GRM5

Summary

GRM5 (glutamate metabotropic receptor 5, HGNC:4597) is a protein-coding gene on chromosome 11q14.2-q14.3, encoding Metabotropic glutamate receptor 5 (P41594). G-protein coupled receptor for glutamate.

This gene encodes a member of the G-protein coupled receptor 3 protein family. The encoded protein is a metabatropic glutamate receptor, whose signaling activates a phosphatidylinositol-calcium second messenger system. This protein may be involved in the regulation of neural network activity and synaptic plasticity. Glutamatergic neurotransmission is involved in most aspects of normal brain function and can be perturbed in many neuropathologic conditions. A pseudogene of this gene has been defined on chromosome 11. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 2915 — RefSeq curated summary.

At a glance

• GWAS associations: 22
• Clinical variants (ClinVar): 176 total
• Druggable target: yes — 9 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001143831

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4597
Approved symbol	GRM5
Name	glutamate metabotropic receptor 5
Location	11q14.2-q14.3
Locus type	gene with protein product
Status	Approved
Aliases	MGLUR5, GPRC1E, mGlu5, PPP1R86
Ensembl gene	ENSG00000168959
Ensembl biotype	protein_coding
OMIM	604102
Entrez	2915

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 6 protein_coding

ENST00000305432, ENST00000305447, ENST00000393294, ENST00000449371, ENST00000455756, ENST00000962224

RefSeq mRNA: 3 — MANE Select: NM_001143831 NM_000842, NM_001143831, NM_001384268

CCDS: CCDS44694, CCDS8283

Canonical transcript exons

ENST00000305447 — 10 exons

Exon	Start	End
ENSE00001148162	88525309	88525404
ENSE00001148167	88567053	88567992
ENSE00001148173	88590601	88590727
ENSE00001148177	88597184	88597352
ENSE00001148180	88604718	88604964
ENSE00001148188	88653168	88653403
ENSE00001661053	88849906	88850155
ENSE00002242728	89047212	89048072
ENSE00003918251	89065776	89065982
ENSE00003921522	88504642	88509504

Expression profiles

Bgee: expression breadth ubiquitous, 107 present calls, max score 94.98.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.7809 / max 71.7681, expressed in 94 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
121780	0.6187	90
121782	0.1160	61
121781	0.0461	26

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
endothelial cell	CL:0000115	94.98	gold quality
buccal mucosa cell	CL:0002336	92.14	gold quality
Brodmann (1909) area 10	UBERON:0013541	92.05	gold quality
Brodmann (1909) area 46	UBERON:0006483	91.90	gold quality
postcentral gyrus	UBERON:0002581	91.86	gold quality
orbitofrontal cortex	UBERON:0004167	91.74	gold quality
Brodmann (1909) area 23	UBERON:0013554	91.12	gold quality
superior frontal gyrus	UBERON:0002661	90.68	gold quality
CA1 field of hippocampus	UBERON:0003881	90.50	gold quality
parietal lobe	UBERON:0001872	90.43	gold quality
frontal pole	UBERON:0002795	90.34	gold quality
entorhinal cortex	UBERON:0002728	90.29	gold quality
middle temporal gyrus	UBERON:0002771	89.44	gold quality
cortical plate	UBERON:0005343	88.90	gold quality
middle frontal gyrus	UBERON:0002702	84.92	gold quality
medial globus pallidus	UBERON:0002477	84.71	gold quality
primary visual cortex	UBERON:0002436	81.39	gold quality
occipital lobe	UBERON:0002021	81.06	gold quality
globus pallidus	UBERON:0001875	80.96	gold quality
prefrontal cortex	UBERON:0000451	80.65	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	78.12	silver quality
frontal cortex	UBERON:0001870	78.01	gold quality
lateral nuclear group of thalamus	UBERON:0002736	77.20	gold quality
neocortex	UBERON:0001950	75.82	gold quality
cerebral cortex	UBERON:0000956	75.03	gold quality
temporal lobe	UBERON:0001871	72.49	gold quality
telencephalon	UBERON:0001893	71.46	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	71.41	gold quality
corpus callosum	UBERON:0002336	71.08	gold quality
lateral globus pallidus	UBERON:0002476	69.56	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-HCAD-35	yes	93.05
E-HCAD-25	yes	76.07
E-ANND-3	yes	5.06

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

307 targeting GRM5, 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-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-4262	100.00	73.26	3931
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-6740-5P	100.00	65.64	932
HSA-MIR-3925-3P	100.00	69.95	1237
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996

Literature-anchored findings (GeneRIF, showing 40)

• mGLUR5 and 1,4,5-InsP3 signaling control calcium release (PMID:12119301)
• Data report the isolation of a novel gene termed metabotropic glutamate receptor 5-related (mGluR5R) [mGluR5R]. (PMID:12531512)
• Data report the identification of a novel variant of the G-protein coupled metabotropic glutamate receptor mGlu5 (hmGlu5d) generated by alternative splicing at the C-terminal domain. (PMID:12531526)
• mGlu5 on nuclear membranes has a role in mediating intranuclear Ca2+ changes in heterologous cell types and neurons (PMID:12736269)
• alternative 5’-splicing and usage of multiple promoters may contribute to regulatory mechanisms for tissue- and context-specific expression of the mGluR5 gene (PMID:12783878)
• mGluR3 and mGluR5 can critically and differentially modulate the expression of glutamate transporters and may represent interesting pharmacological targets to regulate the extracellular levels of glutamate in pathological conditions. (PMID:12786977)
• activation of mGluR5 causes translocation of both gammaPKC and deltaPKC to the plasma membrane. deltaPKC, but not gammaPKC, phosphorylates mGluR5 Thr(840), leading to the blockade of both Ca2+ oscillations and gammaPKC cycling. (PMID:14561742)
• We found a selective expression of the group I receptor mGluR5 in human parasympathetic Onuf’s nucleus, strengthening the hypothesis that mGluR expression may provide a possible clue to the selective vulnerability in ALS. (PMID:15076751)
• glial progenitor cells present in the adult human CNS express mGluR3 and mGluR5a (PMID:15158450)
• metabotropic glutamate receptors 1 and 5 mediate opposite glutamate effects in human lymphocyte activation (PMID:15184389)
• it is phosphorylation of Ser-839, not Thr-840, that is absolutely required for the unique Ca2+ oscillations produced by mGluR5 activation (PMID:15894802)
• there is an alpha-actinin-1-dependent mGlu(5b) receptor association with the actin cytoskeleton modulating receptor cell surface expression and functioning (PMID:17311919)
• We documented for the first time the expression of the mGluR5 and EAAT1 in MG-63 cells, as well as the ability of dexamethasone to upregulate the expression of the mGluR5 and EAAT1 in the MG-63 cells. (PMID:17627080)
• This study provides the first quantitative demonstration and direct comparison of a PET tracer candidate identifying mGluR5 binding sites in mammalian cerebellum. (PMID:17998106)
• deletion of the C terminus of the mGlu5a receptor abolishes both its interaction with the NMDA receptor and reciprocal inhibition of the receptors (PMID:18182392)
• the nucleus can function as an autonomous organelle independent of signals originating in the cytoplasm, and nuclear mGlu5 receptors play a dynamic role in mobilizing Ca2+ in a specific, localized fashion (PMID:18337251)
• These results provide insight into a glutamate-induced regulatory pathway distinct from that described for cytokine-induced NF-kappaB activation and have important implications with regard to both normal glial cell physiology and pathogenesis. (PMID:18541671)
• Review. The structure and function of mGLUR5 and the mechanisms and SARs of its antagonists are reviewed. (PMID:18991960)
• findings suggest that changes in astrocyte mGlu5 receptors may be part of an adaptive response to the progressive nature of Alzheimer’s disease (PMID:19401173)
• NECAB2 by its physical interaction with mGlu(5b) receptor modulates receptor function (PMID:19694902)
• Elevated glutamatergic transmission as measured with increased mGluR5 specific binding is associated with human motor complications; its antagonism can be targeted for patients’ treatment. (PMID:20036444)
• These findings show a differential expression pattern of mGluR1a and mGluR5, suggesting a role for both receptors in the early stages of corticogenesis with, however, a different contribution to human cortical developmental events. (PMID:20149785)
• mGluR5 promoted the proliferation of human embryonic cortical neural stem/progenitor cells (PMID:21723923)
• Metabotropic glutamate receptor 5 upregulation in children with autism is associated with underexpression of both Fragile X mental retardation protein and GABAA receptor beta 3 in adults with autism. (PMID:21901840)
• the results of this study show that using the equilibrium method is an acceptable alternative to the standard kinetic method when using 18F-SP203 to measure mGluR5 (PMID:22032949)
• Human mGluR5, GABA(A,B), and CB(1,2) receptors are abundantly expressed along the vago-vagal neural pathway and involved in the triggering of transient lower esophageal sphincter relaxations (PMID:22256945)
• mGluR5 inhibition and stimulation in the nucleus accumbens can regulate cocaine-seeking, and demonstrate that one mechanism for this effect is via interactions with Homer proteins (PMID:22340009)
• mGluR5 is expressed by a variety of cells such as neural stem cells in the frontal cortex, ventricular zone and subventricular zone in human fetuses. (PMID:22543119)
• data demonstrate that mGluR5 receptors internalize without the application of ligand and the internalized receptors recycle back to the cell surface following constitutive endocytosis. (PMID:22995293)
• the promoter methylation of the GMR2 and GMR5 genes greatly decreased the risk of schizophrenia, and the expression level of the GRM2, GRM5, and GRIA3 genes increased significantly in patients in comparison to healthy controls. (PMID:23149219)
• Calmodulin-regulated Siah-1A binding to mGluR5 dynamically regulates mGluR5 trafficking (PMID:23152621)
• The pattern of mGluR5 expression by neural stem/progenitor cells, neuroblasts and neurons provides important anatomical evidence for the role of mGluR5 in the regulation of human hippocampal development (PMID:23225313)
• Plasma glutamate-modulated interaction of A2AR and mGluR5 on BMDCs aggravates traumatic brain injury-induced acute lung injury. (PMID:23478188)
• Knockdown of mGluR5 inhibited icariin induced reactive oxygen species generation and NF-kappaB nuclear translocation. (PMID:23524143)
• This study demonistrated that metabotropic receptor mGluR5 was found to be expressed by just 40% of striatal neurons in young individuals, with significant intensity variations among the neurons. (PMID:23627706)
• tobacco smoking was associated with lower mGluR5 availability in the brain in both cocaine users and controls, while cocaine use was not linked to detectable mGluR5 alterations (PMID:23628984)
• this study provides evidence that GRK2 mediates phosphorylation-independent mGluR5 desensitization via the interaction between the RGS domain and Galphaq in HEK 293 cells. (PMID:23705503)
• This study demonistrated that mGluR5 upregulation also participates in counterbalance mechanisms along the hyperexcitable circuitry uniquely altered in TLE hippocampal formation. (PMID:23804486)
• Review provides an update of the current state of the art of mGlu5 receptor-based manipulations to alleviate the symptoms of Parkinson’s disease. (PMID:24040811)
• a dysregulation of its signaling in fragile X mental retardation gene 1 premutation carriers, which would likely contribute to the development and severity of fragile X-associated tremor/atasia syndrome. (PMID:24332449)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	grm5a	ENSDARG00000004445
danio_rerio	grm5b	ENSDARG00000102067
mus_musculus	Grm5	ENSMUSG00000049583
rattus_norvegicus	Grm5	ENSRNOG00000016429
caenorhabditis_elegans	mgl-2	WBGENE00003233

Paralogs (7): GRM6 (ENSG00000113262), GRM4 (ENSG00000124493), GRM1 (ENSG00000152822), GRM2 (ENSG00000164082), GRM8 (ENSG00000179603), GRM7 (ENSG00000196277), GRM3 (ENSG00000198822)

Protein

Protein identifiers

Metabotropic glutamate receptor 5 — P41594 (reviewed: P41594)

All UniProt accessions (3): A8MT20, P41594, H7C223

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. Signaling activates a phosphatidylinositol-calcium second messenger system and generates a calcium-activated chloride current. Plays an important role in the regulation of synaptic plasticity and the modulation of the neural network activity.

Subunit / interactions. The PPXXF motif binds HOMER1, HOMER2 and HOMER3. Interacts with SIAH1, RYR1, RYR2, ITPR1, SHANK1, SHANK3 and TAMALIN. Interacts with NCDN. Isoform 2 interacts with NECAB2. Interacts with CAMK2A.

Subcellular location. Cell membrane.

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

Isoforms (3)

UniProt ID	Names	Canonical?
P41594-1	2, 5b	yes
P41594-2	1, 5a
P41594-3	3, 5d

RefSeq proteins (3): NP_000833, NP_001137303, NP_001371197 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000162	GPCR_3_mtglu_rcpt	Family
IPR000202	GPCR_3_mGluR5	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
IPR019588	Metabotropic_Glu_rcpt_Homer-bd	Domain
IPR028082	Peripla_BP_I	Homologous_superfamily
IPR038550	GPCR_3_9-Cys_sf	Homologous_superfamily
IPR050726	mGluR	Family

Pfam: PF00003, PF01094, PF07562, PF10606

UniProt features (134 total): strand 36, helix 29, turn 13, disulfide bond 10, topological domain 8, transmembrane region 7, binding site 6, glycosylation site 6, modified residue 5, mutagenesis site 4, region of interest 3, compositionally biased region 3, splice variant 2, signal peptide 1, chain 1

Structure

Experimental structures (PDB)

29 structures.

PDB	Method	Resolution (Å)
6FFI	X-RAY DIFFRACTION	2.2
9HC0	X-RAY DIFFRACTION	2.33
3LMK	X-RAY DIFFRACTION	2.44
7P2L	X-RAY DIFFRACTION	2.54
4OO9	X-RAY DIFFRACTION	2.6
5CGD	X-RAY DIFFRACTION	2.6
6FFH	X-RAY DIFFRACTION	2.65
8TAO	ELECTRON MICROSCOPY	2.9
9HC3	X-RAY DIFFRACTION	2.9
8T8M	ELECTRON MICROSCOPY	3
8X0G	ELECTRON MICROSCOPY	3
8X0B	ELECTRON MICROSCOPY	3.1
5CGC	X-RAY DIFFRACTION	3.1
8X0C	ELECTRON MICROSCOPY	3.2
9WQL	ELECTRON MICROSCOPY	3.2
6N4Y	X-RAY DIFFRACTION	3.26
8T7H	ELECTRON MICROSCOPY	3.3
8X0F	ELECTRON MICROSCOPY	3.3
8X0E	ELECTRON MICROSCOPY	3.4
8T6J	ELECTRON MICROSCOPY	3.5
8X0D	ELECTRON MICROSCOPY	3.5
9WQK	ELECTRON MICROSCOPY	3.7
6N50	X-RAY DIFFRACTION	3.75
7FD8	ELECTRON MICROSCOPY	3.8
6N4X	X-RAY DIFFRACTION	4
6N51	ELECTRON MICROSCOPY	4
6N52	ELECTRON MICROSCOPY	4
7FD9	ELECTRON MICROSCOPY	4
8X0H	ELECTRON MICROSCOPY	4.1

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P41594-F1	72.16	0.46

Antibody-complex structures (SAbDab): 6 — 6N4Y, 6N50, 6N51, 8T7H, 8T8M, 8TAO

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): 64; 152; 173–175; 223; 305; 396

Post-translational modifications (5): 861, 869, 925, 1018, 1020

Disulfide bonds (10): 57–99, 241–530, 276–278, 365–381, 419–426, 511–531, 515–534, 537–549, 552–565, 644–733

Glycosylation sites (6): 88, 210, 378, 382, 445, 734

Mutagenesis-validated functional residues (4):

Position	Phenotype
613	increased constitutive signaling activity.
614	decreased constitutive signaling activity.
665	increased constitutive signaling activity.
770	increased constitutive signaling activity.

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-416476	G alpha (q) signalling events
R-HSA-420499	Class C/3 (Metabotropic glutamate/pheromone receptors)
R-HSA-6794361	Neurexins and neuroligins

MSigDB gene sets: 416 (showing top): BROWNE_HCMV_INFECTION_30MIN_DN, GOBP_DENDRITE_DEVELOPMENT, GGGACCA_MIR133A_MIR133B, GOBP_NEGATIVE_REGULATION_OF_DENDRITIC_SPINE_DEVELOPMENT, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_RESPONSE_TO_ETHANOL, GOBP_COGNITION, GOBP_SENSORY_PERCEPTION_OF_TEMPERATURE_STIMULUS, GOBP_BEHAVIOR, GOBP_REGULATION_OF_CALCIUM_MEDIATED_SIGNALING, GOBP_RESPONSE_TO_AMINE, GOBP_REGULATION_OF_NEURONAL_SYNAPTIC_PLASTICITY, GOBP_REGULATION_OF_SYNAPTIC_TRANSMISSION_GLUTAMATERGIC, GOBP_RESPONSE_TO_CORTICOSTEROID, GOBP_ASSOCIATIVE_LEARNING

GO Biological Process (41): temperature homeostasis (GO:0001659), response to amphetamine (GO:0001975), desensitization of G protein-coupled receptor signaling pathway (GO:0002029), regulation of DNA-templated transcription (GO:0006355), positive regulation of cytosolic calcium ion concentration (GO:0007204), phospholipase C-activating G protein-coupled glutamate receptor signaling pathway (GO:0007206), G protein-coupled glutamate receptor signaling pathway (GO:0007216), chemical synaptic transmission (GO:0007268), learning or memory (GO:0007611), locomotory behavior (GO:0007626), positive regulation of dopamine secretion (GO:0033603), operant conditioning (GO:0035106), protein localization to nuclear inner membrane (GO:0036228), response to morphine (GO:0043278), positive regulation of MAPK cascade (GO:0043410), response to ethanol (GO:0045471), response to antibiotic (GO:0046677), positive regulation of long-term neuronal synaptic plasticity (GO:0048170), synapse organization (GO:0050808), positive regulation of calcium-mediated signaling (GO:0050850), cognition (GO:0050890), response to corticosterone (GO:0051412), regulation of synaptic transmission, glutamatergic (GO:0051966), negative regulation of dendritic spine morphogenesis (GO:0061002), sensory perception of hot stimulus (GO:0062036), negative regulation of excitatory postsynaptic potential (GO:0090394), positive regulation of cellular response to hypoxia (GO:1900039), regulation of long-term synaptic depression (GO:1900452), positive regulation of sensory perception of pain (GO:1904058), cellular response to amyloid-beta (GO:1904646), conditioned place preference (GO:1990708), positive regulation of neural precursor cell proliferation (GO:2000179), signal transduction (GO:0007165), G protein-coupled receptor signaling pathway (GO:0007186), adenylate cyclase-inhibiting G protein-coupled glutamate receptor signaling pathway (GO:0007196), learning (GO:0007612), regulation of long-term neuronal synaptic plasticity (GO:0048169), modulation of chemical synaptic transmission (GO:0050804), regulation of postsynaptic membrane potential (GO:0060078), regulation of postsynaptic cytosolic calcium ion concentration (GO:0099566)

GO Molecular Function (10): adenylate cyclase inhibiting G protein-coupled glutamate receptor activity (GO:0001640), G protein-coupled receptor activity (GO:0004930), glutamate receptor activity (GO:0008066), protein tyrosine kinase activator activity (GO:0030296), A2A adenosine receptor binding (GO:0031687), identical protein binding (GO:0042802), G protein-coupled receptor activity involved in regulation of postsynaptic membrane potential (GO:0099530), obsolete neurotransmitter receptor activity involved in regulation of postsynaptic cytosolic calcium ion concentration (GO:0099583), protein tyrosine kinase binding (GO:1990782), protein binding (GO:0005515)

GO Cellular Component (15): nuclear inner membrane (GO:0005637), cytoplasm (GO:0005737), plasma membrane (GO:0005886), dendrite (GO:0030425), neuronal cell body (GO:0043025), dendritic spine (GO:0043197), dendritic shaft (GO:0043198), astrocyte projection (GO:0097449), Schaffer collateral - CA1 synapse (GO:0098685), postsynaptic density membrane (GO:0098839), glutamatergic synapse (GO:0098978), membrane (GO:0016020), neuron projection (GO:0043005), neuron spine (GO:0044309), postsynaptic membrane (GO:0045211)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
GPCR downstream signalling	1
GPCR ligand binding	1
Protein-protein interactions at synapses	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
G protein-coupled receptor signaling pathway	2
G protein-coupled glutamate receptor activity	2
behavior	2
positive regulation of intracellular signal transduction	2
transmembrane signaling receptor activity	2
postsynaptic membrane	2
neuron projection	2
dendrite	2
postsynapse	2
synapse	2
multicellular organismal-level homeostasis	1
response to amine	1
negative adaptation of signaling pathway	1
negative regulation of G protein-coupled receptor signaling pathway	1
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
regulation of biological quality	1
PLC activating G protein-coupled glutamate receptor activity	1
phospholipase C-activating G protein-coupled receptor signaling pathway	1
G protein-coupled glutamate receptor signaling pathway	1
glutamate receptor signaling pathway	1
anterograde trans-synaptic signaling	1
cognition	1
dopamine secretion	1
regulation of dopamine secretion	1
positive regulation of catecholamine secretion	1
learning	1
protein localization to membrane	1
protein localization to nuclear envelope	1
response to isoquinoline alkaloid	1
MAPK cascade	1
regulation of MAPK cascade	1
response to alcohol	1
response to chemical	1
regulation of long-term neuronal synaptic plasticity	1
positive regulation of neurogenesis	1
cell junction organization	1
calcium-mediated signaling	1

Protein interactions and networks

STRING

3117 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GRM5	HOMER1	Q86YM7	999
GRM5	GNAQ	P50148	992
GRM5	ADORA2A	P29274	968
GRM5	PRNP	P04156	932
GRM5	HOMER2	Q9NSB8	930
GRM5	GRIA1	P42261	901
GRM5	FMR1	Q06787	864
GRM5	SHANK1	Q9Y566	853
GRM5	HOMER3	Q9NSC5	851
GRM5	GRIK1	P39086	814
GRM5	DLGAP1	P78335	807
GRM5	DAGLA	Q9Y4D2	805
GRM5	GRIA2	P42262	801
GRM5	ITPR1	Q14643	791
GRM5	DLG4	P78352	790

IntAct

129 interactions, top by confidence:

A	B	Type	Score
CEP104	CCDC66	psi-mi:“MI:2364”(proximity)	0.540
GRM5	GRM5	psi-mi:“MI:0407”(direct interaction)	0.520
GRM5	MAST2	psi-mi:“MI:0407”(direct interaction)	0.440
GRM5	PDZK1	psi-mi:“MI:0407”(direct interaction)	0.440
GRM5	SHANK1	psi-mi:“MI:0407”(direct interaction)	0.440
GRM5	MAST1	psi-mi:“MI:0407”(direct interaction)	0.440
GRM5	NHERF2	psi-mi:“MI:0407”(direct interaction)	0.440
TAMALIN	GRM5	psi-mi:“MI:0407”(direct interaction)	0.440
GRM5	ARHGEF12	psi-mi:“MI:0407”(direct interaction)	0.440
GRM5	PTPN3	psi-mi:“MI:0407”(direct interaction)	0.440
GRM5	SNX27	psi-mi:“MI:0407”(direct interaction)	0.440
GRM5	ARHGAP21	psi-mi:“MI:0407”(direct interaction)	0.440
GRM5	NHERF4	psi-mi:“MI:0407”(direct interaction)	0.440
GRM5	GRID2IP	psi-mi:“MI:0407”(direct interaction)	0.440
GRM5	PICK1	psi-mi:“MI:0407”(direct interaction)	0.440
GRM5	SCRIB	psi-mi:“MI:0407”(direct interaction)	0.440
GRM5	DLG3	psi-mi:“MI:0407”(direct interaction)	0.440
GRM5	APBA3	psi-mi:“MI:0407”(direct interaction)	0.440
GRM5	PDZD7	psi-mi:“MI:0407”(direct interaction)	0.440
GRM5	DLG4	psi-mi:“MI:0407”(direct interaction)	0.440
GRM5	DLG1	psi-mi:“MI:0407”(direct interaction)	0.440
GRM5	MPP2	psi-mi:“MI:0407”(direct interaction)	0.440
GRM5	MAGI2	psi-mi:“MI:0407”(direct interaction)	0.440
PCLO	GRM5	psi-mi:“MI:0407”(direct interaction)	0.440
GRM5	PATJ	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (31): GRM5 (Biochemical Activity), HOMER1 (Affinity Capture-Western), GRM5 (Proximity Label-MS), GRM5 (Proximity Label-MS), GRM5 (Co-localization), GRM5 (Co-localization), GRM5 (Affinity Capture-Western), ADORA2A (Affinity Capture-Western), GRM5 (Affinity Capture-Western), ACTN1 (FRET), PRNP (Affinity Capture-Western), GRM5 (Reconstituted Complex), GRM5 (Affinity Capture-Western), GRM5 (Affinity Capture-Western), GOPC (Affinity Capture-Western)

ESM2 similar proteins: A7XY94, B3LZ39, B3P2E5, B4GF83, B4I414, B4JHV0, B4KD90, B4LZB5, B4MU83, B4PVB0, B4QWW7, B7ZSK1, P19490, P19491, P19492, P19493, P22756, P23818, P23819, P31424, P35436, P39086, P41594, P42261, P42262, P42263, P48058, P58421, Q00959, Q00960, Q01097, Q03445, Q12879, Q13224, Q24418, Q296F7, Q38PU4, Q38PU5, Q38PU6, Q38PU7

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

20 interactions.

A	Effect	B	Mechanism
ADX-47273	up-regulates	GRM5	“chemical activation”
“glutamic acid”	“up-regulates activity”	GRM5	“chemical activation”
GRM5	“up-regulates activity”	GNAS	binding
GRM5	up-regulates	Excitatory_synaptic_transmission
GRM5	“up-regulates quantity”	calcium(2+)	relocalization
PRKCA	“up-regulates activity”	GRM5	phosphorylation
PRKCB	“up-regulates activity”	GRM5	phosphorylation
PRKCD	“up-regulates activity”	GRM5	phosphorylation
PRKCE	“up-regulates activity”	GRM5	phosphorylation
PRKCG	“up-regulates activity”	GRM5	phosphorylation
PRKCQ	“up-regulates activity”	GRM5	phosphorylation
PRKCZ	“up-regulates activity”	GRM5	phosphorylation
PKC	“up-regulates activity”	GRM5	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 79 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Ras activation upon Ca2+ influx through NMDA receptor	5	53.9×	2e-06
Unblocking of NMDA receptors, glutamate binding and activation	5	51.3×	2e-06
Negative regulation of NMDA receptor-mediated neuronal transmission	5	51.3×	2e-06
Long-term potentiation	5	44.9×	3e-06
Assembly and cell surface presentation of NMDA receptors	9	43.1×	5e-11
Neurexins and neuroligins	10	37.1×	2e-11
Protein-protein interactions at synapses	6	30.1×	2e-06
RHOA GTPase cycle	5	7.0×	9e-03

GO biological processes:

GO term	Partners	Fold	FDR
establishment or maintenance of epithelial cell apical/basal polarity	11	85.2×	1e-16
protein localization to synapse	6	61.3×	6e-08
receptor clustering	7	58.2×	6e-09
regulation of postsynaptic membrane neurotransmitter receptor levels	7	46.3×	2e-08
protein-containing complex assembly	9	13.7×	2e-06
cell-cell adhesion	10	13.5×	3e-07
protein localization to plasma membrane	6	8.7×	2e-03
chemical synaptic transmission	7	7.2×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	121
Likely benign	24
Benign	15

Top pathogenic / likely-pathogenic (0)

SpliceAI

3739 predictions. Top by Δscore:

Variant	Effect	Δscore
11:88509505:C:CC	acceptor_gain	1.0000
11:88567084:T:TA	donor_gain	1.0000
11:88597178:TTTTA:T	donor_loss	1.0000
11:88597179:TTTA:T	donor_loss	1.0000
11:88597180:TTA:T	donor_loss	1.0000
11:88597181:TA:T	donor_loss	1.0000
11:88597182:A:C	donor_loss	1.0000
11:88597183:C:A	donor_loss	1.0000
11:88597352:CC:C	acceptor_loss	1.0000
11:88604720:T:A	donor_gain	1.0000
11:88604961:GAAC:G	acceptor_gain	1.0000
11:88604965:C:CC	acceptor_gain	1.0000
11:88604965:C:CG	acceptor_loss	1.0000
11:88604966:T:A	acceptor_loss	1.0000
11:88653162:GCTTA:G	donor_loss	1.0000
11:88653163:CTTAC:C	donor_loss	1.0000
11:88653164:TTA:T	donor_loss	1.0000
11:88653165:TACTA:T	donor_loss	1.0000
11:88653166:A:AC	donor_gain	1.0000
11:88653166:A:C	donor_loss	1.0000
11:88653167:C:CA	donor_gain	1.0000
11:88653167:CT:C	donor_gain	1.0000
11:88653167:CTA:C	donor_gain	1.0000
11:88653167:CTAT:C	donor_gain	1.0000
11:88653167:CTATT:C	donor_gain	1.0000
11:88653399:CATCA:C	acceptor_gain	1.0000
11:88653401:TCA:T	acceptor_gain	1.0000
11:88653402:CA:C	acceptor_gain	1.0000
11:88653402:CAC:C	acceptor_gain	1.0000
11:88653404:C:CC	acceptor_gain	1.0000

AlphaMissense

7969 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:88567172:G:C	F837L	1.000
11:88567172:G:T	F837L	1.000
11:88567174:A:G	F837L	1.000
11:88567187:G:C	N832K	1.000
11:88567187:G:T	N832K	1.000
11:88567237:A:G	C816R	1.000
11:88567242:A:G	L814P	1.000
11:88567256:A:C	S809R	1.000
11:88567256:A:T	S809R	1.000
11:88567258:T:G	S809R	1.000
11:88567260:A:G	L808P	1.000
11:88567262:G:C	S807R	1.000
11:88567262:G:T	S807R	1.000
11:88567264:T:G	S807R	1.000
11:88567274:A:C	C803W	1.000
11:88567276:A:G	C803R	1.000
11:88567314:G:C	P790R	1.000
11:88567314:G:T	P790Q	1.000
11:88567319:A:C	F788L	1.000
11:88567319:A:T	F788L	1.000
11:88567321:A:G	F788L	1.000
11:88567323:G:T	A787D	1.000
11:88567326:A:G	L786P	1.000
11:88567330:A:G	W785R	1.000
11:88567330:A:T	W785R	1.000
11:88567332:A:T	I784K	1.000
11:88567339:A:G	C782R	1.000
11:88567348:A:G	Y779H	1.000
11:88567350:A:T	M778K	1.000
11:88567355:G:C	F776L	1.000

dbSNP variants (sampled 300 via entrez): RS1000001012 (11:88558228 C>A,T), RS1000006117 (11:88921200 A>G), RS1000011374 (11:88833731 G>A), RS1000022454 (11:88739290 G>C), RS1000029131 (11:88602350 G>A), RS1000035774 (11:88928031 G>C), RS1000037283 (11:89001407 A>G), RS1000040972 (11:88542548 A>G), RS1000041878 (11:88868803 G>T), RS1000049245 (11:89024342 C>T), RS1000051240 (11:88987765 G>A,C,T), RS1000060556 (11:88517162 C>T), RS1000060936 (11:88684533 G>T), RS1000061 (11:88742609 G>A,C), RS1000062 (11:88742728 T>A,C)

Disease associations

OMIM: gene MIM:604102 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): autism spectrum disorder (MONDO:0005258)

Orphanet (1): NON RARE IN EUROPE: Autism (Orphanet:106)

HPO phenotypes

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

GWAS associations

22 associations (top):

Study	Trait	p-value
GCST000371_5	Tanning	5.000000e-09
GCST001287_1	Attention deficit hyperactivity disorder	1.000000e-06
GCST002357_2	Rheumatoid arthritis (ACPA-negative)	2.000000e-06
GCST005174_39	Coronary artery calcified atherosclerotic plaque score in type 2 diabetes	9.000000e-06
GCST006940_69	Neurociticism	3.000000e-10
GCST006988_162	Blond vs. brown/black hair color	8.000000e-17
GCST007451_5	Skin, hair and eye pigmentation (multivariate analysis)	8.000000e-10
GCST007452_3	Skin pigmentation	1.000000e-09
GCST007454_3	Hair color	3.000000e-06
GCST007709_291	General factor of neuroticism	2.000000e-08
GCST007709_292	General factor of neuroticism	4.000000e-08
GCST008516_4	Skin pigmentation (conditioned on rs1426654 and rs35397)	3.000000e-10
GCST008519_6	Skin pigmentation	9.000000e-08
GCST009357_7	Nonsyndromic cleft lip	3.000000e-08
GCST009685_12	Hypertension	3.000000e-09
GCST009958_1	Retinal detachment	5.000000e-06
GCST009959_18	Retinal detachment or retinal break	2.000000e-08
GCST010135_37	Oily fish consumption	9.000000e-09
GCST010140_27	Pork consumption	9.000000e-09
GCST010142_28	Fish- and plant-related diet	4.000000e-09
GCST010142_73	Fish- and plant-related diet	9.000000e-09
GCST012355_5	Depression	7.000000e-20

EFO canonical traits (8, from GWAS)

EFO ID	Trait name
EFO:0004279	suntan
EFO:0004723	coronary artery calcification
EFO:0007660	neuroticism measurement
EFO:0003924	hair color
EFO:0009764	eye colour measurement
EFO:0003959	cleft lip
EFO:0010698	retinal break
EFO:0008111	diet measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL3227 (SINGLE PROTEIN), CHEMBL4296096 (PROTEIN COMPLEX)

Molecules with ChEMBL bioactivity

9 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 951,147 (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
CHEMBL2346738	DIPRAGLURANT	2	177
CHEMBL239800	FENOBAM ANHYDROUS	2	2,850
CHEMBL275040	KAINIC ACID	2	15,084
CHEMBL3087515	MAVOGLURANT	2	238
CHEMBL3301626	BASIMGLURANT	2	147
CHEMBL3545036	RASEGLURANT	2	57
CHEMBL240773	QUINPIROLE	2	2,815
CHEMBL4571075	BMS-984923	1	23

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 (99 total), top 25:

Ligand	Action	Affinity	Parameter
SP203	Negative	10.44	pIC50
TMP-301	Negative	9.27	pKi
compound 18 [PMID: 17723296]	Negative	9.14	pIC50
compound 20 [PMID: 16439120]	Negative	9.0	pKi
[3H]CTEP	Negative	8.77	pKd
MTEB	Negative	8.7	pIC50
GRN-529	Negative	8.6	pIC50
BOMA	Negative	8.5	pKi
3,3’-difluorobenzaldazine	Positive	8.5	pIC50
[3H]methoxy-PEPy	Negative	8.47	pKd
methoxy-MPEP	Antagonist	8.44	pIC50
compound 8 [PMID: 15482908]	Negative	8.41	pIC50
[3H]M-MPEP	Negative	8.3	pIC50
AZD9272	Negative	8.12	pIC50
alloswitch-1	Negative	8.07	pIC50
CDPPB	Positive	8.0	pEC50
VU-1545	Positive	8.0	pEC50
compound 26 [PMID: 16439120]	Negative	8.0	pKi
compound 10 [PMID: 15482906]	Negative	7.92	pKi
VU0463841	Negative	7.89	pEC50
compound 41 [PMID: 23434029]	Negative	7.89	pEC50
MTEP	Negative	7.8	pKi
compound 29b [PMID: 20809633]	Negative	7.8	pIC50
CTEP	Negative	7.79	pKi
compound 30 [PMID: 21757343]	Negative	7.77	pIC50

Binding affinities (BindingDB)

731 measured of 887 human assays (908 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
(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
6-methyl-N-[(1S,5R)-5-(pyridine-2-carbonylamino)-1-bicyclo[3.2.1]octanyl]pyridine-2-carboxamide	IC50	0.32 nM	US-9656975: Bicyclo[3.2.1]octyl amide derivatives and uses of same
3-chloro-4-fluoro-5-(6-pyrazol-1-ylpyrimidin-4-yl)benzonitrile	KI	0.501 nM	US-10246432: 4-(3-cyanophenyl)-6-pyridinylpyrimidine mGlu5 modulators
3-chloro-5-[6-(5-fluoro-2-pyridinyl)pyrimidin-4-yl]benzonitrile	KI	0.537 nM	US-10246432: 4-(3-cyanophenyl)-6-pyridinylpyrimidine mGlu5 modulators
6-[6-(3-chloro-5-cyanophenyl)pyrimidin-4-yl]pyridine-3-carbonitrile	KI	0.692 nM	US-10246432: 4-(3-cyanophenyl)-6-pyridinylpyrimidine mGlu5 modulators
3-chloro-4-fluoro-5-[6-(5-fluoro-2-pyridinyl)pyrimidin-4-yl]benzonitrile	KI	0.891 nM	US-10246432: 4-(3-cyanophenyl)-6-pyridinylpyrimidine mGlu5 modulators
N-[5-[2-(3-fluorophenyl)ethynyl]-1-bicyclo[3.2.1]octanyl]pyrazine-2-carboxamide	IC50	1.2 nM	US-9212165: Bicarbocyclic and tricarbocyclic ethynyl derivatives and uses of same
3-chloro-4-fluoro-5-(6-pyridin-2-ylpyrimidin-4-yl)benzonitrile	KI	1.23 nM	US-10246432: 4-(3-cyanophenyl)-6-pyridinylpyrimidine mGlu5 modulators
N-[(1R,5S)-5-(2-pyridin-2-ylethynyl)-1-bicyclo[3.2.1]octanyl]pyridine-2-carboxamide	IC50	1.6 nM	US-9212165: Bicarbocyclic and tricarbocyclic ethynyl derivatives and uses of same
5-[6-(5-fluoro-2-pyridinyl)pyrimidin-4-yl]benzene-1,3-dicarbonitrile	KI	1.66 nM	US-10246432: 4-(3-cyanophenyl)-6-pyridinylpyrimidine mGlu5 modulators
(4R,5R)-4-[5-(3-cyclobutylprop-1-ynyl)-3-pyridinyl]-5-(3-fluorophenyl)-1,3-oxazolidin-2-one	EC50	1.7 nM	US-9688669: Oxazolidinones as modulators of mGluR5
3-chloro-5-[6-(5-chloro-2-pyridinyl)pyrimidin-4-yl]benzonitrile	KI	1.7 nM	US-10246432: 4-(3-cyanophenyl)-6-pyridinylpyrimidine mGlu5 modulators
(4R,5R)-4-[5-(3-ethylsulfanylprop-1-ynyl)-3-pyridinyl]-5-(3-fluorophenyl)-1,3-oxazolidin-2-one	EC50	2 nM	US-9688669: Oxazolidinones as modulators of mGluR5
3-methyl-5-[6-(5-	KI	2.14 nM	US-10246432: 4-(3-cyanophenyl)-6-pyridinylpyrimidine mGlu5 modulators
(4R,5R)-5-(3-fluorophenyl)-4-(5-hex-1-ynyl-3-pyridinyl)-1,3-oxazolidin-2-one	EC50	2.2 nM	US-9688669: Oxazolidinones as modulators of mGluR5
3-chloro-5-[6-(5-methyl-2-pyridinyl)pyrimidin-4-yl]benzonitrile	KI	2.45 nM	US-10246432: 4-(3-cyanophenyl)-6-pyridinylpyrimidine mGlu5 modulators
3-[6-(5-fluoropyridin-2-	KI	2.69 nM	US-10246432: 4-(3-cyanophenyl)-6-pyridinylpyrimidine mGlu5 modulators
3-methyl-5-[6-(pyridin-	KI	2.75 nM	US-10246432: 4-(3-cyanophenyl)-6-pyridinylpyrimidine mGlu5 modulators
3-chloro-5-(6-pyrazol-1-ylpyrimidin-4-yl)benzonitrile	KI	2.75 nM	US-10246432: 4-(3-cyanophenyl)-6-pyridinylpyrimidine mGlu5 modulators
3-chloro-5-(6-pyridin-2-ylpyrimidin-4-yl)benzonitrile	KI	3.02 nM	US-10246432: 4-(3-cyanophenyl)-6-pyridinylpyrimidine mGlu5 modulators
(4R,5R)-4-[5-(3-cyclopropylprop-1-ynyl)-3-pyridinyl]-5-(3-fluorophenyl)-1,3-oxazolidin-2-one	EC50	3.6 nM	US-9688669: Oxazolidinones as modulators of mGluR5
tert-butyl 3-[2-(m- tolyl)ethynyl]-3a,4,5,6a- tetrahydropyrrolo[3,2- d]isoxazole-6-carboxylate	IC50	3.65 nM	US-9593127: Heterocyclylalkyne derivatives and their use as modulators of mGluR5 receptors
N-[5-[(3-chlorobenzoyl)amino]-1-bicyclo[3.2.1]octanyl]-6-methylpyridine-2-carboxamide	IC50	3.7 nM	US-9656975: Bicyclo[3.2.1]octyl amide derivatives and uses of same
6-methyl-N-[3-(2-pyridin-3-ylethynyl)-1-adamantyl]pyrazine-2-carboxamide	IC50	3.8 nM	US-9212165: Bicarbocyclic and tricarbocyclic ethynyl derivatives and uses of same
tert-butyl 3-[2-(3- chlorophenyl)ethynyl]- 3a,4,5,6a- tetrahydropyrrolo[3,2- d]isoxazole-6-carboxylate	IC50	3.87 nM	US-9593127: Heterocyclylalkyne derivatives and their use as modulators of mGluR5 receptors
N-[(1R,5S)-5-[(3-fluorobenzoyl)amino]-1-bicyclo[3.2.1]octanyl]-6-methylpyrazine-2-carboxamide	IC50	3.9 nM	US-9656975: Bicyclo[3.2.1]octyl amide derivatives and uses of same
3-methyl-5-(6-pyrazol-1-ylpyrimidin-4-yl)benzonitrile	KI	4.07 nM	US-10246432: 4-(3-cyanophenyl)-6-pyridinylpyrimidine mGlu5 modulators
3-chloro-4-fluoro-5-[4-	KI	4.27 nM	US-10246432: 4-(3-cyanophenyl)-6-pyridinylpyrimidine mGlu5 modulators
3-[6-(5-fluoropyridin-2-	KI	4.27 nM	US-10246432: 4-(3-cyanophenyl)-6-pyridinylpyrimidine mGlu5 modulators
4-methyl-N-[5-[(6-methyl-2-pyridinyl)carbamoyl]-1-bicyclo[3.2.1]octanyl]-1,3-thiazole-2-carboxamide	IC50	4.7 nM	US-9656975: Bicyclo[3.2.1]octyl amide derivatives and uses of same
(4R,5R)-5-(3-fluorophenyl)-4-[5-(5-methylhex-1-ynyl)-3-pyridinyl]-1,3-oxazolidin-2-one	EC50	4.7 nM	US-9688669: Oxazolidinones as modulators of mGluR5
N-[3-(2-pyridin-2-ylethynyl)-1-adamantyl]pyrazine-2-carboxamide	KI	4.7 nM	US-9212165: Bicarbocyclic and tricarbocyclic ethynyl derivatives and uses of same
2-[4-(1,3-oxazol-2-yl)imidazol-1-yl]-9-propyl-7,8-dihydro-4H-[1,4]diazepino[7,1-a]isoquinolin-5-one	IC50	5 nM	US-8853203: Diazepinone derivatives
(4R,5R)-5-(3-fluorophenyl)-4-(5-pent-1-ynyl-3-pyridinyl)-1,3-oxazolidin-2-one	EC50	5.2 nM	US-9688669: Oxazolidinones as modulators of mGluR5
N-[(1S,5R)-5-[2-(6-methyl-2-pyridinyl)ethynyl]-1-bicyclo[3.2.1]octanyl]pyridine-2-carboxamide	IC50	5.3 nM	US-9212165: Bicarbocyclic and tricarbocyclic ethynyl derivatives and uses of same
3-(4,4′-bipyrimidin-6-yl)-5-chlorobenzonitrile	KI	5.37 nM	US-10246432: 4-(3-cyanophenyl)-6-pyridinylpyrimidine mGlu5 modulators
(4R,5R)-5-(3-fluorophenyl)-4-[5-[(5S)-5-hydroxyhex-1-ynyl]-3-pyridinyl]-1,3-oxazolidin-2-one	EC50	5.9 nM	US-9688669: Oxazolidinones as modulators of mGluR5
N-[(1S,5R)-5-(2-pyridin-2-ylethynyl)-1-bicyclo[3.2.1]octanyl]pyridine-2-carboxamide	IC50	5.9 nM	US-9212165: Bicarbocyclic and tricarbocyclic ethynyl derivatives and uses of same
4-methyl-N-[(1R,5S)-5-(2-pyrazin-2-ylethynyl)-1-bicyclo[3.2.1]octanyl]-1,3-thiazole-2-carboxamide	KI	6.2 nM	US-9212165: Bicarbocyclic and tricarbocyclic ethynyl derivatives and uses of same
N-[(1R,5S)-5-(2-pyridin-2-ylethynyl)-1-bicyclo[3.2.1]octanyl]pyrazine-2-carboxamide	IC50	6.6 nM	US-9212165: Bicarbocyclic and tricarbocyclic ethynyl derivatives and uses of same
3-(fluoromethyl)-5-[6-	KI	6.76 nM	US-10246432: 4-(3-cyanophenyl)-6-pyridinylpyrimidine mGlu5 modulators
3-chloro-4-fluoro-5-[2-	KI	6.92 nM	US-10246432: 4-(3-cyanophenyl)-6-pyridinylpyrimidine mGlu5 modulators
3-[2-(3-chlorophenyl)ethynyl]- N-ethyl-N-isopropyl-3a,4,5,6a- tetrahydropyrrolo[3,2- d]isoxazole-6-carboxamide	IC50	6.99 nM	US-9593127: Heterocyclylalkyne derivatives and their use as modulators of mGluR5 receptors
5,5-dimethyl-3-[5-(2-phenylethynyl)-2-pyridinyl]-1,3-oxazolidin-2-one	EC50	7 nM	US-9315498: Arlethynyl derivatives
1-[5-[2-(2,5-difluorophenyl)ethynyl]pyrimidin-2-yl]-3,4,4-trimethylimidazolidin-2-one	EC50	7 nM	US-9315498: Arlethynyl derivatives
9-bromo-2-thiophen-2-yl-7,8-dihydro-4H-[1,4]diazepino[7,1-a]isoquinolin-5-one	IC50	8 nM	US-8853203: Diazepinone derivatives
3-chloro-N-(6-chloro-2-pyridinyl)-5-pyrimidin-5-yloxybenzamide	IC50	8.1 nM	US-8796295: Substituted benzamide analogs as mGluR5 negative allosteric modulators and methods of making and using the same
(4R,5R)-5-(3-fluorophenyl)-4-(5-hept-1-ynyl-3-pyridinyl)-1,3-oxazolidin-2-one	EC50	8.1 nM	US-9688669: Oxazolidinones as modulators of mGluR5
(4R,5R)-4-[5-(2-cyclobutylethynyl)-3-pyridinyl]-5-(3-fluorophenyl)-1,3-oxazolidin-2-one	EC50	8.3 nM	US-9688669: Oxazolidinones as modulators of mGluR5
N-[5-[(3-fluorobenzoyl)amino]-1-bicyclo[3.2.1]octanyl]-6-methylpyrazine-2-carboxamide	IC50	9 nM	US-9656975: Bicyclo[3.2.1]octyl amide derivatives and uses of same

ChEMBL bioactivities

4248 potent at pChembl≥5 of 4328 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.70	EC50	0.2	nM	CHEMBL4550190
9.52	Ki	0.3	nM	CHEMBL3597600
9.52	Ki	0.3	nM	CHEMBL3597597
9.52	Ki	0.3	nM	CHEMBL3597596
9.52	Ki	0.3	nM	CHEMBL3597593
9.49	IC50	0.32	nM	CHEMBL4111384
9.43	Ki	0.37	nM	CHEMBL201943
9.40	Ki	0.4	nM	CHEMBL3597585
9.40	Ki	0.4	nM	CHEMBL3597592
9.40	IC50	0.4	nM	CHEMBL3597593
9.40	IC50	0.3981	nM	CHEMBL3603926
9.40	EC50	0.4	nM	CHEMBL4560002
9.40	IC50	0.3981	nM	CHEMBL403390
9.40	IC50	0.3981	nM	CHEMBL271276
9.30	IC50	0.5	nM	CHEMBL184995
9.30	Ki	0.5	nM	CHEMBL3597584
9.30	Ki	0.5	nM	CHEMBL3597602
9.30	Ki	0.5	nM	CHEMBL3597598
9.30	Ki	0.5	nM	CHEMBL3597594
9.30	Ki	0.5012	nM	CHEMBL3603915
9.30	Ki	0.5012	nM	CHEMBL3603923
9.30	IC50	0.5012	nM	CHEMBL3603923
9.30	Ki	0.501	nM	CHEMBL3603915
9.27	Ki	0.537	nM	CHEMBL3603923
9.22	EC50	0.6	nM	CHEMBL4588437
9.22	Ki	0.6	nM	BMS-984923
9.20	Ki	0.631	nM	CHEMBL3603924
9.20	IC50	0.631	nM	CHEMBL3603923
9.20	IC50	0.631	nM	CHEMBL3603924
9.19	Ki	0.64	nM	CHEMBL5905434
9.16	Ki	0.692	nM	CHEMBL3603924
9.16	Ki	0.692	nM	CHEMBL5963819
9.15	Ki	0.7	nM	CHEMBL4535926
9.15	Ki	0.7	nM	CHEMBL4472693
9.15	EC50	0.7	nM	CHEMBL4580610
9.10	IC50	0.8	nM	CHEMBL3597594
9.10	Ki	0.7943	nM	CHEMBL3603926
9.10	IC50	0.79	nM	CHEMBL3759766
9.10	EC50	0.8	nM	CHEMBL3805542
9.10	IC50	0.7943	nM	CHEMBL257880
9.08	EC50	0.83	nM	CHEMBL3805542
9.08	Ki	0.832	nM	CHEMBL3603915
9.05	Ki	0.9	nM	CHEMBL3122212
9.05	IC50	0.9	nM	CHEMBL3597584
9.05	IC50	0.9	nM	CHEMBL381192
9.05	EC50	0.9	nM	CHEMBL4517787
9.05	Ki	0.9	nM	CHEMBL446543
9.05	Ki	0.891	nM	CHEMBL3603926
9.05	Ki	0.89	nM	CHEMBL5867544
9.03	IC50	0.94	nM	CHEMBL201943

PubChem BioAssay actives

2459 with measured affinity, of 5010 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
(4R,5R)-5-(3,4-difluorophenyl)-4-[5-(2-phenylethynyl)-3-pyridinyl]-1,3-oxazolidin-2-one	1637148: Positive allosteric modulation of human mGluR5A transfected in HEK293 cells assessed as potentiation of L-glutamate-induced calcium release incubated for 10 mins by FLIPR assay	ec50	0.0002	uM
6-[3-[1-(6-methyl-3-nitro-2-pyridinyl)piperidin-4-ylidene]prop-1-ynyl]pyridine-3-carbonitrile	1236883: Displacement of [3H]MPEP from human cloned mGluR5 receptor expressed in CHO-T-Rex cells after 60 mins by liquid scintillation spectrometry	ki	0.0003	uM
2-methyl-6-[3-[1-(2-nitrophenyl)piperidin-4-ylidene]prop-1-ynyl]pyridine	1236883: Displacement of [3H]MPEP from human cloned mGluR5 receptor expressed in CHO-T-Rex cells after 60 mins by liquid scintillation spectrometry	ki	0.0003	uM
3-nitro-2-[4-(3-pyridin-2-ylprop-2-ynylidene)piperidin-1-yl]pyridine	1236883: Displacement of [3H]MPEP from human cloned mGluR5 receptor expressed in CHO-T-Rex cells after 60 mins by liquid scintillation spectrometry	ki	0.0003	uM
2-[4-[3-(3-methylphenyl)prop-2-ynylidene]piperidin-1-yl]-3-nitropyridine	1236883: Displacement of [3H]MPEP from human cloned mGluR5 receptor expressed in CHO-T-Rex cells after 60 mins by liquid scintillation spectrometry	ki	0.0003	uM
3-[2-(2-methyl-1,3-thiazol-4-yl)ethynyl]benzonitrile	259884: Displacement of [3H]MPEP from cloned human mGluR5 transfected in HEK293-T cells	ki	0.0004	uM
1-[4-(2-nitrophenyl)piperazin-1-yl]-3-phenylprop-2-yn-1-one	1236883: Displacement of [3H]MPEP from human cloned mGluR5 receptor expressed in CHO-T-Rex cells after 60 mins by liquid scintillation spectrometry	ki	0.0004	uM
3-nitro-2-[4-(3-phenylprop-2-ynylidene)piperidin-1-yl]pyridine	1236883: Displacement of [3H]MPEP from human cloned mGluR5 receptor expressed in CHO-T-Rex cells after 60 mins by liquid scintillation spectrometry	ki	0.0004	uM
3-methyl-1-(2-thiophen-3-ylethynyl)pyrrolo[1,2-a]pyrazine-7-carbonitrile	319891: Antagonist activity at human mGluR5 expressed in CHO cells assessed as increase in intracellular calcium level by FLIPR	ic50	0.0004	uM
3-methyl-1-[2-(3-methylphenyl)ethynyl]pyrrolo[1,2-a]pyrazine	319891: Antagonist activity at human mGluR5 expressed in CHO cells assessed as increase in intracellular calcium level by FLIPR	ic50	0.0004	uM
(4R,5R)-5-(4-fluorophenyl)-4-[5-(2-phenylethynyl)-3-pyridinyl]-1,3-oxazolidin-2-one	1637148: Positive allosteric modulation of human mGluR5A transfected in HEK293 cells assessed as potentiation of L-glutamate-induced calcium release incubated for 10 mins by FLIPR assay	ec50	0.0004	uM
3-chloro-4-fluoro-5-[6-(5-fluoro-2-pyridinyl)pyrimidin-4-yl]benzonitrile	1240757: Negative allosteric modulation at human mGlu5 receptor expressed in HEK293 cells assessed as inhibition of L-quisqualic acid-induced inositol phosphate turnover preincubated for 45 mins before L-quisqualic acid challenge measured after 15 mins by IPone assay	ic50	0.0004	uM
1-[4-(3-nitro-2-pyridinyl)piperazin-1-yl]-3-phenylprop-2-yn-1-one	1236883: Displacement of [3H]MPEP from human cloned mGluR5 receptor expressed in CHO-T-Rex cells after 60 mins by liquid scintillation spectrometry	ki	0.0005	uM
2-methyl-6-[3-[1-(3-nitro-2-pyridinyl)piperidin-4-ylidene]prop-1-ynyl]pyridine	1236883: Displacement of [3H]MPEP from human cloned mGluR5 receptor expressed in CHO-T-Rex cells after 60 mins by liquid scintillation spectrometry	ki	0.0005	uM
2-methyl-4-[2-(6-phenyl-3-pyridinyl)ethynyl]-1,3-thiazole	242195: In vitro potency against human recombinant mGlu5 receptor was determined by [Ca2+] flux assay using glutamate as agonist	ic50	0.0005	uM
3-chloro-4-fluoro-5-(6-pyrazol-1-ylpyrimidin-4-yl)benzonitrile	1240756: Displacement of [3H]-M-MPEP from human mGlu5 receptor expressed in HEK293 cells after 90 mins by scintillation spectroscopy analysis	ki	0.0005	uM
3-chloro-5-[6-(5-fluoro-2-pyridinyl)pyrimidin-4-yl]benzonitrile	1240756: Displacement of [3H]-M-MPEP from human mGlu5 receptor expressed in HEK293 cells after 90 mins by scintillation spectroscopy analysis	ki	0.0005	uM
2-[4-[3-(6-methyl-2-pyridinyl)prop-2-ynylidene]piperidin-1-yl]-5-phenylpyridine-3-carbonitrile	1236883: Displacement of [3H]MPEP from human cloned mGluR5 receptor expressed in CHO-T-Rex cells after 60 mins by liquid scintillation spectrometry	ki	0.0005	uM
2-[4-[3-(3-chlorophenyl)prop-2-ynylidene]piperidin-1-yl]-3-nitropyridine	1236883: Displacement of [3H]MPEP from human cloned mGluR5 receptor expressed in CHO-T-Rex cells after 60 mins by liquid scintillation spectrometry	ki	0.0005	uM
6-[6-(3-chloro-5-cyanophenyl)pyrimidin-4-yl]pyridine-3-carbonitrile	1240756: Displacement of [3H]-M-MPEP from human mGlu5 receptor expressed in HEK293 cells after 90 mins by scintillation spectroscopy analysis	ki	0.0006	uM
(4R,5R)-5-(4-chlorophenyl)-4-[5-(2-phenylethynyl)-3-pyridinyl]-1,3-oxazolidin-2-one	1637148: Positive allosteric modulation of human mGluR5A transfected in HEK293 cells assessed as potentiation of L-glutamate-induced calcium release incubated for 10 mins by FLIPR assay	ec50	0.0006	uM
(4R,5R)-5-(2-chlorophenyl)-4-[5-(2-phenylethynyl)-3-pyridinyl]-1,3-oxazolidin-2-one	1637150: Displacement of [3H]-MPEPy from human mGluR5A transfected in HEK293 cell membranes after 60 mins by microbeta liquid scintillation counting analysis	ki	0.0006	uM
ethyl 4-[3-(3-chlorophenyl)prop-2-ynylidene]piperidine-1-carboxylate	1614057: Displacement of [3H]MPEP from human mGlu5 receptor expressed in CHO-TREx cell membranes after 60 mins by liquid scintillation spectrometric analysis	ki	0.0007	uM
(3-chlorophenyl)-[4-[3-(6-methyl-2-pyridinyl)prop-2-ynylidene]piperidin-1-yl]methanone	1614057: Displacement of [3H]MPEP from human mGlu5 receptor expressed in CHO-TREx cell membranes after 60 mins by liquid scintillation spectrometric analysis	ki	0.0007	uM
(4R,5R)-5-phenyl-4-[5-(2-phenylethynyl)-3-pyridinyl]-1,3-oxazolidin-2-one	1637148: Positive allosteric modulation of human mGluR5A transfected in HEK293 cells assessed as potentiation of L-glutamate-induced calcium release incubated for 10 mins by FLIPR assay	ec50	0.0007	uM
1-[2-(3-fluorophenyl)ethynyl]-3-methylpyrrolo[1,2-a]pyrazine-7-carbonitrile	319891: Antagonist activity at human mGluR5 expressed in CHO cells assessed as increase in intracellular calcium level by FLIPR	ic50	0.0008	uM
6-chloro-N-(2-chloro-4-pyridinyl)-7-fluoro-4H-triazolo[5,1-c][1,4]benzothiazine-3-carboxamide	1275092: Antagonist activity at human mGluR5 expressed in CHO cells assessed as inhibition of glutamate-induced effect by aequorin bioluminescence assay	ic50	0.0008	uM
(4R,5R)-5-(3-fluorophenyl)-4-[5-(2-phenylethynyl)-3-pyridinyl]-1,3-oxazolidin-2-one	1300117: Positive allosteric modulation of human mGlu5A receptor expressed in HEK293 cells coexpressing rat glutamate-aspartate transporter assessed as potentiation of L-glutamate-induced Ca2+ signal incubated for 60 mins by calcium 4 dye based FLIPR assay	ec50	0.0008	uM
3-chloro-5-[3-(2-pyridin-2-ylethynyl)cyclohex-2-en-1-yl]oxypyridine	255928: In vitro inhibitory concentration against Ca+2 flux mediated by human mGlu5 receptor expressed in Ltk cells using fura-2 dye	ic50	0.0009	uM
3-fluoro-5-[2-(2-methyl-1,3-thiazol-4-yl)ethynyl]benzonitrile	375049: Displacement of [3H]MPEP from cloned mGluR5 expressed in HEK293T cells by scintillation counting	ki	0.0009	uM
(4R,5R)-5-(3-chlorophenyl)-4-[5-(2-phenylethynyl)-3-pyridinyl]-1,3-oxazolidin-2-one	1637148: Positive allosteric modulation of human mGluR5A transfected in HEK293 cells assessed as potentiation of L-glutamate-induced calcium release incubated for 10 mins by FLIPR assay	ec50	0.0009	uM
1-methyl-3-(4-methyl-3-pyridinyl)-6-(pyridin-2-ylmethoxy)pyrazolo[3,4-b]pyrazine	1071426: Displacement of [3H]-MPEPy from human mGluR5 expressed in HEK293FT cells after 1 hr by liquid scintillation counting analysis	ki	0.0009	uM
3-(2-pyridin-2-ylethynyl)-5-(tritritiomethoxy)pyridine	109498: In vitro functional potency using an automated assay employing LtK-cells stably expressing human recombinant mGlu5 receptor by measuring changes in cytosolic [Ca2+] concentration	ic50	0.0010	uM
4-[2-(5-ethenyl-3-pyridinyl)ethynyl]-2-methyl-1,3-thiazole	259884: Displacement of [3H]MPEP from cloned human mGluR5 transfected in HEK293-T cells	ki	0.0010	uM
(6R)-6-benzyl-2-[(3-chlorophenyl)methoxy]-7,9-dihydro-6H-pyrimido[2,1-c][1,4]oxazin-4-one	1451223: Displacement of [3H]MPEPy from human mGlu5 expressed in HEK293FT cell membranes after 1 hr by liquid scintillation counting	ki	0.0010	uM
ethyl 4-[3-(3-cyanophenyl)prop-2-ynylidene]piperidine-1-carboxylate	1614057: Displacement of [3H]MPEP from human mGlu5 receptor expressed in CHO-TREx cell membranes after 60 mins by liquid scintillation spectrometric analysis	ki	0.0010	uM
2-[(3-chlorophenyl)methoxy]-6-methylpyridine-4-carbonitrile	263351: Displacement of [3H]MPEP from recombinant human mGlu5 receptor	ki	0.0010	uM
N-[3-[(3-chlorobenzoyl)amino]phenyl]-2-methoxybenzamide	470078: Antagonist activity at mGluR5	ic50	0.0011	uM
5-(4-fluorophenyl)-1,4-dimethyl-N-(6-methyl-2-pyridinyl)pyrazole-3-carboxamide	738966: Negative allosteric modulation of human mGluR5 expressed in HEK293 cells assessed as calcium mobilization by FLIPR assay	ic50	0.0011	uM
(4R,5R)-5-(2,4-difluorophenyl)-4-[5-(2-phenylethynyl)-3-pyridinyl]-1,3-oxazolidin-2-one	1637148: Positive allosteric modulation of human mGluR5A transfected in HEK293 cells assessed as potentiation of L-glutamate-induced calcium release incubated for 10 mins by FLIPR assay	ec50	0.0012	uM
3-methyl-1-(2-phenylethynyl)pyrrolo[1,2-a]pyrazine-7-carbonitrile	319891: Antagonist activity at human mGluR5 expressed in CHO cells assessed as increase in intracellular calcium level by FLIPR	ic50	0.0013	uM
3-(5-chloro-4-methyl-3-pyridinyl)-1-methyl-6-(pyridin-2-ylmethoxy)pyrazolo[3,4-b]pyrazine	1071426: Displacement of [3H]-MPEPy from human mGluR5 expressed in HEK293FT cells after 1 hr by liquid scintillation counting analysis	ki	0.0013	uM
3-chloro-4-fluoro-5-(6-pyridin-2-ylpyrimidin-4-yl)benzonitrile	1240756: Displacement of [3H]-M-MPEP from human mGlu5 receptor expressed in HEK293 cells after 90 mins by scintillation spectroscopy analysis	ki	0.0013	uM
(4R,5R)-5-(3,5-difluorophenyl)-4-[5-(2-phenylethynyl)-3-pyridinyl]-1,3-oxazolidin-2-one	1637150: Displacement of [3H]-MPEPy from human mGluR5A transfected in HEK293 cell membranes after 60 mins by microbeta liquid scintillation counting analysis	ki	0.0014	uM
3-[[(6R)-6-(2-methylpropyl)-4-oxo-7,9-dihydro-6H-pyrimido[2,1-c][1,4]oxazin-2-yl]oxymethyl]benzonitrile	1451223: Displacement of [3H]MPEPy from human mGlu5 expressed in HEK293FT cell membranes after 1 hr by liquid scintillation counting	ki	0.0015	uM
N-[4-[2-[(5-hydroxy-1,2,3,4-tetrahydronaphthalen-2-yl)-propylamino]ethyl]phenyl]-3-[1-[8-[methyl-[5-[[2-[[5-[2-(2-methyl-1,3-thiazol-4-yl)ethynyl]-3-pyridinyl]oxy]acetyl]amino]pentyl]amino]octyl]triazol-4-yl]propanamide	1400252: Agonist activity at human dopamine D2 receptor /mGluR5a (unknown origin) expressed in HEK293T cells assessed as reduction in forskolin-induced cAMP accumulation preincubated for 15 mins followed by forskolin addition by GloSensor-based assay	ec50	0.0015	uM
2-methyl-6-(2-phenylethynyl)pyridine	291521: Antagonist activity at human mGluR5 receptor expressed in CHOK1 cells assessed as inhibition of glutamate-mediated internal calcium mobilization	ic50	0.0015	uM
(4R,5R)-5-phenyl-4-[2-(2-phenylethynyl)-4-pyridinyl]-1,3-oxazolidin-2-one	1637148: Positive allosteric modulation of human mGluR5A transfected in HEK293 cells assessed as potentiation of L-glutamate-induced calcium release incubated for 10 mins by FLIPR assay	ec50	0.0015	uM
(4R,5R)-5-(2-fluorophenyl)-4-[5-(2-phenylethynyl)-3-pyridinyl]-1,3-oxazolidin-2-one	1637148: Positive allosteric modulation of human mGluR5A transfected in HEK293 cells assessed as potentiation of L-glutamate-induced calcium release incubated for 10 mins by FLIPR assay	ec50	0.0015	uM
5-[6-(5-fluoro-2-pyridinyl)pyrimidin-4-yl]benzene-1,3-dicarbonitrile	1240756: Displacement of [3H]-M-MPEP from human mGlu5 receptor expressed in HEK293 cells after 90 mins by scintillation spectroscopy analysis	ki	0.0016	uM

CTD chemical–gene interactions

26 total (human), top 26 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects cotreatment, increases methylation, decreases methylation	1
perfluorooctanoic acid	affects expression	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	increases methylation	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, decreases expression	1
4-hydroxy-equilenin	decreases expression	1
perfluorooctane sulfonic acid	increases expression	1
3,5-dihydroxyphenylglycine	affects binding, increases activity, increases reaction	1
6-methyl-2-(phenylethynyl)pyridine	decreases reaction, affects binding	1
perfluorohexanesulfonic acid	increases expression	1
3-cyano-N-(1,3-diphenyl-1H-pyrazol-5-yl)benzamide	increases activity, increases reaction, decreases reaction, affects binding	1
3-fluoro-5-(2-(2-(fluoromethyl)thiazol-4-yl)ethynyl)benzonitrile	affects binding	1
perfluorobutanesulfonic acid	affects expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Acetaminophen	decreases expression	1
Acetylcysteine	increases activity	1
Benzo(a)pyrene	increases methylation	1
Diethylhexyl Phthalate	decreases expression	1
Lipopolysaccharides	increases expression, affects response to substance	1
Methapyrilene	increases methylation	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	affects expression	1
Zinc	decreases expression	1
Quisqualic Acid	affects binding, increases activity, increases reaction	1
Aflatoxin B1	decreases methylation	1
1-Butanol	affects localization, affects reaction	1

ChEMBL screening assays

465 unique, capped per target: 263 functional, 201 binding, 1 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1004108	Binding	Displacement of [3H]MPEP from cloned mGluR5 expressed in HEK293T cells by scintillation counting	Structure-activity relationships comparing N-(6-methylpyridin-yl)-substituted aryl amides to 2-methyl-6-(substituted-arylethynyl)pyridines or 2-methyl-4-(substituted-arylethynyl)thiazoles as novel metabotropic glutamate receptor subtype 5 antagonists. — J Med Chem
CHEMBL1004111	Functional	Antagonist activity at cloned mGluR5 expressed in CHO cells co-transfected with chimeric G protein Gqi9 assessed as inhibition of glutamate-induced intracellular inositol phosphate accumulation at 10 uM by phosphoinositide hydrolysis assay	Structure-activity relationships comparing N-(6-methylpyridin-yl)-substituted aryl amides to 2-methyl-6-(substituted-arylethynyl)pyridines or 2-methyl-4-(substituted-arylethynyl)thiazoles as novel metabotropic glutamate receptor subtype 5 antagonists. — J Med Chem
CHEMBL3865445	ADMET	Activity at mGlu5 receptor (unknown origin) assessed as induction of glutamate fold shift after 60 mins by cell based FLIPR assay	Development of 1H-Pyrazolo[3,4-b]pyridines as Metabotropic Glutamate Receptor 5 Positive Allosteric Modulators. — ACS Med Chem Lett

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B0ZE	Abcam SK-N-BE(2) GRM5 KO	Cancer cell line	Male
CVCL_D1T1	Abcam U-87MG GRM5 KO	Cancer cell line	Male
CVCL_KU69	U2OS GRM5 Gq	Cancer cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00391261	PHASE4	COMPLETED	An Open-label Trial of Metformin for Weight Control of Pediatric Patients on Antipsychotic Medications.
NCT01028820	PHASE4	COMPLETED	FMRI Brain Activation of Aripiprazole Treatment in Autism Spectrum Disorders
NCT01333865	PHASE4	COMPLETED	A Study of Memantine Hydrochloride (Namenda®) for Cognitive and Behavioral Impairment in Adults With Autism Spectrum Disorders
NCT01337700	PHASE4	COMPLETED	Milnacipran in Autism and the Functional Locus Coeruleus and Noradrenergic Model of Autism
NCT01695200	PHASE4	COMPLETED	Omega-3 Fatty Acids in Autism Spectrum Disorders
NCT02096952	PHASE4	COMPLETED	Methylphenidate ER Liquid Formulation in Adults With ASD and ADHD
NCT02235467	PHASE4	COMPLETED	Multisite Study: Parental Training Using Video Modelling to Develop Social Skills in Children With Autism
NCT02940574	PHASE4	COMPLETED	Neural and Behavioral Effects of Oxytocin in Autism Spectrum Disorders
NCT03333629	PHASE4	COMPLETED	Promoting Positive Outcomes for Individuals With ASD: Linking Early Detection, Treatment, and Long-term Outcomes
NCT03337646	PHASE4	COMPLETED	Evaluation of the Effect and Safety of Lisdexamfetamine in Children Aged 6-12 With ADHD and Autism
NCT03538431	PHASE4	COMPLETED	Improving Driving in Young People With Autism Spectrum Disorders
NCT03757585	PHASE4	COMPLETED	Natural Treatments for the Management of Emotional Dysregulation in Youth With Non-verbal Learning Disability (NVLD) and/or Autism Spectrum Disorders (ASD)
NCT04903353	PHASE4	COMPLETED	Pragmatic Trial Comparing Weight Gain in Children With Autism Taking Risperidone Versus Aripiprazole
NCT05063656	PHASE4	COMPLETED	Biomarker-Driven Pharmacological Treatment of Adolescents With Autism Spectrum Disorder With Gabapentin
NCT05146245	PHASE4	UNKNOWN	Safety and Pharmacokinetics of Antipsychotics in Children 2: Studying TDM in an RCT
NCT05916339	PHASE4	RECRUITING	AWARE: Management of ADHD in Autism Spectrum Disorder
NCT05954052	PHASE4	TERMINATED	A Study of Glutathione in Children With Autism Spectrum Disorder
NCT06853665	PHASE4	RECRUITING	The TEAM Study - Treatment Efficacy for Autism/Attention Using Mixed Amphetamine
NCT07054697	PHASE4	COMPLETED	Pilot-RCT With Individualized Homeopathic Treatment in the Children With Autism Spectrum Disorder
NCT07161804	PHASE4	COMPLETED	Pilot RCT Using Homeopathic Medicines in ASD
NCT07439042	PHASE4	NOT_YET_RECRUITING	Buspirone for Anxiety in Autistic Youth
NCT01302964	PHASE3	COMPLETED	Mirtazapine Treatment of Anxiety in Children and Adolescents With Pervasive Developmental Disorders
NCT01706523	PHASE3	TERMINATED	Open Label Extension Study of STX209 (Arbaclofen) in Autism Spectrum Disorders
NCT01825798	PHASE3	COMPLETED	Treatment of Overweight Induced by Antipsychotic Medication in Young People With Autism Spectrum Disorders (ASD)
NCT01972074	PHASE3	COMPLETED	Behavioral and Neural Response to Memantine in Adolescents With Autism Spectrum Disorder
NCT02985749	PHASE3	COMPLETED	A Study of Oxytocin for the Treatment of Social Impairment in Individuals With High Functioning Autism Spectrum Disorder
NCT03197922	PHASE3	COMPLETED	Treatment of Encopresis in Children With Autism Spectrum Disorders
NCT03504917	PHASE3	TERMINATED	A Study of Balovaptan in Adults With Autism Spectrum Disorder With a 2-Year Open-Label Extension
NCT03553875	PHASE3	TERMINATED	Memantine for the Treatment of Social Deficits in Youth With Disorders of Impaired Social Interactions
NCT03640156	PHASE3	COMPLETED	Modulating Socially Adaptive Mirror System Functioning in Autism by Oxytocin
NCT03715153	PHASE3	TERMINATED	Efficacy and Safety of Bumetanide Oral Liquid Formulation in Children Aged From 2 to Less Than 7 Years Old With Autism Spectrum Disorder.
NCT03715166	PHASE3	TERMINATED	Efficacy and Safety of Bumetanide Oral Liquid Formulation in Children and Adolescents Aged From 7 to Less Than 18 Years Old With Autism Spectrum Disorder
NCT04233502	PHASE3	WITHDRAWN	Efficacy and Safety of Slenyto for Insomnia in Children With ASD
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