GRM7

Summary

GRM7 (glutamate metabotropic receptor 7, HGNC:4599) is a protein-coding gene on chromosome 3p26.1, encoding Metabotropic glutamate receptor 7 (Q14831). G-protein coupled receptor activated by glutamate that regulates axon outgrowth through the MAPK-cAMP-PKA signaling pathway during neuronal development.

L-glutamate is the major excitatory neurotransmitter in the central nervous system, and it 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 three 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. Multiple transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 2917 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neurodevelopmental disorder with seizures, hypotonia, and brain imaging abnormalities (Strong, GenCC)
• GWAS associations: 29
• Clinical variants (ClinVar): 344 total — 7 pathogenic, 3 likely-pathogenic
• Phenotypes (HPO): 89
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_000844

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4599
Approved symbol	GRM7
Name	glutamate metabotropic receptor 7
Location	3p26.1
Locus type	gene with protein product
Status	Approved
Aliases	GLUR7, GPRC1G, mGlu7, MGLUR7, PPP1R87
Ensembl gene	ENSG00000196277
Ensembl biotype	protein_coding
OMIM	604101
Entrez	2917

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 6 protein_coding, 6 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined, 2 retained_intron

ENST00000357716, ENST00000389335, ENST00000389336, ENST00000435689, ENST00000440923, ENST00000443259, ENST00000445087, ENST00000448328, ENST00000458641, ENST00000461677, ENST00000463676, ENST00000467425, ENST00000471242, ENST00000486284, ENST00000706912, ENST00000706913

RefSeq mRNA: 2 — MANE Select: NM_000844 NM_000844, NM_181874

CCDS: CCDS43042

Canonical transcript exons

ENST00000357716 — 10 exons

Exon	Start	End
ENSE00001295479	7680049	7680295
ENSE00001630473	7740357	7741533
ENSE00001761182	6861115	6861907
ENSE00003470176	7415023	7415163
ENSE00003510384	7298684	7298825
ENSE00003528317	7452607	7452807
ENSE00003624820	7578422	7579357
ENSE00003628466	7306498	7306652
ENSE00003629047	7461583	7461722
ENSE00003647030	7146452	7146668

Expression profiles

Bgee: expression breadth ubiquitous, 168 present calls, max score 91.33.

FANTOM5 (CAGE): breadth broad, TPM avg 1.6451 / max 164.7745, expressed in 183 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
35182	1.6451	183

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
endothelial cell	CL:0000115	91.33	gold quality
middle temporal gyrus	UBERON:0002771	84.33	gold quality
CA1 field of hippocampus	UBERON:0003881	84.32	silver quality
Brodmann (1909) area 23	UBERON:0013554	83.64	gold quality
entorhinal cortex	UBERON:0002728	81.28	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	80.84	gold quality
sperm	CL:0000019	80.62	silver quality
orbitofrontal cortex	UBERON:0004167	79.38	silver quality
dorsolateral prefrontal cortex	UBERON:0009834	79.17	gold quality
male germ cell	CL:0000015	78.96	silver quality
Brodmann (1909) area 9	UBERON:0013540	78.57	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	78.55	gold quality
primary visual cortex	UBERON:0002436	78.53	gold quality
superior frontal gyrus	UBERON:0002661	78.53	gold quality
Brodmann (1909) area 46	UBERON:0006483	78.28	gold quality
prefrontal cortex	UBERON:0000451	77.39	gold quality
cerebral cortex	UBERON:0000956	76.53	gold quality
postcentral gyrus	UBERON:0002581	76.44	gold quality
Ammon’s horn	UBERON:0001954	76.09	gold quality
frontal cortex	UBERON:0001870	75.90	gold quality
cortical plate	UBERON:0005343	75.77	gold quality
neocortex	UBERON:0001950	75.68	gold quality
temporal lobe	UBERON:0001871	75.59	gold quality
corpus callosum	UBERON:0002336	74.75	gold quality
hypothalamus	UBERON:0001898	74.67	gold quality
cingulate cortex	UBERON:0003027	74.38	gold quality
telencephalon	UBERON:0001893	74.26	gold quality
anterior cingulate cortex	UBERON:0009835	74.10	gold quality
right frontal lobe	UBERON:0002810	73.48	gold quality
parietal lobe	UBERON:0001872	73.47	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-HCAD-35	yes	66.12
E-ANND-3	yes	6.45

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): GATA3

miRNA regulators (miRDB)

115 targeting GRM7, 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-5193	100.00	67.26	1744
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-8075	99.97	67.20	962
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-512-3P	99.97	67.35	1049
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488

Literature-anchored findings (GeneRIF, showing 40)

• Identified additional splicing variants involving the 3’ end of the GRM7 coding sequence and resulting in three putative novel isoforms. (PMID:12052533)
• Polymorphism not associated with panic disorder. (PMID:17167337)
• The results of this study support the possible association of a GRM7 gene polymorphism with genetic susceptibility to schizophrenia. (PMID:18329248)
• GRM7 contributes to risk of developing age-related hearing impairment. (PMID:19047183)
• Study results provide support for the idea that glutamatergic neurotransmission and specifically the GRM7 gene might be relevant to the development of schizophrenia. (PMID:19638256)
• As a previous GWAS of a European and Finnish sample set already suggested a role for GRM7 in age-related hearing impairment, this study provides further evidence for the involvement of this gene. (PMID:20068591)
• Copy number variations within GRM7 are not associated with schizophrenia in the Han Chinese population. (PMID:20078931)
• we were unable to detect SUMOylation of full-length mGluR7 in either heterologous cells or neurons (PMID:21255632)
• This suggests that 3p25-26 is a new locus for severe recurrent depression. This represents the first report of a genome-wide significant locus for depression that also has an independent genome-wide significant replication. (PMID:21572164)
• In the Australian heavy smoking families, the authors found a genome-wide significant multipoint LOD score of 4.14 for major depressive disorder on chromosome 3 at 24.9 cM (3p26-3p25). (PMID:21572167)
• Data sets demonstrated a region of association for major depressive disorder within GRM7. Thus, the significance of this finding remains uncertain. (PMID:21813496)
• Mixed modeling analyses explored the relationship of GRM7 haplotype and SNP genotypes with measures of auditory perception. GRM7 alleles are associated primarily with peripheral measures of hearing loss, and with speech detection in older adults. (PMID:23102807)
• SNPs in autism spectrum disorders (PMID:23201551)
• These results provide preliminary evidence of an association between the GRM7 rs37952452 polymorphism and selective attention deficit and anxiety found within the Korean ADHD population (PMID:23295062)
• in an elderly male Han Chinese population, GRM7 SNP rs11928865 (TT) occurs more frequently in age-related hearing impairment patients with SL and AL phenotype patterns. (PMID:24146964)
• For neither PCLO nor GRM7 we found a more associated variant. For SLC6A4, we found a new SNP that showed a lower P-value than in the GAIN-MDD GWAS (PMID:24278217)
• Copy number variants at GRM7 may have a role in the etiology of bipolar disorder. (PMID:24804643)
• results reported here do not support a role for GRM7 in ADHD (PMID:25360607)
• results indicate that the GRM7 SNPs rs13353402 and rs1531939 might be associated with schizophrenia in Chinese Han population. (PMID:26254163)
• 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)
• GRM7 rs2133450 may have translational relevance as a predictor of response to risperidone in schizophrenia. (PMID:26856250)
• Multiple genetic models identified 1 significant locus, GRM7, for 2 hypertension-derived traits. (PMID:26866891)
• Glutamate system genes have been associated with disease risk in recent analyses from the Psychiatric Genomics Consortium. (PMID:26905411)
• Autism spectrum disorder (ASD) as a synaptopathy is revealed to be pertained to aberrant glutamatergic neurotransmission. Glutamate receptor, metabotropic 7 (GRM7) is a receptor coding gene of this pathway. (PMID:27312574)
• study to evaluate evidence for association between GRM7 and alcohol behaviors using an SNP approach, as well as a gene-based approach in two independent samples; Rs3749380 was suggestively associated with alcohol consumption in one sample with the minor T allele conferring risk; there was no evidence for association in the other sample (PMID:27788777)
• The results of this study indicate that the GRM7 rs9814881 might be associated with MDD in the Chinese Han population. (PMID:28027116)
• The mutant allele C in rs1485175 of the GMR7 may decrease individuals’ susceptibility to noise-induced hearing loss. (PMID:29301492)
• revealed significant interethnic differences in allele polymorphisms of NAT2, GRM7 and GRHL2 exhibit quite marked ethnic differences in Roma populations (PMID:29455378)
• The present study showed that the genetic polymorphisms of GRM7 are associated with susceptibility to Age-related Hearing Impairment. The SNP rs9880404 was found to be associated with increased risk for ARHI in a dominant pattern. SNPs rs11928865, rs1353828, and rs9814809 were found not to be associated with susceptibility to ARHI . (PMID:30100543)
• frequency of A allele of the rs779867 OF grm7 was significantly lower in the schizophrenic patients compared with healthy subjects (OR (95% CI) = 0.71 (0.56-0.89), adjusted P value = 0.008) (PMID:30610437)
• GRM7 rs779867 was associated with multiple sclerosis (MS) risk in recessive model. There was no significant difference in allele and genotype frequencies of rs6782011 between cases and controls. None of the estimated haplotype blocks of rs6782011 and rs779867 were associated with MS risk in the assessed population. (PMID:30616226)
• There were no significant differences in genotype, allele and haplotypes frequencies of the GRM7 rs6782011 and rs779867 between bipolar disorder 1 (BPD1) patients and controls. The CC genotype of the rs6782011 was significantly associated with BPD2 in a recessive model and with ADHD in dominant and co-dominant models.The C G haplotype was more prevalent among both BPD2 patients and MDD patients. (PMID:31170425)
• These findings provide a model in which Nedd4 and beta-arrestin act together as a complex to regulate mGlu7 surface expression and function at presynaptic terminals. (PMID:31373553)
• GRM7 polymorphisms are not associated with ischemic stroke in Iranian population. (PMID:32011203)
• Variants of GRM7 as risk factor and response to antipsychotic therapy in schizophrenia. (PMID:32127521)
• Biallelic GRM7 variants cause epilepsy, microcephaly, and cerebral atrophy. (PMID:32286009)
• A polymorphism in the glutamate metabotropic receptor 7 is associated with cognitive deficits in the early phases of psychosis. (PMID:32624350)
• Association between the group III metabotropic glutamate receptor gene polymorphisms and attention-deficit/hyperactivity disorder and functional exploration of risk loci. (PMID:33068816)
• A GRM7 mutation associated with developmental delay reduces mGlu7 expression and produces neurological phenotypes. (PMID:33476302)
• Structures of human mGlu2 and mGlu7 homo- and heterodimers. (PMID:34135509)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	GRM7	ENSDARG00000100267
danio_rerio		ENSDARG00000114852
mus_musculus	Grm7	ENSMUSG00000056755
rattus_norvegicus	Grm7	ENSRNOG00000005662
drosophila_melanogaster	mGluR	FBGN0019985

Paralogs (7): GRM6 (ENSG00000113262), GRM4 (ENSG00000124493), GRM1 (ENSG00000152822), GRM2 (ENSG00000164082), GRM5 (ENSG00000168959), GRM8 (ENSG00000179603), GRM3 (ENSG00000198822)

Protein

Protein identifiers

Metabotropic glutamate receptor 7 — Q14831 (reviewed: Q14831)

All UniProt accessions (8): A0A9L9PXG5, A0A9L9PY31, C9JMT3, C9JU97, Q14831, F8WAW6, F8WCR9, H7C3K2

UniProt curated annotations — full annotation on UniProt →

Function. G-protein coupled receptor activated by glutamate that regulates axon outgrowth through the MAPK-cAMP-PKA signaling pathway during neuronal development. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of downstream effectors, such as adenylate cyclase that it inhibits.

Subunit / interactions. Homodimer. Interacts with PICK1.

Subcellular location. Cell membrane.

Tissue specificity. Expressed in many areas of the brain, especially in the cerebral cortex, hippocampus, and cerebellum. Expression of GRM7 isoforms in non-neuronal tissues appears to be restricted to isoform 3 and isoform 4.

Post-translational modifications. N-glycosylated.

Disease relevance. Neurodevelopmental disorder with seizures, hypotonia, and brain imaging abnormalities (NEDSHBA) [MIM:618922] An autosomal recessive neurodevelopmental disorder characterized by global developmental delay, hypotonia, severe to profound intellectual disability, early-onset epilepsy, and microcephaly. Neuroimaging shows cerebral atrophy, thin corpus callosum and hypomyelination in a majority of cases. Death in childhood may occur. The disease is caused by variants affecting the gene represented in this entry.

Miscellaneous. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

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

Isoforms (5)

UniProt ID	Names	Canonical?
Q14831-1	1, GRM7_v1, mGluR7a	yes
Q14831-2	2, GRM7_v2, mGluR7b
Q14831-3	3, GRM7_v3
Q14831-4	4, GRM7_v4
Q14831-5	5, GRM7_v5

RefSeq proteins (2): NP_000835, NP_870989 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000162	GPCR_3_mtglu_rcpt	Family
IPR000337	GPCR_3	Family
IPR001828	ANF_lig-bd_rcpt	Domain
IPR001883	GPCR_3_mGluR7	Family
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 (95 total): strand 21, helix 14, sequence variant 11, topological domain 8, disulfide bond 8, transmembrane region 7, binding site 5, turn 5, glycosylation site 4, splice variant 4, mutagenesis site 3, signal peptide 1, chain 1, region of interest 1, compositionally biased region 1, modified residue 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
5C5C	X-RAY DIFFRACTION	1.86
3MQ4	X-RAY DIFFRACTION	2.8
7EPD	ELECTRON MICROSCOPY	3.9
7EPC	ELECTRON MICROSCOPY	4
9OMO	ELECTRON MICROSCOPY	4.1
9OMP	ELECTRON MICROSCOPY	4.3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q14831-F1	84.48	0.55

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): 159; 180–182; 230; 314; 407

Post-translational modifications (1): 900

Disulfide bonds (8): 67–109, 249–541, 374–390, 430–437, 523–542, 527–545, 548–560, 563–576

Glycosylation sites (4): 98, 458, 486, 572

Mutagenesis-validated functional residues (3):

Position	Phenotype
622	rescues axon outgrowth defects when expressed in a heterologous system. unchanged protein abundance. does not affect loc
658	does not rescue axon outgrowth defects when expressed in a heterologous system; when associated with k-675. decreased pr
675	does not rescue axon outgrowth defects when expressed in a heterologous system; when associated with w-658. decreased pr

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: 419 (showing top): AHRARNT_01, GOBP_GLUTAMATE_SECRETION, BENPORATH_ES_WITH_H3K27ME3, GOBP_BEHAVIOR, GOBP_REGULATION_OF_ORGANIC_ACID_TRANSPORT, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, GOBP_SENSORY_PERCEPTION_OF_MECHANICAL_STIMULUS, TGCACTT_MIR519C_MIR519B_MIR519A, GOBP_REGULATION_OF_SYNAPTIC_TRANSMISSION_GLUTAMATERGIC, SP3_Q3, GOBP_NEUROGENESIS, GOBP_G_PROTEIN_COUPLED_GLUTAMATE_RECEPTOR_SIGNALING_PATHWAY, GGGTGGRR_PAX4_03, CEBPB_01, GOBP_MULTICELLULAR_ORGANISMAL_RESPONSE_TO_STRESS

GO Biological Process (11): 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), chemical synaptic transmission (GO:0007268), sensory perception of sound (GO:0007605), negative regulation of glutamate secretion (GO:0014050), regulation of synaptic transmission, glutamatergic (GO:0051966), axon development (GO:0061564), signal transduction (GO:0007165), G protein-coupled receptor signaling pathway (GO:0007186), obsolete glycosylation (GO:0070085)

GO Molecular Function (9): group III metabotropic glutamate receptor activity (GO:0001642), calcium ion binding (GO:0005509), glutamate receptor activity (GO:0008066), adenylate cyclase inhibitor activity (GO:0010855), glutamate binding (GO:0016595), PDZ domain binding (GO:0030165), protein dimerization activity (GO:0046983), serine binding (GO:0070905), G protein-coupled receptor activity (GO:0004930)

GO Cellular Component (10): plasma membrane (GO:0005886), cell cortex (GO:0005938), membrane (GO:0016020), axon (GO:0030424), dendrite (GO:0030425), asymmetric synapse (GO:0032279), dendritic shaft (GO:0043198), signaling receptor complex (GO:0043235), postsynaptic membrane (GO:0045211), presynaptic active zone (GO:0048786)

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
cellular anatomical structure	3
adenylate cyclase inhibiting G protein-coupled glutamate receptor activity	2
G protein-coupled receptor signaling pathway	2
transmembrane signaling receptor activity	2
amino acid binding	2
carboxylic acid binding	2
cell periphery	2
neuron projection	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
anterograde trans-synaptic signaling	1
sensory perception of mechanical stimulus	1
glutamate secretion	1
regulation of glutamate secretion	1
negative regulation of organic acid transport	1
negative regulation of amino acid transport	1
negative regulation of secretion by cell	1
synaptic transmission, glutamatergic	1
modulation of chemical synaptic transmission	1
neuron projection development	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
metal ion binding	1
glutamate binding	1
adenylate cyclase activity	1
cyclase inhibitor activity	1
adenylate cyclase regulator activity	1
protein domain specific binding	1
protein binding	1
cation binding	1
membrane	1

Protein interactions and networks

STRING

2149 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GRM7	GRIK1	P39086	924
GRM7	PICK1	Q9NRD5	883
GRM7	GRIA2	P42262	816
GRM7	GRIK2	Q13002	799
GRM7	GRIK5	Q16478	780
GRM7	IQGAP2	Q13576	738
GRM7	GRIA4	P48058	710
GRM7	GRIA1	P42261	710
GRM7	GRIK4	Q16099	690
GRM7	GRIN2D	O15399	666
GRM7	GRM4	Q14833	663
GRM7	GRIN3A	Q8TCU5	663
GRM7	ELFN1	P0C7U0	617
GRM7	CALML6	Q8TD86	614
GRM7	CALML3	P27482	614
GRM7	GRIN2A	Q12879	614

IntAct

2 interactions, top by confidence:

A	B	Type	Score
GRM4	GRM7	psi-mi:“MI:0914”(association)	0.350

BioGRID (15): GRM7 (Two-hybrid), GRM7 (Two-hybrid), PICK1 (Reconstituted Complex), GRIP1 (Reconstituted Complex), SDCBP (Reconstituted Complex), PICK1 (Two-hybrid), PICK1 (Reconstituted Complex), PICK1 (Affinity Capture-Western), GRM7 (Affinity Capture-Western), GRM7 (Biochemical Activity), GNAQ (Reconstituted Complex), GRM7 (Affinity Capture-MS), GRM7 (Proximity Label-MS), PPHLN1 (Cross-Linking-MS (XL-MS)), SAP18 (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: B0BM39, B3VSC2, B5X3I6, F7BWT7, O14494, O14817, O35566, O42602, O42603, O43688, O60636, O75954, O88956, O95857, O95858, P25094, P35400, P47866, P48509, P60588, P61170, P61171, Q01453, Q06AA5, Q13324, Q14831, Q1JQA4, Q3SYV5, Q3ZBH3, Q3ZBV0, Q58CY8, Q5FVL6, Q5RAP3, Q5RAZ3, Q60748, Q6DCQ3, Q6GMK6, Q6GQF5, Q6WL85, Q86UF1

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”	GRM7	“chemical activation”
GRM7	“up-regulates activity”	GNAS	binding
GRM7	up-regulates	Excitatory_synaptic_transmission
GRM7	“up-regulates quantity”	calcium(2+)	relocalization

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	7
Likely pathogenic	3
Uncertain significance	175
Likely benign	116
Benign	23

Top pathogenic / likely-pathogenic (10)

Variant ID	HGVS	Classification
1340517	GRCh37/hg19 3p26.1(chr3:6200935-6981500)x3	Pathogenic
2106836	NM_000844.4(GRM7):c.1546C>T (p.Arg516Ter)	Pathogenic
242895	NM_000844.4(GRM7):c.461T>C (p.Ile154Thr)	Pathogenic
3254966	NM_000844.4(GRM7):c.342C>A (p.Tyr114Ter)	Pathogenic
870348	NM_000844.4(GRM7):c.1180G>A (p.Glu394Lys)	Pathogenic
972736	NM_000844.4(GRM7):c.1757G>A (p.Trp586Ter)	Pathogenic
972738	NM_000844.4(GRM7):c.2671G>A (p.Glu891Lys)	Pathogenic
1676787	NM_000844.4(GRM7):c.2496T>G (p.Ser832Arg)	Likely pathogenic
3246961	NC_000003.11:g.(?7188119)(7348359_?)dup	Likely pathogenic
972739	NM_000844.4(GRM7):c.1975C>T (p.Arg659Ter)	Likely pathogenic

SpliceAI

4285 predictions. Top by Δscore:

Variant	Effect	Δscore
3:6922283:G:GT	donor_gain	1.0000
3:7146450:A:AG	acceptor_gain	1.0000
3:7146450:A:AT	acceptor_loss	1.0000
3:7146451:G:GG	acceptor_gain	1.0000
3:7146451:GA:G	acceptor_gain	1.0000
3:7146451:GAT:G	acceptor_gain	1.0000
3:7146451:GATC:G	acceptor_gain	1.0000
3:7146451:GATCC:G	acceptor_gain	1.0000
3:7237190:TCAA:T	donor_gain	1.0000
3:6861837:T:TA	donor_gain	0.9900
3:6861838:A:AA	donor_gain	0.9900
3:6861903:TCCAG:T	donor_loss	0.9900
3:6861904:CCAGG:C	donor_loss	0.9900
3:6861905:CAG:C	donor_loss	0.9900
3:6861906:AG:A	donor_loss	0.9900
3:6861907:GG:G	donor_loss	0.9900
3:6861908:G:GA	donor_loss	0.9900
3:6861909:T:A	donor_loss	0.9900
3:6937764:G:GT	donor_gain	0.9900
3:7089568:GGCA:G	donor_gain	0.9900
3:7089569:GCAG:G	donor_gain	0.9900
3:7146446:TTGCA:T	acceptor_gain	0.9900
3:7146447:TGCAG:T	acceptor_gain	0.9900
3:7146448:GCAG:G	acceptor_gain	0.9900
3:7146449:CA:C	acceptor_gain	0.9900
3:7146450:AGA:A	acceptor_gain	0.9900
3:7146615:G:GT	donor_gain	0.9900
3:7159506:G:GT	donor_gain	0.9900
3:7215982:GAA:G	donor_gain	0.9900
3:7215988:GAACT:G	donor_gain	0.9900

AlphaMissense

6029 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:6861587:T:A	C67S	1.000
3:6861588:G:A	C67Y	1.000
3:6861588:G:C	C67S	1.000
3:6861707:G:C	D107H	1.000
3:6861713:T:A	C109S	1.000
3:6861713:T:C	C109R	1.000
3:6861714:G:A	C109Y	1.000
3:6861714:G:C	C109S	1.000
3:6861714:G:T	C109F	1.000
3:6861715:T:G	C109W	1.000
3:6861735:T:A	L116H	1.000
3:6861735:T:C	L116P	1.000
3:6861744:C:G	S119W	1.000
3:6861747:T:C	L120P	1.000
3:6861794:T:A	C136S	1.000
3:6861795:G:C	C136S	1.000
3:6861851:G:T	G155W	1.000
3:6861873:C:A	S162Y	1.000
3:6861873:C:T	S162F	1.000
3:6861884:G:C	A166P	1.000
3:6861894:T:C	L169P	1.000
3:6861902:T:C	F172L	1.000
3:6861904:C:A	F172L	1.000
3:6861904:C:G	F172L	1.000
3:7146464:A:C	S178R	1.000
3:7146466:T:A	S178R	1.000
3:7146466:T:G	S178R	1.000
3:7146489:T:C	L186P	1.000
3:7146522:G:C	R197P	1.000
3:7146584:T:A	W218R	1.000

dbSNP variants (sampled 300 via entrez): RS1000000224 (3:6914691 G>A), RS1000000582 (3:7059995 A>G), RS1000002527 (3:7515961 A>C,G), RS1000002917 (3:6892817 GAGGCT>G), RS1000004219 (3:7635841 C>T), RS1000008710 (3:7447399 T>C), RS1000012819 (3:7179398 C>T), RS1000013393 (3:7597340 C>T), RS1000015687 (3:7130563 A>G), RS1000019986 (3:7458581 C>T), RS1000021716 (3:7312462 G>A,C,T), RS1000022921 (3:7423652 C>T), RS1000022982 (3:7027738 C>T), RS1000026229 (3:7716874 G>C), RS1000028061 (3:7282442 C>G)

Disease associations

OMIM: gene MIM:604101 | disease phenotypes: MIM:618922

GenCC curated gene-disease

Disease	Classification	Inheritance
neurodevelopmental disorder with seizures, hypotonia, and brain imaging abnormalities	Strong	Autosomal recessive

Mondo (3): neurodevelopmental disorder with seizures, hypotonia, and brain imaging abnormalities (MONDO:0030063), intellectual disability (MONDO:0001071), microcephaly (MONDO:0001149)

Orphanet (1): NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

89 total (30 of 89 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000054	Micropenis
HP:0000070	Ureterocele
HP:0000110	Renal dysplasia
HP:0000175	Cleft palate
HP:0000252	Microcephaly
HP:0000340	Sloping forehead
HP:0000365	Hearing impairment
HP:0000463	Anteverted nares
HP:0000486	Strabismus
HP:0000729	Autistic behavior
HP:0000742	Self-mutilation
HP:0000752	Hyperactivity
HP:0000821	Hypothyroidism
HP:0000824	Decreased response to growth hormone stimulation test
HP:0000826	Precocious puberty
HP:0000871	Panhypopituitarism
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001254	Lethargy
HP:0001257	Spasticity
HP:0001263	Global developmental delay
HP:0001266	Choreoathetosis
HP:0001272	Cerebellar atrophy
HP:0001302	Pachygyria
HP:0001332	Dystonia
HP:0001336	Myoclonus
HP:0001337	Tremor
HP:0001347	Hyperreflexia
HP:0001500	Broad finger

GWAS associations

29 associations (top):

Study	Trait	p-value
GCST000320_10	Panic disorder	2.000000e-06
GCST000551_5	Major depressive disorder (broad)	1.000000e-06
GCST000995_3	Personality traits in bipolar disorder	8.000000e-07
GCST001442_2	Orofacial clefts	8.000000e-06
GCST001523_40	Visceral adipose tissue adjusted for BMI	3.000000e-06
GCST001994_1	Adverse response to chemotherapy (neutropenia/leucopenia) (all topoisomerase inhibitors)	9.000000e-06
GCST002830_16	Urate levels in lean individuals	4.000000e-06
GCST002830_24	Urate levels in lean individuals	6.000000e-06
GCST002941_10	Airway imaging phenotypes	1.000000e-07
GCST002941_3	Airway imaging phenotypes	3.000000e-07
GCST002982_2	Acute kidney injury in coronary artery bypass surgery (creatinine rise)	5.000000e-07
GCST003133_4	Plasma clusterin levels	4.000000e-06
GCST003432_1	Early response to risperidone in schizophrenia	4.000000e-08
GCST003450_1	Clozapine-induced agranulocytosis/granulocytopenia in treatment-resistant schizophrenia	2.000000e-06
GCST003487_12	Response to fenofibrate (total cholesterol levels)	7.000000e-06
GCST003518_81	Daytime sleep phenotypes	2.000000e-06
GCST003542_14	Night sleep phenotypes	2.000000e-06
GCST005230_12	Recurrent major depressive disorder	9.000000e-06
GCST005352_17	Paclitaxel disposition in epithelial ovarian cancer	6.000000e-06
GCST006485_2	Telomere length	1.000000e-06
GCST006493_5	Systemic sclerosis	2.000000e-06
GCST006616_3	Uterine fibroid number (single vs multiple)	9.000000e-07
GCST006630_53	Diastolic blood pressure	3.000000e-09
GCST007576_77	Chronotype	4.000000e-11
GCST010307_1	Urinary albumin excretion	3.000000e-11
GCST010307_2	Urinary albumin excretion	9.000000e-10
GCST010485_5	Platelet reactivity in response to clopidogrel treatment	3.000000e-06
GCST011743_85	HDL cholesterol levels in HIV infection	4.000000e-06
GCST012170_4	Cognitive function in longevity	4.000000e-07

EFO canonical traits (13, from GWAS)

EFO ID	Trait name
EFO:0004365	personality trait
EFO:0004340	body mass index
EFO:0004531	urate measurement
EFO:0007627	airway imaging measurement
EFO:0007656	plasma clusterin measurement
EFO:0007806	total cholesterol change measurement
EFO:0007828	daytime rest measurement
EFO:0009410	uterine fibroid measurement
EFO:0006336	diastolic blood pressure
EFO:0008328	chronotype measurement
EFO:0004285	albuminuria
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0008354	cognitive function measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D008831	Microcephaly	C05.660.207.620; C10.500.507.400.500; C16.131.621.207.620; C16.131.666.507.400.500

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3777 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 929,756 (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

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs2069062	Efficacy	3	risperidone

PharmGKB variants

2 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs2069062	GRM7	3	1.75	1	risperidone
rs3792452	GRM7		0.00	0

GtoPdb / IUPHAR curated pharmacology

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

Target class: gpcr — Metabotropic glutamate receptors

Most potent curated ligand interactions (25 total), top 25:

Ligand	Action	Affinity	Parameter
MMPIP	Negative	7.6	pIC50
MDIP	Negative	7.6	pIC50
ADX71743	Negative	7.2	pIC50
[3H]LY341495	Antagonist	7.1	pKd
AMN082	Positive	6.8	pEC50
LY341495	Antagonist	6.7	pKi
VU6012962	Negative	6.46	pIC50
VU6010608	Negative	6.12	pIC50
XAP044	Negative	5.55	pIC50
LSP4-2022	Agonist	4.94	pEC50
DCG-IV	Antagonist	4.7	pKi
L-serine-O-phosphate	Agonist	4.5	pEC50
α-methylserine-O-phosphate	Antagonist	4.4	pKi
L-CCG-I	Full agonist	4.3	pKi
LSP1-2111	Agonist	4.28	pEC50
L-AP4	Agonist	3.8	pEC50
MAP4	Antagonist	3.8	pKi
MPPG	Antagonist	3.8	pKi
(R,S)-4-PPG	Full agonist	3.7	pIC50
PPG	Full agonist	3.7	pKi
MSOPPE	Antagonist	3.6	pKi
(+)-MCPG	Antagonist	3.2	pKi
MCCG	Antagonist	3.2	pKi
(1S,3R)-ACPD	Full agonist	3.0	pKi
L-glutamic acid	Agonist	3.0	pEC50

Binding affinities (BindingDB)

1 measured of 1 human assays (3 total across all organisms); most potent 1 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
L-serine O-phosphate	IC50	523000 nM

ChEMBL bioactivities

95 potent at pChembl≥5 of 127 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.00	EC50	1	nM	CHEMBL4456545
8.92	EC50	1.205	nM	CHEMBL4446583
8.22	EC50	6	nM	CHEMBL5285249
8.16	EC50	6.9	nM	CHEMBL4556629
8.15	EC50	7	nM	CHEMBL5266235
7.55	EC50	28	nM	CHEMBL5280256
7.54	EC50	29.2	nM	CHEMBL4443735
7.42	EC50	38	nM	CHEMBL5288955
7.26	EC50	55	nM	CHEMBL5286456
7.20	IC50	63	nM	CHEMBL4174742
7.19	EC50	64	nM	CHEMBL1387826
7.01	EC50	98	nM	CHEMBL4798021
6.97	EC50	106	nM	CHEMBL4777502
6.96	EC50	109.7	nM	CHEMBL4535940
6.96	EC50	110	nM	CHEMBL5272418
6.95	EC50	113	nM	CHEMBL5291195
6.94	EC50	114	nM	CHEMBL4764083
6.83	EC50	148	nM	CHEMBL4162576
6.81	EC50	156	nM	CHEMBL5281755
6.80	EC50	158.5	nM	CHEMBL1387826
6.75	EC50	180	nM	CHEMBL4745982
6.70	EC50	201	nM	CHEMBL4787053
6.66	EC50	218.8	nM	CHEMBL4575681
6.52	EC50	302	nM	CHEMBL4799902
6.43	EC50	372	nM	CHEMBL4792152
6.42	EC50	377	nM	CHEMBL4760570
6.40	EC50	400	nM	CHEMBL4797971
6.31	EC50	487	nM	CHEMBL4746530
6.22	EC50	600	nM	CHEMBL4168668
6.20	IC50	631	nM	CHEMBL4176971
6.19	EC50	650	nM	CHEMBL4160748
6.19	EC50	649	nM	CHEMBL4160748
6.15	IC50	710	nM	CHEMBL4176971
6.13	EC50	740	nM	CHEMBL4446107
6.12	IC50	750	nM	CHEMBL5906357
6.12	IC50	750	nM	CHEMBL5853177
6.12	IC50	750	nM	CHEMBL5958680
6.12	IC50	750	nM	CHEMBL5789272
6.12	IC50	750	nM	CHEMBL5842540
6.12	IC50	750	nM	CHEMBL5875312
6.12	IC50	750	nM	CHEMBL6044274
6.12	IC50	750	nM	CHEMBL5949422
6.12	IC50	750	nM	CHEMBL6060840
6.12	IC50	750	nM	CHEMBL6035941
6.12	IC50	750	nM	CHEMBL6057053
6.12	IC50	750	nM	CHEMBL5906988
6.12	IC50	750	nM	CHEMBL5867385
6.12	IC50	750	nM	CHEMBL5778809
6.12	IC50	750	nM	CHEMBL5752300
6.12	IC50	750	nM	CHEMBL5896765

PubChem BioAssay actives

77 with measured affinity, of 368 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
(3S)-3-(cyclopropylmethylamino)-1-(3,4-dihydro-2H-1,5-benzoxazepin-5-yl)-3-phenylpropan-1-one	1571659: Agonist activity at human mGlu7 expressed in CHO cells assessed as reduction in forskolin-induced cAMP production	ec50	0.0010	uM
(2S)-N-(6-fluoro-4-hydroxy-3,4-dihydro-2H-chromen-3-yl)-2-phenylpropanamide	1571660: Agonist activity at mGlu7 (unknown origin)	ec50	0.0012	uM
(2S)-2-(4-fluorophenyl)-N-[(1R,2R)-1-methylsulfonyl-2,3-dihydro-1H-inden-2-yl]propanamide	1952916: Agonist activity at human mGluR7 expressed in CHO cells expressing CRE-Luc reporter gene assessed as reduction in forskolin-stimulated cAMP production preincubated for 15 mins followed by forskolin stimulation and measured after 5 hrs by luminescence based Steady glo assay	ec50	0.0060	uM
(2S)-2-(4-fluorophenyl)-N-(4-methylsulfonyl-3,4-dihydro-2H-chromen-3-yl)propanamide	1571661: Agonist activity at human mGlu7	ec50	0.0069	uM
(2S)-2-(4-fluorophenyl)-N-[(3S,4S)-4-methylsulfonyl-3,4-dihydro-2H-chromen-3-yl]propanamide	1952916: Agonist activity at human mGluR7 expressed in CHO cells expressing CRE-Luc reporter gene assessed as reduction in forskolin-stimulated cAMP production preincubated for 15 mins followed by forskolin stimulation and measured after 5 hrs by luminescence based Steady glo assay	ec50	0.0070	uM
(2S)-2-(4-fluorophenyl)-N-[(1R,2R)-1-methylsulfonyl-1,2,3,4-tetrahydronaphthalen-2-yl]propanamide	1952916: Agonist activity at human mGluR7 expressed in CHO cells expressing CRE-Luc reporter gene assessed as reduction in forskolin-stimulated cAMP production preincubated for 15 mins followed by forskolin stimulation and measured after 5 hrs by luminescence based Steady glo assay	ec50	0.0280	uM
2-(cyclopropylmethyl)-N-[(2-fluorophenyl)methyl]-3-oxo-1,4-dihydroisoquinoline-1-carboxamide	1571660: Agonist activity at mGlu7 (unknown origin)	ec50	0.0292	uM
(2S)-2-(4-fluorophenyl)-N-[(1S,2S)-1-methylsulfonyl-2,3-dihydro-1H-inden-2-yl]propanamide	1952916: Agonist activity at human mGluR7 expressed in CHO cells expressing CRE-Luc reporter gene assessed as reduction in forskolin-stimulated cAMP production preincubated for 15 mins followed by forskolin stimulation and measured after 5 hrs by luminescence based Steady glo assay	ec50	0.0380	uM
(2S)-N-(2,3-dihydro-1H-inden-2-yl)-2-(4-fluorophenyl)propanamide	1952916: Agonist activity at human mGluR7 expressed in CHO cells expressing CRE-Luc reporter gene assessed as reduction in forskolin-stimulated cAMP production preincubated for 15 mins followed by forskolin stimulation and measured after 5 hrs by luminescence based Steady glo assay	ec50	0.0550	uM
6-(2,4-dimethylphenyl)-2-ethyl-6,7-dihydro-5H-1,3-benzoxazol-4-one	1571676: Negative allosteric modulator activity at human mGlu7 assessed as reduction in Ca2+ mobilization by HTS assay	ic50	0.0630	uM
N,N’-dibenzhydrylethane-1,2-diamine	1952949: Agonist activity at human mGluR7b expressed in CHO cells assessed as inhibition of forskolin-stimulated cAMP accumulation	ec50	0.0640	uM
N-[4-(4-chloro-1,3-dioxoisoindol-2-yl)-5-fluoro-2-methylphenyl]-3-methylfuran-2-carboxamide	1693226: Positive allosteric modulation of human mGluR7 in presence of EC20 concentration of L-AP4 by calcium mobilization assay	ec50	0.0980	uM
N-[5-fluoro-2-methyl-4-(5-methyl-1,3-dioxoisoindol-2-yl)phenyl]-3-methylfuran-2-carboxamide	1693226: Positive allosteric modulation of human mGluR7 in presence of EC20 concentration of L-AP4 by calcium mobilization assay	ec50	0.1060	uM
1-(3,4-dihydro-2H-quinolin-1-yl)-2-[[(1S)-3-(methylamino)-1-phenylpropyl]amino]ethanone	1571657: Allosteric agonist activity at human mGlu7 expressed in CHO cells assessed as reduction in forskolin-induced cAMP production after 30 mins by cAMP reagent-based assay	ec50	0.1096	uM
1-(3,4-dihydro-2H-quinolin-1-yl)-2-[(1S)-2-(methylamino)-1-phenylethoxy]ethanone	1952949: Agonist activity at human mGluR7b expressed in CHO cells assessed as inhibition of forskolin-stimulated cAMP accumulation	ec50	0.1100	uM
(2S)-N-(2,3-dihydro-1H-inden-2-yl)-2-phenylpropanamide	1952916: Agonist activity at human mGluR7 expressed in CHO cells expressing CRE-Luc reporter gene assessed as reduction in forskolin-stimulated cAMP production preincubated for 15 mins followed by forskolin stimulation and measured after 5 hrs by luminescence based Steady glo assay	ec50	0.1130	uM
N-[5-fluoro-4-(4-fluoro-1,3-dioxoisoindol-2-yl)-2-methylphenyl]-3-methylfuran-2-carboxamide	1693226: Positive allosteric modulation of human mGluR7 in presence of EC20 concentration of L-AP4 by calcium mobilization assay	ec50	0.1140	uM
N-[3-chloro-4-[(5-chloro-2-pyridinyl)oxy]phenyl]pyridine-2-carboxamide	1936982: Positive allosteric modulation of mGluR7 (unknown origin)	ec50	0.1480	uM
2-(4-chlorophenyl)-N-(2,3-dihydro-1H-inden-2-yl)acetamide	1952916: Agonist activity at human mGluR7 expressed in CHO cells expressing CRE-Luc reporter gene assessed as reduction in forskolin-stimulated cAMP production preincubated for 15 mins followed by forskolin stimulation and measured after 5 hrs by luminescence based Steady glo assay	ec50	0.1560	uM
N-[4-(1,3-dioxoisoindol-2-yl)-2-fluoro-5-methylphenyl]-3-methylfuran-2-carboxamide	1693226: Positive allosteric modulation of human mGluR7 in presence of EC20 concentration of L-AP4 by calcium mobilization assay	ec50	0.1800	uM
N-[4-(4-chloro-1,3-dioxoisoindol-2-yl)-2,3,5-trifluorophenyl]-3-methylfuran-2-carboxamide	1693226: Positive allosteric modulation of human mGluR7 in presence of EC20 concentration of L-AP4 by calcium mobilization assay	ec50	0.2010	uM
2-(benzhydrylamino)-1-(3,4-dihydro-2H-quinolin-1-yl)ethanone	1571657: Allosteric agonist activity at human mGlu7 expressed in CHO cells assessed as reduction in forskolin-induced cAMP production after 30 mins by cAMP reagent-based assay	ec50	0.2188	uM
N-[4-(1,3-dioxoisoindol-2-yl)-2,3,6-trifluorophenyl]-3-methylfuran-2-carboxamide	1693226: Positive allosteric modulation of human mGluR7 in presence of EC20 concentration of L-AP4 by calcium mobilization assay	ec50	0.3020	uM
N-[4-(1,3-dioxo-4,5,6,7-tetrahydroisoindol-2-yl)-5-fluoro-2-methylphenyl]-3-methylfuran-2-carboxamide	1693226: Positive allosteric modulation of human mGluR7 in presence of EC20 concentration of L-AP4 by calcium mobilization assay	ec50	0.3720	uM
N-[4-(1,3-dioxo-4,5,6,7-tetrahydroisoindol-2-yl)-5-fluoro-2-methylphenyl]furan-2-carboxamide	1693226: Positive allosteric modulation of human mGluR7 in presence of EC20 concentration of L-AP4 by calcium mobilization assay	ec50	0.3770	uM
5-chloro-N-[4-(1,3-dioxo-4,5,6,7-tetrahydroisoindol-2-yl)-5-fluoro-2-methylphenyl]furan-2-carboxamide	1693226: Positive allosteric modulation of human mGluR7 in presence of EC20 concentration of L-AP4 by calcium mobilization assay	ec50	0.4000	uM
3-methyl-N-[2,3,5-trifluoro-4-(4-fluoro-1,3-dioxoisoindol-2-yl)phenyl]furan-2-carboxamide	1693226: Positive allosteric modulation of human mGluR7 in presence of EC20 concentration of L-AP4 by calcium mobilization assay	ec50	0.4870	uM
3-(2,6-difluoro-4-methoxyphenyl)-2,5-dimethyl-7-(trifluoromethyl)pyrazolo[1,5-a]pyrimidine	1571660: Agonist activity at mGlu7 (unknown origin)	ec50	0.6000	uM
3,4-dimethoxy-N-[2-(1,2,4-triazol-1-yl)-5-(trifluoromethoxy)phenyl]benzamide	1851601: Negative allosteric modulation of mGlu7 (unknown origin) in cells expressing G protein-regulated inwardly rectifying potassium channels (GIRKs) assessed as inhibition of L-AP4-induced response measured by thallium flux assay	ic50	0.6310	uM
3-(2,3-difluoro-4-methoxyphenyl)-2,5-dimethyl-7-(trifluoromethyl)pyrazolo[1,5-a]pyrimidine	1936982: Positive allosteric modulation of mGluR7 (unknown origin)	ec50	0.6490	uM
3-(2,5-difluoro-4-methoxyphenyl)-2-ethyl-5-methyl-7-(trifluoromethyl)pyrazolo[1,5-a]pyrimidine	1571660: Agonist activity at mGlu7 (unknown origin)	ec50	0.7400	uM
5-[5-chloro-2-(1,2,4-triazol-1-yl)phenyl]-3-(2,6-difluoro-3,4-dimethoxyphenyl)-1,2,4-oxadiazole	1851601: Negative allosteric modulation of mGlu7 (unknown origin) in cells expressing G protein-regulated inwardly rectifying potassium channels (GIRKs) assessed as inhibition of L-AP4-induced response measured by thallium flux assay	ic50	0.7943	uM
5-[5-chloro-2-(1,2,4-triazol-1-yl)phenyl]-3-(3-fluoro-4,5-dimethoxyphenyl)-1,2,4-oxadiazole	1851601: Negative allosteric modulation of mGlu7 (unknown origin) in cells expressing G protein-regulated inwardly rectifying potassium channels (GIRKs) assessed as inhibition of L-AP4-induced response measured by thallium flux assay	ic50	0.7943	uM
2-[3-methoxy-4-(oxetan-3-yloxy)phenoxy]-N-[2-(1,2,4-triazol-1-yl)-5-(trifluoromethoxy)phenyl]acetamide	1851601: Negative allosteric modulation of mGlu7 (unknown origin) in cells expressing G protein-regulated inwardly rectifying potassium channels (GIRKs) assessed as inhibition of L-AP4-induced response measured by thallium flux assay	ic50	0.8128	uM
trans-(1S,2S)-2-[(1S)-1-amino-1-carboxy-2-(9H-xanthen-9-yl)ethyl]cyclopropane-1-carboxylic acid	107261: Agonist potency against cloned Metabotropic glutamate receptor 7 (mGluR-7).	ki	0.9900	uM
glutamic acid	1289817: Agonist activity at human mGlu7 receptor expressed in HEK293 assessed as inhibition of forskolin stimulated cAMP production	ec50	1.1800	uM
2-(3,4-dimethoxyphenyl)-5-[2-(1,2,4-triazol-1-yl)-5-(trifluoromethoxy)phenyl]-1,3,4-oxadiazole	1851601: Negative allosteric modulation of mGlu7 (unknown origin) in cells expressing G protein-regulated inwardly rectifying potassium channels (GIRKs) assessed as inhibition of L-AP4-induced response measured by thallium flux assay	ic50	1.2589	uM
N-[4-(1,3-dioxo-4,5,6,7-tetrahydroisoindol-2-yl)-5-fluoro-2-methylphenyl]-2-methyl-1,3-thiazole-4-carboxamide	1693226: Positive allosteric modulation of human mGluR7 in presence of EC20 concentration of L-AP4 by calcium mobilization assay	ec50	1.3400	uM
(2R)-N-(2,3-dihydro-1H-inden-2-yl)-2-phenylpropanamide	1952916: Agonist activity at human mGluR7 expressed in CHO cells expressing CRE-Luc reporter gene assessed as reduction in forskolin-stimulated cAMP production preincubated for 15 mins followed by forskolin stimulation and measured after 5 hrs by luminescence based Steady glo assay	ec50	1.3450	uM
3-methoxy-4-propoxy-N-[2-(1,2,4-triazol-1-yl)-5-(trifluoromethoxy)phenyl]benzamide	1851601: Negative allosteric modulation of mGlu7 (unknown origin) in cells expressing G protein-regulated inwardly rectifying potassium channels (GIRKs) assessed as inhibition of L-AP4-induced response measured by thallium flux assay	ic50	1.5000	uM
methyl 4-[3-[2-(4-acetamidophenyl)sulfanylacetyl]-2,5-dimethylpyrrol-1-yl]benzoate	1936982: Positive allosteric modulation of mGluR7 (unknown origin)	ec50	1.5000	uM
4-ethoxy-3-methoxy-N-[2-(1,2,4-triazol-1-yl)-5-(trifluoromethoxy)phenyl]benzamide	1851601: Negative allosteric modulation of mGlu7 (unknown origin) in cells expressing G protein-regulated inwardly rectifying potassium channels (GIRKs) assessed as inhibition of L-AP4-induced response measured by thallium flux assay	ic50	1.5849	uM
3-[(4-benzhydryloxypiperidin-1-yl)methyl]-N-methylpiperidine-1-carboxamide	1571657: Allosteric agonist activity at human mGlu7 expressed in CHO cells assessed as reduction in forskolin-induced cAMP production after 30 mins by cAMP reagent-based assay	ec50	1.5849	uM
1-(3,4-dihydro-2H-quinolin-1-yl)-2-(1-phenylethylamino)ethanone	1571657: Allosteric agonist activity at human mGlu7 expressed in CHO cells assessed as reduction in forskolin-induced cAMP production after 30 mins by cAMP reagent-based assay	ec50	1.5849	uM
2-[5-chloro-2-(2-methylpyrazol-3-yl)phenyl]-5-(3,4-dimethoxyphenyl)-1,3,4-oxadiazole	1851601: Negative allosteric modulation of mGlu7 (unknown origin) in cells expressing G protein-regulated inwardly rectifying potassium channels (GIRKs) assessed as inhibition of L-AP4-induced response measured by thallium flux assay	ic50	1.9953	uM
(1S,2S,3S)-2-[1-amino-1-carboxy-2-(9H-xanthen-9-yl)ethyl]-3-(2-methylpropyl)cyclopropane-1-carboxylic acid	107418: Antagonistic activity against metabotropic glutamate receptor 7 (mGluR7) was evaluated	ic50	2.6000	uM
2-(3,4-dimethoxyphenyl)-5-[2-imidazol-1-yl-5-(trifluoromethoxy)phenyl]-1,3,4-oxadiazole	1851601: Negative allosteric modulation of mGlu7 (unknown origin) in cells expressing G protein-regulated inwardly rectifying potassium channels (GIRKs) assessed as inhibition of L-AP4-induced response measured by thallium flux assay	ic50	3.0000	uM
4-cyclobutyloxy-3-methoxy-N-[2-(1,2,4-triazol-1-yl)-5-(trifluoromethoxy)phenyl]benzamide	1851601: Negative allosteric modulation of mGlu7 (unknown origin) in cells expressing G protein-regulated inwardly rectifying potassium channels (GIRKs) assessed as inhibition of L-AP4-induced response measured by thallium flux assay	ic50	3.1000	uM
2-[5-chloro-2-(1,2,4-triazol-1-yl)phenyl]-4-(3,4-dimethoxyphenyl)-1,3-oxazole	1851601: Negative allosteric modulation of mGlu7 (unknown origin) in cells expressing G protein-regulated inwardly rectifying potassium channels (GIRKs) assessed as inhibition of L-AP4-induced response measured by thallium flux assay	ic50	3.9811	uM
ethyl 4-[6-(5-fluoro-2-methoxy-3-pyridinyl)-3-pyridinyl]-8-methoxyquinoline-3-carboxylate	1851601: Negative allosteric modulation of mGlu7 (unknown origin) in cells expressing G protein-regulated inwardly rectifying potassium channels (GIRKs) assessed as inhibition of L-AP4-induced response measured by thallium flux assay	ic50	4.5709	uM

CTD chemical–gene interactions

17 total (human), top 17 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases methylation	2
bisphenol A	decreases methylation	1
terbufos	increases methylation	1
arsenite	increases methylation	1
2-palmitoylglycerol	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Fonofos	increases methylation	1
Parathion	increases methylation	1
Plant Extracts	affects cotreatment, decreases expression	1
Taurine	decreases expression	1
Testosterone	increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Triclosan	increases expression	1
Valproic Acid	decreases methylation	1
1-Methyl-4-phenylpyridinium	affects expression	1
Aflatoxin B1	decreases methylation	1
Asbestos, Crocidolite	affects expression	1

ChEMBL screening assays

110 unique, capped per target: 56 binding, 54 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1027701	Functional	Antagonist activity at mGlu7 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
CHEMBL1034752	Binding	Activity at human mGluR7	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

3 cell lines: 1 transformed cell line, 1 cancer cell line, 1 induced pluripotent stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_C0SV	ACTOne GRM7	Transformed cell line	Female
CVCL_D1T2	Abcam U-87MG GRM7 KO	Cancer cell line	Male
CVCL_YI67	SDQLCHi014-A	Induced pluripotent stem cell	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT02304302	PHASE2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	PHASE2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	PHASE2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856	PHASE2	COMPLETED	Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
NCT05273320	PHASE1	COMPLETED	Clinical Trial of Nabilone for Aggression in Adults With Intellectual and Developmental Disabilities
NCT05301361	PHASE1	ENROLLING_BY_INVITATION	Sensitivity of the NIH Toolbox to Stimulant Treatment in Intellectual Disabilities
NCT06016764	PHASE1	COMPLETED	Use of MRI and cTBS for Catatonia in Autism
NCT06586827	PHASE1	COMPLETED	Impact of Competency-Based Training and Technical Assistance Employment Outcomes of Individuals With ID/DD
NCT07531940	PHASE1	NOT_YET_RECRUITING	Escalating Doses of Memantine in Down Syndrome (MEDS-123)
NCT03479476	PHASE2/PHASE3	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome
NCT02616796	PHASE1/PHASE2	COMPLETED	Effects of Social Gaze Training on Brain and Behavior in Fragile X Syndrome
NCT06860672	EARLY_PHASE1	RECRUITING	Clinical Trial of the Dual Vector Base Editor for the Treatment of the CHD3-R1025W Mutation
NCT00597948	Not specified	COMPLETED	Healthy Lifestyles for People With Intellectual Disabilities
NCT01087320	Not specified	RECRUITING	Genome Medical Sequencing for Gene Discovery
NCT01652963	Not specified	UNKNOWN	Picture-based Computerised Assessment and Training of Cognitive Behaviour Therapy Skills
NCT01695395	Not specified	COMPLETED	Mental Health Care Provision for Adults With Intellectual Disability and a Mental Disorder
NCT01867554	Not specified	COMPLETED	Research and Characterization of New Genes Involved in Intellectual Disability
NCT01915381	Not specified	COMPLETED	Improving Adherence Healthy Lifestyle With a Smartphone Application Based on Adults With Intellectual Disabilities
NCT01988623	Not specified	COMPLETED	Pivotal Response Treatment for Individuals With Intellectual Disabilities
NCT02099773	Not specified	COMPLETED	Support Staff-client Interactions With Augmentative and Alternative Communication
NCT02136849	Not specified	COMPLETED	Inter-regional Project of the Great Western Exploration Approach for Exome Molecular Causes Severe Intellectual Disability Isolated or Syndromic
NCT02225041	Not specified	COMPLETED	Sedation Strategy and Cognitive Outcome After Critical Illness in Early Childhood
NCT02414438	Not specified	COMPLETED	Establishing the Clinical Utility of First StepDx PLUS and NextStepDx PLUS Study
NCT02451761	Not specified	COMPLETED	Apparently Balanced Chromosomal Translocation/ Next-generation Sequencing/ Intellectual Disability
NCT02461420	Not specified	ACTIVE_NOT_RECRUITING	Mapping the Genotype, Phenotype, and Natural History of Phelan-McDermid Syndrome
NCT02461459	Not specified	ACTIVE_NOT_RECRUITING	Autism Spectrum Disorder (ASD) and Intellectual Disability (ID) Determinants in Tuberous Sclerosis Complex (TSC)
NCT02486081	Not specified	COMPLETED	Development and Application-Smart Football for Movement Evaluation and Training in the Special Education Population
NCT02504502	Not specified	COMPLETED	Enhancing Genomic Laboratory Reports to Enhance Communication and Empower Patients
NCT02513277	Not specified	COMPLETED	Diabetes Screening & Prevention for People With Learning (Intellectual) Disabilities:STOP Diabetes Study
NCT02561754	Not specified	COMPLETED	Weight Management for Adolescents With IDD
NCT02591446	Not specified	COMPLETED	Transcranial Magnetic Stimulation Studies in Autism Spectrum Disorders
NCT02714868	Not specified	COMPLETED	Evaluation of Project TEAM (Teens Making Environmental and Activity Modifications)
NCT02721394	Not specified	UNKNOWN	FCT With Young Children With ID in the UK: A Feasibility Project V.1
NCT02746614	Not specified	COMPLETED	Psychomotor Therapy Effects in Adaptive Behavior and Motor Proficiency in Intellectual Disability
NCT02836405	Not specified	COMPLETED	TMS for the Investigation of Brain Plasticity in Autism Spectrum Disorders