GRID1

Summary

GRID1 (glutamate ionotropic receptor delta type subunit 1, HGNC:4575) is a protein-coding gene on chromosome 10q23.1-q23.2, encoding Glutamate receptor ionotropic, delta-1 (Q9ULK0). Member of the ionotropic glutamate receptor family, which plays a crucial role in synaptic organization and signal transduction in the central nervous system.

This gene encodes a subunit of glutamate receptor channels. These channels mediate most of the fast excitatory synaptic transmission in the central nervous system and play key roles in synaptic plasticity.

Source: NCBI Gene 2894 — RefSeq curated summary.

At a glance

• GWAS associations: 28
• Clinical variants (ClinVar): 161 total — 1 pathogenic
• Phenotypes (HPO): 20
• Druggable target: yes
• Dosage sensitivity (ClinGen): haploinsufficiency no evidence, triplosensitivity no evidence
• MANE Select transcript: NM_017551

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4575
Approved symbol	GRID1
Name	glutamate ionotropic receptor delta type subunit 1
Location	10q23.1-q23.2
Locus type	gene with protein product
Status	Approved
Aliases	GluD1, KIAA1220
Ensembl gene	ENSG00000182771
Ensembl biotype	protein_coding
OMIM	610659
Entrez	2894

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 1 protein_coding, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000327946, ENST00000464741, ENST00000552278

RefSeq mRNA: 1 — MANE Select: NM_017551 NM_017551

CCDS: CCDS31236

Canonical transcript exons

ENST00000327946 — 16 exons

Exon	Start	End
ENSE00001290733	85727855	85728052
ENSE00001291094	85856029	85856190
ENSE00001292711	85916186	85916239
ENSE00001297941	85723003	85723141
ENSE00001301542	85599552	85602701
ENSE00001305002	86363941	86364096
ENSE00001309837	85854496	85854615
ENSE00001311080	85619867	85620033
ENSE00001316713	85869010	85869180
ENSE00001317814	85647202	85647397
ENSE00001317862	85724352	85724676
ENSE00001326681	86206364	86206648
ENSE00001328131	86366314	86366795
ENSE00001345689	86138819	86139024
ENSE00003545652	85613407	85613647
ENSE00003717860	85729513	85729614

Expression profiles

Bgee: expression breadth ubiquitous, 180 present calls, max score 86.67.

FANTOM5 (CAGE): breadth broad, TPM avg 2.9560 / max 162.8225, expressed in 389 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
110405	1.3687	273
110404	0.9425	209
110401	0.3177	112
110402	0.1477	82
110400	0.1396	71
110403	0.0340	25
110399	0.0058	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
prefrontal cortex	UBERON:0000451	86.67	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	86.26	gold quality
spinal cord	UBERON:0002240	85.15	gold quality
nucleus accumbens	UBERON:0001882	85.06	gold quality
putamen	UBERON:0001874	85.04	gold quality
caudate nucleus	UBERON:0001873	84.76	gold quality
hypothalamus	UBERON:0001898	84.68	gold quality
substantia nigra	UBERON:0002038	84.56	gold quality
lateral globus pallidus	UBERON:0002476	84.33	gold quality
substantia nigra pars compacta	UBERON:0001965	84.20	gold quality
amygdala	UBERON:0001876	83.98	gold quality
right frontal lobe	UBERON:0002810	83.89	gold quality
frontal cortex	UBERON:0001870	83.88	gold quality
anterior cingulate cortex	UBERON:0009835	83.82	gold quality
Brodmann (1909) area 9	UBERON:0013540	83.81	gold quality
midbrain	UBERON:0001891	83.78	gold quality
cortical plate	UBERON:0005343	83.48	gold quality
neocortex	UBERON:0001950	83.46	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	83.20	gold quality
Ammon’s horn	UBERON:0001954	83.10	gold quality
cerebral cortex	UBERON:0000956	82.76	gold quality
substantia nigra pars reticulata	UBERON:0001966	82.59	gold quality
lateral nuclear group of thalamus	UBERON:0002736	82.38	silver quality
temporal lobe	UBERON:0001871	81.81	gold quality
forebrain	UBERON:0001890	80.89	gold quality
subthalamic nucleus	UBERON:0001906	80.04	gold quality
inferior vagus X ganglion	UBERON:0005363	79.95	gold quality
brain	UBERON:0000955	79.89	gold quality
entorhinal cortex	UBERON:0002728	79.89	gold quality
left lobe of thyroid gland	UBERON:0001120	79.75	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	3.61

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

137 targeting GRID1, 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-6867-5P	100.00	82.21	3464
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-10401-5P	99.99	65.79	948
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-8075	99.97	67.20	962
HSA-MIR-7152-3P	99.97	67.47	849
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-146A-5P	99.96	68.93	988
HSA-MIR-146B-5P	99.96	69.13	977
HSA-MIR-6755-5P	99.95	65.59	464

Functional genomics

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

Literature-anchored findings (GeneRIF, showing 5)

• results strongly support previously reported association studies, implicating GRID1 in the etiology of schizophrenia (PMID:17490860)
• The results of this study suggested that genetic variants in the GRID1 transcriptional regulatory region may play a role in the etiology of schizophrenia. (PMID:19346103)
• GRID1 genotype is related to gray matter variation in prefrontal and anterior thalamic brain areas in healthy subjects, but not in schizophrenia patients, indicating a potential role in thalamo-cortical functioning. (PMID:23017809)
• GRID1 expression is downregulated in both MECP2- and CDKL5-mutated iPS cells and upregulated in neuronal precursors and mature neurons. (PMID:24916645)
• Clinical features, functional consequences, and rescue pharmacology of missense GRID1 and GRID2 human variants. (PMID:37944084)

Cross-species orthologs

43 orthologs

Organism	Symbol	Gene ID
danio_rerio	grid1b	ENSDARG00000044161
danio_rerio	grid1a	ENSDARG00000074583
mus_musculus	Grid1	ENSMUSG00000041078
rattus_norvegicus	Grid1	ENSRNOG00000055499
drosophila_melanogaster	GluRIA	FBGN0004619
drosophila_melanogaster	GluRIIA	FBGN0004620
drosophila_melanogaster	GluRIIB	FBGN0020429
drosophila_melanogaster	clumsy	FBGN0026255
drosophila_melanogaster	GluRIID	FBGN0028422
drosophila_melanogaster	Ir7b	FBGN0029965
drosophila_melanogaster	Ir7c	FBGN0029966
drosophila_melanogaster	Ir7g	FBGN0029968
drosophila_melanogaster	Ir25a	FBGN0031634
drosophila_melanogaster	Ir60a	FBGN0034994
drosophila_melanogaster	Ir64a	FBGN0035604
drosophila_melanogaster	Ir68a	FBGN0036150
drosophila_melanogaster	Ir68b	FBGN0036250
drosophila_melanogaster	Ir75a	FBGN0036757
drosophila_melanogaster	Ir75d	FBGN0036829
drosophila_melanogaster	Ir76b	FBGN0036937
drosophila_melanogaster	Ir84a	FBGN0037501
drosophila_melanogaster	Ir85a	FBGN0037630
drosophila_melanogaster	Ir92a	FBGN0038789
drosophila_melanogaster	Grik	FBGN0038840
drosophila_melanogaster	Ekar	FBGN0039916
drosophila_melanogaster	CG11155	FBGN0039927
drosophila_melanogaster	Ir41a	FBGN0040849
drosophila_melanogaster	GluRIIC	FBGN0046113
drosophila_melanogaster	GluRIIE	FBGN0051201
drosophila_melanogaster	Nmdar2	FBGN0053513
drosophila_melanogaster	Ir7e	FBGN0259189
drosophila_melanogaster	Ir94d	FBGN0259193
drosophila_melanogaster	Ir93a	FBGN0259215
drosophila_melanogaster	Ir40a	FBGN0259683
drosophila_melanogaster	Ir76a	FBGN0260874
drosophila_melanogaster	Ir75c	FBGN0261401
drosophila_melanogaster	Ir75b	FBGN0261402
drosophila_melanogaster	GluRIB	FBGN0264000
caenorhabditis_elegans		WBGENE00001612
caenorhabditis_elegans	glr-3	WBGENE00001614
caenorhabditis_elegans		WBGENE00001618
caenorhabditis_elegans		WBGENE00003775
caenorhabditis_elegans		WBGENE00012190

Paralogs (17): GRIN2D (ENSG00000105464), GRIK5 (ENSG00000105737), GRIN3B (ENSG00000116032), GRIA2 (ENSG00000120251), GRIA3 (ENSG00000125675), GRIK4 (ENSG00000149403), GRID2 (ENSG00000152208), GRIA4 (ENSG00000152578), GRIA1 (ENSG00000155511), GRIN2C (ENSG00000161509), GRIK3 (ENSG00000163873), GRIK2 (ENSG00000164418), GRIK1 (ENSG00000171189), GRIN1 (ENSG00000176884), GRIN2A (ENSG00000183454), GRIN3A (ENSG00000198785), GRIN2B (ENSG00000273079)

Protein

Protein identifiers

Glutamate receptor ionotropic, delta-1 — Q9ULK0 (reviewed: Q9ULK0)

All UniProt accessions (2): Q9ULK0, G3V186

UniProt curated annotations — full annotation on UniProt →

Function. Member of the ionotropic glutamate receptor family, which plays a crucial role in synaptic organization and signal transduction in the central nervous system. Although it shares structural features with ionotropic glutamate receptors, does not bind glutamate as a primary ligand. Instead, forms trans-synaptic adhesion complexes with presynaptic neurexins and cerebellins, regulating NMDA and AMPA receptor activity and influencing synaptic plasticity through signal transduction. In the presence of neurexins and cerebellins, forms cation-selective channels that are proposed to be gated by glycine and D-serine. However, recent research disputes this ligand-gated cation channel activity. Cation-selective ion channel can be triggered by GRM1 in dopaminergic neurons. Also acts as a receptor for GABA, modulating inhibitory synaptic plasticity through non-ionotropic mechanisms.

Subunit / interactions. Homodimer. Interacts (via extracellular N-terminal domain) with CBLN1 (via C1q domain), and more weakly with CBLN2; the interactions mediate the trans-synaptic adhesion complexes also with neurexins and are required for ligand-gated cation channel activity.

Subcellular location. Postsynaptic cell membrane.

Similarity. Belongs to the glutamate-gated ion channel (TC 1.A.10.1) family. GRID1 subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9ULK0-1	1	yes
Q9ULK0-2	2

RefSeq proteins (1): NP_060021* (*=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

Catalyzed reactions (Rhea), 2 shown:

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

UniProt features (58 total): strand 15, helix 10, binding site 6, topological domain 4, glycosylation site 4, disulfide bond 3, transmembrane region 3, region of interest 2, compositionally biased region 2, mutagenesis site 2, turn 2, signal peptide 1, chain 1, site 1, splice variant 1, sequence variant 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
8BN2	X-RAY DIFFRACTION	1.63
8BN5	X-RAY DIFFRACTION	1.9
8BLJ	X-RAY DIFFRACTION	2.18

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9ULK0-F1	75.52	0.30

Functional residue map

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

Catalytic / active sites (1): 73 (essential for dimerization)

Ligand- & substrate-binding residues (6): 527; 530; 531; 753; 755; 757

Disulfide bonds (3): 80–351, 96–128, 294–306

Glycosylation sites (4): 131, 200, 422, 498

Mutagenesis-validated functional residues (2):

Position	Phenotype
446	loss of gaba recognition. no effect on serine recognition.
645–654	constitutively open the extracellular-ligand-gated ion channel. potentiated by gaba.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 520 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_UP, MODULE_93, ELVIDGE_HYPOXIA_DN, SHEPARD_BMYB_MORPHOLINO_UP, GOBP_GLUTAMINE_FAMILY_AMINO_ACID_BIOSYNTHETIC_PROCESS, BENPORATH_ES_WITH_H3K27ME3, GOBP_BEHAVIOR, GOMF_GLUTAMATE_GATED_RECEPTOR_ACTIVITY, KAAB_FAILED_HEART_ATRIUM_DN, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, GOBP_ALPHA_AMINO_ACID_METABOLIC_PROCESS, GOBP_INSULIN_SECRETION, GOBP_GLUTAMATE_METABOLIC_PROCESS, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP

GO Biological Process (13): phospholipase C-activating G protein-coupled receptor signaling pathway (GO:0007200), negative regulation of synaptic plasticity (GO:0031914), social behavior (GO:0035176), synaptic transmission, glutamatergic (GO:0035249), modulation of chemical synaptic transmission (GO:0050804), regulation of postsynaptic membrane neurotransmitter receptor levels (GO:0099072), regulation of postsynapse organization (GO:0099175), synaptic signaling via neuropeptide (GO:0099538), monoatomic ion transport (GO:0006811), monoatomic ion transmembrane transport (GO:0034220), ionotropic glutamate receptor signaling pathway (GO:0035235), regulation of synaptic plasticity (GO:0048167), regulation of postsynaptic membrane potential (GO:0060078)

GO Molecular Function (9): AMPA glutamate receptor activity (GO:0004971), GABA receptor activity (GO:0016917), identical protein binding (GO:0042802), G protein-coupled receptor activity involved in regulation of postsynaptic membrane potential (GO:0099530), transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential (GO:1904315), monoatomic ion channel activity (GO:0005216), protein binding (GO:0005515), ligand-gated monoatomic ion channel activity (GO:0015276), signaling receptor activity (GO:0038023)

GO Cellular Component (11): plasma membrane (GO:0005886), AMPA glutamate receptor complex (GO:0032281), dendritic spine (GO:0043197), postsynaptic membrane (GO:0045211), extracellular exosome (GO:0070062), trans-synaptic protein complex (GO:0098820), postsynaptic density membrane (GO:0098839), glutamatergic synapse (GO:0098978), GABA-ergic synapse (GO:0098982), membrane (GO:0016020), synapse (GO:0045202)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
chemical synaptic transmission	2
regulation of biological quality	2
glutamate-gated receptor activity	2
postsynaptic membrane	2
regulation of postsynaptic membrane potential	2
postsynapse	2
synapse	2
G protein-coupled receptor signaling pathway	1
phospholipase C activator activity	1
regulation of synaptic plasticity	1
behavior	1
biological process involved in intraspecies interaction between organisms	1
regulation of trans-synaptic signaling	1
regulation of synapse organization	1
postsynapse organization	1
synaptic signaling	1
transport	1
monoatomic ion transport	1
transmembrane transport	1
glutamate receptor signaling pathway	1
ligand-gated ion channel signaling pathway	1
modulation of chemical synaptic transmission	1
regulation of membrane potential	1
transmembrane signaling receptor activity	1
protein binding	1
G protein-coupled receptor activity	1
transmitter-gated monoatomic ion channel activity	1
monoatomic ion transmembrane transporter activity	1
channel activity	1
binding	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
dendrite	1
neuron spine	1
synaptic membrane	1
extracellular vesicle	1

Protein interactions and networks

STRING

1490 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GRID1	CAMK2A	Q9UQM7	734
GRID1	PRKCA	P17252	584
GRID1	GRID2IP	A4D2P6	559
GRID1	GRM4	Q14833	551
GRID1	GRM1	Q13255	530
GRID1	GRM3	Q14832	523
GRID1	GRM5	P41594	507
GRID1	GRM7	Q14831	501
GRID1	CBLN1	P02682	496
GRID1	GRM2	Q14416	494
GRID1	GRM8	O00222	492
GRID1	GABRA1	P14867	488
GRID1	CHRM3	P20309	480
GRID1	DLGAP1	P78335	474
GRID1	CHRNB2	P17787	473

IntAct

19 interactions, top by confidence:

A	B	Type	Score
GRID1	HBB	psi-mi:“MI:0915”(physical association)	0.590
	GRID1	psi-mi:“MI:0915”(physical association)	0.560
DEF6	ARHGAP42	psi-mi:“MI:0914”(association)	0.530
TCTN2	TPST2	psi-mi:“MI:0914”(association)	0.530
LGALS1	PODXL	psi-mi:“MI:0914”(association)	0.530
HTR3A	GPAA1	psi-mi:“MI:0914”(association)	0.350
CACNA1C	DISP2	psi-mi:“MI:0914”(association)	0.350
PDGFRA	GXYLT2	psi-mi:“MI:0914”(association)	0.350
CLEC12B	GXYLT2	psi-mi:“MI:0914”(association)	0.350
TCTN2	TMEM131L	psi-mi:“MI:0914”(association)	0.350
KLRC1	METTL15	psi-mi:“MI:0914”(association)	0.350
GRIA1	GAPDHS	psi-mi:“MI:0914”(association)	0.350
HTR3A	EXTL3	psi-mi:“MI:0914”(association)	0.350
	GRID1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (24): GRID1 (Affinity Capture-MS), GRID1 (Affinity Capture-MS), GRID1 (Affinity Capture-MS), GRID1 (Affinity Capture-MS), GRID1 (Affinity Capture-MS), HBB (Affinity Capture-MS), GRID1 (Protein-RNA), LILRB3 (Two-hybrid), GRID1 (Proximity Label-MS), GRID1 (Proximity Label-MS), GRID1 (Proximity Label-MS), GRID1 (Proximity Label-MS), GRID1 (Affinity Capture-MS), GRID1 (Affinity Capture-MS), HBB (Affinity Capture-MS)

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: A7XY94, O43424, P19439, Q01812, Q16099, Q16478, Q21415, Q5IS46, Q61625, Q61626, Q61627, Q62640, Q63226, Q63273, Q68Y21, Q8BMF5, Q90218, Q91755, Q91756, Q9ULK0, A1VZQ4, A5F353, P0AEM9, P0AEN0, P0AEQ3, P0AEQ4, P0AEQ5, P19490, P19493, P23818, P27676, P30859, P30860, P34299, P42199, P42261, P42400, P45024, P48058, P52626

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
“glutamic acid”	“up-regulates activity”	GRID1	“chemical activation”
GRID1	“up-regulates quantity”	calcium(2+)	relocalization

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	145
Likely benign	2
Benign	4

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
2502404	NM_017551.3(GRID1):c.1948G>A (p.Ala650Thr)	Pathogenic

SpliceAI

4359 predictions. Top by Δscore:

Variant	Effect	Δscore
10:85602700:TC:T	acceptor_gain	1.0000
10:85602701:CC:C	acceptor_gain	1.0000
10:85602702:C:A	acceptor_loss	1.0000
10:85602702:C:CC	acceptor_gain	1.0000
10:85602703:T:A	acceptor_loss	1.0000
10:85613402:CTGA:C	donor_loss	1.0000
10:85613403:TGA:T	donor_loss	1.0000
10:85613404:GACC:G	donor_loss	1.0000
10:85613405:A:T	donor_loss	1.0000
10:85613405:ACCT:A	donor_gain	1.0000
10:85613406:C:CT	donor_loss	1.0000
10:85613406:CCTC:C	donor_gain	1.0000
10:85613408:T:TA	donor_gain	1.0000
10:85613409:C:A	donor_gain	1.0000
10:85613643:GGATC:G	acceptor_gain	1.0000
10:85613644:GATC:G	acceptor_gain	1.0000
10:85613645:ATC:A	acceptor_gain	1.0000
10:85613646:TC:T	acceptor_gain	1.0000
10:85613647:CCTG:C	acceptor_gain	1.0000
10:85613648:C:CA	acceptor_loss	1.0000
10:85613648:C:CC	acceptor_gain	1.0000
10:85619866:CCT:C	donor_gain	1.0000
10:85619919:AAC:A	donor_gain	1.0000
10:85620034:C:CC	acceptor_gain	1.0000
10:85647197:CCTA:C	donor_loss	1.0000
10:85647198:CTA:C	donor_loss	1.0000
10:85647200:A:AC	donor_gain	1.0000
10:85647200:ACCTT:A	donor_gain	1.0000
10:85647201:C:CC	donor_gain	1.0000
10:85647201:C:CG	donor_loss	1.0000

AlphaMissense

6690 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:85723033:A:G	L656P	1.000
10:85723045:A:G	L652P	1.000
10:85723075:A:G	L642P	1.000
10:85723080:G:C	F640L	1.000
10:85723080:G:T	F640L	1.000
10:85723082:A:G	F640L	1.000
10:85723091:A:G	W637R	1.000
10:85723091:A:T	W637R	1.000
10:85723092:G:C	S636R	1.000
10:85723092:G:T	S636R	1.000
10:85723094:T:G	S636R	1.000
10:85724481:C:G	G577R	1.000
10:85724514:A:G	W566R	1.000
10:85724514:A:T	W566R	1.000
10:85727994:C:T	G465E	1.000
10:85856058:C:A	G362W	1.000
10:85856065:C:A	W359C	1.000
10:85856065:C:G	W359C	1.000
10:85856067:A:G	W359R	1.000
10:85856067:A:T	W359R	1.000
10:85856089:G:C	C351W	1.000
10:85856090:C:G	C351S	1.000
10:85856090:C:T	C351Y	1.000
10:85856091:A:G	C351R	1.000
10:85856091:A:T	C351S	1.000
10:85856113:C:A	W343C	1.000
10:85856113:C:G	W343C	1.000
10:85856115:A:G	W343R	1.000
10:85856115:A:T	W343R	1.000
10:85856153:A:G	L330P	1.000

dbSNP variants (sampled 300 via entrez): RS1000000131 (10:86123206 C>G), RS1000006196 (10:85800034 G>A), RS1000018371 (10:86133336 G>A,T), RS1000018776 (10:86367735 G>A,T), RS1000021331 (10:86330158 A>G), RS1000023172 (10:85660704 A>G), RS1000025163 (10:86240561 C>T), RS1000028436 (10:86133633 C>A,G), RS1000035671 (10:86162921 A>G), RS1000037820 (10:85606631 T>C), RS1000054491 (10:85601002 C>T), RS1000061210 (10:86082035 G>T), RS1000061954 (10:85878107 A>C), RS1000062669 (10:85748314 G>A), RS1000067954 (10:85933284 TTAAAAAAA>T)

Disease associations

OMIM: gene MIM:610659 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): prostate cancer (MONDO:0008315)

Orphanet (1): Familial prostate cancer (Orphanet:1331)

HPO phenotypes

20 total (20 of 20 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000825	Hyperinsulinemic hypoglycemia
HP:0001249	Intellectual disability
HP:0001263	Global developmental delay
HP:0001325	Hypoglycemic coma
HP:0001328	Specific learning disability
HP:0001508	Failure to thrive
HP:0002121	Generalized non-motor (absence) seizure
HP:0002173	Hypoglycemic seizures
HP:0002197	Generalized-onset seizure
HP:0002342	Moderate intellectual disability
HP:0003593	Infantile onset
HP:0003623	Neonatal onset
HP:0006476	Abnormality of the pancreatic islet cells
HP:0007018	Attention deficit hyperactivity disorder
HP:0008162	Asymptomatic hyperammonemia
HP:0008283	Fasting hyperinsulinemia
HP:0011198	EEG with generalized epileptiform discharges
HP:0012051	Reactive hypoglycemia
HP:0012402	Increased urine alpha-ketoglutarate concentration

GWAS associations

28 associations (top):

Study	Trait	p-value
GCST000441_3	Cardiac structure and function	7.000000e-07
GCST001588_8	Periodontal microbiota	4.000000e-06
GCST001749_4	Pancreatic cancer	3.000000e-06
GCST001840_11	Stearic acid (18:0) levels	4.000000e-07
GCST001961_5	Anorexia nervosa	2.000000e-06
GCST002783_232	Body mass index	1.000000e-08
GCST002783_412	Body mass index	3.000000e-08
GCST002783_468	Body mass index	2.000000e-06
GCST003480_1	Balding	4.000000e-09
GCST003831_6	Asthma	5.000000e-06
GCST003832_18	Asthma (childhood onset)	8.000000e-06
GCST003832_2	Asthma (childhood onset)	2.000000e-07
GCST004495_132	BMI (adjusted for smoking behaviour)	3.000000e-06
GCST004497_104	Body mass index (joint analysis main effects and smoking interaction)	5.000000e-06
GCST007327_78	Smoking status (ever vs never smokers)	4.000000e-08
GCST008181_21	Spontaneous preterm birth without premature rupture of membranes	4.000000e-06
GCST008270_3	Post-traumatic stress disorder symptoms in trauma-exposed soldiers	1.000000e-06
GCST009256_8	Superior temporal sulcus banks volume	5.000000e-06
GCST009516_8	Non-del(5q) myelodysplastic syndromes	9.000000e-06
GCST009996_12	HDL cholesterol levels	3.000000e-08
GCST009996_4	HDL cholesterol levels	5.000000e-10
GCST010266_9	Femoral neck bone mineral density and trunk fat mass adjusted by trunk lean mass	6.000000e-07
GCST010275_4	Renal overload gout	2.000000e-07
GCST010922_7	Hip bone mineral density and total body fat mass (bivariate analysis)	2.000000e-08
GCST010988_445	Adult body size	6.000000e-11
GCST010989_87	Body size at age 10	4.000000e-14
GCST010989_88	Body size at age 10	2.000000e-08
GCST012490_279	Femur bone mineral density x serum urate levels interaction	3.000000e-09

EFO canonical traits (12, from GWAS)

EFO ID	Trait name
EFO:0004298	cardiovascular measurement
EFO:0004340	body mass index
EFO:0007825	balding measurement
EFO:0004318	smoking behavior
EFO:0006917	spontaneous preterm birth
EFO:0008483	response to trauma exposure
EFO:0008535	post-traumatic stress disorder symptom measurement
EFO:0007805	HDL cholesterol change measurement
EFO:0007785	femoral neck bone mineral density
EFO:0007702	hip bone mineral density
EFO:0009819	comparative body size at age 10, self-reported
EFO:0004531	urate measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D011471	Prostatic Neoplasms	C04.588.945.440.770; C12.100.500.260.750; C12.100.500.565.625; C12.200.294.260.750; C12.200.294.565.625; C12.200.758.409.750; C12.900.619.750

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4524129 (PROTEIN COMPLEX GROUP)

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: lgic — Ionotropic glutamate receptors

CTD chemical–gene interactions

28 total (human), top 28 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression, increases expression, increases methylation	4
Aflatoxin B1	affects methylation, decreases expression, increases methylation	3
sodium arsenite	affects methylation, decreases expression	2
aristolochic acid I	decreases expression	1
bisphenol F	affects cotreatment, decreases methylation	1
methyleugenol	decreases expression	1
bisphenol A	increases methylation	1
benzo(e)pyrene	affects methylation	1
aflatoxin B2	affects methylation	1
abrine	decreases expression	1
bisphenol S	decreases methylation	1
jinfukang	affects cotreatment, decreases expression	1
Decitabine	decreases expression, decreases reaction	1
Sunitinib	decreases expression	1
Fulvestrant	affects cotreatment, decreases methylation, increases methylation	1
Cisplatin	affects cotreatment, decreases expression	1
Lead	affects expression	1
Methapyrilene	affects methylation	1
N-Nitrosopyrrolidine	decreases expression	1
Phthalic Acids	increases methylation	1
Silicon Dioxide	decreases expression	1
Smoke	decreases expression, decreases reaction	1
Tretinoin	decreases expression	1
Valproic Acid	increases expression	1
Antirheumatic Agents	increases expression	1
Okadaic Acid	decreases expression	1
Vitamin K 3	affects expression	1
Permethrin	increases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4886917	Binding	Glutamate, Non-Selective Eurofins-Panlabs radioligand binding assay	Profiling data from Eurofins-Panlabs

Cellosaurus cell lines

2 cell lines: 2 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_YA52	IDG-HEK293T-GRID1-isoform-1-V5-OE	Transformed cell line	Female
CVCL_YA53	IDG-HEK293T-GRID1-isoform-2-V5-OE	Transformed cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00029224	PHASE4	COMPLETED	Treatment With Zoledronic Acid in Patients With Breast Cancer, Multiple Myeloma, and Prostate Cancer With Cancer Related Bone Lesions
NCT00035997	PHASE4	COMPLETED	Open-label Trial on the Effect of I.V. Zoledronic Acid 4 mg on Bone Density in Hormone Sensitive Prostate Cancer Patients With Bone Metastasis
NCT00063609	PHASE4	COMPLETED	The Effect of Zoledronic Acid on Bone Loss in Prostate Cancer Patients Undergoing Androgen Deprivation Therapy
NCT00103623	PHASE4	SUSPENDED	The Plenaxis® Experience Study
NCT00106392	PHASE4	COMPLETED	A Safety and Efficacy Study of Prograf in the Prevention of Erectile Dysfunction After Radical Prostatectomy
NCT00185029	PHASE4	UNKNOWN	MR-Lymphography and Lymph Node Staging in Prostate Cancer
NCT00199485	PHASE4	COMPLETED	Angelica Sinensis for the Treatment of Hot Flashes in Men Undergoing LHRH Therapy for Prostate Cancer
NCT00219219	PHASE4	COMPLETED	Zoledronic Acid in the Prevention of Skeletal-related Events in Hormone Refractory and Hormone-sensitive Prostate Cancer Patients With Bone Metastases
NCT00219271	PHASE4	COMPLETED	Effect Of Zoledronic Acid On Circulating And Bone Marrow-Residing Prostate Cancer Cells In Patients With Clinically Localized Prostate Cancer
NCT00237146	PHASE4	COMPLETED	Study to Evaluate Zoledronic Acid on Quality of Life and Skeletal-related Events as Adjuvant Treatment in Patients With Hormone-naïve Prostate Cancer and Bone Metastasis Who Have Undergone Orchiectomy
NCT00242554	PHASE4	COMPLETED	Open-label Phase IV Clinical Trial to Evaluate the Safety and Tolerability of Zoledronic Acid in Patients With Prostate Cancer and Bone Metastases
NCT00280098	PHASE4	COMPLETED	Docetaxel in the Treatment of Hormone Refractory Prostate Cancer
NCT00293696	PHASE4	COMPLETED	Casodex/Zoladex Biomarkers in Localised Prostate Cancer
NCT00334139	PHASE4	COMPLETED	Effect of Zoledronic Acid on Bone Metabolism in Patients With Bone Metastasis and Prostate or Breast Cancer
NCT00375765	PHASE4	COMPLETED	Effects On Dihydrotestosterone Regulated Gene Expression In Benign Prostatic Hyperplasia Or Prostate Cancer
NCT00391690	PHASE4	COMPLETED	Evaluation of Bone Markers as Diagnostic Tools for Early Detection of Bone Metastases in Patients With High Risk Prostate Cancer
NCT00422708	PHASE4	COMPLETED	Local Anesthesia for Prostate Biopsy
NCT00526331	PHASE4	COMPLETED	Evaluation of Arterial Pressure Based Cardiac Output for Goal-Directed Perioperative Therapy
NCT00590213	PHASE4	COMPLETED	Compare the Value of Prophylactic Versus Therapeutic Breast Radiotherapy in CASODEX
NCT00629330	PHASE4	TERMINATED	Dissemination of Prostate Cancer Screening to PCP’s in African American Communities
NCT00771966	PHASE4	COMPLETED	Radical Prostatectomy and Perioperative Fluid Therapy
NCT00805701	PHASE4	COMPLETED	Study Assessing The Efficacy And Safety Of Avodart (Dutasteride) At Improving Urinary Symptoms In Men With Prostate Cancer Who Are Undergoing Seed Implantation
NCT00859027	PHASE4	COMPLETED	Effect Of Risedronate On Bone Mass In Older Men Receiving Neoadjuvant Therapy For Prostate Cancer
NCT00906269	PHASE4	UNKNOWN	Can Hyperbaric Oxygen Improve Erectile Function Following Surgery for Prostate Cancer
NCT00953277	PHASE4	COMPLETED	Study of Nerve Reconstruction Using AVANCE in Subjects Who Undergo Robotic Assisted Prostatectomy for Treatment of Prostate Cancer
NCT00982800	PHASE4	COMPLETED	Does Postoperative Gabapentin Reduce Pain, Opioid Consumption and Anxiety and Have a Positive Effect on Health Related Quality of Life After Radical Prostatectomy?
NCT01083199	PHASE4	COMPLETED	Global Performance Evaluation of the AMS CONTINUUM™ Device
NCT01136226	PHASE4	COMPLETED	Evaluate Recovery of Testosterone for Patients Using Eligard
NCT01161563	PHASE4	COMPLETED	Randomized Crossover Trial to Assess the Tolerability of Gonadotropin Releasing Hormone (GnRH) Analogue Administration
NCT01230905	PHASE4	COMPLETED	Study to Monitor the Effects of Androgen Suppression Treatment on the Heart
NCT01296672	PHASE4	COMPLETED	3 Month Finasteride Challenge Test Can Significantly Improve the Performance of Screening for Prostate Cancer
NCT01365143	PHASE4	TERMINATED	Prospective Randomized Trial Comparing Robotic Versus Open Radical Prostatectomy
NCT01379742	PHASE4	UNKNOWN	Comparison of Between ThinSeed™ and OncoSeed™ for Permanent Prostate Brachytherapy
NCT01486563	PHASE4	COMPLETED	Hydroxyethyl Starch and Renal Function After Radical Prostatectomy
NCT01511874	PHASE4	COMPLETED	Efficacy and Safety Study of ELIGARD 22.5mg With Prostate Cancer
NCT01512472	PHASE4	TERMINATED	Firmagon (Degarelix) Intermittent Therapy
NCT01547416	PHASE4	COMPLETED	The Effect of Combined General/Epidural Anesthesia Versus General Anesthesia on Diaphragmatic Function
NCT01571544	PHASE4	COMPLETED	The Use of Thermal Suits as Preventing Hypothermia During Surgery
NCT01581749	PHASE4	UNKNOWN	Evaluation of Truebeam for Low-Intermediate Risk Prostate Cancer
NCT01649635	PHASE4	COMPLETED	Study of Cabazitaxel Combined With Prednisone and Prophylaxis of Neutropenia Complications in the Treatment of Patients With Metastatic Castration-resistant Prostate Cancer