GRIK5

Summary

GRIK5 (glutamate ionotropic receptor kainate type subunit 5, HGNC:4583) is a protein-coding gene on chromosome 19q13.2, encoding Glutamate receptor ionotropic, kainate 5 (Q16478). Ionotropic glutamate receptor that functions as a cation-permeable ligand-gated ion channel, gated by L-glutamate and the glutamatergic agonist kainic acid.

This gene encodes a protein that belongs to the glutamate-gated ionic channel family. Glutamate functions as the major excitatory neurotransmitter in the central nervous system through activation of ligand-gated ion channels and G protein-coupled membrane receptors. The protein encoded by this gene forms functional heteromeric kainate-preferring ionic channels with the subunits encoded by related gene family members. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 2901 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 138 total
• Druggable target: yes — 2 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_002088

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4583
Approved symbol	GRIK5
Name	glutamate ionotropic receptor kainate type subunit 5
Location	19q13.2
Locus type	gene with protein product
Status	Approved
Aliases	GluK5, KA2
Ensembl gene	ENSG00000105737
Ensembl biotype	protein_coding
OMIM	600283
Entrez	2901

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 8 protein_coding, 2 retained_intron, 1 nonsense_mediated_decay

ENST00000262895, ENST00000301218, ENST00000454993, ENST00000593562, ENST00000594528, ENST00000602210, ENST00000933560, ENST00000933561, ENST00000933562, ENST00000933563, ENST00000933564

RefSeq mRNA: 2 — MANE Select: NM_002088 NM_001301030, NM_002088

CCDS: CCDS12595, CCDS77305

Canonical transcript exons

ENST00000593562 — 20 exons

Exon	Start	End
ENSE00000709462	42065223	42065387
ENSE00003060739	42065692	42065820
ENSE00003080337	42069241	42070206
ENSE00003179222	41998324	41999299
ENSE00003481583	42042552	42042755
ENSE00003510755	42021947	42022056
ENSE00003526567	42021301	42021474
ENSE00003533428	42056925	42056978
ENSE00003548322	42053602	42053709
ENSE00003553742	42022241	42022354
ENSE00003585061	42062758	42062855
ENSE00003616975	42059349	42059527
ENSE00003622542	42056662	42056823
ENSE00003631365	42062488	42062653
ENSE00003640793	42003332	42003453
ENSE00003646458	42005723	42005948
ENSE00003654880	42054320	42054472
ENSE00003662310	42003555	42003683
ENSE00003688322	42006645	42006810
ENSE00003688355	42053825	42053929

Expression profiles

Bgee: expression breadth ubiquitous, 239 present calls, max score 98.54.

FANTOM5 (CAGE): breadth broad, TPM avg 5.5778 / max 703.5173, expressed in 770 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
69004	5.5778	770
69003	0.9478	324
181127	0.8121	331
181126	0.6364	305
69007	0.2749	91
69009	0.0862	51
69008	0.0270	14
181125	0.0096	7
69000	0.0057	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
olfactory bulb	UBERON:0002264	98.54	silver quality
type B pancreatic cell	CL:0000169	98.42	gold quality
lateral nuclear group of thalamus	UBERON:0002736	97.45	gold quality
cortical plate	UBERON:0005343	96.90	gold quality
diaphragm	UBERON:0001103	96.23	gold quality
ventral tegmental area	UBERON:0002691	96.09	gold quality
subthalamic nucleus	UBERON:0001906	95.88	gold quality
vena cava	UBERON:0004087	95.67	silver quality
dorsal plus ventral thalamus	UBERON:0001897	95.49	gold quality
superior vestibular nucleus	UBERON:0007227	95.35	gold quality
inferior vagus X ganglion	UBERON:0005363	95.18	gold quality
pons	UBERON:0000988	95.00	gold quality
lateral globus pallidus	UBERON:0002476	94.90	gold quality
substantia nigra pars compacta	UBERON:0001965	94.81	gold quality
medulla oblongata	UBERON:0001896	94.41	gold quality
substantia nigra pars reticulata	UBERON:0001966	94.34	gold quality
body of tongue	UBERON:0011876	94.24	silver quality
ganglionic eminence	UBERON:0004023	94.09	gold quality
tongue squamous epithelium	UBERON:0006919	94.00	silver quality
right hemisphere of cerebellum	UBERON:0014890	93.80	gold quality
cardiac muscle of right atrium	UBERON:0003379	93.75	silver quality
CA1 field of hippocampus	UBERON:0003881	93.73	gold quality
embryo	UBERON:0000922	93.53	gold quality
ventricular zone	UBERON:0003053	93.50	gold quality
right testis	UBERON:0004534	93.35	gold quality
orbitofrontal cortex	UBERON:0004167	93.24	gold quality
cerebellar hemisphere	UBERON:0002245	93.10	gold quality
entorhinal cortex	UBERON:0002728	93.10	gold quality
Brodmann (1909) area 46	UBERON:0006483	93.10	gold quality
cerebellar cortex	UBERON:0002129	93.08	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.89

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F1

miRNA regulators (miRDB)

39 targeting GRIK5, 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-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-26A-5P	99.78	73.52	2303
HSA-MIR-26B-5P	99.78	73.51	2305
HSA-MIR-320A-3P	99.77	69.73	2107
HSA-MIR-320B	99.77	69.73	2107
HSA-MIR-320C	99.77	69.73	2107
HSA-MIR-320D	99.77	69.73	2107
HSA-MIR-4429	99.77	69.62	2111
HSA-MIR-4465	99.71	72.56	2096
HSA-MIR-3175	99.65	66.30	2031
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-5697	99.39	67.74	1249
HSA-MIR-6852-5P	99.17	66.69	2073
HSA-MIR-4758-3P	99.12	63.96	869
HSA-MIR-5703	99.10	67.09	2053
HSA-MIR-661	99.09	65.94	2062
HSA-MIR-5197-3P	98.71	67.05	1905
HSA-MIR-4703-5P	98.53	70.13	1645
HSA-MIR-3942-5P	98.52	69.51	1517
HSA-MIR-6878-5P	98.49	67.91	2142
HSA-MIR-4766-3P	98.48	67.94	1347
HSA-MIR-4733-3P	98.35	65.20	994
HSA-MIR-3179	98.22	65.90	1445
HSA-MIR-1233-5P	98.19	66.71	1201

Literature-anchored findings (GeneRIF, showing 8)

• characterization the trafficking and surface expression of KA2 (PMID:14511640)
• GRIK 5 gene is linked to rapid-onset dystonia-parkinsonism. (PMID:15254951)
• Functional dysregulation of glutamate uptake was associated with early increases in mRNA and protein expression of the glial glutamate transporter EAAT-2 followed by a sustained decrease in mRNA expression in astrocytes infected with both HHV-6A & HHV-6B. (PMID:18247129)
• CaMKII-dependent phosphorylation of GluK5 is responsible for synaptic depression by untrapping of KARs from the PSD and increased diffusion away from synaptic sites. (PMID:23288040)
• The AA genotype of GRIK5 had a protective effect against chronic obstructive pulmonary disease. (PMID:28900078)
• Authors present evidence that the ER retention signals in the kainate receptors containing GluK5 impose a requirement for sorting into local dendritic secretory pathways in neurons, as opposed to traversing the somatic Golgi apparatus. (PMID:30339823)
• Low GRIK5 expression is associated with eye diseases. (PMID:30827500)
• GRIK5 stimulates colon cancer growth and metastasis through cAMP/PKA/CADM3 signaling. (PMID:36959746)

Cross-species orthologs

44 orthologs

Organism	Symbol	Gene ID
danio_rerio	si:ch211-264f5.8	ENSDARG00000078151
danio_rerio	grik5	ENSDARG00000101449
danio_rerio	si:ch211-264f5.8	ENSDARG00000111980
mus_musculus	Grik5	ENSMUSG00000003378
rattus_norvegicus	Grik5	ENSRNOG00000020310
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), 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), GRIN2B (ENSG00000273079)

Protein

Protein identifiers

Glutamate receptor ionotropic, kainate 5 — Q16478 (reviewed: Q16478)

Alternative names: Excitatory amino acid receptor 2, Glutamate receptor KA-2

All UniProt accessions (2): Q16478, M0QXF6

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. Cannot form functional channels on its own and produces channel activity only in heteromeric assembly with GRIK1 and GRIK2 subunits. Can form functional heteromeric receptors with GRIK3.

Subunit / interactions. Homotetramer. Heterotetramer with GRIK2. Can form functional heteromeric receptors with GRIK1 and GRIK2. Can form functional heteromeric receptors with GRIK3.

Subcellular location. Cell membrane. Postsynaptic cell membrane. Presynaptic cell membrane.

Similarity. Belongs to the glutamate-gated ion channel (TC 1.A.10.1) family. GRIK5 subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
Q16478-1	1	yes
Q16478-2	2

RefSeq proteins (2): NP_001287959, NP_002079* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001320	Iontro_rcpt_C	Domain
IPR001508	Iono_Glu_rcpt_met	Family
IPR001828	ANF_lig-bd_rcpt	Domain
IPR015683	Ionotropic_Glu_rcpt	Family
IPR019594	Glu/Gly-bd	Domain
IPR028082	Peripla_BP_I	Homologous_superfamily

Pfam: PF00060, PF01094, PF10613

UniProt features (32 total): glycosylation site 11, topological domain 4, disulfide bond 3, sequence conflict 3, transmembrane region 3, region of interest 2, mutagenesis site 2, signal peptide 1, chain 1, compositionally biased region 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q16478-F1	78.46	0.40

Functional residue map

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

Disulfide bonds (3): 36–292, 83–334, 165–170

Glycosylation sites (11): 219, 271, 285, 322, 372, 394, 400, 407, 414, 478, 735

Mutagenesis-validated functional residues (2):

Position	Phenotype
863	retained in the endoplasmic reticulum; when associated with e-865.
865	retained in the endoplasmic reticulum; when associated with e-863.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-451308	Activation of Ca-permeable Kainate Receptor

MSigDB gene sets: 601 (showing top): GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_UP, MORF_RAGE, BROWNE_HCMV_INFECTION_4HR_UP, GOBP_NEGATIVE_REGULATION_OF_NEURON_APOPTOTIC_PROCESS, GOBP_REGULATION_OF_VESICLE_FUSION, REACTOME_IONOTROPIC_ACTIVITY_OF_KAINATE_RECEPTORS, MORF_FLT1, MODULE_274, GOBP_SENSORY_PERCEPTION_OF_TEMPERATURE_STIMULUS, GOBP_BEHAVIOR, MORF_MSH3, GOMF_GLUTAMATE_GATED_RECEPTOR_ACTIVITY, GOBP_REGULATION_OF_NEURONAL_SYNAPTIC_PLASTICITY, GOBP_REGULATION_OF_SYNAPTIC_TRANSMISSION_GLUTAMATERGIC, GOBP_VESICLE_ORGANIZATION

GO Biological Process (10): regulation of synaptic vesicle fusion to presynaptic active zone membrane (GO:0031630), synaptic transmission, glutamatergic (GO:0035249), modulation of chemical synaptic transmission (GO:0050804), excitatory postsynaptic potential (GO:0060079), monoatomic ion transport (GO:0006811), glutamate receptor signaling pathway (GO:0007215), monoatomic ion transmembrane transport (GO:0034220), ionotropic glutamate receptor signaling pathway (GO:0035235), regulation of membrane potential (GO:0042391), regulation of presynaptic membrane potential (GO:0099505)

GO Molecular Function (7): kainate selective glutamate receptor activity (GO:0015277), 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), glutamate-gated receptor activity (GO:0004970), monoatomic ion channel activity (GO:0005216), ligand-gated monoatomic ion channel activity (GO:0015276), signaling receptor activity (GO:0038023)

GO Cellular Component (11): nucleoplasm (GO:0005654), endoplasmic reticulum (GO:0005783), plasma membrane (GO:0005886), kainate selective glutamate receptor complex (GO:0032983), presynaptic membrane (GO:0042734), hippocampal mossy fiber to CA3 synapse (GO:0098686), postsynaptic density membrane (GO:0098839), membrane (GO:0016020), cell projection (GO:0042995), synapse (GO:0045202), postsynaptic membrane (GO:0045211)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Ionotropic activity of kainate receptors	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
chemical synaptic transmission	2
regulation of postsynaptic membrane potential	2
glutamate receptor activity	2
glutamate-gated receptor activity	2
transmitter-gated monoatomic ion channel activity	2
synaptic membrane	2
regulation of vesicle fusion	1
synaptic vesicle fusion to presynaptic active zone membrane	1
regulation of synaptic vesicle membrane organization	1
regulation of trans-synaptic signaling	1
chemical synaptic transmission, postsynaptic	1
transport	1
cell surface receptor signaling pathway	1
monoatomic ion transport	1
transmembrane transport	1
glutamate receptor signaling pathway	1
ligand-gated ion channel signaling pathway	1
monoatomic ion transmembrane transport	1
regulation of biological quality	1
regulation of membrane potential	1
potassium channel activity	1
ligand-gated sodium channel activity	1
ligand-gated monoatomic ion channel activity	1
presynaptic membrane	1
regulation of presynaptic membrane potential	1
dicarboxylic acid transmembrane transporter activity	1
amino acid transmembrane transporter activity	1
ionotropic glutamate receptor signaling pathway	1
monoatomic ion transmembrane transporter activity	1
channel activity	1
monoatomic ion channel activity	1
ligand-gated channel activity	1
molecular transducer activity	1
nuclear lumen	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

1928 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GRIK5	GRIK1	P39086	984
GRIK5	GRIK2	Q13002	983
GRIK5	GRIK4	Q16099	979
GRIK5	GRIK3	Q13003	955
GRIK5	GPR6	P46095	850
GRIK5	NR2E1	Q9Y466	796
GRIK5	GRM7	Q14831	780
GRIK5	DLG4	P78352	769
GRIK5	KARS1	Q15046	692
GRIK5	GRM3	Q14832	675
GRIK5	GABRB3	P28472	617
GRIK5	GAD1	Q99259	583
GRIK5	GRM5	P41594	579
GRIK5	NETO2	Q8NC67	570
GRIK5	PICK1	Q9NRD5	570

IntAct

6 interactions, top by confidence:

A	B	Type	Score
GRIK5	ADCY6	psi-mi:“MI:0914”(association)	0.350
MLF1	GRIK5	psi-mi:“MI:0915”(physical association)	0.000
GOLM1	GRIK5	psi-mi:“MI:0915”(physical association)	0.000
GPAA1	GRIK5	psi-mi:“MI:0915”(physical association)	0.000
LRSAM1	GRIK5	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (23): GRIK5 (Affinity Capture-Western), GRIK5 (Affinity Capture-MS), GRIK5 (Positive Genetic), GRIK5 (Positive Genetic), SKP2 (Positive Genetic), GRIK5 (Affinity Capture-MS), GRID2 (Affinity Capture-Western), GRIK5 (Two-hybrid), DLG4 (Affinity Capture-Western), DLG4 (Affinity Capture-Western), DLG3 (Affinity Capture-Western), DLG4 (Reconstituted Complex), GRIK5 (Affinity Capture-Western), PORCN (Affinity Capture-MS), ADCY6 (Affinity Capture-MS)

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.

A	Effect	B	Mechanism
GRIK5	up-regulates	Excitatory_synaptic_transmission
“glutamic acid”	“up-regulates activity”	GRIK5	“chemical activation”
GRIK5	“up-regulates quantity”	calcium(2+)	relocalization
GRIK5	“up-regulates quantity”	D-serine	relocalization

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	112
Likely benign	14
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

3614 predictions. Top by Δscore:

Variant	Effect	Δscore
19:42005722:CCCAG:C	donor_gain	1.0000
19:42005744:AG:A	donor_gain	1.0000
19:42005744:AGC:A	donor_gain	1.0000
19:42005745:G:C	donor_gain	1.0000
19:42005947:TT:T	acceptor_gain	1.0000
19:42005949:C:CC	acceptor_gain	1.0000
19:42005954:C:CT	acceptor_gain	1.0000
19:42005955:A:T	acceptor_gain	1.0000
19:42005963:C:CT	acceptor_gain	1.0000
19:42005965:C:CT	acceptor_gain	1.0000
19:42005966:A:T	acceptor_gain	1.0000
19:42006641:CCA:C	donor_loss	1.0000
19:42006642:CAC:C	donor_loss	1.0000
19:42006643:A:AT	donor_loss	1.0000
19:42006644:C:G	donor_loss	1.0000
19:42006686:A:AC	donor_gain	1.0000
19:42006687:C:CC	donor_gain	1.0000
19:42006774:C:CT	acceptor_gain	1.0000
19:42006775:G:C	acceptor_gain	1.0000
19:42006806:CCCAC:C	acceptor_gain	1.0000
19:42006807:CCAC:C	acceptor_gain	1.0000
19:42006807:CCACC:C	acceptor_gain	1.0000
19:42006808:CAC:C	acceptor_gain	1.0000
19:42006808:CACC:C	acceptor_gain	1.0000
19:42006808:CACCT:C	acceptor_loss	1.0000
19:42006809:AC:A	acceptor_gain	1.0000
19:42006810:CC:C	acceptor_gain	1.0000
19:42006810:CCT:C	acceptor_loss	1.0000
19:42006811:CTG:C	acceptor_loss	1.0000
19:42006812:T:C	acceptor_loss	1.0000

AlphaMissense

6337 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:42003641:A:G	L769P	1.000
19:42003647:A:G	L767P	1.000
19:42005734:C:T	G751D	1.000
19:42005740:C:T	G749D	1.000
19:42005779:A:G	L736P	1.000
19:42005833:G:T	A718D	1.000
19:42005864:C:G	G708R	1.000
19:42006649:A:G	F678S	1.000
19:42006651:G:C	F677L	1.000
19:42006651:G:T	F677L	1.000
19:42006653:A:G	F677L	1.000
19:42006682:C:T	G667D	1.000
19:42006683:C:G	G667R	1.000
19:42006709:A:G	L658P	1.000
19:42006754:A:G	L643P	1.000
19:42006756:G:C	F642L	1.000
19:42006756:G:T	F642L	1.000
19:42006758:A:G	F642L	1.000
19:42006763:G:T	A640D	1.000
19:42006766:A:G	L639P	1.000
19:42006772:G:T	A637D	1.000
19:42006779:A:G	Y635H	1.000
19:42006801:G:C	F627L	1.000
19:42006801:G:T	F627L	1.000
19:42006803:A:G	F627L	1.000
19:42021302:A:G	W624R	1.000
19:42021302:A:T	W624R	1.000
19:42021970:G:C	S558R	1.000
19:42021970:G:T	S558R	1.000
19:42021972:T:G	S558R	1.000

dbSNP variants (sampled 300 via entrez): RS1000012401 (19:42038455 G>A,C), RS1000064731 (19:42038824 G>A), RS1000101297 (19:42038786 G>A), RS1000160220 (19:42048921 G>A), RS1000216271 (19:42065002 C>A), RS1000238800 (19:42068839 G>A), RS1000265784 (19:42058234 C>A), RS1000274941 (19:42014550 A>C), RS1000315578 (19:42045194 A>G), RS1000374878 (19:42051706 C>T), RS1000397917 (19:42021045 G>A), RS1000427259 (19:42052025 G>A), RS1000488344 (19:42008216 C>T), RS1000571702 (19:42069746 G>A,T), RS1000599636 (19:42050657 C>A)

Disease associations

OMIM: gene MIM:600283 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST001164_1	Bipolar disorder	2.000000e-06
GCST010143_27	Meat-related diet	3.000000e-09
GCST90002388_369	Lymphocyte count	4.000000e-11
GCST90013406_204	Liver enzyme levels (alkaline phosphatase)	2.000000e-10

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0008111	diet measurement
EFO:0004587	lymphocyte count
EFO:0004533	alkaline phosphatase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL2109241 (PROTEIN COMPLEX GROUP), CHEMBL2675 (SINGLE PROTEIN), CHEMBL3038480 (PROTEIN COMPLEX)

Molecules with ChEMBL bioactivity

2 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 944,840 (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
CHEMBL575060	GLUTAMIC ACID	3	929,756
CHEMBL275040	KAINIC ACID	2	15,084

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: lgic — Ionotropic glutamate receptors

Binding affinities (BindingDB)

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

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

ChEMBL bioactivities

54 potent at pChembl≥5 of 75 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.62	Ki	0.24	nM	CHEMBL121915
8.54	Ki	2.9	nM	CHEMBL331644
8.10	Ki	8	nM	KAINIC ACID
8.04	Ki	9.1	nM	CHEMBL333964
7.70	Ki	19.8	nM	CHEMBL121553
7.51	Ki	30.9	nM	CHEMBL331696
7.24	Ki	57.1	nM	CHEMBL121388
7.16	Ki	70	nM	CHEMBL13076
7.11	IC50	77	nM	KAINIC ACID
7.10	Ki	80	nM	KAINIC ACID
7.00	EC50	100	nM	CHEMBL29024
6.96	Ki	110	nM	CHEMBL12696
6.96	Ki	110	nM	CHEMBL273675
6.89	EC50	130	nM	CHEMBL28472
6.75	Ki	177	nM	KAINIC ACID
6.41	Ki	393	nM	CHEMBL121191
6.39	Ki	410	nM	CHEMBL268284
6.32	EC50	480	nM	CHEMBL27130
6.16	Ki	700	nM	CHEMBL84142
6.15	Ki	701	nM	GLUTAMIC ACID
6.12	Ki	750	nM	GLUTAMIC ACID
5.94	Ki	1150	nM	CHEMBL120808
5.92	Ki	1200	nM	CHEMBL82375
5.89	Ki	1300	nM	CHEMBL268284
5.82	Ki	1500	nM	CHEMBL12448
5.78	Ki	1670	nM	CHEMBL12989
5.74	Ki	1820	nM	CHEMBL123132
5.70	Ki	1980	nM	CHEMBL122656
5.67	Ki	2144	nM	(S)-AMPA
5.58	Ki	2600	nM	NBQX
5.58	Ki	2600	nM	CHEMBL12761
5.57	IC50	2700	nM	CHEMBL86313
5.54	IC50	2900	nM	DNQX
5.48	Ki	3300	nM	CHEMBL275334
5.47	Ki	3400	nM	CHEMBL12510
5.44	Ki	3600	nM	CHEMBL309831
5.32	Ki	4800	nM	CHEMBL12358
5.32	Ki	4800	nM	YM-90K
5.31	IC50	4900	nM	CHEMBL310897
5.31	Ki	4900	nM	CHEMBL12730
5.30	Ki	5000	nM	CHEMBL79454
5.28	Ki	5200	nM	CHEMBL305534
5.24	Ki	5700	nM	CHEMBL314248
5.23	Ki	5900	nM	CHEMBL293613
5.17	Ki	6700	nM	CHEMBL310503
5.12	Ki	7500	nM	CHEMBL299180
5.10	IC50	8000	nM	NBQX
5.07	Ki	8500	nM	CHEMBL99012
5.05	Ki	8900	nM	CHEMBL1234118
5.01	Ki	9800	nM	CHEMBL12465

PubChem BioAssay actives

28 with measured affinity, of 80 total; 23 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
(2S)-2-amino-3-(5-iodo-2,4-dioxopyrimidin-1-yl)propanoic acid	93254: Displacement of [3H]kainate from human Ionotropic glutamate receptor ionotropic kainate 1 expressed in HEK293 cells	ki	0.0002	uM
(2S)-2-amino-3-(6-bromo-3,5-dioxo-1,2,4-triazin-2-yl)propanoic acid	93254: Displacement of [3H]kainate from human Ionotropic glutamate receptor ionotropic kainate 1 expressed in HEK293 cells	ki	0.0029	uM
(2S,3S,4S)-3-(carboxymethyl)-4-prop-1-en-2-ylpyrrolidine-2-carboxylic acid	93411: Ability to bind to Ionotropic glutamate receptor kainate (kainate 2) was evaluated.	ki	0.0080	uM
(2S)-2-amino-3-(5-bromo-2,4-dioxopyrimidin-1-yl)propanoic acid	93254: Displacement of [3H]kainate from human Ionotropic glutamate receptor ionotropic kainate 1 expressed in HEK293 cells	ki	0.0091	uM
(2S)-2-amino-3-(6-iodo-3,5-dioxo-1,2,4-triazin-2-yl)propanoic acid	93254: Displacement of [3H]kainate from human Ionotropic glutamate receptor ionotropic kainate 1 expressed in HEK293 cells	ki	0.0198	uM
(2S)-2-amino-3-(6-chloro-3,5-dioxo-1,2,4-triazin-2-yl)propanoic acid	93254: Displacement of [3H]kainate from human Ionotropic glutamate receptor ionotropic kainate 1 expressed in HEK293 cells	ki	0.0309	uM
(2S)-2-amino-3-(5-chloro-2,4-dioxopyrimidin-1-yl)propanoic acid	93254: Displacement of [3H]kainate from human Ionotropic glutamate receptor ionotropic kainate 1 expressed in HEK293 cells	ki	0.0571	uM
(2S)-2-amino-3-(5-tert-butyl-3-oxo-1,2-thiazol-4-yl)propanoic acid	93240: Electrophysiological data on Xenopus oocytes, expressing homomeric kainate receptor (GluR5)	ec50	0.1000	uM
(2S)-2-amino-3-(3-oxo-7,8-dihydro-6H-cyclohepta[d][1,2]oxazol-4-yl)propanoic acid	93127: Electrophysiological data on Xenopus oocytes, expressing homomeric Ionotropic glutamate receptor ionotropic kainate 1 (GluR5)	ec50	0.1300	uM
(2S)-2-amino-3-(5-nitro-2,4-dioxopyrimidin-1-yl)propanoic acid	93254: Displacement of [3H]kainate from human Ionotropic glutamate receptor ionotropic kainate 1 expressed in HEK293 cells	ki	0.3930	uM
(2S)-2-amino-3-(5-tert-butyl-3-oxo-1,2-oxazol-4-yl)propanoic acid	93127: Electrophysiological data on Xenopus oocytes, expressing homomeric Ionotropic glutamate receptor ionotropic kainate 1 (GluR5)	ec50	0.4800	uM
glutamic acid	93254: Displacement of [3H]kainate from human Ionotropic glutamate receptor ionotropic kainate 1 expressed in HEK293 cells	ki	0.7010	uM
(2S)-2-amino-3-(6-methyl-3,5-dioxo-1,2,4-triazin-2-yl)propanoic acid	93254: Displacement of [3H]kainate from human Ionotropic glutamate receptor ionotropic kainate 1 expressed in HEK293 cells	ki	1.1500	uM
2-(6-nitro-2,3-dioxo-7-pyrrol-1-yl-4H-quinoxalin-1-yl)acetic acid	95023: Binding affinity towards cloned human Kai-2 subunit stably expressed in cultured HEK293 cells using [3]H-kainate as radioligand	ki	1.3000	uM
(2S)-2-amino-3-(5-fluoro-2,4-dioxopyrimidin-1-yl)propanoic acid	93254: Displacement of [3H]kainate from human Ionotropic glutamate receptor ionotropic kainate 1 expressed in HEK293 cells	ki	1.8200	uM
(2S)-2-amino-3-(3,5-dioxo-1,2,4-triazin-2-yl)propanoic acid	93254: Displacement of [3H]kainate from human Ionotropic glutamate receptor ionotropic kainate 1 expressed in HEK293 cells	ki	1.9800	uM
(2S)-2-amino-3-(5-methyl-3-oxo-1,2-oxazol-4-yl)propanoic acid	93254: Displacement of [3H]kainate from human Ionotropic glutamate receptor ionotropic kainate 1 expressed in HEK293 cells	ki	2.1440	uM
[(1S)-1-[(7-bromo-2,3-dioxo-1,4-dihydroquinoxalin-5-yl)methylamino]ethyl]phosphonic acid	95024: Compound has been evaluated for its binding affinity towards kainate by displacing the radioligand [3H]kainate	ic50	2.7000	uM
2-amino-3-[3-oxo-5-(1,3-thiazol-2-yl)-1,2-oxazol-4-yl]propanoic acid	91459: In vitro binding affinity against Ionotropic glutamate receptor kainate (kainic acid) using [3H]KAIN as radioligand	ic50	4.9000	uM
(2S,4E)-2-amino-4-(2-methylpropylidene)pentanedioic acid	74823: Binding affinity of compound was determined against KA2 using cell membranes prepared from HEK293 cells	ki	7.5000	uM
(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 acid	1325320: Displacement of [3H]-kainate from human recombinant GluK5 receptor expressed in HEK293 cell membranes after 60 mins	ki	8.9000	uM
2-[7-[3-(aminomethyl)pyrrol-1-yl]-6-nitro-2,3-dioxo-4H-quinoxalin-1-yl]acetic acid	95022: Binding affinity towards Kai-2 using [3]H-kainate as the radioligand	ki	9.8000	uM
(2S)-2-amino-4-cyclopentylidenepentanedioic acid	74822: Binding affinity of compound was determined against Glutamate receptor (KA2) using cell membranes prepared from HEK293 cells	ki	10.0000	uM

CTD chemical–gene interactions

20 total (human), top 20 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases methylation, affects methylation	2
Valproic Acid	decreases expression, increases methylation	2
aristolochic acid I	increases expression	1
methyleugenol	decreases expression	1
sodium arsenite	increases expression	1
benzo(e)pyrene	decreases methylation	1
CGP 52608	affects binding, increases reaction	1
pyrimidifen	decreases expression	1
abrine	increases expression	1
jinfukang	affects cotreatment, decreases expression	1
Sunitinib	decreases expression	1
Arsenic	increases methylation	1
Cisplatin	affects cotreatment, decreases expression	1
Folic Acid	decreases expression	1
Lead	increases expression	1
Methapyrilene	decreases methylation	1
Niclosamide	increases expression	1
Sarin	increases expression	1
Urethane	decreases expression	1
Aflatoxin B1	decreases methylation	1

ChEMBL screening assays

39 unique, capped per target: 39 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL6140042	Binding	Inhibition of kainate receptor (unknown origin) expressed in Xenopus oocytes at 5 uM by radioligand binding assay	Thienopyrimidinone Derivatives as a GluN2B/C/D Biased, Positive Allosteric Modulator of the N-Methyl-d-Aspartate Receptor. — J Med Chem

Clinical trials (associated diseases)

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