GRIK4

Summary

GRIK4 (glutamate ionotropic receptor kainate type subunit 4, HGNC:4582) is a protein-coding gene on chromosome 11q23.3, encoding Glutamate receptor ionotropic, kainate 4 (Q16099). Ionotropic glutamate receptor that functions as a cation-permeable ligand-gated ion channel.

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. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 2900 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 159 total — 1 pathogenic
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_014619

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4582
Approved symbol	GRIK4
Name	glutamate ionotropic receptor kainate type subunit 4
Location	11q23.3
Locus type	gene with protein product
Status	Approved
Aliases	GluK4, KA1
Ensembl gene	ENSG00000149403
Ensembl biotype	protein_coding
OMIM	600282
Entrez	2900

Gene structure

Transcript identifiers

Ensembl transcripts: 24 — 19 protein_coding, 3 protein_coding_CDS_not_defined, 2 retained_intron

ENST00000375081, ENST00000438375, ENST00000526536, ENST00000527130, ENST00000527524, ENST00000530172, ENST00000533291, ENST00000638419, ENST00000903024, ENST00000903025, ENST00000903026, ENST00000903027, ENST00000903028, ENST00000903029, ENST00000903030, ENST00000903031, ENST00000903032, ENST00000903033, ENST00000903034, ENST00000924997, ENST00000924998, ENST00000924999, ENST00000970114, ENST00000970115

RefSeq mRNA: 3 — MANE Select: NM_014619 NM_001282470, NM_001282473, NM_014619

CCDS: CCDS8433

Canonical transcript exons

ENST00000527524 — 21 exons

Exon	Start	End
ENSE00000990318	120962456	120962681
ENSE00000990319	120967195	120967323
ENSE00000990321	120982106	120982224
ENSE00002158881	120985904	120988906
ENSE00002185418	120653685	120653792
ENSE00003472862	120956780	120956953
ENSE00003475314	120815378	120815475
ENSE00003478148	120952855	120952964
ENSE00003483042	120660269	120660400
ENSE00003483958	120940347	120940460
ENSE00003496394	120836791	120836844
ENSE00003519280	120819755	120819920
ENSE00003539786	120905290	120905493
ENSE00003546500	120875139	120875243
ENSE00003568104	120898532	120898639
ENSE00003570421	120960909	120961074
ENSE00003575618	120861959	120862120
ENSE00003580108	120831852	120832030
ENSE00003637907	120874066	120874218
ENSE00003652214	120802693	120802857
ENSE00003810695	120511748	120511887

Expression profiles

Bgee: expression breadth ubiquitous, 150 present calls, max score 85.17.

FANTOM5 (CAGE): breadth broad, TPM avg 1.6665 / max 108.5483, expressed in 364 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
117169	1.6665	364

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	85.17	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	77.50	gold quality
prefrontal cortex	UBERON:0000451	75.60	gold quality
anterior cingulate cortex	UBERON:0009835	75.53	gold quality
cingulate cortex	UBERON:0003027	75.50	gold quality
putamen	UBERON:0001874	74.47	gold quality
caudate nucleus	UBERON:0001873	74.25	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	73.92	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	73.21	gold quality
granulocyte	CL:0000094	72.32	gold quality
spinal cord	UBERON:0002240	72.24	gold quality
right frontal lobe	UBERON:0002810	71.99	gold quality
amygdala	UBERON:0001876	71.85	gold quality
hypothalamus	UBERON:0001898	71.63	gold quality
frontal cortex	UBERON:0001870	71.29	gold quality
neocortex	UBERON:0001950	71.18	gold quality
olfactory bulb	UBERON:0002264	71.05	gold quality
Brodmann (1909) area 9	UBERON:0013540	70.48	gold quality
corpus callosum	UBERON:0002336	70.46	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	70.24	gold quality
telencephalon	UBERON:0001893	69.83	gold quality
nucleus accumbens	UBERON:0001882	69.71	gold quality
forebrain	UBERON:0001890	69.16	gold quality
left adrenal gland cortex	UBERON:0035825	69.14	gold quality
cerebral cortex	UBERON:0000956	69.11	gold quality
Ammon’s horn	UBERON:0001954	69.07	gold quality
left adrenal gland	UBERON:0001234	68.97	gold quality
brain	UBERON:0000955	68.08	gold quality
adrenal cortex	UBERON:0001235	67.95	gold quality
right adrenal gland cortex	UBERON:0035827	67.69	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.67

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

73 targeting GRIK4, 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-3689D	100.00	66.14	1181
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-6077	99.99	68.04	2299
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-145-5P	99.92	71.13	1836
HSA-MIR-5195-3P	99.92	70.92	1877
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-221-5P	99.86	65.45	1052
HSA-MIR-8073	99.86	65.21	1118
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-664B-3P	99.84	71.65	3590
HSA-MIR-6715A-3P	99.83	68.05	1473
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-6817-3P	99.79	68.35	2126
HSA-MIR-577	99.78	69.13	2479
HSA-MIR-6794-5P	99.76	66.38	1048
HSA-MIR-5002-5P	99.76	70.84	1763
HSA-MIR-6733-5P	99.74	67.94	2759
HSA-MIR-4716-3P	99.69	66.73	1022

Literature-anchored findings (GeneRIF, showing 14)

• Cytogenetic and genetic findings provide molecular evidence for common etiologies for schizophrenia and and bipolar disorder and further support the ‘glutamate hypothesis’ of psychotic illness. (PMID:16819533)
• An insertion/deletion (indel) variant in the 3’ untranslated region (3’UTR) of the GRIK4 gene in subjects carrying the protective bipolar disorder haplotype was found. (PMID:18824690)
• This report provides the first evidence that genetic variation in the GRIK4 gene modulates hippocampal function. (PMID:19384319)
• The GRIK4 single nucleotide polymorphism (rs12800734) shows a strong association with disease remission in antidepressant treatment. (PMID:19924111)
• Activation of kainate receptors could serve as a novel mechanism for enhancing B cell activation and immunoglobulin production. (PMID:21215464)
• The deletion allele affords protection against bipolar disorder through increased KA1 protein abundance in neuronal cells. (PMID:22052594)
• Subjects possessing the C allele or CC genotype of the GRIK4 polymorphism rs1954787 are more likely to respond to antidepressant treatment. (PMID:25303296)
• Data suggest the involvement of glutamate receptor, ionotropic, kainate 4 protein (GRIK4) in treatment-resistant depression (TRD) and in the risk of developing psychotic symptoms during depressive episodes. (PMID:26139080)
• This study showed the lower GluK4 mRNA levels in pregnant women. (PMID:28284346)
• Results firstly indicated that rs56275759 of GRIK4 gene might be associated with major depressive disorder in Chinese Han population. (PMID:28583584)
• the GRIK4 polymorphisms genotypes were distributed as follows: rs79526501: CC696: 16, CG302: 274, GG31: 35; rs11218016: CC455: 483, CT473: 436, TT101: 108; and rs6589847: AA32: 29, AG307: 314, GG690: 686. However, there was no significant difference in allelic or genotypic frequency distributions between patients and controls. We did not find any significant association between GRIK4 polymorphisms and schizophrenia. (PMID:28658089)
• GluK4 deletion carriers who had a mental health problem (predominately depression) showed better performance in visuo-spatial ability and mental processing speed compared to individuals with mental health problems homozygous for the insertion. (PMID:29243543)
• In addition, while GRIK4 was not associated with sertraline tolerability and response, both HTR2A and SLC6A4 could influence tolerability and accelerate treatment response in pediatric patients. (PMID:31066578)
• Impact of GRIK4 gene polymorphisms on cognitive dysfunction in patients with major depression. (PMID:32245654)

Cross-species orthologs

42 orthologs

Organism	Symbol	Gene ID
danio_rerio	grik4	ENSDARG00000026753
mus_musculus	Grik4	ENSMUSG00000032017
rattus_norvegicus	Grik4	ENSRNOG00000030910
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), 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 4 — Q16099 (reviewed: Q16099)

Alternative names: Excitatory amino acid receptor 1, Glutamate receptor KA-1

All UniProt accessions (3): Q16099, A0A8D9PH79, A0A8D9UJ88

UniProt curated annotations — full annotation on UniProt →

Function. Ionotropic glutamate receptor that functions as a cation-permeable ligand-gated ion channel. Cannot form functional channels on its own. Shows channel activity only in heteromeric assembly with GRIK1, GRIK2 and GRIK3 subunits.

Subunit / interactions. Homodimer. Can form functional heteromeric receptors with GRIK1, GRIK2 and 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. GRIK4 subfamily.

RefSeq proteins (3): NP_001269399, NP_001269402, NP_055434* (*=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 (30 total): glycosylation site 9, binding site 6, topological domain 4, transmembrane region 3, region of interest 2, sequence variant 2, signal peptide 1, chain 1, compositionally biased region 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q16099-F1	78.56	0.37

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): 500; 502; 507; 674; 675; 723

Glycosylation sites (9): 158, 220, 272, 286, 323, 408, 415, 479, 736

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

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

MSigDB gene sets: 136 (showing top): REACTOME_IONOTROPIC_ACTIVITY_OF_KAINATE_RECEPTORS, GOMF_GLUTAMATE_GATED_RECEPTOR_ACTIVITY, GOBP_CELL_CELL_SIGNALING, GOBP_REGULATION_OF_POSTSYNAPTIC_MEMBRANE_POTENTIAL, KEGG_NEUROACTIVE_LIGAND_RECEPTOR_INTERACTION, GOBP_SYNAPTIC_SIGNALING, CDPCR3HD_01, GOBP_SYNAPTIC_TRANSMISSION_GLUTAMATERGIC, REACTOME_TRANSMISSION_ACROSS_CHEMICAL_SYNAPSES, GOBP_TRANSMEMBRANE_TRANSPORT, GOCC_PLASMA_MEMBRANE_SIGNALING_RECEPTOR_COMPLEX, GOCC_POSTSYNAPSE, GOCC_SODIUM_CHANNEL_COMPLEX, GOCC_POTASSIUM_CHANNEL_COMPLEX, GOBP_REGULATION_OF_MEMBRANE_POTENTIAL

GO Biological Process (9): glutamate receptor signaling pathway (GO:0007215), chemical synaptic transmission (GO:0007268), synaptic transmission, glutamatergic (GO:0035249), modulation of chemical synaptic transmission (GO:0050804), monoatomic ion transport (GO:0006811), monoatomic ion transmembrane transport (GO:0034220), ionotropic glutamate receptor signaling pathway (GO:0035235), regulation of postsynaptic membrane potential (GO:0060078), regulation of presynaptic membrane potential (GO:0099505)

GO Molecular Function (6): 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), monoatomic ion channel activity (GO:0005216), ligand-gated monoatomic ion channel activity (GO:0015276), signaling receptor activity (GO:0038023)

GO Cellular Component (9): 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
chemical synaptic transmission	2
glutamate-gated receptor activity	2
regulation of membrane potential	2
synaptic membrane	2
cellular anatomical structure	2
cell surface receptor signaling pathway	1
glutamate receptor activity	1
anterograde trans-synaptic signaling	1
regulation of trans-synaptic signaling	1
transport	1
monoatomic ion transport	1
transmembrane transport	1
glutamate receptor signaling pathway	1
ligand-gated ion channel signaling pathway	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
transmitter-gated monoatomic ion channel activity	1
regulation of postsynaptic membrane potential	1
monoatomic ion transmembrane transporter activity	1
channel activity	1
monoatomic ion channel activity	1
ligand-gated channel activity	1
molecular transducer activity	1
membrane	1
cell periphery	1
ionotropic glutamate receptor complex	1
potassium channel complex	1
sodium channel complex	1
presynapse	1
thorny excrescence	1
neuron to neuron synapse	1
hippocampal mossy fiber expansion	1
postsynaptic density	1
postsynaptic membrane	1
postsynaptic specialization membrane	1
cell junction	1
postsynapse	1

Protein interactions and networks

STRING

1422 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GRIK4	GRIK1	P39086	984
GRIK4	GRIK2	Q13002	982
GRIK4	GRIK5	Q16478	979
GRIK4	GRIK3	Q13003	978
GRIK4	MARK4	Q96L34	865
GRIK4	C1QL3	Q5VWW1	785
GRIK4	MARK3	P27448	764
GRIK4	KARS1	Q15046	690
GRIK4	GRM7	Q14831	690
GRIK4	C1QL2	Q7Z5L3	688
GRIK4	GRM1	Q13255	624
GRIK4	KCNJ1	P48048	601
GRIK4	KCNJ5	P48544	599
GRIK4	NETO1	Q8TDF5	593
GRIK4	GRM2	Q14416	593

IntAct

0 interactions, top by confidence:

BioGRID (9): GRIK4 (Affinity Capture-MS), GRIK4 (Affinity Capture-MS), GRIK4 (Reconstituted Complex), GRIK4 (Reconstituted Complex), GRIK4 (Reconstituted Complex), GRIK4 (Reconstituted Complex), GRIK4 (Cross-Linking-MS (XL-MS)), GRIK4 (FRET), GRIK4 (Co-fractionation)

ESM2 similar proteins: A0A078BQP2, A0A1J0M738, A8WPG9, B1Q257, E7EAU8, E9NA96, G5EFQ0, H2L002, N1NVB7, O43424, O62026, O62179, P23897, P25092, P26591, P34299, P55204, Q01812, Q03445, Q07553, Q09435, Q10015, Q10028, Q10029, Q10914, Q16099, Q19187, Q20086, Q21415, Q23310, Q23681, Q23682, Q3UWA6, Q5IS46, Q60934, Q61625, Q61627, Q62640, Q63226, Q68Y21

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
GRIK4	up-regulates	Excitatory_synaptic_transmission
“glutamic acid”	“up-regulates activity”	GRIK4	“chemical activation”
GRIK4	“up-regulates quantity”	calcium(2+)	relocalization
GRIK4	“up-regulates quantity”	D-serine	relocalization

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	125
Likely benign	12
Benign	12

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
2506544	GRCh37/hg19 11q23.3-25(chr11:120531028-134257553)	Pathogenic

SpliceAI

6268 predictions. Top by Δscore:

Variant	Effect	Δscore
11:120511884:CCAGG:C	donor_loss	1.0000
11:120511885:CAGGT:C	donor_loss	1.0000
11:120511888:G:GG	donor_gain	1.0000
11:120511888:GT:G	donor_loss	1.0000
11:120511889:T:A	donor_loss	1.0000
11:120539569:G:GT	donor_gain	1.0000
11:120660268:GAGTT:G	acceptor_gain	1.0000
11:120660401:G:GG	donor_gain	1.0000
11:120724501:A:AG	acceptor_gain	1.0000
11:120724501:AAT:A	acceptor_gain	1.0000
11:120802801:TCG:T	donor_gain	1.0000
11:120802834:GCGA:G	donor_gain	1.0000
11:120802858:G:GG	donor_gain	1.0000
11:120815357:T:TA	acceptor_gain	1.0000
11:120815366:C:A	acceptor_gain	1.0000
11:120815369:T:A	acceptor_gain	1.0000
11:120815472:GGAG:G	donor_gain	1.0000
11:120815473:GAGG:G	donor_gain	1.0000
11:120815474:AGGTG:A	donor_loss	1.0000
11:120815475:GGT:G	donor_loss	1.0000
11:120815476:GTGA:G	donor_loss	1.0000
11:120815477:T:G	donor_loss	1.0000
11:120819916:AGAAT:A	donor_gain	1.0000
11:120819917:GAAT:G	donor_gain	1.0000
11:120819917:GAATG:G	donor_gain	1.0000
11:120819918:AAT:A	donor_gain	1.0000
11:120819918:AATGT:A	donor_loss	1.0000
11:120819919:AT:A	donor_gain	1.0000
11:120819919:ATGTA:A	donor_loss	1.0000
11:120819920:TG:T	donor_loss	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000000898 (11:120558481 G>A,T), RS1000003003 (11:120757761 A>G), RS1000004067 (11:120905661 C>T), RS1000004750 (11:120643326 C>G), RS1000008996 (11:120937024 A>G,T), RS1000010501 (11:120857334 G>A), RS1000019302 (11:120600366 A>G), RS1000027706 (11:120678374 A>C,G), RS1000031475 (11:120788363 A>G), RS1000041275 (11:120635622 T>C), RS1000043262 (11:120827358 C>A,T), RS1000075475 (11:120981623 T>A,G), RS1000082483 (11:120532212 C>T), RS1000083501 (11:120788070 C>A,T), RS1000096122 (11:120920497 C>A)

Disease associations

OMIM: gene MIM:600282 | disease phenotypes: MIM:147791

GenCC curated gene-disease

Mondo (1): Jacobsen syndrome (MONDO:0007838)

Orphanet (1): Jacobsen syndrome (Orphanet:2308)

HPO phenotypes

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

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST000579_27	Cognitive performance	8.000000e-06
GCST002048_3	Attention deficit hyperactivity disorder	7.000000e-06
GCST003263_50	Post bronchodilator FEV1 in COPD	1.000000e-06
GCST003263_51	Post bronchodilator FEV1 in COPD	1.000000e-06
GCST003263_52	Post bronchodilator FEV1 in COPD	1.000000e-06
GCST009207_12	Lateral ventricle volume	4.000000e-06

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0003926	neuropsychological test
EFO:0004314	forced expiratory volume
EFO:0008487	lateral ventricle volume measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2109241 (PROTEIN COMPLEX GROUP)

Molecules with ChEMBL bioactivity

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

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

PharmGKB clinical annotations

2 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs12800734	Efficacy	3	antidepressants	Depressive Disorder
rs1954787	Efficacy	3	antidepressants	Depressive Disorder

PharmGKB variants

2 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs1954787	GRIK4	3	2.75	1	antidepressants
rs12800734	GRIK4	3	2.25	1	antidepressants

GtoPdb / IUPHAR curated pharmacology

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

Target class: lgic — Ionotropic glutamate receptors

Binding affinities (BindingDB)

6 measured of 6 human assays (9 total across all organisms); most potent 6 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
(RS)-2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl)-propionicacid	KI	12 nM
NSC_3140	KI	1660 nM
7-Cyano-3-hydroxy-6-nitro-quinoxalin-2-ol anion	KI	2110 nM
Digensaeure	KI	2630 nM
(2S,3S,4S)-2-CARBOXY-4-[(1Z,3E,5R)-5-CARBOXY-1-METHYL-1,3-HEXADIENYL]-3-PYRROLIDINEACETIC ACID	KI	2770 nM
2-amino-3-(3,5-dioxo[1,2,4]oxadiazolidin-2-yl)propionic acid	IC50	9500 nM

ChEMBL bioactivities

29 potent at pChembl≥5 of 38 total, top 27 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.16	Ki	70	nM	CHEMBL13076
7.11	IC50	77	nM	KAINIC ACID
6.96	Ki	110	nM	CHEMBL12696
6.96	Ki	110	nM	CHEMBL273675
6.39	Ki	410	nM	CHEMBL268284
6.16	Ki	700	nM	CHEMBL84142
5.92	Ki	1200	nM	CHEMBL82375
5.82	Ki	1500	nM	CHEMBL12448
5.78	Ki	1670	nM	CHEMBL12989
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
5.10	IC50	8000	nM	NBQX
5.07	Ki	8500	nM	CHEMBL99012

PubChem BioAssay actives

3 with measured affinity, of 31 total; 3 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,3S,4S)-3-(carboxymethyl)-4-prop-1-en-2-ylpyrrolidine-2-carboxylic acid	255267: Percent inhibition against Kainate receptor at a compound concentration of 1 uM	ic50	0.0770	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

CTD chemical–gene interactions

25 total (human), top 25 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression	3
Lead	affects expression, affects methylation	2
Aflatoxin B1	affects methylation, decreases expression	2
GSK-J4	decreases expression	1
methyleugenol	decreases expression	1
bisphenol A	affects cotreatment, affects methylation, decreases methylation	1
11-nor-delta(9)-tetrahydrocannabinol-9-carboxylic acid	affects methylation, increases abundance	1
benzo(e)pyrene	affects methylation	1
aflatoxin B2	affects methylation	1
perfluorooctane sulfonic acid	decreases expression	1
abrine	increases expression	1
Grape Seed Proanthocyanidins	increases expression, affects cotreatment	1
2,6-dichloro-(1,4)benzoquinone	increases expression	1
Arsenic Trioxide	increases expression	1
Fulvestrant	affects cotreatment, affects methylation, decreases methylation	1
Air Pollutants	increases abundance, increases expression	1
Cannabinoids	affects methylation, increases abundance	1
Catechin	affects cotreatment, increases expression	1
Methapyrilene	affects methylation	1
Methylcholanthrene	affects binding, increases reaction	1
Smoke	decreases expression	1
Triiodothyronine	increases expression	1
Valproic Acid	increases methylation	1
Aflatoxin M1	decreases expression	1
Particulate Matter	increases abundance, increases expression	1

ChEMBL screening assays

24 unique, capped per target: 24 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)

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

Trial	Phase	Status	Title
NCT04463316	Not specified	RECRUITING	GROWing Up With Rare GENEtic Syndromes