GRIN2C

Summary

GRIN2C (glutamate ionotropic receptor NMDA type subunit 2C, HGNC:4587) is a protein-coding gene on chromosome 17q25.1, encoding Glutamate receptor ionotropic, NMDA 2C (Q14957). Component of N-methyl-D-aspartate (NMDA) receptors (NMDARs) that function as heterotetrameric, ligand-gated cation channels with high calcium permeability and voltage-dependent block by Mg(2+).

This gene encodes a subunit of the N-methyl-D-aspartate (NMDA) receptor, which is a subtype of ionotropic glutamate receptor. NMDA receptors are found in the central nervous system, are permeable to cations and have an important role in physiological processes such as learning, memory, and synaptic development. The receptor is a tetramer of different subunits (typically heterodimer of subunit 1 with one or more of subunits 2A-D), forming a channel that is permeable to calcium, potassium, and sodium, and whose properties are determined by subunit composition. Alterations in the subunit composition of the receptor are associated with pathophysiological conditions such as Parkinson’s disease, Alzheimer’s disease, depression, and schizophrenia. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 2905 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Alzheimer disease (Limited, GenCC)
• GWAS associations: 2
• Clinical variants (ClinVar): 193 total
• Druggable target: yes — 30 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_000835

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4587
Approved symbol	GRIN2C
Name	glutamate ionotropic receptor NMDA type subunit 2C
Location	17q25.1
Locus type	gene with protein product
Status	Approved
Aliases	GluN2C, NR2C
Ensembl gene	ENSG00000161509
Ensembl biotype	protein_coding
OMIM	138254
Entrez	2905

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 7 protein_coding, 2 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000293190, ENST00000347612, ENST00000578159, ENST00000584176, ENST00000584496, ENST00000891066, ENST00000940917, ENST00000940918, ENST00000940919, ENST00000940920

RefSeq mRNA: 2 — MANE Select: NM_000835 NM_000835, NM_001278553

CCDS: CCDS32724, CCDS62330

Canonical transcript exons

ENST00000293190 — 13 exons

Exon	Start	End
ENSE00001058357	74851577	74851691
ENSE00001058361	74846760	74846920
ENSE00001058364	74847308	74847537
ENSE00001236762	74859744	74859885
ENSE00001308993	74842023	74843553
ENSE00001316172	74850556	74850767
ENSE00001328233	74852013	74852611
ENSE00002475396	74854694	74855107
ENSE00003485222	74846066	74846253
ENSE00003488405	74849780	74849933
ENSE00003504076	74850206	74850371
ENSE00003616762	74844276	74844508
ENSE00003664351	74847852	74847977

Expression profiles

Bgee: expression breadth ubiquitous, 168 present calls, max score 97.70.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.9046 / max 169.7409, expressed in 112 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
168012	0.4645	94
168008	0.1439	62
168006	0.1395	56
168013	0.0694	44
168007	0.0292	10
168011	0.0282	17
168010	0.0169	7
168009	0.0131	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right hemisphere of cerebellum	UBERON:0014890	97.70	gold quality
cerebellar hemisphere	UBERON:0002245	97.68	gold quality
cerebellar cortex	UBERON:0002129	97.66	gold quality
cerebellum	UBERON:0002037	96.76	gold quality
paraflocculus	UBERON:0005351	96.18	gold quality
cerebellar vermis	UBERON:0004720	91.85	gold quality
parotid gland	UBERON:0001831	88.49	gold quality
right atrium auricular region	UBERON:0006631	86.81	gold quality
putamen	UBERON:0001874	85.99	gold quality
right lobe of thyroid gland	UBERON:0001119	85.78	gold quality
cardiac atrium	UBERON:0002081	85.50	gold quality
amygdala	UBERON:0001876	85.43	gold quality
caudate nucleus	UBERON:0001873	85.33	gold quality
right frontal lobe	UBERON:0002810	85.27	gold quality
left lobe of thyroid gland	UBERON:0001120	84.73	gold quality
nucleus accumbens	UBERON:0001882	84.52	gold quality
thyroid gland	UBERON:0002046	83.62	gold quality
cingulate cortex	UBERON:0003027	82.57	gold quality
anterior cingulate cortex	UBERON:0009835	82.52	gold quality
Brodmann (1909) area 9	UBERON:0013540	80.23	gold quality
temporal lobe	UBERON:0001871	79.90	gold quality
telencephalon	UBERON:0001893	79.04	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	78.63	gold quality
frontal cortex	UBERON:0001870	78.47	gold quality
cranial nerve II	UBERON:0000941	78.36	gold quality
neocortex	UBERON:0001950	78.34	gold quality
brain	UBERON:0000955	77.88	gold quality
Ammon’s horn	UBERON:0001954	77.77	gold quality
central nervous system	UBERON:0001017	77.56	gold quality
Brodmann (1909) area 10	UBERON:0013541	77.36	silver quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.39
E-GEOD-75367	no	7.68

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ETV1, NR5A1, NRF1, SP4

miRNA regulators (miRDB)

19 targeting GRIN2C, 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-370-5P	99.78	66.81	706
HSA-MIR-7-5P	99.67	70.53	1809
HSA-MIR-4502	99.65	66.99	1021
HSA-MIR-3975	99.62	65.97	697
HSA-MIR-1253	99.12	67.08	1688
HSA-MIR-6770-5P	98.97	66.76	1853
HSA-MIR-299-5P	98.56	71.14	1140
HSA-MIR-5691	98.23	67.02	1335
HSA-MIR-6805-3P	98.23	67.02	1334
HSA-MIR-6732-3P	98.17	67.52	802
HSA-MIR-6773-3P	98.17	65.51	1213
HSA-MIR-615-5P	98.10	63.76	591
HSA-MIR-876-5P	97.99	68.49	1345
HSA-MIR-6747-3P	97.73	64.84	1596
HSA-MIR-4732-3P	97.15	65.45	881
HSA-MIR-3167	96.81	67.09	1236
HSA-MIR-591	96.29	68.16	611
HSA-MIR-4520-5P	93.54	65.23	140
HSA-MIR-4732-5P	90.07	64.77	412

Literature-anchored findings (GeneRIF, showing 12)

• The authors identified and cloned sequences of NMDA receptor subunits 2A, 2B, and 2C from rat. They characterized the properties of the receptors composed of heteromeric 1-2A and heteromeric 1-2C and found that the latter had reduced sensitivity to magnesium and smaller conductance compared to the former. (PMID:1350383)
• Functional compensation could occur to counteract the loss of one allele in GRIN2C and GRIN3 family genes. (PMID:22833210)
• Reduction in NR1 and NR2C in the DLPFC of people with schizophrenia may lead to altered NMDAR stoichiometry and provides compelling evidence for an endogenous NMDAR deficit in schizophrenia. (PMID:23070074)
• TNFalpha significantly upregulates NMDA-R2C mRNA expression, in differentiated, confluent, normal keratinocytes but not in involved or uninvolved psoriatic keratinocyte monolayers (PMID:24102971)
• The major depression subjects exhibited significantly higher expression levels of the NMDA receptor subunit genes GRIN2C. (PMID:24925192)
• NMDARs have a dual role during erythropoiesis, supporting survival of polychromatic erythroblasts and contributing to the Ca(2+) homeostasis from the orthochromatic erythroblast stage to circulating red blood cells. (PMID:25788577)
• these findings highlight the isoform-specific structural and functional differences within the 14-3-3 family of proteins, which determine GluN2C binding and its essential role in targeting the receptor to the cell surface (PMID:26229101)
• Findings indicate that SNPs in the GRIN2C gene is associated with altered cue-induced brain activation that is related to craving for alcohol and relapse risk. (PMID:26289945)
• ultra-rare variants with loss of function (frameshift, nonsense or splice site) in NMDARs genes like GRIN2C and GRIN2D may contribute to possible risk of schizophrenia (PMID:29317596)
• Positions in the N-methyl-D-aspartate Receptor GluN2C Subunit M3 and M4 Domains Regulate Alcohol Sensitivity and Receptor Kinetics. (PMID:30964201)
• Amyloid-beta (1-42) peptide induces rapid NMDA receptor-dependent alterations at glutamatergic synapses in the entorhinal cortex. (PMID:34144329)
• Structural insights into assembly and function of GluN1-2C, GluN1-2A-2C, and GluN1-2D NMDARs. (PMID:36309015)

Cross-species orthologs

43 orthologs

Organism	Symbol	Gene ID
danio_rerio	grin2cb	ENSDARG00000077560
danio_rerio	grin2ca	ENSDARG00000078149
mus_musculus	Grin2c	ENSMUSG00000020734
rattus_norvegicus	Grin2c	ENSRNOG00000003280
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), GRIK3 (ENSG00000163873), GRIK2 (ENSG00000164418), GRIK1 (ENSG00000171189), GRIN1 (ENSG00000176884), GRID1 (ENSG00000182771), GRIN2A (ENSG00000183454), GRIN3A (ENSG00000198785), GRIN2B (ENSG00000273079)

Protein

Protein identifiers

Glutamate receptor ionotropic, NMDA 2C — Q14957 (reviewed: Q14957)

Alternative names: Glutamate [NMDA] receptor subunit epsilon-3, N-methyl D-aspartate receptor subtype 2C

All UniProt accessions (3): A0A8D9PH81, Q14957, H0Y2V8

UniProt curated annotations — full annotation on UniProt →

Function. Component of N-methyl-D-aspartate (NMDA) receptors (NMDARs) that function as heterotetrameric, ligand-gated cation channels with high calcium permeability and voltage-dependent block by Mg(2+). Participates in synaptic plasticity for learning and memory formation by contributing to the slow phase of excitatory postsynaptic current and long-term synaptic potentiation. Channel activation requires binding of the neurotransmitter L-glutamate to the GluN2 subunit, glycine or D-serine binding to the GluN1 subunit, plus membrane depolarization to eliminate channel inhibition by Mg(2+). NMDARs mediate simultaneously the potassium efflux and the influx of calcium and sodium. Each GluN2 subunit confers differential attributes to channel properties, including activation, deactivation and desensitization kinetics, pH sensitivity, Ca2(+) permeability, and binding to allosteric modulators.

Subunit / interactions. Heterotetramer. Forms heterotetrameric channels composed of two GluN1/zeta subunits (GRIN1), and two identical GluN2/epsilon subunits (GRIN2A, GRIN2B, GRIN2C or GRIN2D) or GluN3 subunits (GRIN3A or GRIN3B) (in vitro). In vivo, the subunit composition may depend on the expression levels of the different subunits. Interacts with PDZ domains of PATJ and DLG4. Interacts (via PDZ-binding motif) with SNX27 (via PDZ domain); the interaction is required for recycling to the plasma membrane when endocytosed and prevent degradation in lysosomes.

Subcellular location. Cell membrane. Postsynaptic cell membrane.

Tissue specificity. Mainly expressed in brain with predominant expression is in the cerebellum, also present in the hippocampus, amygdala, caudate nucleus, corpus callosum, subthalamic nuclei and thalamus. Detected in the heart, skeletal muscle and pancreas.

Domain organisation. A hydrophobic region that gives rise to the prediction of a transmembrane span does not cross the membrane, but is part of a discontinuously helical region that dips into the membrane and is probably part of the pore and of the selectivity filter.

Similarity. Belongs to the glutamate-gated ion channel (TC 1.A.10.1) family. NR2C/GRIN2C subfamily.

RefSeq proteins (2): NP_000826, NP_001265482 (=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
IPR018884	NMDAR2_C	Domain
IPR019594	Glu/Gly-bd	Domain
IPR028082	Peripla_BP_I	Homologous_superfamily

Pfam: PF00060, PF01094, PF10565, PF10613

Catalyzed reactions (Rhea), 3 shown:

• K(+)(in) = K(+)(out) (RHEA:29463)
• Ca(2+)(in) = Ca(2+)(out) (RHEA:29671)
• Na(+)(in) = Na(+)(out) (RHEA:34963)

UniProt features (56 total): sequence variant 18, binding site 6, glycosylation site 6, topological domain 5, disulfide bond 4, modified residue 3, transmembrane region 3, region of interest 2, compositionally biased region 2, sequence conflict 2, signal peptide 1, chain 1, short sequence motif 1, site 1, intramembrane region 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
8E93	ELECTRON MICROSCOPY	3.71
8E94	ELECTRON MICROSCOPY	3.72
8E98	ELECTRON MICROSCOPY	3.75
8E92	ELECTRON MICROSCOPY	3.96
8E97	ELECTRON MICROSCOPY	4.19
8E99	ELECTRON MICROSCOPY	4.24

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q14957-F1	68.06	0.21

Antibody-complex structures (SAbDab): 1 — 8E99

Functional residue map

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

Catalytic / active sites (1): 612 (functional determinant of nmda receptors)

Ligand- & substrate-binding residues (6): 509; 511; 516; 687; 688; 729

Post-translational modifications (3): 875, 881, 912

Disulfide bonds (4): 82–317, 426–453, 433–454, 743–798

Glycosylation sites (6): 70, 73, 337, 438, 539, 685

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-438066	Unblocking of NMDA receptors, glutamate binding and activation
R-HSA-6794361	Neurexins and neuroligins
R-HSA-8849932	Synaptic adhesion-like molecules
R-HSA-9609736	Assembly and cell surface presentation of NMDA receptors
R-HSA-9617324	Negative regulation of NMDA receptor-mediated neuronal transmission
R-HSA-9620244	Long-term potentiation

MSigDB gene sets: 184 (showing top): GOBP_POSITIVE_REGULATION_OF_SYNAPTIC_TRANSMISSION_GLUTAMATERGIC, GOMF_GLUTAMATE_GATED_RECEPTOR_ACTIVITY, GOBP_REGULATION_OF_NEURONAL_SYNAPTIC_PLASTICITY, GOBP_REGULATION_OF_SYNAPTIC_TRANSMISSION_GLUTAMATERGIC, KAAB_HEART_ATRIUM_VS_VENTRICLE_UP, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, BIOCARTA_NOS1_PATHWAY, GOBP_PROTEIN_LOCALIZATION_TO_CELL_PERIPHERY, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_CATABOLIC_PROCESS, GOBP_NEUROMUSCULAR_PROCESS_CONTROLLING_BALANCE, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_CELL_CELL_SIGNALING, GOBP_REGULATION_OF_SYNAPTIC_PLASTICITY, GOBP_REGULATION_OF_CATABOLIC_PROCESS, GOBP_REGULATION_OF_POSTSYNAPTIC_MEMBRANE_POTENTIAL

GO Biological Process (22): glutamate receptor signaling pathway (GO:0007215), brain development (GO:0007420), response to wounding (GO:0009611), directional locomotion (GO:0033058), ionotropic glutamate receptor signaling pathway (GO:0035235), synaptic transmission, glutamatergic (GO:0035249), negative regulation of protein catabolic process (GO:0042177), regulation of synaptic plasticity (GO:0048167), regulation of neuronal synaptic plasticity (GO:0048168), neuromuscular process controlling balance (GO:0050885), positive regulation of synaptic transmission, glutamatergic (GO:0051968), excitatory postsynaptic potential (GO:0060079), long-term synaptic potentiation (GO:0060291), calcium ion transmembrane import into cytosol (GO:0097553), monoatomic cation transmembrane transport (GO:0098655), excitatory chemical synaptic transmission (GO:0098976), protein localization to postsynaptic membrane (GO:1903539), regulation of monoatomic cation transmembrane transport (GO:1904062), positive regulation of excitatory postsynaptic potential (GO:2000463), monoatomic ion transport (GO:0006811), monoatomic ion transmembrane transport (GO:0034220), regulation of membrane potential (GO:0042391)

GO Molecular Function (7): NMDA glutamate receptor activity (GO:0004972), monoatomic cation channel activity (GO:0005261), 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), signaling receptor activity (GO:0038023)

GO Cellular Component (9): endoplasmic reticulum membrane (GO:0005789), plasma membrane (GO:0005886), NMDA selective glutamate receptor complex (GO:0017146), postsynaptic membrane (GO:0045211), postsynaptic density membrane (GO:0098839), glutamatergic synapse (GO:0098978), membrane (GO:0016020), organelle (GO:0043226), synapse (GO:0045202)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Activation of NMDA receptors and postsynaptic events	3
Protein-protein interactions at synapses	2
Post NMDA receptor activation events	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
glutamate-gated receptor activity	2
chemical synaptic transmission	2
regulation of synaptic plasticity	2
positive regulation of synaptic transmission	2
regulation of postsynaptic membrane potential	2
excitatory postsynaptic potential	2
monoatomic ion channel activity	2
cellular anatomical structure	2
cell surface receptor signaling pathway	1
glutamate receptor activity	1
central nervous system development	1
animal organ development	1
head development	1
response to stress	1
locomotion	1
glutamate receptor signaling pathway	1
ligand-gated ion channel signaling pathway	1
negative regulation of catabolic process	1
protein catabolic process	1
regulation of protein catabolic process	1
negative regulation of protein metabolic process	1
modulation of chemical synaptic transmission	1
regulation of biological quality	1
musculoskeletal movement	1
neuromuscular process	1
synaptic transmission, glutamatergic	1
regulation of synaptic transmission, glutamatergic	1
chemical synaptic transmission, postsynaptic	1
calcium ion transmembrane transport	1
monoatomic cation transport	1
monoatomic ion transmembrane transport	1
protein localization to postsynapse	1
protein localization to membrane	1
protein localization to cell periphery	1
regulation of monoatomic ion transmembrane transport	1
monoatomic cation transmembrane transport	1
positive regulation of signal transduction	1
modulation of excitatory postsynaptic potential	1
transport	1
voltage-gated monoatomic ion channel activity	1

Protein interactions and networks

STRING

1550 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GRIN2C	GRIN1	P35437	990
GRIN2C	GRIN3A	Q8TCU5	986
GRIN2C	GRIN3B	O60391	985
GRIN2C	GRIN2D	O15399	983
GRIN2C	GRIN2A	Q12879	983
GRIN2C	GRIN2B	Q13224	983
GRIN2C	DLG4	P78352	831
GRIN2C	PVALB	P20472	673
GRIN2C	DLG3	Q92796	648
GRIN2C	BDNF	P23560	624
GRIN2C	DLG2	Q15700	600
GRIN2C	GRM2	Q14416	594
GRIN2C	GRM8	O00222	587
GRIN2C	GRM4	Q14833	580
GRIN2C	GPRIN2	O60269	578

IntAct

468 interactions, top by confidence:

A	B	Type	Score
DLG1	GRIN2C	psi-mi:“MI:0407”(direct interaction)	0.620
DLG3	GRIN2C	psi-mi:“MI:0407”(direct interaction)	0.620
GRIN2C	TRIM23	psi-mi:“MI:0915”(physical association)	0.560
GRIN2C		psi-mi:“MI:0915”(physical association)	0.560
GRIN2C	CDK2	psi-mi:“MI:0915”(physical association)	0.560
GRIN2C	TEN1	psi-mi:“MI:0915”(physical association)	0.560
GRIN2C	COL2A1	psi-mi:“MI:0915”(physical association)	0.560
GRIN2C	DPYS	psi-mi:“MI:0915”(physical association)	0.560
GRIN2C	GABPB1	psi-mi:“MI:0915”(physical association)	0.560
GRIN2C	HSPD1	psi-mi:“MI:0915”(physical association)	0.560
GRIN2C	LASP1	psi-mi:“MI:0915”(physical association)	0.560
GRIN2C	PPP1R12B	psi-mi:“MI:0915”(physical association)	0.560
GRIN2C	NBL1	psi-mi:“MI:0915”(physical association)	0.560
GRIN2C	NPAS2	psi-mi:“MI:0915”(physical association)	0.560
GRIN2C	ODF2	psi-mi:“MI:0915”(physical association)	0.560
GRIN2C	PER1	psi-mi:“MI:0915”(physical association)	0.560
GRIN2C	POLR2E	psi-mi:“MI:0915”(physical association)	0.560
GRIN2C	PPARA	psi-mi:“MI:0915”(physical association)	0.560
GRIN2C	PRKAB2	psi-mi:“MI:0915”(physical association)	0.560
GRIN2C	PSMC6	psi-mi:“MI:0915”(physical association)	0.560
GRIN2C	PSME1	psi-mi:“MI:0915”(physical association)	0.560
GRIN2C	PTMA	psi-mi:“MI:0915”(physical association)	0.560
GRIN2C	RGR	psi-mi:“MI:0915”(physical association)	0.560
GRIN2C	RHEB	psi-mi:“MI:0915”(physical association)	0.560
GRIN2C	RPS4X	psi-mi:“MI:0915”(physical association)	0.560
GRIN2C	SHOX2	psi-mi:“MI:0915”(physical association)	0.560
GRIN2C	STIM1	psi-mi:“MI:0915”(physical association)	0.560
GRIN2C	TERF1	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (19): GRIN2C (Reconstituted Complex), GRIN2C (Affinity Capture-Western), PTPRK (Affinity Capture-MS), OAF (Affinity Capture-MS), TUBA4A (Affinity Capture-MS), HSPA5 (Affinity Capture-MS), BCHE (Affinity Capture-MS), ATP12A (Affinity Capture-MS), TSEN2 (Affinity Capture-MS), DDX19B (Affinity Capture-MS), MANBA (Affinity Capture-MS), GRIN2C (Affinity Capture-Western), GRIN2C (Affinity Capture-Western), GRIN2C (Reconstituted Complex), GRIN2C (Reconstituted Complex)

ESM2 similar proteins: A2A259, A2AIR5, H2Q5A1, O00222, O15399, O60242, O75077, O75882, O97741, P15209, P24786, P31423, P35400, P37088, P47743, P55270, P70579, Q00961, Q01098, Q03351, Q03391, Q13507, Q14833, Q14957, Q16288, Q1ZZH0, Q4R766, Q5IS37, Q5RDQ8, Q62645, Q63604, Q68ED2, Q68EF4, Q6AYT7, Q80ZF8, Q8CIW5, Q8TCU5, Q8VHN2, Q91044, Q91YD4

Diamond homologs: A0A2R8QF68, A7XY94, B1AS29, B7ZSK1, O15399, O43424, O60391, P0AEQ3, P0AEQ4, P0AEQ5, P22756, P35436, P39086, P42264, Q00959, Q00960, Q00961, Q01097, Q01098, Q01812, Q03391, Q10914, Q12879, Q13003, Q13224, Q14957, Q38PU2, Q38PU4, Q5IS45, Q5R1P3, Q60934, Q61625, Q62645, Q63226, Q68Y21, A2AIR5, P0AEM9, P0AEN0, P19491, P19492

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
GRIN2C	“form complex”	“NMDA receptor_2C”	binding
AKT	“up-regulates activity”	GRIN2C	phosphorylation
GRIN2C	“up-regulates activity”	GRIN1	binding
YWHAE	“up-regulates quantity by stabilization”	GRIN2C	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 103 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
Chromosome Maintenance	5	17.6×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	154
Likely benign	18
Benign	6

Top pathogenic / likely-pathogenic (0)

SpliceAI

3463 predictions. Top by Δscore:

Variant	Effect	Δscore
17:74843552:CC:C	acceptor_gain	1.0000
17:74843553:CC:C	acceptor_gain	1.0000
17:74843553:CCTGG:C	acceptor_loss	1.0000
17:74843554:CT:C	acceptor_loss	1.0000
17:74843555:T:A	acceptor_loss	1.0000
17:74843559:CAG:C	acceptor_gain	1.0000
17:74843560:A:T	acceptor_gain	1.0000
17:74843561:G:GC	acceptor_gain	1.0000
17:74844274:AC:A	donor_gain	1.0000
17:74844275:CC:C	donor_gain	1.0000
17:74844275:CCCTG:C	donor_gain	1.0000
17:74844335:T:TA	donor_gain	1.0000
17:74846062:CCA:C	donor_loss	1.0000
17:74846063:CACCG:C	donor_loss	1.0000
17:74846064:A:C	donor_loss	1.0000
17:74846064:ACCGT:A	donor_gain	1.0000
17:74846065:C:T	donor_loss	1.0000
17:74846065:CCGTC:C	donor_gain	1.0000
17:74846108:T:TA	donor_gain	1.0000
17:74846286:CA:C	acceptor_gain	1.0000
17:74846756:CCACC:C	donor_loss	1.0000
17:74846757:CAC:C	donor_loss	1.0000
17:74846758:A:AC	donor_gain	1.0000
17:74846758:A:C	donor_loss	1.0000
17:74846758:AC:A	donor_gain	1.0000
17:74846758:ACC:A	donor_gain	1.0000
17:74846758:ACCC:A	donor_gain	1.0000
17:74846759:C:CC	donor_gain	1.0000
17:74846759:C:CG	donor_loss	1.0000
17:74846759:CC:C	donor_gain	1.0000

AlphaMissense

7985 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:74844410:C:G	G817R	1.000
17:74844430:A:G	L810P	1.000
17:74844430:A:T	L810Q	1.000
17:74844466:C:G	C798S	1.000
17:74844467:A:T	C798S	1.000
17:74844478:A:G	L794P	1.000
17:74844480:C:A	W793C	1.000
17:74844480:C:G	W793C	1.000
17:74844482:A:G	W793R	1.000
17:74844482:A:T	W793R	1.000
17:74846131:G:T	A762D	1.000
17:74846141:A:G	Y759H	1.000
17:74846154:A:C	F754L	1.000
17:74846154:A:T	F754L	1.000
17:74846155:A:C	F754C	1.000
17:74846156:A:G	F754L	1.000
17:74846182:A:G	L745P	1.000
17:74846187:G:C	C743W	1.000
17:74846188:C:G	C743S	1.000
17:74846188:C:T	C743Y	1.000
17:74846189:A:G	C743R	1.000
17:74846189:A:T	C743S	1.000
17:74846218:A:G	L733P	1.000
17:74846218:A:T	L733H	1.000
17:74846230:T:A	D729V	1.000
17:74846230:T:C	D729G	1.000
17:74846230:T:G	D729A	1.000
17:74846231:C:A	D729Y	1.000
17:74846231:C:G	D729H	1.000
17:74846236:A:T	I727N	1.000

dbSNP variants (sampled 300 via entrez): RS1000196557 (17:74848570 C>T), RS1000450102 (17:74844069 T>G), RS1000546368 (17:74849789 C>A), RS1000709621 (17:74849256 C>T), RS1000741279 (17:74855046 C>A,T), RS1001033501 (17:74844214 C>G,T), RS1001405250 (17:74844916 T>C), RS1001527887 (17:74853777 G>A,C), RS1001882854 (17:74848971 T>C), RS1001927642 (17:74859960 G>A), RS1001977036 (17:74853546 A>G), RS1002012392 (17:74854157 A>C,G), RS1002124482 (17:74860938 C>A,G), RS1002357972 (17:74848646 G>A), RS1002525210 (17:74858630 C>A)

Disease associations

OMIM: gene MIM:138254 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
Alzheimer disease	Limited	Autosomal dominant

Mondo (1): Alzheimer disease (MONDO:0004975)

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST004721_20	Congenital heart disease (maternal effect)	4.000000e-06
GCST012490_239	Femur bone mineral density x serum urate levels interaction	7.000000e-10

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004531	urate measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D000544	Alzheimer Disease	C10.228.140.380.100; C10.574.945.249; F03.615.400.100

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (4): CHEMBL2094124 (PROTEIN COMPLEX GROUP), CHEMBL3038504 (PROTEIN COMPLEX), CHEMBL4109 (SINGLE PROTEIN), CHEMBL6066548 (PROTEIN COMPLEX)

Molecules with ChEMBL bioactivity

30 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,394,487 (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
CHEMBL771	CYCLOSERINE	4	23,487
CHEMBL575060	GLUTAMIC ACID	3	929,756
CHEMBL350719	ESMETHADONE	3	26,004
CHEMBL5095095	DALZANEMDOR	3	20
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
CHEMBL39664	SELFOTEL	2
CHEMBL452461	PERZINFOTEL	2
CHEMBL467084	LANICEMINE	2
CHEMBL159659	LEVOMETHADONE	2
CHEMBL159660	ALPHAMETHADOL	2
CHEMBL162243	BETAMETHADOL	2
CHEMBL305187	IFENPRODIL	2
CHEMBL5314944	ZELQUISTINEL	2
CHEMBL299155	TRANSTORINE	1

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 (8 total), top 8:

Ligand	Action	Affinity	Parameter
DQP-1105	Negative	8.15	pIC50
phencyclidine	Channel blocker	7.11	pIC50
dextrorphan	Channel blocker	6.94	pIC50
dextromethorphan	Channel blocker	6.33	pIC50
levorphanol	Channel blocker	6.22	pIC50
ketamine	Channel blocker	6.18	pIC50
memantine	Antagonist	6.15	pKi
amantadine	Channel blocker	4.65	pIC50

ChEMBL bioactivities

489 potent at pChembl≥5 of 652 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	EC50	3	nM	CHEMBL562641
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

PubChem BioAssay actives

388 with measured affinity, of 951 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

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases expression, increases methylation	2
Hydrogen Peroxide	affects expression, increases expression	2
Aflatoxin B1	increases expression	2
aristolochic acid I	increases expression	1
methyleugenol	increases expression	1
propionaldehyde	increases expression	1
bisphenol A	increases expression	1
terbufos	increases methylation	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
conotoxin GV	decreases activity, affects cotreatment	1
cordycepin	increases expression	1
di-n-butylphosphoric acid	affects expression	1
abrine	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
jinfukang	decreases expression, affects cotreatment, increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Cisplatin	affects cotreatment, increases expression	1
Citrulline	increases expression	1
Fonofos	increases methylation	1
Ethyl Methanesulfonate	increases expression	1
Melphalan	increases expression	1
Menthol	decreases expression	1
Methotrexate	increases expression	1
N-Nitrosopyrrolidine	increases expression	1
Parathion	increases methylation	1
Phthalic Acids	increases methylation	1
Plant Extracts	affects cotreatment, decreases expression	1
Silicon Dioxide	decreases expression	1
Thalidomide	decreases expression	1
Thiram	increases expression	1

ChEMBL screening assays

225 unique, capped per target: 211 binding, 9 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

Cellosaurus cell lines

2 cell lines: 2 spontaneously immortalized cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B3U0	CHO-hGluN1-hGluN2C	Spontaneously immortalized cell line	Female
CVCL_B3U1	CHO-hGluN1-hGluN2D	Spontaneously immortalized cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00009191	PHASE4	COMPLETED	The Depression in Alzheimer’s Disease Study (DIADS)
NCT00009217	PHASE4	COMPLETED	Treatment of Behavioral Symptoms in Alzheimer’s Disease
NCT00018278	PHASE4	COMPLETED	Electrophysiologic Measures of Treatment Response in Alzheimer Disease
NCT00035204	PHASE4	COMPLETED	A Study of the Effects on Sleep, Attention, and Gastrointestinal Tolerance of Galantamine and Donepezil in Patients With Alzheimer’s Disease
NCT00042172	PHASE4	COMPLETED	Treatment for Early Memory Loss
NCT00046358	PHASE4	COMPLETED	The Effect of Short-Term Statins and NSAIDs on Levels of Beta-Amyloid, a Protein Associated With Alzheimer’s Disease
NCT00104442	PHASE4	COMPLETED	Study of the Effects of Current Drug Treatments on Levels of Certain Brain Chemicals in Alzheimer’s Disease
NCT00120874	PHASE4	COMPLETED	Memantine and Comprehensive, Individualized Management of Alzheimer’s Disease and Caregiver Training
NCT00142324	PHASE4	UNKNOWN	CALM-AD
NCT00165724	PHASE4	COMPLETED	Alzheimer’s Disease Long-term Follow-up Study (ALF Study)
NCT00165750	PHASE4	TERMINATED	Correlation Between Regional Brain Volume and Response to Donepezil Treatment in AD Patients
NCT00202124	PHASE4	COMPLETED	Double Blind Study of Trp01 in Patients With Alzheimer’s Disease
NCT00208819	PHASE4	COMPLETED	A Comparison of Two Standard Therapies in the Management of Dementia With Agitation
NCT00216515	PHASE4	COMPLETED	The Efficacy of Galantamine on the Attention and the Frontal Function of the Patients With Dementia of Alzheimer Type
NCT00230568	PHASE4	COMPLETED	EARTH 413: A Study of Aricept in Hispanic Patients With Mild to Moderate Alzheimer’s Disease (AD)
NCT00234637	PHASE4	COMPLETED	Rivastigmine Monotherapy and Combination Therapy With Memantine in Patients With Moderately Severe Alzheimer’s Disease Who Failed to Benefit From Previous Cholinesterase Inhibitor Treatment
NCT00245206	PHASE4	COMPLETED	Side Effects of Newer Antipsychotics in Older Adults
NCT00254033	PHASE4	COMPLETED	Apathy Associated With Alzheimer’s Disease
NCT00260624	PHASE4	COMPLETED	Escitalopram Treatment of Patients With Agitated Dementia
NCT00303277	PHASE4	COMPLETED	Do HMG CoA Reductase Inhibitors Affect Abeta Levels?
NCT00305903	PHASE4	COMPLETED	Safety and Tolerability of Rivastigmine With Add-on Memantine in Patients With Probable Alzheimer’s Disease
NCT00306124	PHASE4	UNKNOWN	Dopaminergic Enhancement of Learning and Memory in Healthy Adults and Patients With Dementia/Mild Cognitive Impairment
NCT00334906	PHASE4	COMPLETED	Study of Memantine in Assessment of Selected Measures of Volumetric Magnetic Resonance Imaging (MRI) and Cognition in Moderate AD (Alzheimer’s Disease)
NCT00369603	PHASE4	TERMINATED	Functional Brain Imaging of Medication Treatment Response in Mild Alzheimer’s Disease Patients
NCT00375557	PHASE4	WITHDRAWN	Safety and Efficacy of Divalproex and Quetiapine in Elderly Alzheimer’s Dementia Patients
NCT00381381	PHASE4	COMPLETED	The Clinical Response of Choline Acetyltransferase and Apolipoprotein Epsilon Gene Polymorphisms to Donepezil in Alzheimer’s Disease
NCT00385684	PHASE4	COMPLETED	Low-Dose Opiate Therapy for Discomfort in Dementia (L-DOT)
NCT00401167	PHASE4	COMPLETED	Memantine for Agitation and Aggression in Severe Alzheimer’s Disease
NCT00403520	PHASE4	COMPLETED	Hippocampus Study: Comparative Effect of Donepezil 10mg/d and Placebo on Clinical and Radiological Markers
NCT00417482	PHASE4	COMPLETED	Antipsychotic Discontinuation in Alzheimer’s Disease
NCT00443014	PHASE4	COMPLETED	The Dementia Study in Northern Norway
NCT00469456	PHASE4	COMPLETED	Effect of Memantine on Functional Communication in Patients With Alzheimer’s Disease
NCT00476008	PHASE4	COMPLETED	Delaying the Progression of Driving Impairment in Individuals With Mild Alzheimer’s Disease
NCT00477659	PHASE4	COMPLETED	Neural Correlates In Mild Alzheimer’s Disease
NCT00480870	PHASE4	COMPLETED	The Effect of Anticholinesterase Drugs on Sleep in Alzheimer’s Disease Patients
NCT00495820	PHASE4	COMPLETED	Methylphenidate for Apathy in Alzheimer’s Dementia: A Controlled Study
NCT00523666	PHASE4	UNKNOWN	Diffusion Tensor Weighted MRI in Alzheimer’s Disease Modifying Treatment Effects of Galantamine (Reminyl®)
NCT00549601	PHASE4	COMPLETED	Convenience, Tolerability, and Safety of Change in the Administration of Rivastigmine From Capsules to a Transdermal Patch in Patients With Mild to Moderate Alzheimer’s Disease
NCT00551161	PHASE4	COMPLETED	Magnetic Resonance Spectroscopy Study of Memantine in Alzheimer’s Disease
NCT00561392	PHASE4	COMPLETED	Clinical Effectiveness of 10 cm^2 Rivastigmine Patch in Patients With Alzheimer’s Disease