◎ Sugi Atlas

Atlas / Gene / GRIK1

GRIK1

gene
On this page

Also known as GluK1

Summary

GRIK1 (glutamate ionotropic receptor kainate type subunit 1, HGNC:4579) is a protein-coding gene on chromosome 21q21.3, encoding Glutamate receptor ionotropic, kainate 1 (P39086). Ionotropic glutamate receptor that functions as a cation-permeable ligand-gated ion channel, gated by L-glutamate and the glutamatergic agonist kainic acid.

Glutamate receptors are the predominant excitatory neurotransmitter receptors in the mammalian brain and are activated in a variety of normal neurophysiologic processes. This gene product belongs to the kainate family of glutamate receptors, which are composed of four subunits and function as ligand-activated ion channels. The subunit encoded by this gene is subject to RNA editing (CAG->CGG; Q->R) within the second transmembrane domain, which is thought to alter the properties of ion flow. Alternative splicing, resulting in transcript variants encoding different isoforms, has been noted for this gene.

Source: NCBI Gene 2897 — RefSeq curated summary.

At a glance

  • GWAS associations: 16
  • Clinical variants (ClinVar): 171 total
  • Druggable target: yes — 3 molecules with ChEMBL bioactivity
  • MANE Select transcript: NM_001330994

Identifiers

Gene identifiers

FieldValue
HGNC IDHGNC:4579
Approved symbolGRIK1
Nameglutamate ionotropic receptor kainate type subunit 1
Location21q21.3
Locus typegene with protein product
StatusApproved
AliasesGluK1
Ensembl geneENSG00000171189
Ensembl biotypeprotein_coding
OMIM138245
Entrez2897

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 7 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000327783, ENST00000389124, ENST00000389125, ENST00000399907, ENST00000399909, ENST00000399913, ENST00000399914, ENST00000472429

RefSeq mRNA: 12 — MANE Select: NM_001330994 NM_000830, NM_001320616, NM_001320618, NM_001320621, NM_001320630, NM_001330993, NM_001330994, NM_001393424, NM_001393425, NM_001393426, NM_001410706, NM_175611

CCDS: CCDS33530, CCDS42913, CCDS82656, CCDS82658, CCDS82659, CCDS93084

Canonical transcript exons

ENST00000327783 — 18 exons

ExonStartEnd
ENSE000011372662959883029598937
ENSE000011433632956162429561849
ENSE000011433912958883929589042
ENSE000011433982959111229591225
ENSE000011920272955505229555302
ENSE000013138122959652629596570
ENSE000015407502953693329537385
ENSE000015407552953779829537884
ENSE000016257312958142529581543
ENSE000016406092958736629587589
ENSE000017781842957696429577181
ENSE000034681562967298329673164
ENSE000034780562965111829651291
ENSE000035046572965481029654863
ENSE000036044332969389629694063
ENSE000036802982964282629642969
ENSE000036807412968972829689985
ENSE000039293042993938329939996

Expression profiles

Bgee: expression breadth ubiquitous, 183 present calls, max score 81.90.

FANTOM5 (CAGE): breadth broad, TPM avg 2.1370 / max 309.4253, expressed in 195 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter IDTPM avgSamples expressed
1900981.2868163
1900990.2795116
1900970.2574100
1901000.197193
1900940.084457
1900950.02168
1900960.01024

Top tissues by expression

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

TissueAnatomy IDExpression scoreQuality
male germ line stem cell (sensu Vertebrata) in testisCL:0000089 ∩ UBERON:000047381.90gold quality
cingulate cortexUBERON:000302780.79gold quality
anterior cingulate cortexUBERON:000983580.70gold quality
amygdalaUBERON:000187679.19gold quality
prefrontal cortexUBERON:000045178.28gold quality
dorsolateral prefrontal cortexUBERON:000983478.02gold quality
frontal poleUBERON:000279577.99gold quality
hypothalamusUBERON:000189877.92gold quality
paraflocculusUBERON:000535177.92silver quality
right frontal lobeUBERON:000281077.78gold quality
Brodmann (1909) area 9UBERON:001354076.54gold quality
neocortexUBERON:000195076.36gold quality
middle frontal gyrusUBERON:000270276.04gold quality
frontal cortexUBERON:000187075.80gold quality
ponsUBERON:000098875.41gold quality
cerebral cortexUBERON:000095675.39gold quality
buccal mucosa cellCL:000233675.33silver quality
Ammon’s hornUBERON:000195475.25gold quality
temporal lobeUBERON:000187174.30gold quality
telencephalonUBERON:000189373.61gold quality
Brodmann (1909) area 10UBERON:001354173.47gold quality
primary visual cortexUBERON:000243673.18gold quality
right hemisphere of cerebellumUBERON:001489072.15gold quality
middle temporal gyrusUBERON:000277171.60silver quality
caudate nucleusUBERON:000187371.14gold quality
forebrainUBERON:000189071.11gold quality
adrenal tissueUBERON:001830370.77gold quality
brainUBERON:000095570.63gold quality
putamenUBERON:000187470.52gold quality
central nervous systemUBERON:000101770.49gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 6.

ExperimentMarker?Max mean expression
E-HCAD-35yes5268.25
E-HCAD-25yes5097.94
E-HCAD-30yes4871.15
E-GEOD-137537yes850.54
E-MTAB-7316yes769.53
E-MTAB-11121yes522.51
E-ANND-3no5.35

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F6, ESR1

miRNA regulators (miRDB)

129 targeting GRIK1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNAMax scoreAvg scoremiRNA target_count
HSA-MIR-4481100.0066.421669
HSA-MIR-5692A100.0074.406850
HSA-MIR-3646100.0073.565283
HSA-MIR-3134100.0066.43777
HSA-MIR-196A-5P100.0068.16684
HSA-MIR-196B-5P100.0068.16681
HSA-MIR-3163100.0077.238605
HSA-MIR-4747-5P100.0067.902681
HSA-MIR-5196-5P100.0067.982761
HSA-MIR-186-5P99.9970.833707
HSA-MIR-223-3P99.9970.141140
HSA-MIR-4745-5P99.9865.951028
HSA-MIR-548P99.9872.253784
HSA-MIR-4482-3P99.9872.503147
HSA-MIR-569699.9872.364487
HSA-MIR-314899.9775.066478
HSA-MIR-3065-5P99.9771.563281
HSA-MIR-1250-3P99.9670.044038
HSA-MIR-570-3P99.9672.414910
HSA-MIR-365899.9673.874379
HSA-MIR-302E99.9670.742669
HSA-MIR-3605-5P99.9667.12932
HSA-MIR-9-3P99.9670.882068
HSA-MIR-335-3P99.9373.364958
HSA-MIR-314399.9371.963104
HSA-MIR-6753-3P99.9366.57637
HSA-MIR-7107-3P99.9366.73627
HSA-MIR-568099.9169.833421
HSA-MIR-464899.9167.00710
HSA-MIR-219A-5P99.9173.36735

Literature-anchored findings (GeneRIF, showing 24)

  • GRIK1 does not play a major role in schizophrenia pathogenesis in the Japanese population (PMID:11702055)
  • there are trafficking signals in the C-terminal domain of GluR5-2b; alternative splicing is an important mechanism regulating KAR function (PMID:14527949)
  • Two amino acids,competitive GluR5 KA receptor antagonists, exhibited high GluR5 receptor affinity over other glutamate receptors. (PMID:15974569)
  • This kainate receptor subunit appears to be selectively altered in the anterior cingulate cortex in schizophrenia and bipolar disorder. (PMID:17698324)
  • Variation in the 3’ portion of the gene encoding the GluR5 kainate receptor subunit contributes to the risk for alcohol dependence. (PMID:19320626)
  • GluK1 kainate receptor polymorphisms are associated with Down syndrome. (PMID:19893199)
  • findings show GluR5 was upregulated in the hippocampus, but not in the temporal neocortex, of patients with temporal lobe epilepsy (TLE)compared to controls; mossy fiber sprouting in the hippocampus of TLE patients was correlated with GluR5 upregulation (PMID:19941835)
  • The GRIK1 promoter is activated by Trichostatin A (TSA) treatment and by serum depletion according to promoter reporter assays in HEK 293 cells. (PMID:20494980)
  • Presynaptic Gluk1 kainate receptors that reduce transmitter release downstream are independent of divalent calcium ion Ca2+ influx. (PMID:20848601)
  • The amino acid sequence of the GluK1 kainate receptor near or within the carboxyl-terminal endoplasmic reticulum retention signal sequence, which affects receptor trafficking and/or expression, does not affect channel gating properties. (PMID:22191429)
  • GRIK1 rs469472 to be possibly associated with schizophrenia in our independent case-control and family samples (PMID:22730074)
  • The association at rs455804 implicates GRIK1 as a novel susceptibility gene for HBV-related HCC, suggesting the involvement of glutamate signaling in the development of HBV-related HCC. (PMID:22807686)
  • Using the SNaPshot assay, we present evidence for allelic nondisjunction at rs363506 in the GRIK1 gene and rs2834235 and rs7283354 in the GARS-AIRS-GART gene in Down syndrome in India. (PMID:22931243)
  • Reduced Homer binding to mGluR5 supports an inhibitory role for Homer interactions with mGluR5 in mediating neuropathy. (PMID:23685007)
  • Topiramate treatment for alcohol dependence was significantly more effective in rs2832407 C-allele homozygotes. (PMID:24525690)
  • This found that, among rs2832407*C of GRIK1 homozygotes, topiramate treatment produced the greatest reductions in the expected positive effects of drinking and desire to drink during the treatment period. (PMID:24786948)
  • These results suggest that the effect of topiramate on drinking behavior, in which the GluK1-containing kainate receptor appears to play a key role, can be dissociated from its effect on weight. (PMID:24978347)
  • The findings reported here suggest that, in participants with the GRIK1 rs2832407*CC genotype, topiramate treatment enhances self-efficacy and reduces heavy drinking. (PMID:25496338)
  • In the present study, we have shown that gene-gene interaction of components of different systems associated with nicotine reinforcing effects, such as OPRM1 and GRIK1, rather than one gene polymorphism, is associated with smoking behavior. (PMID:25941919)
  • Results suggested that the extracellular N-terminal region including the two CUB domains was largely responsible for the distinct regulatory effects of Neto1 and Neto2 on the desensitization properties of GluK1 homomeric receptors (PMID:26277340)
  • Findings indicate that SNPs in the GRIK1 gene is associated with altered cue-induced brain activation that is related to craving for alcohol and relapse risk. (PMID:26289945)
  • DRD2 A2/A1, DRD3 Ser9Gly, DbetaH -1021C>T, OPRM1 A118G and GRIK1 rs2832407C>A are not associated with alcoholism alone or in interaction. (PMID:27447243)
  • In vivo hippocampal cornu ammonis 1-3 glutamatergic abnormalities are associated with temporal lobe epilepsy surgery outcomes. (PMID:34060082)
  • Kainate receptor subunit 1 (GRIK1) risk variants and GRIK1 deficiency were detected in the Indian ADHD probands. (PMID:36323684)

Cross-species orthologs

43 orthologs

OrganismSymbolGene ID
danio_reriogrik1bENSDARG00000040627
danio_reriogrik1aENSDARG00000069139
mus_musculusGrik1ENSMUSG00000022935
rattus_norvegicusGrik1ENSRNOG00000001575
drosophila_melanogasterGluRIAFBGN0004619
drosophila_melanogasterGluRIIAFBGN0004620
drosophila_melanogasterGluRIIBFBGN0020429
drosophila_melanogasterclumsyFBGN0026255
drosophila_melanogasterGluRIIDFBGN0028422
drosophila_melanogasterIr7bFBGN0029965
drosophila_melanogasterIr7cFBGN0029966
drosophila_melanogasterIr7gFBGN0029968
drosophila_melanogasterIr25aFBGN0031634
drosophila_melanogasterIr60aFBGN0034994
drosophila_melanogasterIr64aFBGN0035604
drosophila_melanogasterIr68aFBGN0036150
drosophila_melanogasterIr68bFBGN0036250
drosophila_melanogasterIr75aFBGN0036757
drosophila_melanogasterIr75dFBGN0036829
drosophila_melanogasterIr76bFBGN0036937
drosophila_melanogasterIr84aFBGN0037501
drosophila_melanogasterIr85aFBGN0037630
drosophila_melanogasterIr92aFBGN0038789
drosophila_melanogasterGrikFBGN0038840
drosophila_melanogasterEkarFBGN0039916
drosophila_melanogasterCG11155FBGN0039927
drosophila_melanogasterIr41aFBGN0040849
drosophila_melanogasterGluRIICFBGN0046113
drosophila_melanogasterGluRIIEFBGN0051201
drosophila_melanogasterNmdar2FBGN0053513
drosophila_melanogasterIr7eFBGN0259189
drosophila_melanogasterIr94dFBGN0259193
drosophila_melanogasterIr93aFBGN0259215
drosophila_melanogasterIr40aFBGN0259683
drosophila_melanogasterIr76aFBGN0260874
drosophila_melanogasterIr75cFBGN0261401
drosophila_melanogasterIr75bFBGN0261402
drosophila_melanogasterGluRIBFBGN0264000
caenorhabditis_elegansWBGENE00001612
caenorhabditis_elegansglr-3WBGENE00001614
caenorhabditis_elegansWBGENE00001618
caenorhabditis_elegansWBGENE00003775
caenorhabditis_elegansWBGENE00012190

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), GRIN1 (ENSG00000176884), GRID1 (ENSG00000182771), GRIN2A (ENSG00000183454), GRIN3A (ENSG00000198785), GRIN2B (ENSG00000273079)

Protein

Protein identifiers

Glutamate receptor ionotropic, kainate 1 — P39086 (reviewed: P39086)

Alternative names: Excitatory amino acid receptor 3, Glutamate receptor 5

All UniProt accessions (6): E7ENK3, E7EPY9, E7EPZ0, E9PD61, P39086, H7BYG7

UniProt curated annotations — full annotation on UniProt →

Function. Ionotropic glutamate receptor that functions as a cation-permeable ligand-gated ion channel, gated by L-glutamate and the glutamatergic agonist kainic acid. L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system. Binding of the excitatory neurotransmitter L-glutamate induces a conformation change, leading to the opening of the cation channel, and thereby converts the chemical signal to an electrical impulse. The receptor then desensitizes rapidly and enters a transient inactive state, characterized by the presence of bound agonist. Ionotropic glutamate receptor that functions as a cation-permeable ligand-gated ion channel, gated by L-glutamate and the glutamatergic agonist kainic acid.

Subunit / interactions. Homotetramer or heterotetramer of pore-forming glutamate receptor subunits. Tetramers may be formed by the dimerization of dimers. Can form functional heteromeric receptors with GRIK5. Can form functional heteromeric receptors with GRIK4. Interacts with KLHL17.

Subcellular location. Cell membrane. Postsynaptic cell membrane.

Miscellaneous. The postsynaptic actions of Glu are mediated by a variety of receptors that are named according to their selective agonists. This receptor binds domoate > kainate > L-glutamate = quisqualate > CNQX = DNQX > AMPA > dihydrokainate > NMDA.

Similarity. Belongs to the glutamate-gated ion channel (TC 1.A.10.1) family. GRIK1 subfamily.

Isoforms (2)

UniProt IDNamesCanonical?
P39086-11, GluR5-1Dyes
P39086-22, EAA3A

RefSeq proteins (11): NP_000821, NP_001307545, NP_001307547, NP_001307550, NP_001317922, NP_001317923, NP_001380353, NP_001380354, NP_001380355, NP_001397635, NP_783300 (=MANE)

Domains & families (InterPro)

IDNameType
IPR001320Iontro_rcpt_CDomain
IPR001508Iono_Glu_rcpt_metFamily
IPR001828ANF_lig-bd_rcptDomain
IPR015683Ionotropic_Glu_rcptFamily
IPR019594Glu/Gly-bdDomain
IPR028082Peripla_BP_IHomologous_superfamily

Pfam: PF00060, PF01094, PF10613

Catalyzed reactions (Rhea), 1 shown:

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

UniProt features (63 total): strand 14, helix 12, glycosylation site 9, binding site 6, sequence variant 6, topological domain 4, transmembrane region 3, modified residue 2, splice variant 2, signal peptide 1, chain 1, disulfide bond 1, sequence conflict 1, turn 1

Structure

Experimental structures (PDB)

11 structures.

PDBMethodResolution (Å)
3FV1X-RAY DIFFRACTION1.5
3FV2X-RAY DIFFRACTION1.5
3FVGX-RAY DIFFRACTION1.5
3FVKX-RAY DIFFRACTION1.5
3FVNX-RAY DIFFRACTION1.5
3FVOX-RAY DIFFRACTION1.5
2ZNTX-RAY DIFFRACTION1.6
3FUZX-RAY DIFFRACTION1.65
2ZNUX-RAY DIFFRACTION1.8
2ZNSX-RAY DIFFRACTION2
4MF3X-RAY DIFFRACTION3

Predicted structure (AlphaFold)

ModelpLDDTFraction very-high
AF-P39086-F181.390.45

Functional residue map

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

Ligand- & substrate-binding residues (6): 533; 538; 704; 705; 753; 531

Post-translational modifications (2): 725, 761

Disulfide bonds (1): 765–819

Glycosylation sites (9): 68, 74, 276, 379, 428, 439, 446, 561, 766

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

IDPathway
R-HSA-451307Activation of Na-permeable kainate receptors
R-HSA-451308Activation of Ca-permeable Kainate Receptor

MSigDB gene sets: 228 (showing top): REACTOME_IONOTROPIC_ACTIVITY_OF_KAINATE_RECEPTORS, TAATAAT_MIR126, BENPORATH_ES_WITH_H3K27ME3, MODULE_274, PAX4_01, GOMF_GLUTAMATE_GATED_RECEPTOR_ACTIVITY, GOBP_REGULATION_OF_SYNAPTIC_TRANSMISSION_GLUTAMATERGIC, MODULE_64, GGGTGGRR_PAX4_03, MORF_RAD51L3, GOBP_CELL_CELL_SIGNALING, MODULE_66, MODULE_289, GOBP_REGULATION_OF_POSTSYNAPTIC_MEMBRANE_POTENTIAL, MORF_CTSB

GO Biological Process (12): glutamate receptor signaling pathway (GO:0007215), chemical synaptic transmission (GO:0007268), nervous system development (GO:0007399), central nervous system development (GO:0007417), synaptic transmission, glutamatergic (GO:0035249), modulation of chemical synaptic transmission (GO:0050804), regulation of synaptic transmission, glutamatergic (GO:0051966), monoatomic ion transport (GO:0006811), calcium-mediated signaling (GO:0019722), monoatomic ion transmembrane transport (GO:0034220), ionotropic glutamate receptor signaling pathway (GO:0035235), regulation of postsynaptic membrane potential (GO:0060078)

GO Molecular Function (7): glutamate-gated receptor activity (GO:0004970), kainate selective glutamate receptor activity (GO:0015277), glutamate-gated calcium ion channel activity (GO:0022849), transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential (GO:1904315), monoatomic ion channel activity (GO:0005216), ligand-gated monoatomic ion channel activity (GO:0015276), signaling receptor activity (GO:0038023)

GO Cellular Component (7): plasma membrane (GO:0005886), kainate selective glutamate receptor complex (GO:0032983), presynaptic membrane (GO:0042734), postsynaptic density membrane (GO:0098839), membrane (GO:0016020), synapse (GO:0045202), postsynaptic membrane (GO:0045211)

Reactome top-level categories

Rollup of top-1 pathways:

CategoryPathways
Ionotropic activity of kainate receptors2

GO top-level categories

Rollup of top GO terms by namespace:

CategoryTerms
glutamate-gated receptor activity3
glutamate receptor activity2
system development2
chemical synaptic transmission2
transmitter-gated monoatomic ion channel activity2
synaptic membrane2
cell surface receptor signaling pathway1
anterograde trans-synaptic signaling1
nervous system development1
regulation of trans-synaptic signaling1
synaptic transmission, glutamatergic1
modulation of chemical synaptic transmission1
transport1
intracellular signaling cassette1
monoatomic ion transport1
transmembrane transport1
glutamate receptor signaling pathway1
ligand-gated ion channel signaling pathway1
regulation of membrane potential1
dicarboxylic acid transmembrane transporter activity1
amino acid transmembrane transporter activity1
ionotropic glutamate receptor signaling pathway1
potassium channel activity1
ligand-gated sodium channel activity1
ligand-gated calcium channel activity1
regulation of postsynaptic membrane potential1
monoatomic ion transmembrane transporter activity1
channel activity1
monoatomic ion channel activity1
ligand-gated channel activity1
molecular transducer activity1
membrane1
cell periphery1
ionotropic glutamate receptor complex1
potassium channel complex1
sodium channel complex1
presynapse1
postsynaptic density1
postsynaptic membrane1
postsynaptic specialization membrane1

Protein interactions and networks

STRING

1656 interactions, top by confidence (×1000):

Protein AProtein BPartner UniProtScore
GRIK1GRIK5Q16478984
GRIK1GRIK4Q16099984
GRIK1GRIK2Q13002980
GRIK1GRIK3Q13003977
GRIK1GRM7Q14831924
GRIK1DLG4P78352838
GRIK1NCDNQ9UBB6825
GRIK1GRM5P41594814
GRIK1KARS1Q15046791
GRIK1NETO1Q8TDF5773
GRIK1GRM4Q14833767
GRIK1GRM6O15303759
GRIK1GRM1Q13255758
GRIK1GRM2Q14416757
GRIK1GRM3Q14832703

IntAct

29 interactions, top by confidence:

ABTypeScore
GRIK1psi-mi:“MI:0407”(direct interaction)0.440
GRIK1CYSLTR2psi-mi:“MI:0915”(physical association)0.370
GRIK1TAAR1psi-mi:“MI:0915”(physical association)0.370
GRIK1SRIpsi-mi:“MI:0915”(physical association)0.000
GRIK1GORASP2psi-mi:“MI:0915”(physical association)0.000
GRIK1SIPA1L3psi-mi:“MI:0915”(physical association)0.000
GRIK1ST13psi-mi:“MI:0915”(physical association)0.000
GRIK1ZNF592psi-mi:“MI:0915”(physical association)0.000
GRIK1ZFC3H1psi-mi:“MI:0915”(physical association)0.000
GRIK1UBE2Opsi-mi:“MI:0915”(physical association)0.000
GRIK1PTPRDpsi-mi:“MI:0915”(physical association)0.000
GRIK1DNAJB9psi-mi:“MI:0915”(physical association)0.000
GRIK1COPS5psi-mi:“MI:0915”(physical association)0.000
GRIK1KALRNpsi-mi:“MI:0915”(physical association)0.000
GRIK1LDB2psi-mi:“MI:0915”(physical association)0.000
GRIK1RANBP9psi-mi:“MI:0915”(physical association)0.000
GRIK1PICK1psi-mi:“MI:0915”(physical association)0.000
GRIK1SNAPINpsi-mi:“MI:0915”(physical association)0.000
GRIK1SEPTIN7psi-mi:“MI:0915”(physical association)0.000
GRIK1RNF123psi-mi:“MI:0915”(physical association)0.000
GRIK1KCNQ2psi-mi:“MI:0915”(physical association)0.000
GRIK1DLSTpsi-mi:“MI:0915”(physical association)0.000
GRIK1HSP90B1psi-mi:“MI:0915”(physical association)0.000

BioGRID (40): GRIK1 (Affinity Capture-RNA), PICK1 (Reconstituted Complex), SDCBP (Reconstituted Complex), DLG4 (Reconstituted Complex), GRIP1 (Reconstituted Complex), DLG4 (Affinity Capture-Western), SDCBP (Affinity Capture-Western), PICK1 (Affinity Capture-Western), GRIK1 (Synthetic Lethality), GRIK1 (Affinity Capture-MS), GRIK1 (Two-hybrid), GRIK1 (Two-hybrid), GRIK1 (Reconstituted Complex), GRIK1 (Co-fractionation), GRIK2 (Reconstituted Complex)

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

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

SIGNOR signaling

4 interactions.

AEffectBMechanism
GRIK1up-regulatesExcitatory_synaptic_transmission
“glutamic acid”“up-regulates activity”GRIK1“chemical activation”
GRIK1“up-regulates quantity”calcium(2+)relocalization
GRIK1“up-regulates quantity”D-serinerelocalization

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

ClassificationCount (floor)
Pathogenic0
Likely pathogenic0
Uncertain significance143
Likely benign11
Benign5

Top pathogenic / likely-pathogenic (0)

SpliceAI

5722 predictions. Top by Δscore:

VariantEffectΔscore
21:29555047:CTCA:Cdonor_loss1.0000
21:29555048:TCACC:Tdonor_loss1.0000
21:29555049:CA:Cdonor_loss1.0000
21:29555050:ACC:Adonor_loss1.0000
21:29588837:A:ACdonor_gain1.0000
21:29588838:C:CCdonor_gain1.0000
21:29597692:GAA:Gdonor_gain1.0000
21:29597695:G:GGdonor_gain1.0000
21:29598824:GGTTA:Gdonor_loss1.0000
21:29598825:GTTA:Gdonor_loss1.0000
21:29598826:TTA:Tdonor_loss1.0000
21:29598827:TA:Tdonor_loss1.0000
21:29598829:C:CAdonor_loss1.0000
21:29598843:T:TAdonor_gain1.0000
21:29598938:C:CCacceptor_gain1.0000
21:29651111:GACTT:Gdonor_loss1.0000
21:29651112:ACTTA:Adonor_loss1.0000
21:29651113:CTT:Cdonor_loss1.0000
21:29651114:TTA:Tdonor_loss1.0000
21:29651115:TA:Tdonor_loss1.0000
21:29651116:A:ACdonor_gain1.0000
21:29651117:C:Adonor_loss1.0000
21:29651117:C:CTdonor_gain1.0000
21:29651117:CT:Cdonor_gain1.0000
21:29651117:CTGT:Cdonor_gain1.0000
21:29651303:C:CTacceptor_gain1.0000
21:29651304:A:Tacceptor_gain1.0000
21:29654805:CTTA:Cdonor_loss1.0000
21:29654807:T:TGdonor_loss1.0000
21:29654808:A:ACdonor_gain1.0000

AlphaMissense

6272 scored. Top likely-pathogenic:

VariantProtein changeam_pathogenicity
21:29555122:A:GL846P1.000
21:29555126:C:GG845R1.000
21:29555126:C:TG845R1.000
21:29555134:A:GL842P1.000
21:29555260:A:GL800P1.000
21:29555266:A:GL798P1.000
21:29555266:A:TL798H1.000
21:29561635:C:TG782E1.000
21:29561636:C:GG782R1.000
21:29561636:C:TG782R1.000
21:29561641:C:TG780E1.000
21:29576970:G:CF708L1.000
21:29576970:G:TF708L1.000
21:29576972:A:GF708L1.000
21:29577028:A:GL689P1.000
21:29577075:G:CF673L1.000
21:29577075:G:TF673L1.000
21:29577077:A:GF673L1.000
21:29577082:G:TA671D1.000
21:29577085:A:GL670P1.000
21:29577091:G:TA668D1.000
21:29577098:A:GY666H1.000
21:29577115:A:GL660P1.000
21:29577131:A:GW655R1.000
21:29577131:A:TW655R1.000
21:29577166:G:TP643H1.000
21:29587389:G:CS590R1.000
21:29587389:G:TS590R1.000
21:29587391:T:GS590R1.000
21:29587424:A:GW579R1.000

dbSNP variants (sampled 300 via entrez): RS1000007076 (21:29654044 C>T), RS1000011187 (21:29855474 A>C), RS1000013828 (21:29835400 C>G), RS1000036462 (21:29575303 T>C), RS1000039591 (21:29921552 C>T), RS1000043119 (21:29698908 C>T), RS1000046085 (21:29739243 G>A), RS1000050356 (21:29900160 A>C,G), RS1000055945 (21:29581387 T>C), RS1000063750 (21:29875758 G>A), RS1000074012 (21:29840928 A>G), RS1000087216 (21:29912484 G>A), RS1000103376 (21:29733987 A>G), RS1000110288 (21:29577598 G>A), RS1000112638 (21:29774827 T>C)

Disease associations

OMIM: gene MIM:138245 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

16 associations (top):

StudyTraitp-value
GCST000079_7Breast cancer6.000000e-06
GCST000278_6Hyperactive-impulsive symptoms4.000000e-06
GCST000635_20Response to statin therapy8.000000e-06
GCST001448_1Body mass index6.000000e-06
GCST001603_2Hepatocellular carcinoma5.000000e-10
GCST001877_41Autism spectrum disorder, attention deficit-hyperactivity disorder, bipolar disorder, major depressive disorder, and schizophrenia (combined)5.000000e-06
GCST002129_3Periodontitis (DPAL)7.000000e-06
GCST003084_2Glucocorticoid-induced osteonecrosis1.000000e-06
GCST005175_67Coronary artery calcified atherosclerotic plaque (90 or 130 HU threshold) in type 2 diabetes9.000000e-06
GCST006106_2Forehead morphology1.000000e-06
GCST006291_2Spherical equivalent or myopia (age of diagnosis)9.000000e-09
GCST006431_3Plasma parathyroid hormone levels4.000000e-07
GCST007353_11Generalized epilepsy2.000000e-08
GCST009616_6HDL cholesterol levels x thiazide or thiazide-like diuretics use interaction3.000000e-07
GCST010002_73Refractive error1.000000e-10
GCST011974_12Lung cancer1.000000e-06

EFO canonical traits (4, from GWAS)

EFO IDTrait name
EFO:0004340body mass index
EFO:0004723coronary artery calcification
EFO:0004847age at onset
EFO:0004612high density lipoprotein cholesterol measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL1918 (SINGLE PROTEIN), CHEMBL2109241 (PROTEIN COMPLEX GROUP)

Molecules with ChEMBL bioactivity

3 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 944,946 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

MoleculeNamePhasePatents
CHEMBL575060GLUTAMIC ACID3929,756
CHEMBL14935TEZAMPANEL ANHYDROUS2106
CHEMBL275040KAINIC ACID215,084

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

PharmGKB clinical annotations

1 annotations.

VariantTypeLevelDrugsPhenotypes
rs2832407Efficacy,Metabolism/PK3topiramateAlcohol-Related Disorders

PharmGKB variants

1 variants.

VariantGenesLevelScore#Clin annotsDrugs
rs2832407GRIK1, GRIK1-AS232.501topiramate

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:

LigandActionAffinityParameter
dysiherbaineFull agonist9.13pKi
SYM2081Full agonist8.52pKi
LY339434Agonist7.89pKi
[3H]UBP310Antagonist7.7pKd
kainateFull agonist6.75pKi

Binding affinities (BindingDB)

13 measured of 14 human assays (15 total across all organisms); most potent 13 below. Values come from heterogeneous assays and are not directly comparable.

LigandMeasureValuePatent
6-methyl-N-[(1S,5R)-5-(pyridine-2-carbonylamino)-1-bicyclo[3.2.1]octanyl]pyridine-2-carboxamideIC500.32 nMUS-9656975: Bicyclo[3.2.1]octyl amide derivatives and uses of same
N-[5-[(3-chlorobenzoyl)amino]-1-bicyclo[3.2.1]octanyl]-6-methylpyridine-2-carboxamideIC503.7 nMUS-9656975: Bicyclo[3.2.1]octyl amide derivatives and uses of same
N-[(1R,5S)-5-[(3-fluorobenzoyl)amino]-1-bicyclo[3.2.1]octanyl]-6-methylpyrazine-2-carboxamideIC503.9 nMUS-9656975: Bicyclo[3.2.1]octyl amide derivatives and uses of same
4-methyl-N-[5-[(6-methyl-2-pyridinyl)carbamoyl]-1-bicyclo[3.2.1]octanyl]-1,3-thiazole-2-carboxamideIC504.7 nMUS-9656975: Bicyclo[3.2.1]octyl amide derivatives and uses of same
N-[5-[(3-fluorobenzoyl)amino]-1-bicyclo[3.2.1]octanyl]-6-methylpyrazine-2-carboxamideIC509 nMUS-9656975: Bicyclo[3.2.1]octyl amide derivatives and uses of same
N-[5-[(3-chlorobenzoyl)amino]-1-bicyclo[3.2.1]octanyl]-2-methyl-1,3-thiazole-5-carboxamideIC5026 nMUS-9656975: Bicyclo[3.2.1]octyl amide derivatives and uses of same
5-[(3-chlorobenzoyl)amino]-N-(6-methyl-2-pyridinyl)bicyclo[3.2.1]octane-1-carboxamideIC5033 nMUS-9656975: Bicyclo[3.2.1]octyl amide derivatives and uses of same
N-[5-[(3-methylbenzoyl)amino]-1-bicyclo[3.2.1]octanyl]pyridine-4-carboxamideIC5035 nMUS-9656975: Bicyclo[3.2.1]octyl amide derivatives and uses of same
6-methyl-N-[5-[(2-methylpyrimidin-4-yl)carbamoyl]-1-bicyclo[3.2.1]octanyl]pyridine-2-carboxamideIC5038 nMUS-9656975: Bicyclo[3.2.1]octyl amide derivatives and uses of same
N-[(1S,5R)-5-[(3-fluorobenzoyl)amino]-1-bicyclo[3.2.1]octanyl]-6-methylpyrazine-2-carboxamideIC50134 nMUS-9656975: Bicyclo[3.2.1]octyl amide derivatives and uses of same
SPD 502KI620 nM
SR 147778KI1000 nM
NS3763KI1600 nM

ChEMBL bioactivities

218 potent at pChembl≥5 of 282 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChemblTypeValueUnitMolecule
9.13Ki0.74nMDYSIHERBAINE
8.96Ki1.11nMDOMOIC ACID
8.72IC501.9nMCHEMBL492630
8.52Ki3nM2S,4R-4-METHYLGLUTAMATE
8.42IC503.8nMCHEMBL492469
8.42Ki3.8nMCHEMBL63861
8.15Ki7nMCHEMBL61751
8.10Ki8nMCHEMBL58590
7.94Ki11.6nMCHEMBL59551
7.92Ki12nMCHEMBL67828
7.85Ki14nMCHEMBL301536
7.83Ki14.8nMCHEMBL301536
7.82Ki15nMCHEMBL301536
7.70Ki20nMCHEMBL3088070
7.68Ki21nMCHEMBL294139
7.58Ki26nMCHEMBL59284
7.54Ki28.9nMCHEMBL62086
7.52Ki30nMCHEMBL59284
7.52Ki30nMCHEMBL301915
7.50Ki32nMCHEMBL300368
7.49Ki32.6nMCHEMBL51660
7.40Ki40nMCHEMBL305346
7.39Ki41nMCHEMBL60406
7.36Ki44nMCHEMBL58095
7.31Ki49nMCHEMBL293118
7.30Ki50nMCHEMBL1234118
7.28Ki52nMCHEMBL291491
7.26Ki54.4nMCHEMBL299180
7.25Ki56nMCHEMBL62057
7.24Ki58nMCHEMBL302680
7.23Ki59nMCHEMBL60168
7.22Ki60.5nMCHEMBL52295
7.22Ki60nMCHEMBL58054
7.16Ki70nMCHEMBL13076
7.11IC5077nMKAINIC ACID
7.11Ki78nMCHEMBL294683
7.09Ki80.4nMCHEMBL50041
7.09Ki81nMCHEMBL370038
7.07Ki85.7nMCHEMBL52742
7.05Ki90nMCHEMBL3088072
7.03Ki93.6nMCHEMBL298800
7.00EC50100nMCHEMBL29024
7.00Ki100nMCHEMBL3088064
7.00Ki100nMCHEMBL13076
6.96Ki110nMCHEMBL12696
6.96Ki110nMCHEMBL273675
6.91Ki123nMCHEMBL61997
6.88Ki133nMCHEMBL292896
6.88Ki131nMCHEMBL59297
6.82Ki150nMCHEMBL297919

PubChem BioAssay actives

192 with measured affinity, of 372 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.

CompoundAssayTypeValueUnit
(2R,3aR,6S,7R,7aR)-2-[(2S)-2-amino-2-carboxyethyl]-6-hydroxy-7-(methylamino)-3,3a,5,6,7,7a-hexahydrofuro[3,2-b]pyran-2-carboxylic acid1325014: Displacement of [3H]kianic acid from recombinant GluK1 kainate receptor (unknown origin) expressed in HEK293 cell membranes measured after 1 hrki0.0007uM
(2S,3S,4S)-4-[(2Z,4E,6R)-6-carboxyhepta-2,4-dien-2-yl]-3-(carboxymethyl)pyrrolidine-2-carboxylic acid2114773: Displacement of [3H](2S, 4R)-4-MeGlu (SYM-2081) from GluK1 (unknown origin)ki0.0011uM
(2S)-2-amino-3-(2,4-dioxothieno[3,2-d]pyrimidin-1-yl)propanoic acid391459: Antagonist activity at human iGluR5(Q)1b expressed in CHO-K1 cells by whole cell patch-clamp methodic500.0019uM
(2S,4R)-2-amino-4-methylpentanedioic acid93250: Binding affinity against human ionotropic glutamate receptor kainate 1 in HK293 cells using [3H]kainate as radioligandki0.0030uM
(2S)-2-amino-3-(2,4-dioxo-5,7-dihydrothieno[3,4-d]pyrimidin-1-yl)propanoic acid391459: Antagonist activity at human iGluR5(Q)1b expressed in CHO-K1 cells by whole cell patch-clamp methodic500.0038uM
2-[7-[3-[(4-benzylpiperazin-1-yl)methyl]pyrrol-1-yl]-6-nitro-2,3-dioxo-4H-quinoxalin-1-yl]acetic acid75678: Binding affinity towards cloned human GluR5 subunit stably expressed in cultured HEK293 cells using [3]H-kainate as radioligandki0.0038uM
(2S,4R)-2-amino-4-[(E)-3-naphthalen-1-ylprop-2-enyl]pentanedioic acid93250: Binding affinity against human ionotropic glutamate receptor kainate 1 in HK293 cells using [3H]kainate as radioligandki0.0070uM
(2S,4R)-2-amino-4-[(E)-3-(4-chlorophenyl)prop-2-enyl]pentanedioic acid93248: Compound was tested for binding affinity against Ionotropic glutamate receptor ionotropic kainate 1 in HK293 cells using [3H]kainate as radioligand; value according to table 1ki0.0080uM
(2S,4R)-2-amino-4-prop-2-ynylpentanedioic acid93250: Binding affinity against human ionotropic glutamate receptor kainate 1 in HK293 cells using [3H]kainate as radioligandki0.0116uM
2-[6-nitro-2,3-dioxo-7-[3-[[4-(2-phenylethyl)piperazin-1-yl]methyl]pyrrol-1-yl]-4H-quinoxalin-1-yl]acetic acid75678: Binding affinity towards cloned human GluR5 subunit stably expressed in cultured HEK293 cells using [3]H-kainate as radioligandki0.0120uM
(2S,4R)-2-amino-4-[(E)-3-naphthalen-2-ylprop-2-enyl]pentanedioic acid93248: Compound was tested for binding affinity against Ionotropic glutamate receptor ionotropic kainate 1 in HK293 cells using [3H]kainate as radioligand; value according to table 1ki0.0140uM
(3S,4aS,6S,8aR)-6-[5-(4-chlorophenyl)-2-(2H-tetrazol-5-yl)phenoxy]-1,2,3,4,4a,5,6,7,8,8a-decahydroisoquinoline-3-carboxylic acid;hydrochloride1054526: Displacement of [3H]ATPA from human Gluk1 receptorki0.0200uM
(2S,4R)-2-amino-4-[(E)-but-2-enyl]pentanedioic acid93250: Binding affinity against human ionotropic glutamate receptor kainate 1 in HK293 cells using [3H]kainate as radioligandki0.0210uM
(2S,4R)-2-amino-4-[(E)-3-(2-methoxyphenyl)prop-2-enyl]pentanedioic acid93250: Binding affinity against human ionotropic glutamate receptor kainate 1 in HK293 cells using [3H]kainate as radioligandki0.0260uM
(2S,4R)-2-amino-4-but-2-ynylpentanedioic acid93250: Binding affinity against human ionotropic glutamate receptor kainate 1 in HK293 cells using [3H]kainate as radioligandki0.0289uM
(2S,4R)-2-amino-4-[(E)-3-(4-bromophenyl)prop-2-enyl]pentanedioic acid93250: Binding affinity against human ionotropic glutamate receptor kainate 1 in HK293 cells using [3H]kainate as radioligandki0.0300uM
(2S,4R)-2-amino-4-[(E)-3-(4-methylsulfanylphenyl)prop-2-enyl]pentanedioic acid93250: Binding affinity against human ionotropic glutamate receptor kainate 1 in HK293 cells using [3H]kainate as radioligandki0.0320uM
(2S)-2-amino-4-cyclopentylidenepentanedioic acid93247: Binding affinity of compound was determined against Ionotropic glutamate receptor ionotropic kainate 1 using cell membranes prepared from HEK293 cellski0.0326uM
(2S,4R)-2-amino-4-[(E)-3-(3-methoxyphenyl)prop-2-enyl]pentanedioic acid93250: Binding affinity against human ionotropic glutamate receptor kainate 1 in HK293 cells using [3H]kainate as radioligandki0.0400uM
(2S,4R)-2-amino-4-[(E)-3-chloroprop-2-enyl]pentanedioic acid93250: Binding affinity against human ionotropic glutamate receptor kainate 1 in HK293 cells using [3H]kainate as radioligandki0.0410uM
(2S,4R)-2-amino-4-[(E)-3-phenylprop-2-enyl]pentanedioic acid93250: Binding affinity against human ionotropic glutamate receptor kainate 1 in HK293 cells using [3H]kainate as radioligandki0.0440uM
(2S,4R)-2-amino-4-[(E)-3-(3,4-dichlorophenyl)prop-2-enyl]pentanedioic acid93250: Binding affinity against human ionotropic glutamate receptor kainate 1 in HK293 cells using [3H]kainate as radioligandki0.0490uM
(3S,4aR,6S,8aR)-6-[[(2S)-2-carboxy-4,4-difluoropyrrolidin-1-yl]methyl]-1,2,3,4,4a,5,6,7,8,8a-decahydroisoquinoline-3-carboxylic acid1434141: Displacement of [3H]kainate from human GluK1 expressed in HEK293 cell membranes after 60 mins by scintillation counting methodki0.0500uM
(2S,4R)-2-amino-4-[(E)-3-[4-(trifluoromethyl)phenyl]prop-2-enyl]pentanedioic acid93250: Binding affinity against human ionotropic glutamate receptor kainate 1 in HK293 cells using [3H]kainate as radioligandki0.0520uM
(2S,4E)-2-amino-4-(2-methylpropylidene)pentanedioic acid93255: Binding affinity of compound was determined against Ionotropic glutamate receptor ionotropic kainate 1 using cell membranes prepared from HEK293 cellski0.0544uM
(2S,4R)-2-amino-4-prop-2-enylpentanedioic acid93250: Binding affinity against human ionotropic glutamate receptor kainate 1 in HK293 cells using [3H]kainate as radioligandki0.0560uM
(2S,4R)-2-amino-4-[(E)-3-(4-propan-2-ylphenyl)prop-2-enyl]pentanedioic acid93250: Binding affinity against human ionotropic glutamate receptor kainate 1 in HK293 cells using [3H]kainate as radioligandki0.0580uM
(2S,4R)-2-amino-4-[(E)-3-(4-nitrophenyl)prop-2-enyl]pentanedioic acid93250: Binding affinity against human ionotropic glutamate receptor kainate 1 in HK293 cells using [3H]kainate as radioligandki0.0590uM
(2S,4R)-2-amino-4-[(E)-3-(3-chlorophenyl)prop-2-enyl]pentanedioic acid93250: Binding affinity against human ionotropic glutamate receptor kainate 1 in HK293 cells using [3H]kainate as radioligandki0.0600uM
(2S,4Z)-2-amino-4-propylidenepentanedioic acid93247: Binding affinity of compound was determined against Ionotropic glutamate receptor ionotropic kainate 1 using cell membranes prepared from HEK293 cellski0.0605uM
(2S,3S,4S)-3-(carboxymethyl)-4-prop-1-en-2-ylpyrrolidine-2-carboxylic acid255267: Percent inhibition against Kainate receptor at a compound concentration of 1 uMic500.0770uM
(2S,4R)-2-amino-4-[(E)-3-(4-fluorophenyl)prop-2-enyl]pentanedioic acid93250: Binding affinity against human ionotropic glutamate receptor kainate 1 in HK293 cells using [3H]kainate as radioligandki0.0780uM
(2S,4Z)-2-amino-4-butylidenepentanedioic acid93247: Binding affinity of compound was determined against Ionotropic glutamate receptor ionotropic kainate 1 using cell membranes prepared from HEK293 cellski0.0804uM
(2S)-2-amino-3-[5-(2-methyltetrazol-5-yl)-3-oxo-1,2-oxazol-4-yl]propanoic acid239055: Binding affinity for kainate Glutamate receptor GluR5 expressed in Sf9 cellski0.0810uM
(2S,4E)-2-amino-4-(2,2-dimethylpropylidene)pentanedioic acid93247: Binding affinity of compound was determined against Ionotropic glutamate receptor ionotropic kainate 1 using cell membranes prepared from HEK293 cellski0.0857uM
(3S,4aS,6S,8aR)-6-[2-(2H-tetrazol-5-yl)-5-thiophen-2-ylphenoxy]-1,2,3,4,4a,5,6,7,8,8a-decahydroisoquinoline-3-carboxylic acid;hydrochloride1054526: Displacement of [3H]ATPA from human Gluk1 receptorki0.0900uM
(2S,4Z)-2-amino-4-(2-methylpropylidene)pentanedioic acid93247: Binding affinity of compound was determined against Ionotropic glutamate receptor ionotropic kainate 1 using cell membranes prepared from HEK293 cellski0.0936uM
2-[7-[3-[[(4-nitrophenyl)carbamoylamino]methyl]pyrrol-1-yl]-2,3-dioxo-6-(trifluoromethyl)-4H-quinoxalin-1-yl]acetic acid75678: Binding affinity towards cloned human GluR5 subunit stably expressed in cultured HEK293 cells using [3]H-kainate as radioligandki0.1000uM
(2S)-2-amino-3-(5-tert-butyl-3-oxo-1,2-thiazol-4-yl)propanoic acid726238: Agonist activity at GluK1 (unknown origin)ec500.1000uM
(3S,4aS,6S,8aR)-6-[5-phenyl-2-(2H-tetrazol-5-yl)phenoxy]-1,2,3,4,4a,5,6,7,8,8a-decahydroisoquinoline-3-carboxylic acid;hydrochloride1054526: Displacement of [3H]ATPA from human Gluk1 receptorki0.1000uM
(2S,4R)-2-amino-4-propylpentanedioic acid93250: Binding affinity against human ionotropic glutamate receptor kainate 1 in HK293 cells using [3H]kainate as radioligandki0.1230uM
(2S,4R)-2-amino-4-[(E)-3-(2,6-dichlorophenyl)prop-2-enyl]pentanedioic acid93250: Binding affinity against human ionotropic glutamate receptor kainate 1 in HK293 cells using [3H]kainate as radioligandki0.1310uM
(2S,4R)-2-amino-4-[(E)-3-(4-phenylphenyl)prop-2-enyl]pentanedioic acid93250: Binding affinity against human ionotropic glutamate receptor kainate 1 in HK293 cells using [3H]kainate as radioligandki0.1330uM
(2S,4Z)-2-amino-4-pentylidenepentanedioic acid93247: Binding affinity of compound was determined against Ionotropic glutamate receptor ionotropic kainate 1 using cell membranes prepared from HEK293 cellski0.1500uM
(2S,4E)-2-amino-4-(cyclopentylmethylidene)pentanedioic acid93247: Binding affinity of compound was determined against Ionotropic glutamate receptor ionotropic kainate 1 using cell membranes prepared from HEK293 cellski0.1520uM
(2S,4R)-2-amino-4-[(Z)-3-phenylprop-2-enyl]pentanedioic acid93250: Binding affinity against human ionotropic glutamate receptor kainate 1 in HK293 cells using [3H]kainate as radioligandki0.1570uM
(2S,4R)-2-amino-4-[(Z)-pent-2-enyl]pentanedioic acid93250: Binding affinity against human ionotropic glutamate receptor kainate 1 in HK293 cells using [3H]kainate as radioligandki0.1600uM
(3S,4aS,6S,8aR)-6-[5-phenylmethoxy-2-(2H-tetrazol-5-yl)phenoxy]-1,2,3,4,4a,5,6,7,8,8a-decahydroisoquinoline-3-carboxylic acid;hydrochloride1054526: Displacement of [3H]ATPA from human Gluk1 receptorki0.1600uM
(3S,4aS,6S,8aR)-6-[5-benzyl-2-(2H-tetrazol-5-yl)phenoxy]-1,2,3,4,4a,5,6,7,8,8a-decahydroisoquinoline-3-carboxylic acid;hydrochloride1054526: Displacement of [3H]ATPA from human Gluk1 receptorki0.1600uM
(2S,4R)-2-amino-4-[(E)-pent-2-enyl]pentanedioic acid93250: Binding affinity against human ionotropic glutamate receptor kainate 1 in HK293 cells using [3H]kainate as radioligandki0.1610uM

CTD chemical–gene interactions

18 total (human), top 18 by PubMed support.

ChemicalActions (top 5)PubMed papers
Benzo(a)pyrenedecreases methylation, increases expression, increases methylation, affects methylation3
selenomethylselenocysteineincreases expression1
triphenyl phosphateaffects expression1
bisphenol Aaffects cotreatment, decreases methylation, affects methylation1
benzo(e)pyreneincreases methylation1
di-n-butylphosphoric acidaffects expression1
CGP 52608affects binding, increases reaction1
belinostatincreases expression1
Topiramateaffects response to substance1
Fulvestrantaffects cotreatment, decreases methylation1
Benzoatesaffects binding, decreases activity1
Methapyrileneincreases methylation1
Tetrachlorodibenzodioxindecreases expression1
Dronabinolincreases expression1
Tretinoinincreases expression1
Triclosandecreases expression1
Sodium Seleniteincreases expression1
Lactic Acidincreases expression1

ChEMBL screening assays

70 unique, capped per target: 55 binding, 15 functional

Representative assays (with source publication via chembl_document):

Assay IDTypeDescriptionSource paper
CHEMBL1032297FunctionalAntagonist activity at human iGluR5(Q)1b expressed in CHO-K1 cells by whole cell patch-clamp method1H-cyclopentapyrimidine-2,4(1H,3H)-dione-related ionotropic glutamate receptors ligands. structure-activity relationships and identification of potent and Selective iGluR5 modulators. — J Med Chem
CHEMBL1217038BindingBinding affinity to GluR5alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) antagonists: from bench to bedside. — J Med Chem

Clinical trials (associated diseases)

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

About this page

Generated deterministically by Sugi Atlas from primary biomedical databases via BioBTree. Every record on this page traces to a primary source.

Generated
Atlas version
v1.1.2
BioBTree
v2.0.2

Sources 81

This page pulls from 81 datasets indexed by BioBTree:

alphafoldalphamissenseantibodybgeebgee_evidencebindingdbbiogrid_interactionbrendabrenda_kineticsccdscellosauruschembl_activitychembl_assaychembl_documentchembl_moleculechembl_targetciviccivic_evidenceclingen_dosageclingen_gene_validityclinical_trialsclinvarcollectrictd_gene_interactiondbsnpdepmapdiamond_similarityefoensemblentrezesm2_similarityexonfantom5_genefantom5_promotergenccgenerifgogoparentgtopdbgtopdb_interactiongwasgwas_studyhgnchpointactinterprointogenjasparmeshmimmirdbmondomsigdborphanetorthologparalogpatentpatent_compoundpdbpfampharmgkb_clinicalpharmgkb_genepharmgkb_guidelinepharmgkb_variantpubchempubchem_activitypubchem_assaypubmedreactomereactomeparentrefseqrhearnacentralscxa_expressionscxa_gene_experimentsignorspliceaistring_interactiontranscriptufeatureuniprot