174428 (9:101633483 C>A,T)

Disease associations

OMIM: gene MIM:606650 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): myoepithelial tumor (MONDO:0002380)

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

16 associations (top):

Study	Trait	p-value
GCST001762_410	Obesity-related traits	1.000000e-06
GCST001762_566	Obesity-related traits	2.000000e-06
GCST001859_23	Thiazide-induced adverse metabolic effects in hypertensive patients	7.000000e-06
GCST002097_47	Coronary artery calcification	3.000000e-06
GCST003081_2	Glucocorticoid-induced osteonecrosis (age 10 years and older)	1.000000e-06
GCST003083_1	Glucocorticoid-induced osteonecrosis (time dependent analysis)	4.000000e-07
GCST003083_3	Glucocorticoid-induced osteonecrosis (time dependent analysis)	2.000000e-06
GCST003084_1	Glucocorticoid-induced osteonecrosis	3.000000e-08
GCST003192_1	Coronary artery aneurysm in Kawasaki disease	8.000000e-06
GCST003427_185	Alzheimer disease and age of onset	7.000000e-07
GCST003488_7	Response to fenofibrate (triglyceride levels)	2.000000e-06
GCST003831_29	Asthma	2.000000e-06
GCST008367_6	Plasma anti-thyroglobulin and anti-thyroid peroxidase levels (bivariate analysis)	8.000000e-09
GCST008368_11	Plasma anti-thyroid peroxidase levels	9.000000e-08
GCST008369_4	Plasma anti-thyroglobulin levels	1.000000e-06
GCST011536_14	Intestinal permeability measurement	1.000000e-06

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0003940	physical activity
EFO:0004723	coronary artery calcification
EFO:0004847	age at onset
EFO:0007681	triglyceride change measurement
EFO:0011031	intestinal permeability measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D009208	Myoepithelioma	C04.557.435.585

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL2094124 (PROTEIN COMPLEX GROUP), CHEMBL4787 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

22 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,350,441 (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
CHEMBL52440	DEXTROMETHORPHAN	4	33,223
CHEMBL592	LEVORPHANOL	4	75,131
CHEMBL660	AMANTADINE	4	69,750
CHEMBL71	CHLORPROMAZINE	4	45,827
CHEMBL742	KETAMINE	4	101,983
CHEMBL807	MEMANTINE	4	34,597
CHEMBL86715	PROCYCLIDINE	4	5,456
CHEMBL900	ORPHENADRINE	4	8,087
CHEMBL575060	GLUTAMIC ACID	3	929,756
CHEMBL1254766	DEXTRORPHAN	2	6,521
CHEMBL14935	TEZAMPANEL ANHYDROUS	2	106
CHEMBL17350	TRAXOPRODIL	2	2,547
CHEMBL182066	RADIPRODIL	2	126
CHEMBL22207	RACEMETHORPHAN	2	748
CHEMBL275528	PHENCYCLIDINE	2	25,537
CHEMBL284237	DIZOCILPINE	2	5,015
CHEMBL289832	LICOSTINEL	2	566
CHEMBL334491	BUDIPINE	2	2,513
CHEMBL39664	SELFOTEL	2	2,588
CHEMBL452461	PERZINFOTEL	2	364
CHEMBL467084	LANICEMINE	2
CHEMBL299155	TRANSTORINE	1

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

PharmGKB clinical annotations

2 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs10121600	Other	3	nicotine	Tobacco Use Disorder
rs11788456	Other	3	nicotine	Tobacco Use Disorder

PharmGKB variants

8 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs10121600	GRIN3A	3	1.50	1	nicotine
rs11788456	GRIN3A	3	1.50	1	nicotine
rs17189632	GRIN3A		0.00	0
rs942142	GRIN3A		0.00	0
rs10512285	GRIN3A		0.00	0
rs7030238	GRIN3A		0.00	0
rs1983812	GRIN3A		0.00	0
rs3983721	GRIN3A		0.00	0

GtoPdb / IUPHAR curated pharmacology

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

Target class: lgic — Ionotropic glutamate receptors

ChEMBL bioactivities

423 potent at pChembl≥5 of 551 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.30	IC50	0.5	nM	CHEMBL276708
9.10	IC50	0.8	nM	CHEMBL12513
9.02	Ki	0.96	nM	CHEMBL39881
9.00	IC50	1	nM	CHEMBL12804
8.92	IC50	1.2	nM	CHEMBL12242
8.92	Ki	1.2	nM	DIZOCILPINE
8.85	Ki	1.4	nM	CHEMBL5185347
8.82	IC50	1.5	nM	CHEMBL537478
8.82	IC50	1.5	nM	CHEMBL274422
8.82	IC50	1.5	nM	CHEMBL273662
8.77	IC50	1.7	nM	CHEMBL269683
8.71	Ki	1.94	nM	CNS-5161
8.70	IC50	2	nM	CHEMBL536107
8.70	Ki	2	nM	CHEMBL299294
8.64	Ki	2.3	nM	CHEMBL39773
8.59	Ki	2.6	nM	CHEMBL290738
8.59	IC50	2.6	nM	CHEMBL450325
8.52	Ki	3	nM	CHEMBL5208012
8.52	IC50	3	nM	CHEMBL552664
8.52	Ki	3	nM	CHEMBL166935
8.52	Ki	3	nM	CHEMBL166991
8.51	Ki	3.1	nM	CHEMBL290649
8.48	Ki	3.3	nM	CHEMBL5208606
8.47	Ki	3.4	nM	CHEMBL66626
8.46	Ki	3.5	nM	CHEMBL50872
8.42	Ki	3.8	nM	CHEMBL68831
8.42	Ki	3.8	nM	CHEMBL306899
8.40	IC50	4	nM	CHEMBL363010
8.40	IC50	4	nM	BESONPRODIL
8.40	IC50	4	nM	CHEMBL317229
8.40	Ki	4	nM	CHEMBL354482
8.40	Ki	4	nM	CHEMBL170552
8.40	Ki	4	nM	CHEMBL169695
8.39	IC50	4.1	nM	CHEMBL557993
8.36	Ki	4.4	nM	CHEMBL40730
8.36	IC50	4.4	nM	CHEMBL61720
8.35	Ki	4.5	nM	CHEMBL100656
8.33	IC50	4.7	nM	CHEMBL297881
8.31	Ki	4.9	nM	CHEMBL70918
8.30	IC50	5	nM	CHEMBL363722
8.30	Ki	5	nM	CHEMBL166697
8.29	Ki	5.1	nM	CHEMBL38994
8.25	Ki	5.6	nM	CHEMBL305195
8.23	IC50	5.9	nM	LICOSTINEL
8.22	IC50	6	nM	RADIPRODIL
8.22	IC50	6	nM	CHEMBL305195
8.22	Ki	6	nM	CHEMBL305195
8.22	IC50	6	nM	CHEMBL126929
8.18	Ki	6.6	nM	CHEMBL289607
8.17	Ki	6.8	nM	DIZOCILPINE

PubChem BioAssay actives

376 with measured affinity, of 894 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
(2,3-dioxo-1,4-dihydroquinoxalin-5-yl)methylphosphonic acid	144039: Compound was tested in vitro for its inhibitory activity at 1 uM concentration against N-methyl-D-aspartate glutamate receptor by using [3H]CGP-39653 binding assay	ic50	0.0005	uM
[7-(4-chlorophenyl)-2,3-dioxo-1,4-dihydroquinoxalin-5-yl]methylphosphonic acid	144043: In vitro inhibitory activity at 1 uM concentration against N-methyl-D-aspartate glutamate receptor, using [3H]CGP-39653 binding assay	ic50	0.0008	uM
(7-fluoro-2,3-dioxo-1,4-dihydroquinoxalin-5-yl)methylphosphonic acid	144043: In vitro inhibitory activity at 1 uM concentration against N-methyl-D-aspartate glutamate receptor, using [3H]CGP-39653 binding assay	ic50	0.0010	uM
2-[(12S)-7-bromo-2,3-dioxo-1,4-diazatricyclo[7.3.1.05,13]trideca-5,7,9(13)-trien-12-yl]-N-phenylacetamide	1859114: Displacement of [3H]DCKA from NMDA receptor (unknown origin)	ki	0.0010	uM
(1S,9R)-1-methyl-16-azatetracyclo[7.6.1.02,7.010,15]hexadeca-2,4,6,10,12,14-hexaene	156805: The compound was tested for its ability to block PCP N-methyl-D-aspartate glutamate receptor at the PCP (phencyclidine) binding site in postmortem human frontal cortex.	ki	0.0012	uM
[hydroxy-(7-nitro-2,3-dioxo-1,4-dihydroquinoxalin-5-yl)methyl]phosphonic acid	144043: In vitro inhibitory activity at 1 uM concentration against N-methyl-D-aspartate glutamate receptor, using [3H]CGP-39653 binding assay	ic50	0.0012	uM
2-[(11S)-7-bromo-11-ethyl-2,3-dioxo-1,4-diazatricyclo[7.3.1.05,13]trideca-5,7,9(13)-trien-12-yl]acetic acid	1859114: Displacement of [3H]DCKA from NMDA receptor (unknown origin)	ki	0.0014	uM
(7-bromo-2,3-dioxo-1,4-dihydroquinoxalin-5-yl)methylphosphonic acid	144043: In vitro inhibitory activity at 1 uM concentration against N-methyl-D-aspartate glutamate receptor, using [3H]CGP-39653 binding assay	ic50	0.0015	uM
[(2,3-dioxo-1,4-dihydroquinoxalin-5-yl)-hydroxymethyl]phosphonic acid	144043: In vitro inhibitory activity at 1 uM concentration against N-methyl-D-aspartate glutamate receptor, using [3H]CGP-39653 binding assay	ic50	0.0015	uM
[(benzylamino)-(7-nitro-2,3-dioxo-1,4-dihydroquinoxalin-5-yl)methyl]phosphonic acid;hydrobromide	144043: In vitro inhibitory activity at 1 uM concentration against N-methyl-D-aspartate glutamate receptor, using [3H]CGP-39653 binding assay	ic50	0.0015	uM
(7-chloro-2,3-dioxo-1,4-dihydroquinoxalin-5-yl)methylphosphonic acid	144043: In vitro inhibitory activity at 1 uM concentration against N-methyl-D-aspartate glutamate receptor, using [3H]CGP-39653 binding assay	ic50	0.0017	uM
2-(2-chloro-5-methylsulfanylphenyl)-1-methyl-1-(3-methylsulfanylphenyl)guanidine	143453: In vitro displacement of [3H]MK-801 from N-methyl-D-aspartate glutamate receptor	ki	0.0019	uM
[(benzylamino)-(2,3-dioxo-1,4-dihydroquinoxalin-5-yl)methyl]phosphonic acid;hydrobromide	144043: In vitro inhibitory activity at 1 uM concentration against N-methyl-D-aspartate glutamate receptor, using [3H]CGP-39653 binding assay	ic50	0.0020	uM
2-[[2-(3,4-dihydro-1H-isoquinolin-2-yl)-4-pyridinyl]amino]ethanol	143451: Binding affinity against NMDA receptor by displacement of [3H]Ro-256981	ki	0.0020	uM
2-[(12S)-7-bromo-2,3-dioxo-1,4-diazatricyclo[7.3.1.05,13]trideca-5,7,9(13)-trien-12-yl]acetic acid	1859114: Displacement of [3H]DCKA from NMDA receptor (unknown origin)	ki	0.0023	uM
2-(7-bromo-2,3-dioxo-1,4-diazatricyclo[7.3.1.05,13]trideca-5,7,9(13)-trien-12-yl)-N-phenylacetamide	1859114: Displacement of [3H]DCKA from NMDA receptor (unknown origin)	ki	0.0026	uM
6,7-dichloro-5-[1-(1,2,4-triazol-4-yl)propyl]-1,4-dihydroquinoxaline-2,3-dione	1859120: Displacement of [3H]L-689560 from NMDA receptor (unknown origin)	ic50	0.0026	uM
2-[(11S)-7-bromo-11-methyl-2,3-dioxo-1,4-diazatricyclo[7.3.1.05,13]trideca-5,7,9(13)-trien-12-yl]-N-phenylacetamide	1859114: Displacement of [3H]DCKA from NMDA receptor (unknown origin)	ki	0.0030	uM
[(cyclohexylmethylamino)-(7-nitro-2,3-dioxo-1,4-dihydroquinoxalin-5-yl)methyl]phosphonic acid;hydrochloride	144043: In vitro inhibitory activity at 1 uM concentration against N-methyl-D-aspartate glutamate receptor, using [3H]CGP-39653 binding assay	ic50	0.0030	uM
2-(3,4-dihydro-1H-isoquinolin-2-yl)pyridin-4-amine	143451: Binding affinity against NMDA receptor by displacement of [3H]Ro-256981	ki	0.0030	uM
2-(3,4-dihydro-1H-isoquinolin-2-yl)-6-ethylpyridin-4-amine	143451: Binding affinity against NMDA receptor by displacement of [3H]Ro-256981	ki	0.0030	uM
2-[(11S)-7-chloro-11-methyl-2,3-dioxo-1,4-diazatricyclo[7.3.1.05,13]trideca-5,7,9(13)-trien-12-yl]-N-phenylacetamide	1859114: Displacement of [3H]DCKA from NMDA receptor (unknown origin)	ki	0.0031	uM
2-[(11S)-7-bromo-11-methyl-2,3-dioxo-1,4-diazatricyclo[7.3.1.05,13]trideca-5,7,9(13)-trien-12-yl]acetic acid	1859114: Displacement of [3H]DCKA from NMDA receptor (unknown origin)	ki	0.0033	uM
4-[3-(4-benzylpiperidin-1-yl)-2-methylpropyl]phenol	143454: Displacement of [3H]25-6981 from N-methyl-D-aspartate glutamate receptor	ki	0.0034	uM
2-[[2-(3,4-dihydro-1H-isoquinolin-2-yl)quinolin-4-yl]amino]ethanol	143451: Binding affinity against NMDA receptor by displacement of [3H]Ro-256981	ki	0.0035	uM
4-[3-(4-benzylpiperidin-1-yl)-1-hydroxypropyl]phenol	143454: Displacement of [3H]25-6981 from N-methyl-D-aspartate glutamate receptor	ki	0.0038	uM
4-[3-(4-benzylpiperidin-1-yl)-2-hydroxypropyl]phenol	143454: Displacement of [3H]25-6981 from N-methyl-D-aspartate glutamate receptor	ki	0.0038	uM
2-(4-benzylpiperidin-1-yl)-2-oxo-N-(2-oxo-1,3-dihydrobenzimidazol-5-yl)acetamide	241037: Inhibition of [3H]-Ro-25-6981 binding to NMDA receptor	ic50	0.0040	uM
6-[2-[4-[(4-fluorophenyl)methyl]piperidin-1-yl]ethylsulfinyl]-3H-1,3-benzoxazol-2-one	143455: Inhibition of [3H]Ro-256981 binding to N-methyl-D-aspartate glutamate receptor	ic50	0.0040	uM
1-[2-(4-hydroxyphenoxy)ethyl]-4-[(4-methylphenyl)methyl]piperidin-4-ol	241037: Inhibition of [3H]-Ro-25-6981 binding to NMDA receptor	ic50	0.0040	uM
[4-amino-6-(3,4-dihydro-1H-isoquinolin-2-yl)-2-pyridinyl]methanol	143451: Binding affinity against NMDA receptor by displacement of [3H]Ro-256981	ki	0.0040	uM
2-[[2-(3,4-dihydro-1H-isoquinolin-2-yl)-6-methyl-4-pyridinyl]amino]ethanol	143451: Binding affinity against NMDA receptor by displacement of [3H]Ro-256981	ki	0.0040	uM
2-(3,4-dihydro-1H-isoquinolin-2-yl)-5-methylpyridin-4-amine	143451: Binding affinity against NMDA receptor by displacement of [3H]Ro-256981	ki	0.0040	uM
[(furan-2-ylmethylamino)-(7-nitro-2,3-dioxo-1,4-dihydroquinoxalin-5-yl)methyl]phosphonic acid;hydrobromide	144043: In vitro inhibitory activity at 1 uM concentration against N-methyl-D-aspartate glutamate receptor, using [3H]CGP-39653 binding assay	ic50	0.0041	uM
6,7-dichloro-5-[(1-propylimidazol-4-yl)methyl]-1,4-dihydroquinoxaline-2,3-dione	1859120: Displacement of [3H]L-689560 from NMDA receptor (unknown origin)	ic50	0.0044	uM
2-[(11S)-7-chloro-11-methyl-2,3-dioxo-1,4-diazatricyclo[7.3.1.05,13]trideca-5,7,9(13)-trien-12-yl]acetic acid	1859114: Displacement of [3H]DCKA from NMDA receptor (unknown origin)	ki	0.0044	uM
(1S,9R)-10-[(2R)-2-methoxypropyl]-1,13,13-trimethyl-10-azatricyclo[7.3.1.02,7]trideca-2(7),3,5-trien-5-ol	1960006: Antagonist activity at NMDA receptor (unknown origin) assessed as inhibition constant	ki	0.0045	uM
7-chloro-6-methyl-5-nitro-1,4-dihydroquinoxaline-2,3-dione	143443: Inhibition of [3H]DCKA binding to N-methyl-D-aspartate glutamate receptor	ic50	0.0047	uM
1-[(2R)-2-hydroxy-3-(4-hydroxyphenyl)propyl]-4-[(4-methylphenyl)methyl]piperidin-4-ol	143454: Displacement of [3H]25-6981 from N-methyl-D-aspartate glutamate receptor	ki	0.0049	uM
2-[4-[(4-fluorophenyl)methyl]piperidin-1-yl]-2-oxo-N-(2-oxo-1,3-dihydrobenzimidazol-5-yl)acetamide	241037: Inhibition of [3H]-Ro-25-6981 binding to NMDA receptor	ic50	0.0050	uM
2-(3,4-dihydro-1H-isoquinolin-2-yl)-6-methylpyridin-4-amine	143451: Binding affinity against NMDA receptor by displacement of [3H]Ro-256981	ki	0.0050	uM
2-(7-chloro-2,3-dioxo-1,4-diazatricyclo[7.3.1.05,13]trideca-5,7,9(13)-trien-12-yl)acetic acid	1859114: Displacement of [3H]DCKA from NMDA receptor (unknown origin)	ki	0.0051	uM
4-[(1R,2S)-3-(4-benzylpiperidin-1-yl)-1-hydroxy-2-methylpropyl]phenol	143454: Displacement of [3H]25-6981 from N-methyl-D-aspartate glutamate receptor	ki	0.0056	uM
6,7-dichloro-5-nitro-1,4-dihydroquinoxaline-2,3-dione	143443: Inhibition of [3H]DCKA binding to N-methyl-D-aspartate glutamate receptor	ic50	0.0059	uM
2-[4-[(4-fluorophenyl)methyl]piperidin-1-yl]-2-oxo-N-(2-oxo-3H-1,3-benzoxazol-6-yl)acetamide	241037: Inhibition of [3H]-Ro-25-6981 binding to NMDA receptor	ic50	0.0060	uM
(4-benzylpiperidin-1-yl)-(4,6-dihydroxy-1H-indol-2-yl)methanone	143455: Inhibition of [3H]Ro-256981 binding to N-methyl-D-aspartate glutamate receptor	ic50	0.0060	uM
2-(7-chloro-2,3-dioxo-1,4-diazatricyclo[7.3.1.05,13]trideca-5,7,9(13)-trien-12-yl)-N-phenylacetamide	1859114: Displacement of [3H]DCKA from NMDA receptor (unknown origin)	ki	0.0066	uM
5,6,7-trichloro-4-hydroxy-3-nitroso-1H-quinolin-2-one	143443: Inhibition of [3H]DCKA binding to N-methyl-D-aspartate glutamate receptor	ic50	0.0070	uM
1-[(1S,2S)-1-hydroxy-1-(4-hydroxyphenyl)propan-2-yl]-4-phenylpiperidin-4-ol	241037: Inhibition of [3H]-Ro-25-6981 binding to NMDA receptor	ic50	0.0070	uM
(1R)-1-(4-chlorophenyl)-2-[(1R)-6,7-dimethoxy-2-methyl-3,4-dihydro-1H-isoquinolin-1-yl]ethanol	238983: Mean inhibitory constant against porcine N-methyl-D-aspartate (NMDA) glutamate receptor; n=3	ki	0.0070	uM

CTD chemical–gene interactions

23 total (human), top 23 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	increases expression	1
arsenite	increases methylation	1
11-nor-delta(9)-tetrahydrocannabinol-9-carboxylic acid	affects methylation, increases abundance	1
sodium arsenite	affects expression	1
2-bromopalmitate	decreases reaction, increases abundance, increases palmitoylation	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
2,2’,4,4’,5-brominated diphenyl ether	decreases expression	1
Resveratrol	decreases expression, affects cotreatment	1
Sunitinib	decreases expression	1
Fulvestrant	increases methylation	1
Vorinostat	decreases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Cadmium	decreases reaction, increases abundance, increases palmitoylation	1
Cannabinoids	affects methylation, increases abundance	1
Copper	affects cotreatment, decreases expression	1
Methotrexate	increases expression	1
Nickel	decreases expression	1
Silicon Dioxide	increases expression	1
Dihydrotestosterone	increases expression	1
8-Bromo Cyclic Adenosine Monophosphate	decreases expression	1
Citalopram	affects response to substance	1
Cadmium Chloride	decreases reaction, increases abundance, increases palmitoylation	1

ChEMBL screening assays

195 unique, capped per target: 183 binding, 7 functional, 4 admet, 1 toxicity

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1247908	Binding	Binding affinity to human recombinant NMDA receptor	Spiroindolones, a potent compound class for the treatment of malaria. — Science
CHEMBL2208698	Functional	Antagonist activity at NMDA receptor (unknwon origin)	Synopsis of some recent tactical application of bioisosteres in drug design. — J Med Chem
CHEMBL4680007	ADMET	Inhibition of NMDA receptor (unknown origin)	Fragment-Based Discovery of Novel Allosteric MEK1 Binders. — ACS Med Chem Lett

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03600649	PHASE1	UNKNOWN	Clinical Trial of SP-2577 (Seclidemstat) in Patients With Relapsed or Refractory Ewing or Ewing-related Sarcomas
NCT05266196	PHASE1/PHASE2	UNKNOWN	A Rollover Protocol to Allow for Continued Access to the LSD1 Inhibitor Seclidemstat (SP-2577)
NCT06239272	PHASE1/PHASE2	RECRUITING	NRSTS2021, A Risk Adapted Study Evaluating Maintenance Pazopanib, Limited Margin, Dose-Escalated Radiation Therapy and Selinexor in Non-Rhabdomyosarcoma Soft Tissue Sarcoma (NRSTS)
NCT06625190	PHASE1/PHASE2	RECRUITING	Alpha/Beta T and B Cell Depletion With Zoledronic Acid for Solid Tumors
NCT06244420	Not specified	COMPLETED	Malignant Myoepithelioma of Bone and Soft Tissues: Diagnostic Imaging and Histology in Relation to Prognosis