GRM8

Summary

GRM8 (glutamate metabotropic receptor 8, HGNC:4600) is a protein-coding gene on chromosome 7q31.33, encoding Metabotropic glutamate receptor 8 (O00222). G-protein coupled receptor for glutamate.

L-glutamate is the major excitatory neurotransmitter in the central nervous system and activates both ionotropic and metabotropic glutamate receptors. Glutamatergic neurotransmission is involved in most aspects of normal brain function and can be perturbed in many neuropathologic conditions. The metabotropic glutamate receptors are a family of G protein-coupled receptors, that have been divided into 3 groups on the basis of sequence homology, putative signal transduction mechanisms, and pharmacologic properties. Group I includes GRM1 and GRM5 and these receptors have been shown to activate phospholipase C. Group II includes GRM2 and GRM3 while Group III includes GRM4, GRM6, GRM7 and GRM8. Group II and III receptors are linked to the inhibition of the cyclic AMP cascade but differ in their agonist selectivities. Alternatively spliced transcript variants encoding different isoforms have been described for this gene.

Source: NCBI Gene 2918 — RefSeq curated summary.

At a glance

• GWAS associations: 26
• Clinical variants (ClinVar): 169 total — 1 pathogenic
• Druggable target: yes — 3 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_000845

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4600
Approved symbol	GRM8
Name	glutamate metabotropic receptor 8
Location	7q31.33
Locus type	gene with protein product
Status	Approved
Aliases	GLUR8, GPRC1H, mGlu8, MGLUR8
Ensembl gene	ENSG00000179603
Ensembl biotype	protein_coding
OMIM	601116
Entrez	2918

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 8 protein_coding, 7 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay

ENST00000339582, ENST00000341617, ENST00000358373, ENST00000412160, ENST00000423518, ENST00000448250, ENST00000457830, ENST00000465800, ENST00000465844, ENST00000472701, ENST00000473254, ENST00000480995, ENST00000489939, ENST00000495315, ENST00000706915, ENST00000706916, ENST00000706917

RefSeq mRNA: 7 — MANE Select: NM_000845 NM_000845, NM_001127323, NM_001371083, NM_001371084, NM_001371085, NM_001371086, NM_001371087

CCDS: CCDS47696, CCDS5794

Canonical transcript exons

ENST00000339582 — 11 exons

Exon	Start	End
ENSE00001514832	127242695	127243515
ENSE00001514833	127252797	127252941
ENSE00003502910	126769865	126770065
ENSE00003525161	127106496	127106712
ENSE00003542674	126609362	126609498
ENSE00003563458	126902542	126902679
ENSE00003574672	126532952	126533887
ENSE00003592965	126904548	126904683
ENSE00003636699	126903972	126904126
ENSE00003661295	126446126	126446372
ENSE00003997441	126438598	126439168

Expression profiles

Bgee: expression breadth ubiquitous, 171 present calls, max score 84.86.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.4161 / max 121.5997, expressed in 179 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
86022	0.2838	166
86014	0.0915	5
86021	0.0217	9
86020	0.0128	3
204681	0.0063	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	84.86	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	82.94	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	80.93	gold quality
left testis	UBERON:0004533	78.83	gold quality
right testis	UBERON:0004534	78.37	gold quality
oocyte	CL:0000023	76.95	gold quality
testis	UBERON:0000473	76.80	gold quality
choroid plexus epithelium	UBERON:0003911	76.65	gold quality
prefrontal cortex	UBERON:0000451	76.34	gold quality
Brodmann (1909) area 9	UBERON:0013540	75.57	gold quality
corpus callosum	UBERON:0002336	74.93	gold quality
cingulate cortex	UBERON:0003027	74.69	gold quality
anterior cingulate cortex	UBERON:0009835	74.51	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	74.31	gold quality
ventricular zone	UBERON:0003053	73.96	gold quality
putamen	UBERON:0001874	73.32	gold quality
caudate nucleus	UBERON:0001873	73.06	gold quality
right frontal lobe	UBERON:0002810	72.79	gold quality
neocortex	UBERON:0001950	71.98	gold quality
triceps brachii	UBERON:0001509	71.89	gold quality
gluteal muscle	UBERON:0002000	71.77	gold quality
frontal cortex	UBERON:0001870	71.69	gold quality
biceps brachii	UBERON:0001507	71.66	gold quality
inferior olivary complex	UBERON:0002127	71.17	gold quality
parotid gland	UBERON:0001831	70.89	gold quality
hypothalamus	UBERON:0001898	70.80	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	70.69	gold quality
sperm	CL:0000019	70.52	silver quality
cerebral cortex	UBERON:0000956	70.48	gold quality
telencephalon	UBERON:0001893	70.19	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-HCAD-35	yes	6.85
E-ANND-3	yes	6.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

45 targeting GRM8, 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-4795-3P	100.00	74.62	4024
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-3163	100.00	77.23	8605
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-33A-5P	99.99	68.62	1055
HSA-MIR-33B-5P	99.99	68.58	1062
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-4648	99.91	67.00	710
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-6515-3P	99.82	68.19	1933
HSA-MIR-944	99.82	70.85	3042
HSA-MIR-548AJ-5P	99.78	71.12	3085
HSA-MIR-548F-5P	99.78	71.02	3093
HSA-MIR-548G-5P	99.78	71.12	3085
HSA-MIR-548X-5P	99.78	71.12	3085
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-7157-5P	99.66	69.33	1829
HSA-MIR-4310	99.59	68.84	2527
HSA-MIR-543	99.52	69.03	2595
HSA-MIR-1324	99.46	66.57	1302
HSA-MIR-4705	99.10	69.10	1091

Literature-anchored findings (GeneRIF, showing 16)

• Pias1 binds to and sumoylates metabotropic glutamate receptor 8 (PMID:16144832)
• Polymorphism not associated with panic disorder. (PMID:17167337)
• GRM8 genes are likely involved in the pathogenesis of autistic disorder. (PMID:17955477)
• Association of suingle nucleotide polymorphisms in GRM8 with theta power of event-related oscillations and alcohol dependence are reported. (PMID:18618593)
• Eight suggestive significant loci were detected with a series of genes expressed within the inner ear that underlie the auditory function, such as: DCLK1, PTPRD, GRM8, CMIP. (PMID:21493956)
• Glutamate acts as a partial inverse agonist to metabotropic glutamate receptor with a single amino acid mutation in the transmembrane domain (PMID:23420844)
• propose three potential human candidate genes for voluntary physical exercise levels (MC3R, CYP24A1, and GRM8). (PMID:24821406)
• The GRM8 gene might play an important role in the pathogenesis of schizophrenia. (PMID:25588301)
• Genome wide association study and meta-analysis results detected rs6951643, a GRM8 genetic variant as suggestive marker for sporadic Creutzfeldt-Jakob disease risk mapping outside the PRNP region. (PMID:25918841)
• These results further implicate the role of glutamate receptor genes such as GRM8 in the development of alcohol dependence. (PMID:25978827)
• Study represents a genetic association test towards single variant and multi-markers interaction of GRM7 and GRM8 genes in both schizophrenia and major depressive disorders in Han Chinese population (PMID:26655190)
• This study showed that GRM8 was nominally associated (p < 0.05) with both delta measures (energy and intertrial phase coherence). (PMID:27871913)
• rs712723 in GRM8 was selected for genotyping. The allele C and genotype CC (allele C: OR 1.48, 95% CI 1.13-1.94; genotype CC: OR 1.71, 95% CI 1.09-2.68) of rs712723 polymorphism was found to have a significant association with risk of schizophrenia while allele T (P = 0.003) and genotype TT (P = 0.028) frequencies were found lower in control patients. (PMID:30288643)
• Transcriptional activation of GRM8 lung squamous cell carcinoma tumor cells induced cell proliferation by inhibiting cAMP pathway and activating MAPK pathway. (PMID:30391781)
• GRM8 genotype is associated with externalizing disorders and greater inter-trial variability in brain activation during a response inhibition task. (PMID:32299001)
• Association between the group III metabotropic glutamate receptor gene polymorphisms and attention-deficit/hyperactivity disorder and functional exploration of risk loci. (PMID:33068816)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	grm8b	ENSDARG00000076508
danio_rerio	grm8a	ENSDARG00000077654
mus_musculus	Grm8	ENSMUSG00000024211
rattus_norvegicus	Grm8	ENSRNOG00000021468
drosophila_melanogaster	mGluR	FBGN0019985

Paralogs (7): GRM6 (ENSG00000113262), GRM4 (ENSG00000124493), GRM1 (ENSG00000152822), GRM2 (ENSG00000164082), GRM5 (ENSG00000168959), GRM7 (ENSG00000196277), GRM3 (ENSG00000198822)

Protein

Protein identifiers

Metabotropic glutamate receptor 8 — O00222 (reviewed: O00222)

All UniProt accessions (5): A0A9L9PYG5, C9J7I1, E7ETK3, O00222, H7C4V5

UniProt curated annotations — full annotation on UniProt →

Function. G-protein coupled receptor for glutamate. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Signaling inhibits adenylate cyclase activity.

Subunit / interactions. Interacts with PICK1.

Subcellular location. Cell membrane.

Similarity. Belongs to the G-protein coupled receptor 3 family.

Isoforms (3)

UniProt ID	Names	Canonical?
O00222-1	A, mGluR8a	yes
O00222-2	B, mGluR8b
O00222-3	C, mGluR8c

RefSeq proteins (7): NP_000836, NP_001120795, NP_001358012, NP_001358013, NP_001358014, NP_001358015, NP_001358016 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000144	GPCR_3_mGluR8	Family
IPR000162	GPCR_3_mtglu_rcpt	Family
IPR000337	GPCR_3	Family
IPR001828	ANF_lig-bd_rcpt	Domain
IPR011500	GPCR_3_9-Cys_dom	Domain
IPR017978	GPCR_3_C	Domain
IPR017979	GPCR_3_CS	Conserved_site
IPR028082	Peripla_BP_I	Homologous_superfamily
IPR038550	GPCR_3_9-Cys_sf	Homologous_superfamily
IPR050726	mGluR	Family

Pfam: PF00003, PF01094, PF07562

UniProt features (101 total): strand 20, helix 15, sequence variant 11, turn 11, topological domain 8, disulfide bond 8, transmembrane region 7, binding site 5, glycosylation site 5, sequence conflict 5, splice variant 3, signal peptide 1, chain 1, cross-link 1

Structure

Experimental structures (PDB)

8 structures.

PDB	Method	Resolution (Å)
6BSZ	X-RAY DIFFRACTION	2.65
6BT5	X-RAY DIFFRACTION	2.92
6E5V	X-RAY DIFFRACTION	2.95
9MB9	ELECTRON MICROSCOPY	2.97
9MBC	ELECTRON MICROSCOPY	2.97
9MBA	ELECTRON MICROSCOPY	3.14
9MBB	ELECTRON MICROSCOPY	3.25
9MBD	ELECTRON MICROSCOPY	3.32

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O00222-F1	84.11	0.52

Antibody-complex structures (SAbDab): 1 — 9MBA

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 (5): 156; 177–179; 227; 309; 401

Post-translational modifications (1): 882

Disulfide bonds (8): 64–106, 246–534, 369–384, 424–431, 516–535, 520–538, 541–553, 556–569

Glycosylation sites (5): 95, 298, 452, 480, 565

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-418594	G alpha (i) signalling events
R-HSA-420499	Class C/3 (Metabotropic glutamate/pheromone receptors)

MSigDB gene sets: 145 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_UP, GSE18804_BRAIN_VS_COLON_TUMORAL_MACROPHAGE_UP, BROWNE_HCMV_INFECTION_6HR_DN, TAATAAT_MIR126, GOBP_REGULATION_OF_SYNAPTIC_TRANSMISSION_GLUTAMATERGIC, TGACCTY_ERR1_Q2, TAL1ALPHAE47_01, TACAATC_MIR508, GOBP_G_PROTEIN_COUPLED_GLUTAMATE_RECEPTOR_SIGNALING_PATHWAY, ACEVEDO_LIVER_CANCER_WITH_H3K27ME3_UP, GOBP_CELL_CELL_SIGNALING, BROWNE_HCMV_INFECTION_48HR_DN, GOBP_ADENYLATE_CYCLASE_MODULATING_G_PROTEIN_COUPLED_RECEPTOR_SIGNALING_PATHWAY, MORF_ZNF10, MODULE_289

GO Biological Process (7): adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway (GO:0007193), adenylate cyclase-inhibiting G protein-coupled glutamate receptor signaling pathway (GO:0007196), G protein-coupled glutamate receptor signaling pathway (GO:0007216), visual perception (GO:0007601), regulation of synaptic transmission, glutamatergic (GO:0051966), signal transduction (GO:0007165), G protein-coupled receptor signaling pathway (GO:0007186)

GO Molecular Function (3): group III metabotropic glutamate receptor activity (GO:0001642), G protein-coupled receptor activity (GO:0004930), glutamate receptor activity (GO:0008066)

GO Cellular Component (2): plasma membrane (GO:0005886), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
GPCR downstream signalling	1
GPCR ligand binding	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
adenylate cyclase inhibiting G protein-coupled glutamate receptor activity	2
G protein-coupled receptor signaling pathway	2
transmembrane signaling receptor activity	2
adenylate cyclase-modulating G protein-coupled receptor signaling pathway	1
adenylate cyclase inhibitor activity	1
adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway	1
G protein-coupled glutamate receptor signaling pathway	1
glutamate receptor signaling pathway	1
G protein-coupled glutamate receptor activity	1
sensory perception of light stimulus	1
synaptic transmission, glutamatergic	1
modulation of chemical synaptic transmission	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
G protein-coupled receptor activity	1
signal transduction	1
glutamate binding	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1983 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GRM8	ADGRB3	O60242	717
GRM8	HYAL4	Q2M3T9	681
GRM8	GRIK1	P39086	672
GRM8	CHRM2	P08172	667
GRM8	ADGRL3	Q9HAR2	640
GRM8	GRIN2D	O15399	625
GRM8	GRIN3A	Q8TCU5	615
GRM8	GRIA4	P48058	599
GRM8	HTR2A	P28223	596
GRM8	GRIN2C	Q14957	587
GRM8	GRIA2	P42262	586
GRM8	GRIA1	P42261	570
GRM8	GRIN2B	Q13224	563
GRM8	APLNR	P35414	561
GRM8	GRIN2A	Q12879	555

IntAct

2 interactions, top by confidence:

A	B	Type	Score
DNAJC5	GRM8	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (1): DNAJC5 (FRET)

ESM2 similar proteins: A2A259, A2AIR5, H2Q5A1, O00222, O15399, O60242, O75077, O75882, O97741, P15209, P24786, P31423, P35400, P37088, P47743, P55270, P70579, Q00961, Q01098, Q03351, Q03391, Q13507, Q14833, Q14957, Q16288, Q1ZZH0, Q4R766, Q5IS37, Q5RDQ8, Q62645, Q63604, Q68ED2, Q68EF4, Q6AYT7, Q80ZF8, Q8CIW5, Q8TCU5, Q8VHN2, Q91044, Q91YD4

Diamond homologs: O00222, O15303, O62714, P23385, P31421, P31422, P31423, P31424, P35349, P35400, P41180, P41594, P47743, P48442, P70579, P91685, P97772, Q09630, Q13255, Q14416, Q14831, Q14832, Q14833, Q14BI2, Q1ZZH0, Q1ZZH1, Q3UVX5, Q5NCH9, Q5RAL3, Q5RDQ8, Q68ED2, Q68EF4, Q863I4, Q9QY96, Q9QYS2, P35384, A3QNZ8, A3QNZ9, A3QP00, A3QP01

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
“glutamic acid”	“up-regulates activity”	GRM8	“chemical activation”
GRM8	“up-regulates activity”	GNAS	binding
GRM8	up-regulates	Excitatory_synaptic_transmission
GRM8	“up-regulates quantity”	calcium(2+)	relocalization

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	118
Likely benign	24
Benign	14

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
57069	GRCh38/hg38 7q31.33(chr7:126029439-126947804)x1	Pathogenic

SpliceAI

5371 predictions. Top by Δscore:

Variant	Effect	Δscore
7:126446124:A:AC	donor_gain	1.0000
7:126446125:C:CC	donor_gain	1.0000
7:126609356:A:AC	donor_gain	1.0000
7:126609357:C:CC	donor_gain	1.0000
7:126609357:CTTG:C	donor_gain	1.0000
7:126609360:G:GC	donor_gain	1.0000
7:126609361:C:CC	donor_gain	1.0000
7:126609495:CTGC:C	acceptor_gain	1.0000
7:126609496:TGC:T	acceptor_gain	1.0000
7:126609498:CCTA:C	acceptor_loss	1.0000
7:126609499:C:CC	acceptor_gain	1.0000
7:126609509:T:C	acceptor_gain	1.0000
7:126769858:AACTT:A	donor_loss	1.0000
7:126769859:ACTT:A	donor_loss	1.0000
7:126769860:CTT:C	donor_loss	1.0000
7:126769861:TTA:T	donor_loss	1.0000
7:126769862:TAC:T	donor_loss	1.0000
7:126769863:ACCAT:A	donor_loss	1.0000
7:126770061:CAGCC:C	acceptor_gain	1.0000
7:126770062:AGCC:A	acceptor_gain	1.0000
7:126770063:GCC:G	acceptor_gain	1.0000
7:126770064:CC:C	acceptor_gain	1.0000
7:126770064:CCC:C	acceptor_gain	1.0000
7:126770065:CC:C	acceptor_gain	1.0000
7:126770066:C:CC	acceptor_gain	1.0000
7:126770066:CTGCA:C	acceptor_loss	1.0000
7:126902537:GTTA:G	donor_loss	1.0000
7:126902538:TTA:T	donor_loss	1.0000
7:126902539:TA:T	donor_loss	1.0000
7:126902540:A:AT	donor_loss	1.0000

AlphaMissense

5975 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:126533002:A:G	W794R	1.000
7:126533002:A:T	W794R	1.000
7:126533011:A:G	C791R	1.000
7:126533031:C:T	G784E	1.000
7:126533051:G:C	F777L	1.000
7:126533051:G:T	F777L	1.000
7:126533053:A:G	F777L	1.000
7:126533093:A:C	C763W	1.000
7:126533351:A:C	F677L	1.000
7:126533351:A:T	F677L	1.000
7:126533353:A:G	F677L	1.000
7:126533355:A:G	I676T	1.000
7:126533355:A:T	I676K	1.000
7:126533358:C:G	R675P	1.000
7:126533367:C:G	R672P	1.000
7:126533375:T:A	K669N	1.000
7:126533375:T:G	K669N	1.000
7:126533382:A:G	L667P	1.000
7:126533774:C:A	W536C	1.000
7:126533774:C:G	W536C	1.000
7:126533835:C:G	C516S	1.000
7:126533836:A:G	C516R	1.000
7:126533836:A:T	C516S	1.000
7:126769975:A:G	L416P	1.000
7:126770000:C:G	A408P	1.000
7:126770010:A:C	F404L	1.000
7:126770010:A:T	F404L	1.000
7:126770012:A:G	F404L	1.000
7:126902546:G:C	C384W	1.000
7:126902547:C:G	C384S	1.000

dbSNP variants (sampled 300 via entrez): RS1000006992 (7:126908573 G>T), RS1000008357 (7:126951214 A>G), RS1000009216 (7:126569623 T>C), RS1000012563 (7:126992362 T>A), RS1000013556 (7:127248887 A>G,T), RS1000019620 (7:127118826 G>A), RS1000020035 (7:127129967 AG>A), RS1000024209 (7:127248065 A>T), RS1000032462 (7:126676158 C>G,T), RS1000041956 (7:126777063 A>AT), RS1000042269 (7:126927253 A>C,G), RS1000042765 (7:126652027 C>A), RS1000048944 (7:126765955 T>C), RS1000056778 (7:126986593 T>C), RS1000060328 (7:127205447 T>C)

Disease associations

OMIM: gene MIM:601116 | disease phenotypes:

GenCC curated gene-disease

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

Orphanet (2): Familial prostate cancer (Orphanet:1331), Syndromic anorectal malformation (Orphanet:117573)

HPO phenotypes

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

GWAS associations

26 associations (top):

Study	Trait	p-value
GCST000555_2	Carotid atherosclerosis in HIV infection	9.000000e-07
GCST000628_6	Chemerin levels	9.000000e-06
GCST000779_10	Depression (quantitative trait)	6.000000e-06
GCST002543_2	Hearing function	1.000000e-07
GCST002710_2	Anti-saccade response	5.000000e-06
GCST002878_2	Creutzfeldt-Jakob disease (sporadic)	2.000000e-08
GCST003809_4	Response to selective serotonin reuptake inhibitors and depression	1.000000e-06
GCST004865_36	Itch intensity from mosquito bite adjusted by bite size	8.000000e-06
GCST005025_28	Anti-saccade response	6.000000e-06
GCST006940_82	Neurociticism	7.000000e-14
GCST006940_86	Neurociticism	5.000000e-09
GCST006944_7	Experiencing mood swings	4.000000e-08
GCST006946_1	Worry too long after an embarrassing experience	2.000000e-10
GCST006950_18	Feeling worry	2.000000e-10
GCST006951_13	Feeling hurt	1.000000e-11
GCST006951_14	Feeling hurt	7.000000e-11
GCST006951_15	Feeling hurt	1.000000e-16
GCST007603_22	Smoking initiation	1.000000e-08
GCST007708_8	Worry/vulnerability (special factor of neuroticism)	4.000000e-08
GCST007709_30	General factor of neuroticism	2.000000e-08
GCST008156_83	Hip circumference adjusted for BMI	6.000000e-06
GCST008504_6	Fasting glucose change (long-term)	3.000000e-06
GCST008832_13	Gastroesophageal reflux disease	8.000000e-09
GCST010118_154	Type 2 diabetes	3.000000e-31
GCST012354_25	Anxiety	2.000000e-20
GCST90000514_12	Gastroesophageal reflux disease	1.000000e-10

EFO canonical traits (13, from GWAS)

EFO ID	Trait name
EFO:0004573	chemerin measurement
EFO:0006874	antisaccade response measurement
EFO:1000656	sporadic Creutzfeld Jacob disease
EFO:0005658	response to selective serotonin reuptake inhibitor
EFO:0008377	mosquito bite reaction itch intensity measurement
EFO:0008378	mosquito bite reaction size measurement
EFO:0007660	neuroticism measurement
EFO:0008475	mood instability measurement
EFO:0009589	worry measurement
EFO:0009599	feeling emotionally hurt measurement
EFO:0005670	smoking initiation
EFO:0008039	BMI-adjusted hip circumference
EFO:0009863	anxiety 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): CHEMBL3228 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

3 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 929,874 (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
CHEMBL8759	EGLUMETAD	2	81
CHEMBL375611	LY404039	1	37

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: gpcr — Metabotropic glutamate receptors

Most potent curated ligand interactions (20 total), top 20:

Ligand	Action	Affinity	Parameter
MAP4	Antagonist	7.6	pIC50
(S)-3,4-DCPG	Full agonist	7.5	pEC50
L-AP4	Full agonist	7.2	pIC50
L-serine-O-phosphate	Full agonist	7.2	pIC50
LY341495	Antagonist	6.8	pIC50
(R,S)-4-PPG	Full agonist	6.7	pEC50
[3H]AP4	Full agonist	6.7	pKd
VU0422288	Positive	6.7	pKB
L-CCG-I	Full agonist	6.3	pIC50
CPPG	Antagonist	6.3	pKi
AZ12216052	Positive	6.0	pEC50
L-glutamic acid	Agonist	5.6	pEC50
DCG-IV	Antagonist	5.5	pIC50
D-AP4	Full agonist	5.5	pEC50
α-methylserine-O-phosphate	Antagonist	5.3	pIC50
eglumegad	Full agonist	5.1	pEC50
ACPT-I	Partial agonist	5.1	pEC50
VU0155094	Positive	5.0	pKB
(1S,3R)-ACPD	Full agonist	4.4	pEC50
MPPG	Antagonist	4.33	pIC50

Binding affinities (BindingDB)

1 measured of 2 human assays (4 total across all organisms); most potent 1 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
(2S,4aR,6aR,7R,9S,10aS,10bR)-9-(acetyloxy)-2-(furan-3-yl)dodecahydro-6a,10b-dimethyl-4,10-dioxo-2H-naphtho-[2,1-c]pyran-7-carboxylic acid methyl ester	EC50	0.3 nM

ChEMBL bioactivities

92 potent at pChembl≥5 of 136 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.29	IC50	5.1	nM	CHEMBL285843
8.24	IC50	5.7	nM	GLUTAMIC ACID
8.20	Kd	6.3	nM	CHEMBL180822
7.64	EC50	23	nM	CHEMBL143210
7.51	EC50	31	nM	CHEMBL143210
7.36	EC50	44	nM	CHEMBL143210
7.22	EC50	60	nM	CHEMBL33567
7.21	Ki	61	nM	CHEMBL33567
6.90	EC50	125	nM	CHEMBL4162576
6.77	Ki	170	nM	CHEMBL432038
6.77	IC50	170	nM	CHEMBL432038
6.72	EC50	189	nM	CHEMBL4745982
6.68	Ki	210	nM	CHEMBL277475
6.54	EC50	290	nM	CHEMBL33567
6.52	EC50	300	nM	CHEMBL4067923
6.47	EC50	340	nM	CHEMBL229697
6.47	IC50	340	nM	CHEMBL329920
6.42	EC50	380	nM	CHEMBL4061423
6.42	IC50	380	nM	CHEMBL97200
6.31	EC50	490	nM	CHEMBL4088782
6.31	IC50	490	nM	CHEMBL95868
6.29	EC50	510	nM	CHEMBL4061423
6.28	EC50	530	nM	CHEMBL4088782
6.25	EC50	560	nM	CHEMBL33567
6.18	EC50	660	nM	CHEMBL4091029
6.12	IC50	750	nM	CHEMBL319732
6.05	EC50	890	nM	CHEMBL4446107
6.05	EC50	900	nM	CHEMBL1585091
6.01	EC50	980	nM	CHEMBL4078629
6.00	EC50	1000	nM	CHEMBL4064187
6.00	IC50	990	nM	CHEMBL319279
5.92	EC50	1200	nM	CHEMBL4093492
5.92	EC50	1200	nM	CHEMBL3609729
5.91	IC50	1230	nM	CHEMBL97574
5.90	EC50	1250	nM	CHEMBL4072781
5.89	EC50	1300	nM	CHEMBL4091029
5.89	EC50	1300	nM	CHEMBL4085750
5.82	EC50	1500	nM	CHEMBL4093492
5.81	EC50	1540	nM	CHEMBL4063142
5.80	EC50	1590	nM	CHEMBL2381641
5.80	EC50	1600	nM	CHEMBL4101241
5.77	EC50	1690	nM	LY-379268
5.77	Ki	1700	nM	LY-379268
5.75	EC50	1800	nM	CHEMBL4075877
5.75	EC50	1770	nM	CHEMBL4751065
5.72	IC50	1900	nM	CHEMBL3947221
5.72	EC50	1900	nM	CHEMBL4090179
5.67	EC50	2150	nM	CHEMBL227288
5.66	EC50	2200	nM	CHEMBL4072409
5.66	EC50	2200	nM	CHEMBL4085327

PubChem BioAssay actives

91 with measured affinity, of 363 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
2-amino-4-phosphonobutanoic acid	242207: Inhibitory concentration against [3H]1 binding to recombinant human Metabotropic glutamate receptor 8	ic50	0.0051	uM
glutamic acid	242207: Inhibitory concentration against [3H]1 binding to recombinant human Metabotropic glutamate receptor 8	ic50	0.0057	uM
cis-(2S,3R)-2-[(S)-amino(carboxy)methyl]-3-(hydroxymethyl)cyclopropane-1-carboxylic acid	238140: Dissociation constant of radiolabeled compound against recombinant human Metabotropic glutamate receptor 8	kd	0.0063	uM
4-[(S)-amino(carboxy)methyl]phthalic acid	1455155: Agonist activity at mGlu8 (unknown origin) expressed in HEK293 cells coexpressing chimeric Gq/i protein assessed as [3H]inositol phosphate accumulation after 30 mins by scintillation and luminescence counting method	ec50	0.0230	uM
(2S)-2-amino-4-phosphonobutanoic acid	1573602: Activation of human metabotropic glutamate 8 receptor expressed in golden hamster AV12-664 cells	ec50	0.0600	uM
N-[3-chloro-4-[(5-chloro-2-pyridinyl)oxy]phenyl]pyridine-2-carboxamide	1936983: Positive allosteric modulation of mGluR8 (unknown origin)	ec50	0.1250	uM
trans-(1S,2S)-2-[(1S)-1-amino-1-carboxy-2-(9H-xanthen-9-yl)ethyl]cyclopropane-1-carboxylic acid	107274: Agonist potency against cloned Metabotropic glutamate receptor 8 (mGluR-8).	ki	0.1700	uM
N-[4-(1,3-dioxoisoindol-2-yl)-2-fluoro-5-methylphenyl]-3-methylfuran-2-carboxamide	1693230: Positive allosteric modulation of mGluR8 (unknown origin) by calcium mobilization assay	ec50	0.1890	uM
2-amino-2-(4-phosphonophenyl)acetic acid	107274: Agonist potency against cloned Metabotropic glutamate receptor 8 (mGluR-8).	ki	0.2100	uM
(2S)-2-amino-4-[hydroxy-[hydroxy-(5-nitrofuran-2-yl)methyl]phosphoryl]butanoic acid	1455155: Agonist activity at mGlu8 (unknown origin) expressed in HEK293 cells coexpressing chimeric Gq/i protein assessed as [3H]inositol phosphate accumulation after 30 mins by scintillation and luminescence counting method	ec50	0.3000	uM
cis-(1S,2R)-1-amino-2-(phosphonomethyl)cyclopropane-1-carboxylic acid	292381: Agonist activity at mGlu8 receptor expressed in HEK 293 cells assessed as effect on inositol phosphate production	ec50	0.3400	uM
(1S,2S,3S)-2-[1-amino-1-carboxy-2-(9H-xanthen-9-yl)ethyl]-3-pentylcyclopropane-1-carboxylic acid	107419: Antagonistic activity against metabotropic glutamate receptor 8 (mGluR8) was evaluated	ic50	0.3400	uM
(1S,2S,3S)-2-[1-amino-1-carboxy-2-(9H-xanthen-9-yl)ethyl]-3-(2-methylpropyl)cyclopropane-1-carboxylic acid	107419: Antagonistic activity against metabotropic glutamate receptor 8 (mGluR8) was evaluated	ic50	0.3800	uM
(2S)-2-amino-4-[hydroxy-[hydroxy-(5-nitrothiophen-3-yl)methyl]phosphoryl]butanoic acid	1455161: Agonist activity at mGlu8 (unknown origin) expressed in HEK293 cells coexpressing chimeric Gq/i protein assessed as increase in intracellular calcium accumulation by Fluo-4 AM dye based fluorescence assay	ec50	0.3800	uM
(1S,2S,3S)-2-[1-amino-1-carboxy-2-(9H-xanthen-9-yl)ethyl]-3-butylcyclopropane-1-carboxylic acid	107419: Antagonistic activity against metabotropic glutamate receptor 8 (mGluR8) was evaluated	ic50	0.4900	uM
(2S)-2-amino-4-[hydroxy-[hydroxy-(4-nitrophenyl)methyl]phosphoryl]butanoic acid	1455161: Agonist activity at mGlu8 (unknown origin) expressed in HEK293 cells coexpressing chimeric Gq/i protein assessed as increase in intracellular calcium accumulation by Fluo-4 AM dye based fluorescence assay	ec50	0.4900	uM
(2S)-2-amino-4-[[(4-fluoro-3-nitrophenyl)-hydroxymethyl]-hydroxyphosphoryl]butanoic acid	1455161: Agonist activity at mGlu8 (unknown origin) expressed in HEK293 cells coexpressing chimeric Gq/i protein assessed as increase in intracellular calcium accumulation by Fluo-4 AM dye based fluorescence assay	ec50	0.6600	uM
(1S,2S,3S)-2-[1-amino-1-carboxy-2-(9H-xanthen-9-yl)ethyl]-3-hexylcyclopropane-1-carboxylic acid	107419: Antagonistic activity against metabotropic glutamate receptor 8 (mGluR8) was evaluated	ic50	0.7500	uM
3-(2,5-difluoro-4-methoxyphenyl)-2-ethyl-5-methyl-7-(trifluoromethyl)pyrazolo[1,5-a]pyrimidine	1571667: Agonist activity at mGlu8 (unknown origin)	ec50	0.8900	uM
methyl 4-[3-[2-(4-acetamidophenyl)sulfanylacetyl]-2,5-dimethylpyrrol-1-yl]benzoate	1936983: Positive allosteric modulation of mGluR8 (unknown origin)	ec50	0.9000	uM
(2S)-2-amino-4-[hydroxy-[hydroxy-[4-nitro-3-(trifluoromethyl)phenyl]methyl]phosphoryl]butanoic acid	1455155: Agonist activity at mGlu8 (unknown origin) expressed in HEK293 cells coexpressing chimeric Gq/i protein assessed as [3H]inositol phosphate accumulation after 30 mins by scintillation and luminescence counting method	ec50	0.9800	uM
(1S,2S,3S)-2-[1-amino-1-carboxy-2-(9H-xanthen-9-yl)ethyl]-3-(2-phenylethyl)cyclopropane-1-carboxylic acid	107419: Antagonistic activity against metabotropic glutamate receptor 8 (mGluR8) was evaluated	ic50	0.9900	uM
(2S)-2-amino-4-[hydroxy-[(3-nitrophenyl)methyl]phosphoryl]butanoic acid	1455161: Agonist activity at mGlu8 (unknown origin) expressed in HEK293 cells coexpressing chimeric Gq/i protein assessed as increase in intracellular calcium accumulation by Fluo-4 AM dye based fluorescence assay	ec50	1.0000	uM
5-methyl-N-(4-methylpyrimidin-2-yl)-4-(1H-pyrazol-4-yl)-1,3-thiazol-2-amine	1936983: Positive allosteric modulation of mGluR8 (unknown origin)	ec50	1.2000	uM
(2S)-2-amino-4-[hydroxy-[hydroxy-(3-nitrophenyl)methyl]phosphoryl]butanoic acid	1455161: Agonist activity at mGlu8 (unknown origin) expressed in HEK293 cells coexpressing chimeric Gq/i protein assessed as increase in intracellular calcium accumulation by Fluo-4 AM dye based fluorescence assay	ec50	1.2000	uM
(1S,2S,3S)-2-[1-amino-1-carboxy-2-(9H-xanthen-9-yl)ethyl]-3-methylcyclopropane-1-carboxylic acid	107419: Antagonistic activity against metabotropic glutamate receptor 8 (mGluR8) was evaluated	ic50	1.2300	uM
(2S)-2-amino-4-[hydroxy-[(S)-hydroxy-(3-nitrophenyl)methyl]phosphoryl]butanoic acid	1455161: Agonist activity at mGlu8 (unknown origin) expressed in HEK293 cells coexpressing chimeric Gq/i protein assessed as increase in intracellular calcium accumulation by Fluo-4 AM dye based fluorescence assay	ec50	1.2500	uM
(2S)-2-amino-4-[hydroxy-[(R)-hydroxy-(3-nitrophenyl)methyl]phosphoryl]butanoic acid	1455161: Agonist activity at mGlu8 (unknown origin) expressed in HEK293 cells coexpressing chimeric Gq/i protein assessed as increase in intracellular calcium accumulation by Fluo-4 AM dye based fluorescence assay	ec50	1.3000	uM
(2S)-2-amino-4-[hydroxy-[hydroxy-[3-nitro-4-(trifluoromethyl)phenyl]methyl]phosphoryl]butanoic acid	1455161: Agonist activity at mGlu8 (unknown origin) expressed in HEK293 cells coexpressing chimeric Gq/i protein assessed as increase in intracellular calcium accumulation by Fluo-4 AM dye based fluorescence assay	ec50	1.5400	uM
(1S,2S,5R,6S)-2-amino-4-methylidenebicyclo[3.1.0]hexane-2,6-dicarboxylic acid	748159: Agonist activity at human mGlu8 receptor expressed in golden Syrian hamster AV12 cells coexpressing EAAT1 after 20 mins by FLIPR assay	ec50	1.5900	uM
(2S)-2-amino-4-[hydroxy-[hydroxy-(4-methyl-3-nitrophenyl)methyl]phosphoryl]butanoic acid	1455161: Agonist activity at mGlu8 (unknown origin) expressed in HEK293 cells coexpressing chimeric Gq/i protein assessed as increase in intracellular calcium accumulation by Fluo-4 AM dye based fluorescence assay	ec50	1.6000	uM
(1R,4R,5S,6R)-4-amino-2-oxabicyclo[3.1.0]hexane-4,6-dicarboxylic acid	221697: Inhibition of forskolin stimulated cAMP production in RGT cells expressing recombinant human mGluR8	ec50	1.6900	uM
(1S,2R,3S,4S,5R,6R)-2-amino-3-[(3,4-difluorophenyl)sulfanylmethyl]-4-hydroxybicyclo[3.1.0]hexane-2,6-dicarboxylic acid;hydrochloride	1714588: Antagonist activity at human recombinant mGlu8 stably expressed in golden hamster AV12 cell membrane co-expressing Galpha15 assessed as reduction in glutamate-induced calcium influx incubated for 90 to 120 min by Fluo-4-AM dye based FLIPR assay	ec50	1.7700	uM
(2S)-2-amino-4-[[amino-(5-nitrothiophen-3-yl)methyl]-hydroxyphosphoryl]butanoic acid	1455155: Agonist activity at mGlu8 (unknown origin) expressed in HEK293 cells coexpressing chimeric Gq/i protein assessed as [3H]inositol phosphate accumulation after 30 mins by scintillation and luminescence counting method	ec50	1.8000	uM
(1S,2R,3S,4S,5R,6R)-2-amino-3-[(3,4-dichlorophenyl)methoxy]-4-hydroxybicyclo[3.1.0]hexane-2,6-dicarboxylic acid	1329869: Antagonist activity at recombinant human mGlu8 receptor expressed in hamster AV12 cells co-expressing human EAAT1/Galpha1s assessed as inhibition of Ca2+ flux by Fluo-3-AM dye based FLIPR assay	ic50	1.9000	uM
(2S)-2-amino-4-[hydroxy-[hydroxy-(5-nitrothiophen-2-yl)methyl]phosphoryl]butanoic acid	1455155: Agonist activity at mGlu8 (unknown origin) expressed in HEK293 cells coexpressing chimeric Gq/i protein assessed as [3H]inositol phosphate accumulation after 30 mins by scintillation and luminescence counting method	ec50	1.9000	uM
trans-(1S,2S)-1-amino-2-(phosphonomethyl)cyclopropane-1-carboxylic acid	292381: Agonist activity at mGlu8 receptor expressed in HEK 293 cells assessed as effect on inositol phosphate production	ec50	2.1500	uM
(2S)-2-amino-4-[hydroxy-[(R)-hydroxy-(4-methoxy-3-nitrophenyl)methyl]phosphoryl]butanoic acid	1455161: Agonist activity at mGlu8 (unknown origin) expressed in HEK293 cells coexpressing chimeric Gq/i protein assessed as increase in intracellular calcium accumulation by Fluo-4 AM dye based fluorescence assay	ec50	2.2000	uM
(2S)-2-amino-4-[[amino-(3-nitrophenyl)methyl]-hydroxyphosphoryl]butanoic acid	1455155: Agonist activity at mGlu8 (unknown origin) expressed in HEK293 cells coexpressing chimeric Gq/i protein assessed as [3H]inositol phosphate accumulation after 30 mins by scintillation and luminescence counting method	ec50	2.2000	uM
(1S,2S,3S)-2-[1-amino-1-carboxy-2-(9H-xanthen-9-yl)ethyl]-3-propylcyclopropane-1-carboxylic acid	107419: Antagonistic activity against metabotropic glutamate receptor 8 (mGluR8) was evaluated	ic50	2.2500	uM
(2S)-2-amino-4-[hydroxy-[(S)-hydroxy-(4-methoxy-3-nitrophenyl)methyl]phosphoryl]butanoic acid	1455161: Agonist activity at mGlu8 (unknown origin) expressed in HEK293 cells coexpressing chimeric Gq/i protein assessed as increase in intracellular calcium accumulation by Fluo-4 AM dye based fluorescence assay	ec50	2.5000	uM
(2S)-2-amino-4-[[(4-chloro-3-nitrophenyl)-hydroxymethyl]-hydroxyphosphoryl]butanoic acid	1455155: Agonist activity at mGlu8 (unknown origin) expressed in HEK293 cells coexpressing chimeric Gq/i protein assessed as [3H]inositol phosphate accumulation after 30 mins by scintillation and luminescence counting method	ec50	2.5000	uM
(1S,2S,3S)-2-[1-amino-1-carboxy-2-(9H-xanthen-9-yl)ethyl]-3-ethylcyclopropane-1-carboxylic acid	107419: Antagonistic activity against metabotropic glutamate receptor 8 (mGluR8) was evaluated	ic50	2.5200	uM
3-(2,3-difluoro-4-methoxyphenyl)-2,5-dimethyl-7-(trifluoromethyl)pyrazolo[1,5-a]pyrimidine	1571667: Agonist activity at mGlu8 (unknown origin)	ec50	2.6000	uM
(2S)-2-amino-4-[hydroxy-[hydroxy-(4-methoxy-3-nitrophenyl)methyl]phosphoryl]butanoic acid	1455155: Agonist activity at mGlu8 (unknown origin) expressed in HEK293 cells coexpressing chimeric Gq/i protein assessed as [3H]inositol phosphate accumulation after 30 mins by scintillation and luminescence counting method	ec50	2.7000	uM
3-(2,6-difluoro-4-methoxyphenyl)-2,5-dimethyl-7-(trifluoromethyl)pyrazolo[1,5-a]pyrimidine	1571667: Agonist activity at mGlu8 (unknown origin)	ec50	2.9000	uM
(2S)-2-amino-4-[[(2,6-dinitrophenyl)-hydroxymethyl]-hydroxyphosphoryl]butanoic acid	1455155: Agonist activity at mGlu8 (unknown origin) expressed in HEK293 cells coexpressing chimeric Gq/i protein assessed as [3H]inositol phosphate accumulation after 30 mins by scintillation and luminescence counting method	ec50	2.9000	uM
(1R,4S,5S,6S)-4-amino-2-oxo-2lambda4-thiabicyclo[3.1.0]hexane-4,6-dicarboxylic acid	275491: Agonist activity at human mGluR8 assessed as effect on cAMP production in RGT cells	ec50	3.0700	uM
trans-(1S,2S)-2-[(S)-amino(carboxy)methyl]cyclopropane-1-carboxylic acid	107274: Agonist potency against cloned Metabotropic glutamate receptor 8 (mGluR-8).	ki	3.4000	uM
(2S)-2-amino-4-[hydroxy-[hydroxy-(2-hydroxy-5-nitrophenyl)methyl]phosphoryl]butanoic acid	1455155: Agonist activity at mGlu8 (unknown origin) expressed in HEK293 cells coexpressing chimeric Gq/i protein assessed as [3H]inositol phosphate accumulation after 30 mins by scintillation and luminescence counting method	ec50	4.2000	uM

CTD chemical–gene interactions

22 total (human), top 22 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects methylation, increases expression	2
Valproic Acid	decreases methylation, increases expression	2
methyleugenol	decreases expression	1
bisphenol A	decreases methylation	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, increases expression	1
nutlin 3	increases expression, affects cotreatment	1
quinocetone	decreases expression	1
bisphenol S	decreases methylation	1
Resveratrol	affects cotreatment, decreases expression	1
Zoledronic Acid	decreases expression	1
Atrazine	decreases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Cadmium	decreases expression	1
Dactinomycin	affects cotreatment, increases expression	1
Lipopolysaccharides	affects cotreatment, increases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Thallium	increases transport, affects binding, increases activity	1
Tretinoin	decreases expression	1
Triclosan	decreases expression	1
Cyclosporine	increases methylation	1
Aflatoxin B1	increases methylation	1
Asbestos, Crocidolite	affects expression	1

ChEMBL screening assays

111 unique, capped per target: 57 functional, 54 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1027702	Functional	Antagonist activity at mGlu8 receptor	Discovery of molecular switches that modulate modes of metabotropic glutamate receptor subtype 5 (mGlu5) pharmacology in vitro and in vivo within a series of functionalized, regioisomeric 2- and 5-(phenylethynyl)pyrimidines. — J Med Chem
CHEMBL1034753	Binding	Activity at human mGluR8 assessed as fold shifting of glutamate-induced response to left	Synthesis and evaluation of a series of heterobiarylamides that are centrally penetrant metabotropic glutamate receptor 4 (mGluR4) positive allosteric modulators (PAMs). — J Med Chem

Cellosaurus cell lines

4 cell lines: 2 transformed cell line, 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_C0SW	ACTOne GRM8	Transformed cell line	Female
CVCL_D9FY	Ubigene HEK293 GRM8 KO	Transformed cell line	Female
CVCL_SQ59	HAP1 GRM8 (-) 1	Cancer cell line	Male
CVCL_SQ60	HAP1 GRM8 (-) 2	Cancer cell line	Male

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
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