GRIN2B

Summary

GRIN2B (glutamate ionotropic receptor NMDA type subunit 2B, HGNC:4586) is a protein-coding gene on chromosome 12p13.1, encoding Glutamate receptor ionotropic, NMDA 2B (Q13224). 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+). It is haploinsufficient (ClinGen: sufficient evidence).

This gene encodes a member of the N-methyl-D-aspartate (NMDA) receptor family within the ionotropic glutamate receptor superfamily. The encoded protein is a subunit of the NMDA receptor ion channel which acts as an agonist binding site for glutamate. The NMDA receptors mediate a slow calcium-permeable component of excitatory synaptic transmission in the central nervous system. The NMDA receptors are heterotetramers of seven genetically encoded, differentially expressed subunits including NR1 (GRIN1), NR2 (GRIN2A, GRIN2B, GRIN2C, or GRIN2D) and NR3 (GRIN3A or GRIN3B). The early expression of this gene in development suggests a role in brain development, circuit formation, synaptic plasticity, and cellular migration and differentiation. Naturally occurring mutations within this gene are associated with neurodevelopmental disorders including autism spectrum disorder, attention deficit hyperactivity disorder, epilepsy, and schizophrenia.

Source: NCBI Gene 2904 — RefSeq curated summary.

At a glance

• Gene–disease (curated): complex neurodevelopmental disorder (Definitive, ClinGen) — +5 more curated relationships
• GWAS associations: 25
• Clinical variants (ClinVar): 1,825 total — 114 pathogenic, 131 likely-pathogenic
• Phenotypes (HPO): 37
• Druggable target: yes — 35 molecules with ChEMBL bioactivity
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• MANE Select transcript: NM_000834

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4586
Approved symbol	GRIN2B
Name	glutamate ionotropic receptor NMDA type subunit 2B
Location	12p13.1
Locus type	gene with protein product
Status	Approved
Aliases	GluN2B, NR2B
Ensembl gene	ENSG00000273079
Ensembl biotype	protein_coding
OMIM	138252
Entrez	2904

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 5 protein_coding_CDS_not_defined, 4 protein_coding, 1 nonsense_mediated_decay

ENST00000609686, ENST00000627535, ENST00000628166, ENST00000630791, ENST00000636207, ENST00000636855, ENST00000636856, ENST00000637214, ENST00000637875, ENST00000714048

RefSeq mRNA: 2 — MANE Select: NM_000834 NM_000834, NM_001413992

CCDS: CCDS8662

Canonical transcript exons

ENST00000609686 — 14 exons

Exon	Start	End
ENSE00000993715	13567025	13567263
ENSE00000993719	13608603	13608832
ENSE00000993720	13616455	13616657
ENSE00000993722	13615493	13615664
ENSE00000993723	13571804	13571964
ENSE00000993725	13675745	13675859
ENSE00000993729	13611725	13611850
ENSE00000993731	13753317	13753915
ENSE00000993733	13865798	13866226
ENSE00001667846	13615114	13615267
ENSE00003770327	13979928	13980356
ENSE00003903818	13981342	13981602
ENSE00004022628	13569830	13570017
ENSE00004022629	13537337	13564639

Expression profiles

Bgee: expression breadth ubiquitous, 138 present calls, max score 97.05.

FANTOM5 (CAGE): breadth broad, TPM avg 5.3294 / max 354.4116, expressed in 233 samples.

FANTOM5 promoters (17 alternative TSS)

Promoter ID	TPM avg	Samples expressed
129820	1.7234	125
129816	1.3671	100
129826	0.5273	141
129825	0.4179	90
129811	0.1987	58
129817	0.1671	63
129812	0.1414	60
129814	0.1407	49
129823	0.1239	56
129824	0.1192	53

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	97.05	silver quality
cortical plate	UBERON:0005343	92.06	gold quality
Brodmann (1909) area 23	UBERON:0013554	85.81	gold quality
sural nerve	UBERON:0015488	85.20	gold quality
middle temporal gyrus	UBERON:0002771	80.99	gold quality
primary visual cortex	UBERON:0002436	79.92	gold quality
corpus callosum	UBERON:0002336	76.01	gold quality
occipital lobe	UBERON:0002021	75.71	gold quality
prefrontal cortex	UBERON:0000451	74.06	gold quality
cervix squamous epithelium	UBERON:0006922	73.42	gold quality
endothelial cell	CL:0000115	73.15	silver quality
nucleus accumbens	UBERON:0001882	73.15	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	72.98	gold quality
entorhinal cortex	UBERON:0002728	72.88	gold quality
superior frontal gyrus	UBERON:0002661	72.51	gold quality
neocortex	UBERON:0001950	72.38	gold quality
cerebral cortex	UBERON:0000956	72.02	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	71.87	gold quality
frontal cortex	UBERON:0001870	71.87	gold quality
cingulate cortex	UBERON:0003027	71.76	gold quality
anterior cingulate cortex	UBERON:0009835	71.50	gold quality
right frontal lobe	UBERON:0002810	71.37	gold quality
telencephalon	UBERON:0001893	71.32	gold quality
Brodmann (1909) area 9	UBERON:0013540	70.87	gold quality
Ammon’s horn	UBERON:0001954	70.81	gold quality
caudate nucleus	UBERON:0001873	70.27	gold quality
temporal lobe	UBERON:0001871	69.75	gold quality
putamen	UBERON:0001874	69.44	gold quality
parietal lobe	UBERON:0001872	68.47	gold quality
postcentral gyrus	UBERON:0002581	68.21	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-HCAD-35	yes	79.99
E-HCAD-25	yes	49.09
E-GEOD-93593	yes	16.19
E-ANND-3	yes	7.08
E-GEOD-84465	yes	6.92

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, CREB1, CUX2, FOXC1, FOXP2, HDAC1, MECP2, NFE2L2, REST, SP4, TBR1, TTBK1

miRNA regulators (miRDB)

60 targeting GRIN2B, 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-12118	100.00	65.88	1270
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-3120-5P	100.00	65.56	965
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-4778-3P	99.93	70.40	1818
HSA-MIR-6857-5P	99.87	65.32	985
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-11181-3P	99.75	66.38	2205
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-4677-5P	99.70	70.09	1940
HSA-MIR-4687-3P	99.48	66.41	968
HSA-MIR-330-3P	99.41	69.95	2521
HSA-MIR-508-5P	99.41	64.25	1248
HSA-MIR-1276	99.36	68.18	1642
HSA-MIR-185-5P	99.35	68.60	2497
HSA-MIR-4644	99.35	69.12	2514
HSA-MIR-145-3P	99.33	67.66	764
HSA-MIR-190B-3P	99.33	68.29	1382
HSA-MIR-7515	99.31	68.22	1795
HSA-MIR-410-3P	99.27	69.98	2457
HSA-MIR-7974	99.24	65.48	1137
HSA-MIR-3925-5P	99.21	67.90	1466
HSA-MIR-7109-5P	99.18	66.13	1057
HSA-MIR-6877-3P	98.98	65.83	560

Functional genomics

ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• NMDA receptor subunit 2B (GRIN2B) genetic variants and psychopathology and clozapine response in schizophrenia (PMID:11807413)
• hypothesis that the allelic variant (C2664T) of the NR2b confers susceptibility to AD . (PMID:11844890)
• It is unlikely that the GRIN2B C2664T polymorphism plays a substantial role in conferring susceptibility to Parkinson’s disease in the Chinese population. (PMID:11956967)
• The levels of Nr2B mRNA are decreased in Alzheimer disease hippocampus and entorhinal cortex compared to controls. (PMID:12127670)
• identification of a novel variant of the human gene promoter region and its possible association with schizophrenia (PMID:12476325)
• The results show that GRIN2B genetic variations are not a major risk factor for treatment-refractory schizophrenic patients, but may influence the effect of clozapine during treatment. (PMID:12824739)
• human cerebral endothelial cells express the message and protein for NMDA receptors. (PMID:12893641)
• Variants in NMDAR genes are associated with alcoholism and related traits. (PMID:14573320)
• NR2B was located in the midpiece of sperm, whereas GLT1 mainly existed in the head (PMID:14662797)
• Increased coassembly of NR2B and NR1 with PSD-95 may underlie one of the cellular mechanisms that contributes to in situ increased hyperexcitability, leading to seizure generation in focal cortical dysplasia. (PMID:15030493)
• These results provide evidence that GRIN2B may be associated with susceptibility to OCD. (PMID:15083261)
• Reviews the role of altered structure and function of NMDA receptors after ethanol exposure and summarizes the recent data about the activity of NR2B subunit selective NMDA receptor antagonists in model systems related to alcoholism. (PMID:15180478)
• results suggest that GRIN2B single nucleotide polymorphisms might be linked with susceptibility to schizophrenia (PMID:15211626)
• NR2B subtypes mainly expressed in the striatum, may influence the variability in age of onset of Huntington disease. (PMID:15742215)
• the combined effects of the polymorphisms in the GRIN1 and GRIN2B genes might be involved in the etiology of schizophrenia. (PMID:15841096)
• novel mechanism for Ca2+-dependent negative-feedback regulation of NR2B-containing NMDARs in a CaMKII activity- and autophosphorylation-dependent manner that may modulate NMDAR-mediated synaptic plasticity (PMID:15866054)
• These results demonstrate that human T lymphocytes express the NR2B subunit of NMDA receptors, which are functionally active in controlling cell activation. (PMID:16289038)
• The genetic findings suggest a role for GRIN2B in schizophrenia and bipolar disorder. (PMID:16549338)
• Results describe the successful replacement of murine N-methyl-d-aspartate receptor (NR)2B gene function by “knocking-in” a chimeric human NR2A/B cDNA containing the minimal domain abolishing ifenprodil binding into the endogenous NR2B locus. (PMID:16870468)
• These findings suggest new candidate SNPs(rs1806201) in GRIN2B for studying the genetic susceptibility to alcoholism. (PMID:16911840)
• data suggest an association between variations in the GRIN2B subunit gene and ADHD as measured categorically or as a quantitatively distributed trait. (PMID:17010153)
• The results show evidence of a statistically significant association for GRIN2B. The association seems weaker, but nonetheless interesting (PMID:17224684)
• the three amino acid tail following the TM4 region of the N-methyl-D-aspartate receptor (NR) 2 subunits is sufficient to overcome endoplasmic reticulum retention of NR1-1a subunit (PMID:17255096)
• The results clearly indicate that D1R-modulated NR1a/NR2B receptor function depends on PSD-95 and is subjected to the regulation of PKA and PKC. (PMID:17506933)
• postsynaptic density-93 and N-methyl-D-aspartate receptors subunits 2B mRNA are upregulated in temporal lobe tissue of epilepsy (PMID:17506987)
• NR2A and NR2B receptor gene variations modify age at onset in Huntington disease in a sex-specific manner. (PMID:17569088)
• NMDAR2B methylation is a common and important biologically relevant event in gastric cancer progression (PMID:17620329)
• genetic variations in the human GRIN2B gene probably do not play a major role in susceptibility to, or severity of Tardive dyskinesia (PMID:17669510)
• 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)
• The interaction between NR2B subunit and Mind bomb-2 reveal a possible mechanism for the regulation of NMDAR function involving both phosphorylation and ubiquitination. (PMID:17962190)
• results on chromosome 12p support GRIN2B as a candidate gene for bipolar disorder that needs further investigation (PMID:18007143)
• the synaptic NMDA receptor extracellular signal-regulated kinase activation pathway is coupled to both NR2A and NR2B containing receptors (PMID:18068304)
• GRIN2B gene is associated with Alzheimer’s disease. (PMID:18303265)
• analysis of the role of the fourth membrane domain of the NR2B subunit in the assembly of the NMDA receptor (PMID:18836292)
• Our study suggests that the -421C allele may induce lower GRIN2B transcriptional activity and NR2B protein expression, thus it is associated with AD. (PMID:18983893)
• Data show that expression of NMDA receptor NR1, NR2A, and NR2B subunits is significantly lower in brains of cirrhotic alcoholics than in the corresponding areas in both controls and alcoholics without co-morbid disease. (PMID:18991843)
• In linkage disequilibrium analysis we did not find linkage between the three polymorphisms of GRIN2B gene. The polymorphisms of GRIN2B gene analysed in this study are not likely to be associated with bipolar disorder. (PMID:19005876)
• An innovative design to establish proof of concept of the antidepressant effects of the NR2B subunit selective N-methyl-D-aspartate antagonist, CP-101,606, in patients with treatment-refractory major depressive disorder. (PMID:19011431)
• SGK1 phosphorylation of IkappaB Kinase alpha and p300 Up-regulates NF-kappaB activity and increases N-Methyl-D-aspartate receptor NR2A and NR2B expression. (PMID:19088076)
• A comparison of the molecular bases for NR1/NR2B receptor inhibition versus immobilizing activities of volatile aromatic anesthetics. (PMID:19095845)

Cross-species orthologs

43 orthologs

Organism	Symbol	Gene ID
danio_rerio	grin2bb	ENSDARG00000030376
danio_rerio	grin2ba	ENSDARG00000079348
mus_musculus	Grin2b	ENSMUSG00000030209
rattus_norvegicus	Grin2b	ENSRNOG00000008766
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), GRIN3A (ENSG00000198785)

Protein

Protein identifiers

Glutamate receptor ionotropic, NMDA 2B — Q13224 (reviewed: Q13224)

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

All UniProt accessions (6): A0A0D9SFA0, A0A0D9SFK0, A0A1B0GU78, A0A8D9PHB2, A0AAQ5BH89, Q13224

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 long-term depression (LTD) of hippocampus membrane currents. 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. In concert with DAPK1 at extrasynaptic sites, acts as a central mediator for stroke damage. Its phosphorylation at Ser-1303 by DAPK1 enhances synaptic NMDA receptor channel activity inducing injurious Ca2+ influx through them, resulting in an irreversible neuronal death.

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). Can also form heterotetrameric channels that contain at least two GluN1 subunits and at least two different GluN2 subunits (or a combination of one GluN2 and one GluN3 subunits) (in vitro). In vivo, the subunit composition may depend on the expression levels of the different subunits. Found in a complex with GRIN1 and GRIN3B. Found in a complex with GRIN1, GRIN3A and PPP2CB. Interacts with PDZ domains of PATJ, DLG3 and DLG4. Interacts with HIP1 and NETO1. Interacts with MAGI3. Interacts with DAPK1. Found in a complex with GRIN1 and PRR7. Interacts with PRR7. Interacts with CAMK2A. Interacts with ARC; preventing ARC oligomerization. Interacts with TMEM25. Interacts (via the extreme C-terminus) with FRMPD2 (via the second PDZ domain); the interaction is direct and is likely to promote NMDAR-mediated neural signal transmission. Interacts with FAM81A; the interaction facilitates condensate formation via liquid-liquid phase separation.

Subcellular location. Cell membrane. Postsynaptic cell membrane. Cell projection. Dendrite. Late endosome. Lysosome. Cytoplasm. Cytoskeleton.

Tissue specificity. Primarily found in the fronto-parieto-temporal cortex and hippocampus pyramidal cells, lower expression in the basal ganglia.

Post-translational modifications. Phosphorylated on tyrosine residues. Phosphorylation at Ser-1303 by DAPK1 enhances synaptic NMDA receptor channel activity.

Disease relevance. Intellectual developmental disorder, autosomal dominant 6, with or without seizures (MRD6) [MIM:613970] A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRD6 additional features may include seizures, hypotonia, abnormal movements, such as dystonia, and autistic features. The disease is caused by variants affecting the gene represented in this entry. Developmental and epileptic encephalopathy 27 (DEE27) [MIM:616139] A form of epileptic encephalopathy, a heterogeneous group of severe early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. The disease is caused by variants affecting the gene represented in this entry. A chromosomal aberrations involving GRIN2B has been found in patients with intellectual disability. Translocations t(9;12)(p23;p13.1) and t(10;12)(q21.1;p13.1) with a common breakpoint in 12p13.1.

Domain organisation. The extracellular N-terminal domain (NTD) endows NMDARs with a unique capacity for allosteric modulation, harboring several binding sites for small molecule ligands that act as subunit-specific allosteric modulators of ion channel activity. 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. NR2B/GRIN2B subfamily.

RefSeq proteins (2): NP_000825, NP_001400921 (=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 (173 total): strand 34, sequence variant 29, helix 28, modified residue 17, sequence conflict 11, turn 9, mutagenesis site 9, glycosylation site 7, binding site 6, topological domain 5, region of interest 5, transmembrane region 3, disulfide bond 3, compositionally biased region 2, signal peptide 1, chain 1, short sequence motif 1, site 1, intramembrane region 1

Structure

Experimental structures (PDB)

36 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
7UJR	X-RAY DIFFRACTION	1.95
7UJT	X-RAY DIFFRACTION	2.1
7UJQ	X-RAY DIFFRACTION	2.25
7KL0	X-RAY DIFFRACTION	2.4
7KL1	X-RAY DIFFRACTION	2.4
7KL2	X-RAY DIFFRACTION	2.56
7UJP	X-RAY DIFFRACTION	2.56
7UIS	X-RAY DIFFRACTION	2.58
7UJS	X-RAY DIFFRACTION	2.75
5EWM	X-RAY DIFFRACTION	2.76
5EWJ	X-RAY DIFFRACTION	2.77
5EWL	X-RAY DIFFRACTION	2.98
9OOS	ELECTRON MICROSCOPY	3.03
10FD	ELECTRON MICROSCOPY	3.09
9OOT	ELECTRON MICROSCOPY	3.13
9OOR	ELECTRON MICROSCOPY	3.15
9IYQ	ELECTRON MICROSCOPY	3.18
9OOQ	ELECTRON MICROSCOPY	3.2
9IYP	ELECTRON MICROSCOPY	3.27
9D37	ELECTRON MICROSCOPY	3.34
9D39	ELECTRON MICROSCOPY	3.65
8VUV	ELECTRON MICROSCOPY	3.69
9D3B	ELECTRON MICROSCOPY	3.71
10EZ	ELECTRON MICROSCOPY	3.76
9D3A	ELECTRON MICROSCOPY	3.78
10FL	ELECTRON MICROSCOPY	3.81
9D38	ELECTRON MICROSCOPY	3.95
9D3C	ELECTRON MICROSCOPY	3.96
8VUU	ELECTRON MICROSCOPY	4.05
10FF	ELECTRON MICROSCOPY	4.06

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q13224-F1	60.66	0.18

Antibody-complex structures (SAbDab): 2 — 8VUU, 8VUV

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): 615 (functional determinant of nmda receptors)

Ligand- & substrate-binding residues (6): 127; 284; 514; 519; 690–691; 732

Post-translational modifications (17): 882, 886, 917, 920, 962, 1039, 1058, 1061, 1064, 1109, 1133, 1143, 1155, 1255, 1259, 1303, 1474

Disulfide bonds (3): 86–321, 429–456, 436–457

Glycosylation sites (7): 74, 341, 348, 444, 491, 542, 688

Mutagenesis-validated functional residues (9):

Position	Phenotype
553	changed glutamate-gated calcium ion channel activity characterized by increased glutamate and glycine potency and slowed
636	severely reduced localization to cell membrane.
636	reduced localization to cell membrane. affects glutamate-gated calcium ion channel activity resulting in increased agoni
639	reduced localization to cell membrane. affects glutamate-gated calcium ion channel activity resulting in increased agoni
641	reduced localization to cell membrane. affects glutamate-gated calcium ion channel activity resulting in increased agoni
649	affects glutamate-gated calcium ion channel activity resulting in increased agonist potency and mutant channels activate
652	no significant effect on glutamate and glycine agonist potency.
655	reduced localization to cell membrane.
818	increased glutamate and glycine agonist potency.

Function

Pathways and Gene Ontology

Reactome pathways

11 pathways

ID	Pathway
R-HSA-3928662	EPHB-mediated forward signaling
R-HSA-438066	Unblocking of NMDA receptors, glutamate binding and activation
R-HSA-442982	Ras activation upon Ca2+ influx through NMDA receptor
R-HSA-5673001	RAF/MAP kinase cascade
R-HSA-6794361	Neurexins and neuroligins
R-HSA-8849932	Synaptic adhesion-like molecules
R-HSA-9022699	MECP2 regulates neuronal receptors and channels
R-HSA-9032500	Activated NTRK2 signals through FYN
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: 364 (showing top): GOBP_POSITIVE_REGULATION_OF_SYNAPTIC_TRANSMISSION_GLUTAMATERGIC, GOBP_RESPONSE_TO_ETHANOL, GOBP_COGNITION, GOBP_BEHAVIOR, GOMF_GLUTAMATE_GATED_RECEPTOR_ACTIVITY, GOBP_REGULATION_OF_NEURONAL_SYNAPTIC_PLASTICITY, GOBP_REGULATION_OF_SYNAPTIC_TRANSMISSION_GLUTAMATERGIC, SP3_Q3, GOCC_CELL_SURFACE, GOBP_CELLULAR_COMPONENT_MAINTENANCE, AP4_Q6, MEF2_02, GGGTGGRR_PAX4_03, AAAYRNCTG_UNKNOWN, BIOCARTA_NOS1_PATHWAY

GO Biological Process (24): glutamate receptor signaling pathway (GO:0007215), chemical synaptic transmission (GO:0007268), brain development (GO:0007420), learning or memory (GO:0007611), ionotropic glutamate receptor signaling pathway (GO:0035235), synaptic transmission, glutamatergic (GO:0035249), response to ethanol (GO:0045471), regulation of synaptic plasticity (GO:0048167), regulation of neuronal synaptic plasticity (GO:0048168), protein heterotetramerization (GO:0051290), 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), negative regulation of dendritic spine maintenance (GO:1902951), regulation of monoatomic cation transmembrane transport (GO:1904062), positive regulation of excitatory postsynaptic potential (GO:2000463), monoatomic ion transport (GO:0006811), calcium-mediated signaling (GO:0019722), monoatomic ion transmembrane transport (GO:0034220), regulation of membrane potential (GO:0042391), regulation of presynaptic membrane potential (GO:0099505)

GO Molecular Function (13): amyloid-beta binding (GO:0001540), NMDA glutamate receptor activity (GO:0004972), zinc ion binding (GO:0008270), glycine binding (GO:0016594), glutamate binding (GO:0016595), glutamate-gated calcium ion channel activity (GO:0022849), ligand-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential (GO:0099507), transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential (GO:1904315), monoatomic ion channel activity (GO:0005216), protein binding (GO:0005515), ligand-gated monoatomic ion channel activity (GO:0015276), signaling receptor activity (GO:0038023), metal ion binding (GO:0046872)

GO Cellular Component (18): cytoplasm (GO:0005737), lysosome (GO:0005764), late endosome (GO:0005770), endoplasmic reticulum membrane (GO:0005789), cytoskeleton (GO:0005856), plasma membrane (GO:0005886), cell surface (GO:0009986), postsynaptic density (GO:0014069), NMDA selective glutamate receptor complex (GO:0017146), dendrite (GO:0030425), neuron projection (GO:0043005), postsynaptic membrane (GO:0045211), synaptic membrane (GO:0097060), postsynaptic density membrane (GO:0098839), endosome (GO:0005768), membrane (GO:0016020), cell projection (GO:0042995), synapse (GO:0045202)

Reactome top-level categories

Rollup of top-8 pathways:

Category	Pathways
Activation of NMDA receptors and postsynaptic events	3
Protein-protein interactions at synapses	2
EPH-Ephrin signaling	1
CREB1 phosphorylation through NMDA receptor-mediated activation of RAS signaling	1
MAPK1/MAPK3 signaling	1
Transcriptional Regulation by MECP2	1
Signaling by NTRK2 (TRKB)	1
Post NMDA receptor activation events	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
glutamate-gated receptor activity	3
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
amino acid binding	2
carboxylic acid binding	2
cation binding	2
cell surface receptor signaling pathway	1
glutamate receptor activity	1
anterograde trans-synaptic signaling	1
central nervous system development	1
animal organ development	1
head development	1
behavior	1
cognition	1
glutamate receptor signaling pathway	1
ligand-gated ion channel signaling pathway	1
response to alcohol	1
modulation of chemical synaptic transmission	1
regulation of biological quality	1
protein tetramerization	1
protein heterooligomerization	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
negative regulation of cell projection organization	1
dendritic spine maintenance	1
regulation of dendritic spine maintenance	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
peptide binding	1

Protein interactions and networks

STRING

3300 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GRIN2B	DLG4	P78352	999
GRIN2B	DLG3	Q92796	994
GRIN2B	GRIN1	P35437	989
GRIN2B	DLG2	Q15700	988
GRIN2B	GRIN3A	Q8TCU5	987
GRIN2B	GRIN3B	O60391	985
GRIN2B	GRIN2D	O15399	984
GRIN2B	GRIN2C	Q14957	983
GRIN2B	GRIN2A	Q12879	983
GRIN2B	FYN	P06241	981
GRIN2B	DLG1	Q12959	970
GRIN2B	CAMK2A	Q9UQM7	965
GRIN2B	KIF17	Q9P2E2	955
GRIN2B	RASGRF1	Q13972	935
GRIN2B	SYNGAP1	Q96PV0	910

IntAct

151 interactions, top by confidence:

A	B	Type	Score
DLG4	GRIN2B	psi-mi:“MI:0407”(direct interaction)	0.820
DLG4	GRIN2B	psi-mi:“MI:0915”(physical association)	0.820
GRIN2B	DLG4	psi-mi:“MI:0407”(direct interaction)	0.820
GRIN2B	DLG1	psi-mi:“MI:0915”(physical association)	0.790
DLG1	GRIN2B	psi-mi:“MI:0407”(direct interaction)	0.790
GRIN2B	DLG1	psi-mi:“MI:0407”(direct interaction)	0.790
SCRIB	GRIN2B	psi-mi:“MI:0407”(direct interaction)	0.620
DLG3	GRIN2B	psi-mi:“MI:0407”(direct interaction)	0.620
GRIN2B	DLG3	psi-mi:“MI:0407”(direct interaction)	0.620
GRIN2B	SCRIB	psi-mi:“MI:0407”(direct interaction)	0.620
CAMK2A	GRIN2B	psi-mi:“MI:0407”(direct interaction)	0.600
GRIN2B	CAMK2A	psi-mi:“MI:0403”(colocalization)	0.600
DLG2	GRIN2B	psi-mi:“MI:0915”(physical association)	0.590
GRIN2B	DLG2	psi-mi:“MI:0407”(direct interaction)	0.590
Dlg4	GRIN2B	psi-mi:“MI:0407”(direct interaction)	0.560
Dlg3	GRIN2B	psi-mi:“MI:0407”(direct interaction)	0.560

BioGRID (160): GRIN2B (Synthetic Growth Defect), GRIN2B (Co-localization), GRIN2B (Co-localization), GRIN2B (Affinity Capture-Western), GRIN2B (Affinity Capture-Western), GRIN2B (Reconstituted Complex), ARHGAP32 (Two-hybrid), GRIN2B (Affinity Capture-Western), DLG4 (Affinity Capture-Western), DLG3 (Affinity Capture-Western), EXOC4 (Affinity Capture-Western), EXOC3 (Affinity Capture-Western), GRIN2B (Affinity Capture-Western), GRIN2B (Reconstituted Complex), CAMK2A (Reconstituted Complex)

ESM2 similar proteins: A7XY94, B3LZ39, B3P2E5, B4GF83, B4I414, B4JHV0, B4KD90, B4LZB5, B4MU83, B4PVB0, B4QWW7, B7ZSK1, P19490, P19491, P19492, P19493, P22756, P23818, P23819, P31424, P35436, P39086, P41594, P42261, P42262, P42263, P48058, P58421, Q00959, Q00960, Q01097, Q03445, Q12879, Q13224, Q24418, Q296F7, Q38PU4, Q38PU5, Q38PU6, Q38PU7

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

34 interactions.

A	Effect	B	Mechanism
CSNK2A1	down-regulates	GRIN2B	phosphorylation
FYN	unknown	GRIN2B	phosphorylation
GRIN2B	“form complex”	“NMDA receptor_2B”	binding
DLG4	“up-regulates activity”	GRIN2B	relocalization
FOXP2	“up-regulates quantity by expression”	GRIN2B	“transcriptional regulation”
PRKACA	“up-regulates activity”	GRIN2B	phosphorylation
PKA	“up-regulates activity”	GRIN2B	phosphorylation
PTPN11	“down-regulates activity”	GRIN2B	dephosphorylation
PTPN5	“down-regulates activity”	GRIN2B	dephosphorylation
PTEN	“down-regulates activity”	GRIN2B	dephosphorylation
CDK5	“down-regulates quantity”	GRIN2B	phosphorylation
DAPK1	“up-regulates activity”	GRIN2B	phosphorylation
MIB2	“down-regulates quantity”	GRIN2B	ubiquitination
EPHB2	“up-regulates quantity”	GRIN2B	phosphorylation
MECP2	“down-regulates quantity by repression”	GRIN2B	“transcriptional regulation”
FYN	“up-regulates activity”	GRIN2B	phosphorylation
SRC	“up-regulates activity”	GRIN2B	phosphorylation
PRKCA	“up-regulates activity”	GRIN2B	phosphorylation
PRKCB	“up-regulates activity”	GRIN2B	phosphorylation
PRKCG	“up-regulates activity”	GRIN2B	phosphorylation
CAMK2A	“up-regulates activity”	GRIN2B	phosphorylation
CAMK2B	“up-regulates activity”	GRIN2B	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 92 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
Unblocking of NMDA receptors, glutamate binding and activation	7	60.4×	9e-10
Negative regulation of NMDA receptor-mediated neuronal transmission	7	60.4×	9e-10
Ras activation upon Ca2+ influx through NMDA receptor	6	54.4×	4e-08
Long-term potentiation	7	52.9×	2e-09
Assembly and cell surface presentation of NMDA receptors	12	48.3×	9e-16
Synaptic adhesion-like molecules	5	43.2×	3e-06
Neurexins and neuroligins	13	40.6×	9e-16
Dopamine Neurotransmitter Release Cycle	5	39.4×	4e-06

GO biological processes:

GO term	Partners	Fold	FDR
establishment or maintenance of epithelial cell apical/basal polarity	10	67.6×	1e-13
protein localization to synapse	6	53.4×	3e-07
receptor clustering	6	43.5×	6e-07
regulation of postsynaptic membrane neurotransmitter receptor levels	7	40.3×	1e-07
excitatory postsynaptic potential	5	25.8×	1e-04
protein dephosphorylation	6	15.5×	2e-04
protein-containing complex assembly	9	11.9×	7e-06
cell-cell adhesion	9	10.6×	2e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

1825 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	114
Likely pathogenic	131
Uncertain significance	583
Likely benign	607
Benign	143

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1164046	NM_000834.5(GRIN2B):c.1928T>C (p.Leu643Pro)	Pathogenic
1218814	NM_000834.5(GRIN2B):c.2455G>T (p.Ala819Ser)	Pathogenic
1299652	NM_000834.5(GRIN2B):c.1606G>A (p.Val536Ile)	Pathogenic
1323037	NM_000834.5(GRIN2B):c.2010+1del	Pathogenic
1364424	NC_000012.11:g.(?13906231)(13906869_?)del	Pathogenic
1401421	NM_000834.5(GRIN2B):c.2150C>T (p.Ala717Val)	Pathogenic
1408815	NM_000834.5(GRIN2B):c.2410G>A (p.Glu804Lys)	Pathogenic
1421943	NM_000834.5(GRIN2B):c.3789_3837dup (p.Lys1280delinsGlyProAlaGlyCysProSerGlyGlyAspValLysArgLeuHisHisTer)	Pathogenic
143189	NM_000834.5(GRIN2B):c.1238A>G (p.Glu413Gly)	Pathogenic
1458907	NM_000834.5(GRIN2B):c.1628G>A (p.Gly543Glu)	Pathogenic
1527685	GRCh37/hg19 12p13.1(chr12:14070549-14224680)	Pathogenic
1685866	NM_000834.5(GRIN2B):c.2402G>A (p.Cys801Tyr)	Pathogenic
1685867	NM_000834.5(GRIN2B):c.2192A>G (p.Tyr731Cys)	Pathogenic
1685868	NM_000834.5(GRIN2B):c.2072C>G (p.Thr691Arg)	Pathogenic
1685869	NM_000834.5(GRIN2B):c.1849T>A (p.Ser617Thr)	Pathogenic
1685870	NM_000834.5(GRIN2B):c.1477_1499dup (p.Glu500_Val501insProGlyMetValTer)	Pathogenic
1690349	NM_000834.5(GRIN2B):c.1848C>A (p.Asn616Lys)	Pathogenic
1696671	NM_000834.5(GRIN2B):c.2117T>A (p.Met706Lys)	Pathogenic
1708206	NM_000834.5(GRIN2B):c.1621A>G (p.Ser541Gly)	Pathogenic
1768892	NM_000834.5(GRIN2B):c.99del (p.Ser34fs)	Pathogenic
1793740	NM_000834.5(GRIN2B):c.2607C>A (p.Tyr869Ter)	Pathogenic
1800708	NM_000834.5(GRIN2B):c.1931C>A (p.Ala644Asp)	Pathogenic
1803124	NM_000834.5(GRIN2B):c.3937_3940del (p.Glu1313fs)	Pathogenic
1878839	NM_000834.5(GRIN2B):c.1654+1G>A	Pathogenic
2118872	NM_000834.5(GRIN2B):c.1623C>A (p.Ser541Arg)	Pathogenic
2133232	NM_000834.5(GRIN2B):c.1011-1G>C	Pathogenic
218471	NM_000834.5(GRIN2B):c.2430C>A (p.Ser810Arg)	Pathogenic
2292351	NM_000834.5(GRIN2B):c.2249_2250dup (p.Ile751fs)	Pathogenic
2423420	NC_000012.11:g.(?13828659)(13828813_?)del	Pathogenic
2429917	NM_000834.5(GRIN2B):c.1108G>T (p.Glu370Ter)	Pathogenic

SpliceAI

3501 predictions. Top by Δscore:

Variant	Effect	Δscore
12:13564636:TACC:T	acceptor_gain	1.0000
12:13564638:CC:C	acceptor_gain	1.0000
12:13564639:CC:C	acceptor_gain	1.0000
12:13564639:CCTGA:C	acceptor_loss	1.0000
12:13564640:C:CC	acceptor_gain	1.0000
12:13564640:CT:C	acceptor_loss	1.0000
12:13564641:T:G	acceptor_loss	1.0000
12:13567021:TTACT:T	donor_loss	1.0000
12:13567022:TACTC:T	donor_loss	1.0000
12:13567023:A:AC	donor_gain	1.0000
12:13567024:C:CA	donor_gain	1.0000
12:13567024:CT:C	donor_gain	1.0000
12:13567024:CTCT:C	donor_gain	1.0000
12:13567024:CTCTG:C	donor_gain	1.0000
12:13567259:CTCCC:C	acceptor_gain	1.0000
12:13567260:TCCC:T	acceptor_gain	1.0000
12:13567261:CCC:C	acceptor_gain	1.0000
12:13567261:CCCC:C	acceptor_gain	1.0000
12:13567262:CCC:C	acceptor_gain	1.0000
12:13567264:C:CC	acceptor_gain	1.0000
12:13567264:CTGGG:C	acceptor_loss	1.0000
12:13569823:AACT:A	donor_loss	1.0000
12:13569824:ACTC:A	donor_loss	1.0000
12:13569826:TCA:T	donor_loss	1.0000
12:13569828:A:AC	donor_gain	1.0000
12:13569828:AC:A	donor_gain	1.0000
12:13569829:C:CC	donor_gain	1.0000
12:13569829:C:CT	donor_loss	1.0000
12:13569829:CC:C	donor_gain	1.0000
12:13569829:CCAT:C	donor_gain	1.0000

AlphaMissense

9926 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:13564524:G:T	A905D	1.000
12:13567028:G:C	S865R	1.000
12:13567028:G:T	S865R	1.000
12:13567030:T:G	S865R	1.000
12:13567127:G:C	S832R	1.000
12:13567127:G:T	S832R	1.000
12:13567129:T:G	S832R	1.000
12:13567140:G:T	A828D	1.000
12:13567149:A:C	L825W	1.000
12:13567149:A:G	L825S	1.000
12:13567152:A:C	M824R	1.000
12:13567152:A:T	M824K	1.000
12:13567157:G:C	F822L	1.000
12:13567157:G:T	F822L	1.000
12:13567159:A:G	F822L	1.000
12:13567164:C:T	G820E	1.000
12:13567165:C:A	G820W	1.000
12:13567165:C:G	G820R	1.000
12:13567165:C:T	G820R	1.000
12:13567168:C:G	A819P	1.000
12:13567169:C:A	M818I	1.000
12:13567169:C:G	M818I	1.000
12:13567169:C:T	M818I	1.000
12:13567170:A:C	M818R	1.000
12:13567172:G:C	N817K	1.000
12:13567172:G:T	N817K	1.000
12:13567185:A:C	L813R	1.000
12:13567185:A:G	L813P	1.000
12:13567185:A:T	L813Q	1.000
12:13567220:A:C	C801W	1.000

dbSNP variants (sampled 300 via entrez): RS1000002313 (12:13658329 A>G), RS1000009308 (12:13919544 GT>G), RS1000014852 (12:13605983 T>C), RS1000026531 (12:13981949 C>A), RS1000029846 (12:13817049 G>C), RS1000031413 (12:13770164 A>G), RS1000041488 (12:13936008 C>T), RS1000046386 (12:13840383 A>C), RS1000049239 (12:13689632 T>G), RS1000059630 (12:13609818 T>C,G), RS1000060485 (12:13778662 T>A,C,G), RS1000074125 (12:13935812 G>A), RS1000080396 (12:13817220 G>A), RS1000081475 (12:13607716 T>C), RS1000087256 (12:13695491 T>C)

Disease associations

OMIM: gene MIM:138252 | disease phenotypes: MIM:613970, MIM:616139, MIM:606369, MIM:603047, MIM:123100

GenCC curated gene-disease

Disease	Classification	Inheritance
complex neurodevelopmental disorder	Definitive	Autosomal dominant
intellectual disability, autosomal dominant 6	Definitive	Autosomal dominant
developmental and epileptic encephalopathy, 27	Definitive	Autosomal dominant
GRIN2B-related complex neurodevelopmental disorder	Strong	Autosomal dominant
autosomal dominant non-syndromic intellectual disability	Supportive	Autosomal dominant
infantile spasms	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
complex neurodevelopmental disorder	Definitive	AD

Mondo (19): intellectual disability, autosomal dominant 6 (MONDO:0013509), developmental and epileptic encephalopathy, 27 (MONDO:0014505), cerebral palsy (MONDO:0006497), intellectual disability (MONDO:0001071), complex neurodevelopmental disorder (MONDO:0100038), neurodevelopmental disorder (MONDO:0700092), autism spectrum disorder (MONDO:0005258), Lennox-Gastaut syndrome (MONDO:0016532), infantile spasms (MONDO:0018097), astigmatism (MONDO:0011284), epilepsy (MONDO:0005027), Landau-Kleffner syndrome (MONDO:0009509), GRIN2B-related complex neurodevelopmental disorder (MONDO:0700350), microcephaly (MONDO:0001149), fetal growth restriction (MONDO:0005030)

Orphanet (13): West syndrome (Orphanet:3451), GRIN2B-related developmental delay, intellectual disability and autism spectrum disorder (Orphanet:589547), Non-specific syndromic intellectual disability (Orphanet:528084), Lennox-Gastaut syndrome (Orphanet:2382), Infantile epileptic spasms syndrome (Orphanet:697160), Self-limited epilepsy with centrotemporal spikes (Orphanet:1945), Developmental and epileptic encephalopathy with spike-wave activation in sleep (Orphanet:725), Landau-Kleffner syndrome (Orphanet:98818), Craniosynostosis (Orphanet:1531), Paroxysmal dystonia (Orphanet:200037), Autosomal dominant non-syndromic intellectual disability (Orphanet:178469), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658), NON RARE IN EUROPE: Autism (Orphanet:106)

HPO phenotypes

37 total (30 of 37 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000023	Inguinal hernia
HP:0000028	Cryptorchidism
HP:0000252	Microcephaly
HP:0000453	Choanal atresia
HP:0000707	Abnormality of the nervous system
HP:0000708	Atypical behavior
HP:0000817	Reduced eye contact
HP:0000821	Hypothyroidism
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001252	Hypotonia
HP:0001257	Spasticity
HP:0001263	Global developmental delay
HP:0001290	Generalized hypotonia
HP:0001332	Dystonia
HP:0001336	Myoclonus
HP:0001344	Absent speech
HP:0001763	Pes planus
HP:0002069	Bilateral tonic-clonic seizure
HP:0002072	Chorea
HP:0002133	Status epilepticus
HP:0002353	EEG abnormality
HP:0002376	Developmental regression
HP:0002384	Focal impaired awareness seizure
HP:0002521	Hypsarrhythmia
HP:0003593	Infantile onset
HP:0008936	Axial hypotonia
HP:0011097	Epileptic spasm
HP:0011121	Abnormal skin morphology

GWAS associations

25 associations (top):

Study	Trait	p-value
GCST000477_27	Cognitive performance	2.000000e-06
GCST000614_3	Brain structure (temporal lobe volume)	3.000000e-06
GCST000898_7	Total ventricular volume	3.000000e-06
GCST001166_2	Aging (time to event)	6.000000e-06
GCST001330_1	Ovarian reserve	9.000000e-07
GCST001535_16	Immune reponse to smallpox (secreted IL-2)	1.000000e-08
GCST001850_11	Major depressive disorder	8.000000e-06
GCST005725_1	Egg allergy (parent-of-origin effect)	2.000000e-06
GCST006267_2	Response to selective serotonin reuptake inhibitors in depression	4.000000e-06
GCST006291_78	Spherical equivalent or myopia (age of diagnosis)	6.000000e-10
GCST006628_48	Systolic blood pressure	7.000000e-10
GCST007001_6	Cerebrospinal AB1-42 levels in normal cognition	3.000000e-08
GCST007324_84	Adventurousness	4.000000e-09
GCST007325_112	General risk tolerance (MTAG)	3.000000e-10
GCST007538_5	Cellular nuclear factor (erythroid-derived 2)-like 2 levels	7.000000e-07
GCST008155_72	Waist-hip ratio	1.000000e-06
GCST008159_76	Waist-to-hip ratio adjusted for BMI	1.000000e-06
GCST008438_1	Alzheimer’s disease in hypertension	4.000000e-06
GCST008839_27	Height	3.000000e-09
GCST010002_209	Refractive error	4.000000e-34
GCST010599_6	Dietary fat liking	4.000000e-06
GCST012221_2	Opioid dependence (time to event)	1.000000e-07
GCST012222_6	Opioid dependence (time to event)	2.000000e-07
GCST012354_42	Anxiety	4.000000e-06
GCST90013442_19	Keratoconus	2.000000e-09

EFO canonical traits (17, from GWAS)

EFO ID	Trait name
EFO:0003926	neuropsychological test
EFO:0022597	aging
EFO:0004770	ovarian reserve
EFO:0004645	response to vaccine
EFO:0004873	cytokine measurement
EFO:0005939	parental genotype effect measurement
EFO:0007018	egg allergy measurement
EFO:0005658	response to selective serotonin reuptake inhibitor
EFO:0004847	age at onset
EFO:0006335	systolic blood pressure
EFO:0004670	beta-amyloid 1-42 measurement
EFO:0008579	risk-taking behaviour
EFO:0009794	NRF2 measurement
EFO:0004343	waist-hip ratio
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0010816	dietary fat liking measurement
EFO:0009863	anxiety measurement

MeSH disease descriptors (11)

Descriptor	Name	Tree numbers
D001251	Astigmatism	C11.744.212
D002547	Cerebral Palsy	C10.228.140.140.254
D003398	Craniosynostoses	C05.116.099.370.894.232; C05.660.207.240; C05.660.906.364; C16.131.621.207.240; C16.131.621.906.364
D004827	Epilepsy	C10.228.140.490
D005317	Fetal Growth Retardation	C12.050.703.277.370; C16.300.390; C23.550.393.450
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D018887	Landau-Kleffner Syndrome	C10.228.140.490.493.500
D065768	Lennox Gastaut Syndrome	C10.228.140.490.493.750; C16.320.495
D008831	Microcephaly	C05.660.207.620; C10.500.507.400.500; C16.131.621.207.620; C16.131.666.507.400.500
D065886	Neurodevelopmental Disorders	F03.625
D012600	Scoliosis	C05.116.900.800.875

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (4): CHEMBL1904 (SINGLE PROTEIN), CHEMBL1907603 (PROTEIN COMPLEX), CHEMBL2094124 (PROTEIN COMPLEX GROUP), CHEMBL5483086 (PROTEIN COMPLEX)

Molecules with ChEMBL bioactivity

35 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,461,577 (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
CHEMBL54	HALOPERIDOL	4	60,883
CHEMBL52440	DEXTROMETHORPHAN	4	33,223
CHEMBL742	KETAMINE	4	101,983
CHEMBL771	CYCLOSERINE	4	23,487
CHEMBL807	MEMANTINE	4	34,597
CHEMBL95	TACRINE	4	35,360
CHEMBL592	LEVORPHANOL	4	75,131
CHEMBL660	AMANTADINE	4	69,750
CHEMBL71	CHLORPROMAZINE	4	45,827
CHEMBL86715	PROCYCLIDINE	4	5,456
CHEMBL900	ORPHENADRINE	4	8,087
CHEMBL5095095	DALZANEMDOR	3	20
CHEMBL589390	LATREPIRDINE	3	466
CHEMBL350719	ESMETHADONE	3	26,004
CHEMBL575060	GLUTAMIC ACID	3	929,756
CHEMBL17350	TRAXOPRODIL	2	2,547
CHEMBL28564	ELIPRODIL	2	3,130
CHEMBL305187	IFENPRODIL	2	5,708
CHEMBL3545350	EVT-101 FREE BASE	2	138
CHEMBL5314944	ZELQUISTINEL	2	24
CHEMBL1254766	DEXTRORPHAN	2
CHEMBL159659	LEVOMETHADONE	2
CHEMBL159660	ALPHAMETHADOL	2
CHEMBL182066	RADIPRODIL	2
CHEMBL275528	PHENCYCLIDINE	2
CHEMBL284237	DIZOCILPINE	2
CHEMBL5095074	ONFASPRODIL	2
CHEMBL14935	TEZAMPANEL ANHYDROUS	2
CHEMBL22207	RACEMETHORPHAN	2
CHEMBL289832	LICOSTINEL	2

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

PharmGKB clinical annotations

6 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs1019385	Dosage	3	valproic acid	Epilepsy
rs1072388	Efficacy	3	clozapine	Schizophrenia
rs1806201	Toxicity	3	quetiapine	Drug Toxicity
rs1806201	Toxicity	3	risperidone	Drug Toxicity
rs1806201	Other	3	sevoflurane
rs2058878	Efficacy	3	acamprosate	Alcohol abuse

PharmGKB variants

9 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs890	GRIN2B		0.00	0
rs1019385	GRIN2B	3	5.00	1	valproic acid
rs1072388	GRIN2B	3	0.00	1	clozapine
rs1806201	GRIN2B	3	1.75	3	sevoflurane;risperidone;quetiapine
rs2058878	GRIN2B	3	2.00	1	acamprosate
rs2160733	GRIN2B		0.00	0
rs2160734	GRIN2B		0.00	0
rs2284411	GRIN2B		0.00	0
rs1806191	GRIN2B		0.00	0

GtoPdb / IUPHAR curated pharmacology

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

Target class: lgic — Ionotropic glutamate receptors

Most potent curated ligand interactions (5 total), top 5:

Ligand	Action	Affinity	Parameter
onfasprodil	Negative	8.08	pIC50
NP10679	Inhibition	7.64	pIC50
SAGE-718	Positive	7.1	pEC50
DQP-1105	Negative	6.95	pIC50
S-deschloroketamine	Antagonist	5.44	pKd

Binding affinities (BindingDB)

1153 measured of 1190 human assays (1190 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
2-[6-(4-Fluoro-3-methyl-phenyl)pyrrolo[3,2-b]pyridin-1-yl]-N,N-	IC50	2 nM	US-10377753: Substituted 4-azaindoles and their use as GluN2B receptor modulators
6-[2-[(3aR,6aS)-5-(4-fluorophenoxy)-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrol-2-yl]-1-hydroxyethyl]pyridin-3-ol	IC50	4.41 nM	US-10239835: N-alkylaryl-5-oxyaryl-octahydro-cyclopenta[c]pyrrole negative allosteric modulators of NR2B
4-[2-[(3aS,6aR)-5-(2-fluorophenoxy)-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrol-2-yl]-1-hydroxyethyl]phenol	IC50	4.44 nM	US-10239835: N-alkylaryl-5-oxyaryl-octahydro-cyclopenta[c]pyrrole negative allosteric modulators of NR2B
6-[(1R)-2-[(3aS,6aR)-5-phenoxy-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrol-2-yl]-1-hydroxyethyl]pyridin-3-ol	IC50	5.24 nM	US-10239835: N-alkylaryl-5-oxyaryl-octahydro-cyclopenta[c]pyrrole negative allosteric modulators of NR2B
6-[(1S)-2-[(3aR,6aS)-5-phenoxy-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrol-2-yl]-1-hydroxyethyl]pyridin-3-ol	IC50	5.25 nM	US-10239835: N-alkylaryl-5-oxyaryl-octahydro-cyclopenta[c]pyrrole negative allosteric modulators of NR2B
6-[2-[(3aS,6aR)-5-phenoxy-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrol-2-yl]-1-hydroxyethyl]pyridin-3-ol	IC50	5.72 nM	US-10239835: N-alkylaryl-5-oxyaryl-octahydro-cyclopenta[c]pyrrole negative allosteric modulators of NR2B
4-[2-[(3aR,6aS)-5-phenoxy-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrol-2-yl]-1-hydroxyethyl]phenol	IC50	5.96 nM	US-10239835: N-alkylaryl-5-oxyaryl-octahydro-cyclopenta[c]pyrrole negative allosteric modulators of NR2B
6-[2-[(3aR,6aS)-5-(2-fluorophenoxy)-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrol-2-yl]-1-hydroxyethyl]pyridin-3-ol	IC50	6.2 nM	US-10239835: N-alkylaryl-5-oxyaryl-octahydro-cyclopenta[c]pyrrole negative allosteric modulators of NR2B
2-[6-(5-Chloro-2-thienyl)pyrrolo[3,2-b]pyridin-1-yl]-N,N-	IC50	6.31 nM	US-10377753: Substituted 4-azaindoles and their use as GluN2B receptor modulators
6-[2-[(3aS,6aR)-5-(2,4-difluorophenoxy)-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrol-2-yl]-1-hydroxyethyl]pyridin-3-ol	IC50	6.81 nM	US-10239835: N-alkylaryl-5-oxyaryl-octahydro-cyclopenta[c]pyrrole negative allosteric modulators of NR2B
6-[(1S)-2-[(3aR,6aS)-5-(2-fluorophenoxy)-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrol-2-yl]-1-hydroxyethyl]pyridin-3-ol	IC50	8.3 nM	US-10239835: N-alkylaryl-5-oxyaryl-octahydro-cyclopenta[c]pyrrole negative allosteric modulators of NR2B
6-[(1R)-2-[(3aR,6aS)-5-(2-fluorophenoxy)-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrol-2-yl]-1-hydroxyethyl]pyridin-3-ol	IC50	8.5 nM	US-10239835: N-alkylaryl-5-oxyaryl-octahydro-cyclopenta[c]pyrrole negative allosteric modulators of NR2B
4-[2-[(3aR,6aS)-5-(2,4-difluorophenoxy)-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrol-2-yl]-1-hydroxyethyl]phenol	IC50	8.62 nM	US-10239835: N-alkylaryl-5-oxyaryl-octahydro-cyclopenta[c]pyrrole negative allosteric modulators of NR2B
6-[2-[(3aR,6aS)-5-(2,3-difluorophenoxy)-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrol-2-yl]-1-hydroxyethyl]pyridin-3-ol	IC50	8.78 nM	US-10239835: N-alkylaryl-5-oxyaryl-octahydro-cyclopenta[c]pyrrole negative allosteric modulators of NR2B
4-[2-[(3aS,6aR)-5-phenylsulfanyl-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrol-2-yl]-1-hydroxyethyl]phenol	IC50	9.36 nM	US-10239835: N-alkylaryl-5-oxyaryl-octahydro-cyclopenta[c]pyrrole negative allosteric modulators of NR2B
6-[2-[(3aR,6aS)-5-(2,6-difluorophenoxy)-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrol-2-yl]-1-hydroxyethyl]pyridin-3-ol	IC50	9.6 nM	US-10239835: N-alkylaryl-5-oxyaryl-octahydro-cyclopenta[c]pyrrole negative allosteric modulators of NR2B
2-[6-[3-(Difluoromethyl)phenyl]pyrrolo[3,2-b]pyridin-1-yl]-N,N-	IC50	10 nM	US-10377753: Substituted 4-azaindoles and their use as GluN2B receptor modulators
1-(Azetidin-1-yl)-2-[6-(5-methyl-2-thienyl)pyrrolo[3,2-b]pyridin-	IC50	10 nM	US-10377753: Substituted 4-azaindoles and their use as GluN2B receptor modulators
2-[6-(3-Chlorophenyl)-3-fluoro-pyrrolo[3,2-b]pyridin-1-yl]-1-(3-	IC50	10 nM	US-10377753: Substituted 4-azaindoles and their use as GluN2B receptor modulators
2-[3-Chloro-6-(5-chloro-4-methyl-2-thienyl)pyrrolo[3,2-b]pyridin-	IC50	10 nM	US-10377753: Substituted 4-azaindoles and their use as GluN2B receptor modulators
2-[6-(3,5-Difluorophenyl)-3-(trifluoromethyl)pyrrolo[3,2-	IC50	10 nM	US-10377753: Substituted 4-azaindoles and their use as GluN2B receptor modulators
2-[(3aR,6aS)-5-phenoxy-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrol-2-yl]-1-(4-hydroxyphenyl)ethanone	IC50	10.7 nM	US-10239835: N-alkylaryl-5-oxyaryl-octahydro-cyclopenta[c]pyrrole negative allosteric modulators of NR2B
(3aS,6aR)-5-[(4-chlorophenyl)methyl]-2-[2-hydroxy-2-(5-hydroxy-2-pyridinyl)ethyl]-1,3,3a,4,6,6a-hexahydrocyclopenta[c]pyrrol-5-ol	IC50	11.5 nM	US-10052306: Selective octahydro-cyclopenta[C] pyrrole negative modulators of NR2B
4-[2-[(3aS,6aR)-5-benzyl-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrol-2-yl]-1-hydroxyethyl]phenol	IC50	11.7 nM	US-10052306: Selective octahydro-cyclopenta[C] pyrrole negative modulators of NR2B
4-[2-[(3aR,6aS)-5-benzyl-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrol-2-yl]-1-hydroxyethyl]-2-fluorophenol	IC50	12.2 nM	US-10052306: Selective octahydro-cyclopenta[C] pyrrole negative modulators of NR2B
(3aR,6aS)-2-[2-hydroxy-2-(4-hydroxyphenyl)ethyl]-5-(thiophen-2-ylmethyl)-1,3,3a,4,6,6a-hexahydrocyclopenta[c]pyrrol-5-ol	IC50	12.6 nM	US-10052306: Selective octahydro-cyclopenta[C] pyrrole negative modulators of NR2B
1-[3-Fluoro-6-(4-fluoro-3-methyl-phenyl)pyrrolo[3,2-b]pyridin-1-	IC50	12.6 nM	US-10377753: Substituted 4-azaindoles and their use as GluN2B receptor modulators
1-[3-Fluoro-6-(4-methyl-2-thienyl)pyrrolo[3,2-b]pyridin-1-	IC50	12.6 nM	US-10377753: Substituted 4-azaindoles and their use as GluN2B receptor modulators
4-[6-(4-Fluorophenyl)pyrrolo[3,2-b]pyridin-1-yl]butan-2-one;	IC50	12.6 nM	US-10377753: Substituted 4-azaindoles and their use as GluN2B receptor modulators
N,N-Dimethyl-2-[6-(3,4,5-trifluorophenyl)pyrrolo[3,2-b]pyridin-1-	IC50	12.6 nM	US-10377753: Substituted 4-azaindoles and their use as GluN2B receptor modulators
N-Ethyl-2-[6-[2-fluoro-3-(trifluoromethyl)phenyl]pyrrolo[3,2-	IC50	12.6 nM	US-10377753: Substituted 4-azaindoles and their use as GluN2B receptor modulators
1-(3-Fluoroazetidin-1-yl)-2-[3-fluoro-6-[3-	IC50	12.6 nM	US-10377753: Substituted 4-azaindoles and their use as GluN2B receptor modulators
2-(3-Fluoro-6-phenyl-pyrrolo[3,2-b]pyridin-1-yl)-N,N-dimethyl-	IC50	12.6 nM	US-10377753: Substituted 4-azaindoles and their use as GluN2B receptor modulators
2-[6-(3-Chloro-4-fluoro-phenyl)-3-fluoro-pyrrolo[3,2-b]pyridin-1-	IC50	12.6 nM	US-10377753: Substituted 4-azaindoles and their use as GluN2B receptor modulators
2-[3-Chloro-6-(3,5-difluorophenyl)pyrrolo[3,2-b]pyridin-1-yl]-1-	IC50	12.6 nM	US-10377753: Substituted 4-azaindoles and their use as GluN2B receptor modulators
2-[3-Chloro-6-(3-chlorophenyl)pyrrolo[3,2-b]pyridin-1-yl]-1-(3-	IC50	12.6 nM	US-10377753: Substituted 4-azaindoles and their use as GluN2B receptor modulators
4-[2-[(3aR,6aS)-5-(4-fluorophenoxy)-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrol-2-yl]-1-hydroxyethyl]phenol	IC50	13 nM	US-10239835: N-alkylaryl-5-oxyaryl-octahydro-cyclopenta[c]pyrrole negative allosteric modulators of NR2B
4-[2-[(3aS,6aR)-5-benzyl-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrol-2-yl]-1-hydroxyethyl]phenol	IC50	13.9 nM	US-10052306: Selective octahydro-cyclopenta[C] pyrrole negative modulators of NR2B
4-[2-[(3aR,6aS)-5-(3,4-difluorophenoxy)-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrol-2-yl]-1-hydroxyethyl]phenol	IC50	14 nM	US-10239835: N-alkylaryl-5-oxyaryl-octahydro-cyclopenta[c]pyrrole negative allosteric modulators of NR2B
6-[2-[(3aR,6aS)-5-(2-fluoro-4-methylphenoxy)-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrol-2-yl]-1-hydroxyethyl]pyridin-3-ol	IC50	14.4 nM	US-10239835: N-alkylaryl-5-oxyaryl-octahydro-cyclopenta[c]pyrrole negative allosteric modulators of NR2B
(3aS,6aR)-5-[(2-fluorophenyl)methyl]-2-[2-hydroxy-2-(4-hydroxyphenyl)ethyl]-1,3,3a,4,6,6a-hexahydrocyclopenta[c]pyrrol-5-ol	IC50	15.5 nM	US-10052306: Selective octahydro-cyclopenta[C] pyrrole negative modulators of NR2B
2-[3-Chloro-6-(3,4-difluorophenyl)pyrrolo[3,2-b]pyridin-1-yl]-1-	IC50	15.8 nM	US-10377753: Substituted 4-azaindoles and their use as GluN2B receptor modulators
1-[6-[3-(Difluoromethyl)phenyl]-3-fluoro-pyrrolo[3,2-b]pyridin-1-	IC50	15.8 nM	US-10377753: Substituted 4-azaindoles and their use as GluN2B receptor modulators
1-[6-(5-Chloro-2-thienyl)-3-fluoro-pyrrolo[3,2-b]pyridin-1-	IC50	15.8 nM	US-10377753: Substituted 4-azaindoles and their use as GluN2B receptor modulators
N-Cyclopropyl-2-[6-(3,5-difluorophenyl)pyrrolo[3,2-b]pyridin-1-	IC50	15.8 nM	US-10377753: Substituted 4-azaindoles and their use as GluN2B receptor modulators
1-(3-Fluoroazetidin-1-yl)-2-[6-(3,4,5-trifluorophenyl)pyrrolo[3,2-	IC50	15.8 nM	US-10377753: Substituted 4-azaindoles and their use as GluN2B receptor modulators
2-[6-(5-Chloro-2-thienyl)pyrrolo[3,2-b]pyridin-1-yl]-1-(3-	IC50	15.8 nM	US-10377753: Substituted 4-azaindoles and their use as GluN2B receptor modulators
1-(Azetidin-1-yl)-2-[3-chloro-6-(5-chloro-2-thienyl)pyrrolo[3,2-	IC50	15.8 nM	US-10377753: Substituted 4-azaindoles and their use as GluN2B receptor modulators
1-(Azetidin-1-yl)-2-[6-(3,4-difluorophenyl)-3-fluoro-pyrrolo[3,2-	IC50	15.8 nM	US-10377753: Substituted 4-azaindoles and their use as GluN2B receptor modulators
1-(Azetidin-1-yl)-2-[3-fluoro-6-(3,4,5-trifluorophenyl)pyrrolo[3,2-	IC50	15.8 nM	US-10377753: Substituted 4-azaindoles and their use as GluN2B receptor modulators

ChEMBL bioactivities

4741 potent at pChembl≥5 of 4978 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.40	Ki	0.4	nM	CHEMBL416690
9.30	Ki	0.5	nM	CHEMBL423244
9.30	IC50	0.5	nM	CHEMBL276708
9.22	Ki	0.6	nM	CHEMBL159675
9.22	Ki	0.6	nM	CHEMBL161180
9.22	Ki	0.6	nM	DITOLYLGUANIDINE
9.17	Ki	0.68	nM	CHEMBL65693
9.15	Ki	0.7	nM	CHEMBL158737
9.15	IC50	0.7	nM	CHEMBL274422
9.14	IC50	0.72	nM	CHEMBL65693
9.10	Ki	0.8	nM	CHEMBL159762
9.10	IC50	0.8	nM	CHEMBL12513
9.09	Ki	0.82	nM	CHEMBL65454
9.07	Ki	0.85	nM	CHEMBL68134
9.02	Ki	0.96	nM	CHEMBL39881
9.00	Ki	1	nM	CHEMBL159761
9.00	Kd	1	nM	CHEMBL158737
9.00	IC50	1	nM	CHEMBL5916023
9.00	IC50	1	nM	CHEMBL5924093
9.00	IC50	1	nM	CHEMBL5958626
9.00	IC50	1	nM	CHEMBL5963003
9.00	IC50	1	nM	CHEMBL5824795
9.00	IC50	1	nM	CHEMBL5795644
9.00	IC50	1	nM	CHEMBL5820376
9.00	IC50	1	nM	CHEMBL5994695
9.00	IC50	1	nM	CHEMBL5499329
9.00	IC50	1	nM	CHEMBL6056265
9.00	IC50	1	nM	CHEMBL5992919
9.00	IC50	1	nM	CHEMBL5929772
9.00	IC50	1	nM	CHEMBL5904651
9.00	IC50	1	nM	CHEMBL12804
9.00	Ki	0.99	nM	CHEMBL436521
8.96	Ki	1.1	nM	CHEMBL64941
8.92	Ki	1.2	nM	CHEMBL159744
8.92	IC50	1.2	nM	CHEMBL12242
8.92	Ki	1.2	nM	DIZOCILPINE
8.89	Ki	1.3	nM	CHEMBL159416
8.85	Ki	1.4	nM	CHEMBL159902
8.85	Ki	1.4	nM	CHEMBL159453
8.85	Ki	1.4	nM	CHEMBL5185347
8.85	IC50	1.4	nM	CHEMBL436521
8.82	Ki	1.5	nM	CHEMBL65231
8.82	IC50	1.5	nM	CHEMBL537478
8.82	IC50	1.5	nM	CHEMBL274422
8.82	IC50	1.5	nM	CHEMBL273662
8.80	Ki	1.6	nM	CHEMBL159790
8.80	Ki	1.6	nM	CHEMBL3735947
8.80	EC50	1.6	nM	CHEMBL219060
8.77	Ki	1.7	nM	CHEMBL160027
8.77	IC50	1.7	nM	CHEMBL269683

PubChem BioAssay actives

1118 with measured affinity, of 2208 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-[[4-[(4-methylphenyl)methyl]piperidin-1-yl]methyl]-3H-benzimidazol-5-ol	146213: Compound was evaluated for in vitro inhibition of [3H][(E)-N-(2-methoxybenzyl)cinnamamidine binding to human NR1a/NR2B receptors expressed in LtK-cells	ki	0.0004	uM
(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
(E)-N’-[(2-ethoxyphenyl)methyl]-3-phenylprop-2-enimidamide	144050: Displacement of [3H]ifenprodil binding to recombinant human NR1a/NR2B receptors expressed in L(tk-) cells	ki	0.0005	uM
(E)-3-phenyl-N’-[[2-(trifluoromethoxy)phenyl]methyl]prop-2-enimidamide	144050: Displacement of [3H]ifenprodil binding to recombinant human NR1a/NR2B receptors expressed in L(tk-) cells	ki	0.0006	uM
N’-[(3,5-dichlorophenyl)methyl]-4-(trifluoromethoxy)benzenecarboximidamide	143916: Displacement of NMDA receptor-specific [3H]ifenprodil binding to recombinant human NMDA receptor, NR2B subtype expressed in L cells	ki	0.0006	uM
[(2,3-dioxo-1,4-dihydroquinoxalin-5-yl)-hydroxymethyl]phosphonic acid	144694: Inhibitory activity against Xenopus laevis oocyte expressing 1A/2B heteromeric human NMDA (hNMDA) receptor	ic50	0.0007	uM
N-[2-[(4-phenoxyphenyl)methyl]-3H-benzimidazol-5-yl]methanesulfonamide	102503: In vitro inhibition of Glu/Gly stimulated [Ca2+] influx in LtK-cells expressing the hNR1a/NR2B receptor	ic50	0.0007	uM
(E)-N’-[(2-methoxyphenyl)methyl]-3-phenylprop-2-enimidamide	143916: Displacement of NMDA receptor-specific [3H]ifenprodil binding to recombinant human NMDA receptor, NR2B subtype expressed in L cells	ki	0.0007	uM
2-[[4-[(2,6-difluorophenyl)methyl]piperidin-1-yl]methyl]-3H-benzimidazol-5-ol	146213: Compound was evaluated for in vitro inhibition of [3H][(E)-N-(2-methoxybenzyl)cinnamamidine binding to human NR1a/NR2B receptors expressed in LtK-cells	ki	0.0008	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
2-[[4-[(2-fluorophenyl)methyl]piperidin-1-yl]methyl]-3H-benzimidazol-5-ol	146213: Compound was evaluated for in vitro inhibition of [3H][(E)-N-(2-methoxybenzyl)cinnamamidine binding to human NR1a/NR2B receptors expressed in LtK-cells	ki	0.0008	uM
(E)-N’-[(3-chlorophenyl)methyl]-3-phenylprop-2-enimidamide	144050: Displacement of [3H]ifenprodil binding to recombinant human NR1a/NR2B receptors expressed in L(tk-) cells	ki	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
N-[2-[(4-benzylpiperidin-1-yl)methyl]-3H-benzimidazol-5-yl]methanesulfonamide	146213: Compound was evaluated for in vitro inhibition of [3H][(E)-N-(2-methoxybenzyl)cinnamamidine binding to human NR1a/NR2B receptors expressed in LtK-cells	ki	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
(E)-N’-[(2-chlorophenyl)methyl]-3-phenylprop-2-enimidamide	144050: Displacement of [3H]ifenprodil binding to recombinant human NR1a/NR2B receptors expressed in L(tk-) cells	ki	0.0010	uM
2-[[4-[(4-fluorophenyl)methyl]piperidin-1-yl]methyl]-3H-benzimidazol-5-ol	146213: Compound was evaluated for in vitro inhibition of [3H][(E)-N-(2-methoxybenzyl)cinnamamidine binding to human NR1a/NR2B receptors expressed in LtK-cells	ki	0.0011	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
N’-[(3,5-dimethylphenyl)methyl]-4-(trifluoromethoxy)benzenecarboximidamide	143916: Displacement of NMDA receptor-specific [3H]ifenprodil binding to recombinant human NMDA receptor, NR2B subtype expressed in L cells	ki	0.0012	uM
N’-[(2-methoxyphenyl)methyl]naphthalene-2-carboximidamide	144050: Displacement of [3H]ifenprodil binding to recombinant human NR1a/NR2B receptors expressed in L(tk-) cells	ki	0.0013	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
(E)-N’-[(3,5-dichlorophenyl)methyl]-3-phenylprop-2-enimidamide	144050: Displacement of [3H]ifenprodil binding to recombinant human NR1a/NR2B receptors expressed in L(tk-) cells	ki	0.0014	uM
(E)-3-phenyl-N’-[[2-(trifluoromethyl)phenyl]methyl]prop-2-enimidamide	144050: Displacement of [3H]ifenprodil binding to recombinant human NR1a/NR2B receptors expressed in L(tk-) cells	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
[(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
2-[(4-benzylpiperidin-1-yl)methyl]-3H-benzimidazol-5-ol	146213: Compound was evaluated for in vitro inhibition of [3H][(E)-N-(2-methoxybenzyl)cinnamamidine binding to human NR1a/NR2B receptors expressed in LtK-cells	ki	0.0015	uM
3-nitro-N-(3-phenylpropyl)-6,7,8,9-tetrahydro-5H-benzo[7]annulen-7-amine	1262298: Displacement of [3H]ifenprodil from Glun2B receptor (unknown origin) expressed in mouse L(tk-) cell membranes after 120 mins by scintillation counting analysis	ki	0.0016	uM
N’-[(3-chlorophenyl)methyl]naphthalene-2-carboximidamide	144050: Displacement of [3H]ifenprodil binding to recombinant human NR1a/NR2B receptors expressed in L(tk-) cells	ki	0.0016	uM
benzyl 4-[(pyridin-4-ylamino)methyl]piperidine-1-carboxylate	277225: Antagonist activity at human NR2B expressed in Ltk- cells by calcium flux assay	ec50	0.0016	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
(E)-N’-benzyl-3-(3,4-difluorophenyl)prop-2-enimidamide	144050: Displacement of [3H]ifenprodil binding to recombinant human NR1a/NR2B receptors expressed in L(tk-) cells	ki	0.0017	uM
2-[[1-[4-chloro-3-(difluoromethoxy)phenyl]triazol-4-yl]methoxy]-5-methylpyrimidine	1967556: Negative allosteric modulation of human GluN1A/GluN2B receptor expressed in T-REX-CHO cells preincubated for 5 mins followed by glutamate and glycine addition and measured after 5 mins by FLIPR assay	ic50	0.0019	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
(E)-N’-[(3-methoxyphenyl)methyl]-3-phenylprop-2-enimidamide	144050: Displacement of [3H]ifenprodil binding to recombinant human NR1a/NR2B receptors expressed in L(tk-) cells	ki	0.0019	uM
2-[4-[(4-fluorophenyl)methyl]piperidin-1-yl]-2-oxo-N-(2-oxo-1,3-dihydrobenzimidazol-5-yl)acetamide	242374: Inhibition of NMDA-evoked increased intracellular [Ca2+] in cells expressing NR1/NR2B receptor	ic50	0.0020	uM
2-[2-deuterio-6-(4-fluoro-3-methylphenyl)pyrrolo[3,2-b]pyridin-1-yl]-N,N-dimethylacetamide	1379888: Modulation of recombinant human GluN1/GluN2B NMDA receptor expressed in mammalian cells assessed as inhibition of glutamate/glycine-induced intracellular calcium flux pretreated for 5 mins followed by glutamate/glycine addition measured after 5 mins by calcium 5 dye based FLIPR assay	ic50	0.0020	uM
1-[4-(4-cyclohexylpiperazin-1-yl)butyl]-3,4-dihydroquinolin-2-one	1511006: Displacement of [3H]ifenprodil from GluN1a/GluN2B (unknown origin) expressed in mouse L(tk-) cell membranes after 120 mins by solid scintillation counting method	ki	0.0020	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-[(3,5-dimethylphenyl)methyl]-5-(trifluoromethoxy)-3H-isoindol-1-imine	307754: Binding affinity to NMDA NR2B receptor	ki	0.0020	uM
3-chloro-N-(3-phenylpropyl)-6,7,8,9-tetrahydro-5H-benzo[7]annulen-7-amine	1650557: Displacement of [3H]ifenprodil from human recombinant GluN2B expressed in mouse L(tk-) cell membranes co-expressing GluN1a incubated for 120 mins by scintillation counting method	ki	0.0021	uM
N-[2-[(4-phenoxyphenyl)methyl]-3H-benzimidazol-5-yl]ethanesulfonamide	102503: In vitro inhibition of Glu/Gly stimulated [Ca2+] influx in LtK-cells expressing the hNR1a/NR2B receptor	ic50	0.0021	uM
2-(1-benzofuran-7-ylmethyl)-5-(trifluoromethoxy)-3H-isoindol-1-imine	307754: Binding affinity to NMDA NR2B receptor	ki	0.0022	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
N-(4-phenylcyclohexyl)-6,7,8,9-tetrahydro-5H-benzo[7]annulen-7-amine	1174070: Displacement of [3H]ifenprodil from human GluN2B expressed in mouse L(tk-) cells co-expressing GluN1a after 120 mins by scintillation counting method	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
(E)-N’-[(2,5-dichlorophenyl)methyl]-3-phenylprop-2-enimidamide	144050: Displacement of [3H]ifenprodil binding to recombinant human NR1a/NR2B receptors expressed in L(tk-) cells	ki	0.0027	uM
4-benzyl-1-(6,7,8,9-tetrahydro-5H-benzo[7]annulen-7-yl)piperidine	1174070: Displacement of [3H]ifenprodil from human GluN2B expressed in mouse L(tk-) cells co-expressing GluN1a after 120 mins by scintillation counting method	ki	0.0029	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, increases expression	3
bisphenol A	affects cotreatment, decreases methylation, affects methylation	2
Aflatoxin B1	decreases methylation, increases methylation	2
Excitatory Amino Acid Agonists	affects cotreatment, increases response to substance, decreases expression	2
arsenite	increases methylation	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	affects methylation	1
conotoxin GV	affects cotreatment, decreases activity	1
polyhexamethyleneguanidine	affects expression	1
notoginsenoside R1	affects cotreatment, increases response to substance	1
CGP 52608	affects binding, increases reaction	1
asparanin A	decreases expression	1
kukoamine B	affects binding, decreases reaction, increases expression	1
(+)-JQ1 compound	decreases expression	1
Resveratrol	decreases expression, affects cotreatment	1
Sunitinib	decreases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Leflunomide	decreases expression	1
Cyclic AMP	affects cotreatment, increases expression	1
Ascorbic Acid	affects cotreatment, increases expression	1
Methapyrilene	increases methylation	1
Plant Extracts	affects cotreatment, decreases expression	1
Sarin	increases expression	1
Silver	decreases expression	1
Dronabinol	decreases expression	1
Tretinoin	increases expression	1
Valproic Acid	increases methylation	1
N-Methylaspartate	decreases reaction, increases expression	1
Dizocilpine Maleate	affects cotreatment, increases response to substance	1
Asbestos, Crocidolite	decreases expression	1

ChEMBL screening assays

471 unique, capped per target: 429 binding, 36 functional, 5 admet, 1 toxicity

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1047321	Functional	Antagonistic activity against NR2B receptor expressed in mouse Ltk cells assessed as inhibition of calcium influx by FLIPR assay	Synthesis and evaluation of novel tricyclic benzo[4.5]cyclohepta[1.2]pyridine derivatives as NMDA/NR2B antagonists. — Bioorg Med Chem Lett
CHEMBL2013395	Binding	Displacement of [3H]-Ro256981 from human NR2B receptor	A novel series of benzimidazole NR2B-selective NMDA receptor antagonists. — Bioorg Med Chem Lett
CHEMBL3871166	ADMET	Positive allosteric modulation of GluN1/GluN2B receptor (unknown origin) expressed in HEK293 cells assessed as increase in glutamate-induced calcium flux at 125 uM measured at time interval of 5 mins in presence of saturating glycine by cal	GluN2A-Selective Pyridopyrimidinone Series of NMDAR Positive Allosteric Modulators with an Improved in Vivo Profile. — ACS Med Chem Lett

Cellosaurus cell lines

10 cell lines: 5 cancer cell line, 3 induced pluripotent stem cell, 1 spontaneously immortalized cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B3TZ	CHO-hGluN1-hGluN2B	Spontaneously immortalized cell line	Female
CVCL_C9D3	B’SYS HEK 293 NMDA NR1/NR2B	Transformed cell line	Female
CVCL_D1SY	Abcam U-87MG GRIN2B KO	Cancer cell line	Male
CVCL_D1WN	Abcam A-549 GRIN2B KO	Cancer cell line	Male
CVCL_D2B1	Abcam HCT 116 GRIN2B KO	Cancer cell line	Male
CVCL_D7QY	Ubigene A-549 GRIN2B KO	Cancer cell line	Male
CVCL_D8M3	Ubigene HCT 116 GRIN2B KO	Cancer cell line	Male
CVCL_E4CM	GM07492 iPSC GRIN2B LOF	Induced pluripotent stem cell	Male
CVCL_E4CN	GM07492 iPSC GRIN2B RD	Induced pluripotent stem cell	Male
CVCL_VN40	TUSMi006-A	Induced pluripotent stem cell	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01413711	PHASE4	WITHDRAWN	An Open-Label, Single and Multiple Oral Dose Pharmacokinetic Study of Vigabatrin in Infants With Infantile Spasms
NCT02092883	PHASE4	COMPLETED	Evaluation of Neuroinflammation in Children With Infantile Spasms
NCT00154830	PHASE4	COMPLETED	Alterations of Functional Activities and Leg Stiffness After Hamstring Lengthening in Cerebral Palsy Children
NCT00432055	PHASE4	COMPLETED	Effects of Botulinum Toxin Type A in Adults With Cerebral Palsy
NCT00549471	PHASE4	TERMINATED	Improvement After Botulinum Toxin Injections to the Arms in Children With Cerebral Palsy
NCT00752934	PHASE4	TERMINATED	Does Oral Baclofen Improve Care and Comfort in Spastic Children in Nursing Homes?
NCT00964639	PHASE4	COMPLETED	Postoperative Pain in Children With Cerebral Palsy After Pelvic and Femoral Osteotomies
NCT01386255	PHASE4	WITHDRAWN	Placebo Controlled Study of Baclofen for GERD in Children With Cerebral Palsy
NCT02546999	PHASE4	COMPLETED	Does Botulinum Toxin A Make Walking Easier in Children With Cerebral Palsy?
NCT02633241	PHASE4	COMPLETED	A Pilot Study of Dexmedetomidine-Propofol in Children Undergoing Magnetic Resonance Imaging
NCT03117322	PHASE4	COMPLETED	Synbiotic, Prebiotics and Probiotics in Children With Cerebral Palsy and Constipation
NCT03648658	PHASE4	UNKNOWN	Paracetamol Study in Patients With Low Muscle Mass
NCT04074265	PHASE4	COMPLETED	Peri-operative Use of a Pain Injection in Pediatric Patients With Cerebral Palsy
NCT04273737	PHASE4	TERMINATED	Amantadine in Treating Cognitive & Motor Impairments in Adolescents and Adults With Cerebral Palsy
NCT04523935	PHASE4	COMPLETED	Excessive Crying in Children With Cerebral Palsy and Communication Deficits
NCT05887765	PHASE4	COMPLETED	Effect of Systematic Dexamethasone on the Duration of Popliteal Nerve Block for Anesthesia After Pediatric Ankle Surgery
NCT06176430	PHASE4	UNKNOWN	Comparison of Twice Weekly Versus Daily Iron Therapy in Treating Anemia in Children With Cerebral Palsy
NCT06189781	PHASE4	RECRUITING	Pain Injection Versus Epidural Anesthesia for Hip Surgery in Pediatric Patients With Cerebral Palsy
NCT01575639	PHASE3	COMPLETED	Prednisolone in Infantile Spasms- High Dose Versus Usual Dose
NCT01828437	PHASE3	COMPLETED	Addition of Pyridoxine to Prednisolone in Infantile Spasms
NCT02299115	PHASE3	WITHDRAWN	Prednisolone Versus Vigabatrin in the First-line Treatment of Infantile Spasms
NCT02953548	PHASE3	COMPLETED	Trial of Cannabidiol (CBD; GWP42003-P) for Infantile Spasms (GWPCARE7)
NCT02954887	PHASE3	COMPLETED	Phase 3 Trial of Cannabidiol (CBD; GWP42003-P) for Infantile Spasms: Open-label Extension Phase (GWPCARE7)
NCT00014989	PHASE3	COMPLETED	Beneficial Effects of Antenatal Magnesium Sulfate (BEAM Trial)
NCT00065949	PHASE3	UNKNOWN	Magnesium Sulfate to Prevent Brain Injury in Premature Infants
NCT00367068	PHASE3	COMPLETED	Dutch National ITB Study in Children With Cerebral Palsy
NCT00491894	PHASE3	COMPLETED	Safety and Efficacy Study of Oral Glycopyrrolate Liquid for the Treatment of Pathologic (Chronic Moderate to Severe) Drooling in Pediatric Patients 3 to 18 Years of Age With Cerebral Palsy or Other Neurologic Conditions
NCT00632528	PHASE3	COMPLETED	MEOPA to Improve Physical Therapy Results After Multilevel Surgery
NCT00822029	PHASE3	TERMINATED	Use of Oral Bisphosphonates in the Treatment of Osteoporosis of Non-walking Children With Cerebral Palsy
NCT00922077	PHASE3	COMPLETED	Individualized Neurodevelopmental Treatment
NCT01249417	PHASE3	COMPLETED	Dysport® Pediatric Lower Limb Spasticity Study
NCT01251380	PHASE3	COMPLETED	Dysport® Pediatric Lower Limb Spasticity Follow-on Study
NCT01437644	PHASE3	COMPLETED	The Post-Operative Pain in Cerebral Palsy (POPPIES) Trial
NCT01492608	PHASE3	COMPLETED	Magnesium Sulphate for Preterm Birth (MASP Study)
NCT01603602	PHASE3	COMPLETED	BOTOX® Treatment in Pediatric Upper Limb Spasticity
NCT01603615	PHASE3	COMPLETED	BOTOX® Open-Label Treatment in Pediatric Upper Limb Spasticity
NCT01603628	PHASE3	COMPLETED	BOTOX® Treatment in Pediatric Lower Limb Spasticity
NCT01603641	PHASE3	COMPLETED	BOTOX® Open-Label Treatment in Pediatric Lower Limb Spasticity
NCT01633736	PHASE3	UNKNOWN	Targeted Hip Strength Training in Children With Cerebral Palsy (CP)
NCT01898520	PHASE3	COMPLETED	A Safety, Efficacy and Tolerability Study of Sativex for the Treatment of Spasticity in Children Aged 8 to 18 Years