GRM6

Summary

GRM6 (glutamate metabotropic receptor 6, HGNC:4598) is a protein-coding gene on chromosome 5q35.3, encoding Metabotropic glutamate receptor 6 (O15303). G-protein coupled receptor for glutamate.

L-glutamate is the major excitatory neurotransmitter in the central nervous system and activates both ionotropic and metabotropic glutamate receptors. Glutamatergic neurotransmission is involved in most aspects of normal brain function and can be perturbed in many neuropathologic conditions. The metabotropic glutamate receptors are a family of G protein-coupled receptors, that have been divided into 3 groups on the basis of sequence homology, putative signal transduction mechanisms, and pharmacologic properties. Group I includes GRM1 and GRM5 and these receptors have been shown to activate phospholipase C. Group II includes GRM2 and GRM3 while Group III includes GRM4, GRM6, GRM7 and GRM8. Group II and III receptors are linked to the inhibition of the cyclic AMP cascade but differ in their agonist selectivities. Mutations in this gene result in congenital stationary night blindness type 1B.

Source: NCBI Gene 2916 — RefSeq curated summary.

At a glance

• Gene–disease (curated): GRM6-related retinopathy (Definitive, ClinGen) — +2 more curated relationships
• GWAS associations: 4
• Clinical variants (ClinVar): 854 total — 42 pathogenic, 12 likely-pathogenic
• Phenotypes (HPO): 8
• Druggable target: yes — 3 molecules with ChEMBL bioactivity
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_000843

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4598
Approved symbol	GRM6
Name	glutamate metabotropic receptor 6
Location	5q35.3
Locus type	gene with protein product
Status	Approved
Aliases	GPRC1F, mGlu6, MGLUR6, CSNB1B
Ensembl gene	ENSG00000113262
Ensembl biotype	protein_coding
OMIM	604096
Entrez	2916

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 3 protein_coding, 3 retained_intron

ENST00000231188, ENST00000517717, ENST00000518082, ENST00000519003, ENST00000650031, ENST00000650488

RefSeq mRNA: 1 — MANE Select: NM_000843 NM_000843

CCDS: CCDS4442

Canonical transcript exons

ENST00000517717 — 11 exons

Exon	Start	End
ENSE00000770343	178991424	178991559
ENSE00000853518	178986130	178986753
ENSE00000897552	178982910	178983221
ENSE00001194466	178989265	178989405
ENSE00001259159	178991867	178992083
ENSE00001259207	178988935	178989135
ENSE00001259217	178990592	178990746
ENSE00002094112	178995276	178995320
ENSE00002137228	178994441	178994960
ENSE00002238661	178986838	178986983
ENSE00002266056	178978327	178981854

Expression profiles

Bgee: expression breadth ubiquitous, 140 present calls, max score 73.09.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.1728 / max 83.6563, expressed in 10 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
65186	0.1202	8
65187	0.0385	6
65188	0.0112	3
65189	0.0030	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	73.09	gold quality
pancreatic ductal cell	CL:0002079	71.22	silver quality
tibialis anterior	UBERON:0001385	70.63	gold quality
ileal mucosa	UBERON:0000331	68.38	silver quality
cortical plate	UBERON:0005343	65.85	gold quality
mucosa of urinary bladder	UBERON:0001259	64.00	gold quality
diaphragm	UBERON:0001103	63.23	gold quality
cerebellar hemisphere	UBERON:0002245	61.94	gold quality
cerebellar cortex	UBERON:0002129	61.84	gold quality
ganglionic eminence	UBERON:0004023	61.15	gold quality
right hemisphere of cerebellum	UBERON:0014890	60.74	gold quality
cerebellum	UBERON:0002037	60.29	gold quality
adenohypophysis	UBERON:0002196	60.11	gold quality
pituitary gland	UBERON:0000007	59.44	gold quality
deltoid	UBERON:0001476	58.22	silver quality
hair follicle	UBERON:0002073	56.87	gold quality
decidua	UBERON:0002450	56.55	gold quality
hypothalamus	UBERON:0001898	56.49	gold quality
embryo	UBERON:0000922	55.81	gold quality
Brodmann (1909) area 9	UBERON:0013540	54.52	gold quality
anterior cingulate cortex	UBERON:0009835	54.23	gold quality
left testis	UBERON:0004533	54.22	gold quality
cingulate cortex	UBERON:0003027	54.21	gold quality
amygdala	UBERON:0001876	53.82	gold quality
right frontal lobe	UBERON:0002810	53.82	gold quality
right testis	UBERON:0004534	53.78	gold quality
testis	UBERON:0000473	53.75	gold quality
apex of heart	UBERON:0002098	53.32	gold quality
choroid plexus epithelium	UBERON:0003911	53.12	silver quality
skin of hip	UBERON:0001554	52.47	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-137537	yes	1629.69
E-MTAB-7316	yes	44.30
E-ANND-3	yes	3.70

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

135 targeting GRM6, 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-450A-1-3P	100.00	69.33	1837
HSA-MIR-518D-5P	100.00	67.51	979
HSA-MIR-518E-5P	100.00	67.66	954
HSA-MIR-518F-5P	100.00	67.51	979
HSA-MIR-519A-5P	100.00	67.66	954
HSA-MIR-519B-5P	100.00	67.66	954
HSA-MIR-519C-5P	100.00	67.66	954
HSA-MIR-520C-5P	100.00	67.51	979
HSA-MIR-522-5P	100.00	67.66	954
HSA-MIR-523-5P	100.00	67.66	954
HSA-MIR-526A-5P	100.00	67.51	979
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-223-3P	99.99	70.14	1140
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-4760-3P	99.93	70.50	2385
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 14)

• Affected individuals in three of five families carried either compound heterozygous or homozygous mutations in GRM6. (PMID:16249515)
• The ligand-binding and the poorly characterized cysteine-rich domains, in addition to the intracellular domains, have a pivotal role in correct trafficking of metabotropic glutamate receptors to the cell surface. (PMID:17405131)
• A switch in G-protein coupling, in which glutamate775lysine loses G(o) subunit coupling but retains coupling to G(i), may explain the highly specialized metabotropic glutamate receptor mGlur6 phenotype. (PMID:19666700)
• Three novel variations with potential functional consequences were identified in the GRM6 of patients with high myopia, suggesting a potential role in the development of myopia in rare cases. (PMID:19862333)
• A positive association was observed between response to methadone and two variants in the genes MYOCD and GRM6. (PMID:20560679)
• The phenotype associated with GRM6 mutation is variable in terms of presentation, refractive error, visual acuity and macular function. ERGs are electronegative and suggest ON-pathway dysfunction. (PMID:22008250)
• The results expand the mutation spectrum of NYX, CACNA1F and GRM6. They also suggest that NYX mutations are a common cause of congenital stationary night blindness (CSNB). (PMID:22735794)
• The selective thinning of the inner retinal layers in patients with GRM6 mutations suggests either reduced bipolar or ganglion cell numbers or altered synaptic structure in the inner retina. (PMID:22959359)
• These data suggest differences in coupling of TRPM1 function to mGluR6 signaling explain different cellular responses to glutamate in the retina and the skin. (PMID:23452348)
• We found 5 different mutations in GRM6, in congenital stationary night blindness. (PMID:23714322)
• Two mutations in GRM6 gene have been identified in two consanguineous Pakistani families with congenital stationary night blindness. (PMID:26628857)
• Our data suggested that genetic variants in GRM6 are associated with high myopia. The mechanism of GRM6 in the development of high myopia need to be further investigated. (PMID:27034204)
• We identified a novel homozygous missense mutation in exon 8 of GRM6 (NM_000843.3). (PMID:31063016)
• Study reported a rare case of pseudodominantly inherited autosomal recessive congenital stationary night blindness in a family with three co-segregating deleterious variants (p.Arg621Ter, p.Gly51Val, and p.Gly464Arg) of GRM6. (PMID:31677249)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	grm6a	ENSDARG00000017742
danio_rerio	grm6b	ENSDARG00000025671
mus_musculus	Grm6	ENSMUSG00000000617
rattus_norvegicus	Grm6	ENSRNOG00000000233
drosophila_melanogaster	mGluR	FBGN0019985

Paralogs (7): GRM4 (ENSG00000124493), GRM1 (ENSG00000152822), GRM2 (ENSG00000164082), GRM5 (ENSG00000168959), GRM8 (ENSG00000179603), GRM7 (ENSG00000196277), GRM3 (ENSG00000198822)

Protein

Protein identifiers

Metabotropic glutamate receptor 6 — O15303 (reviewed: O15303)

All UniProt accessions (1): O15303

UniProt curated annotations — full annotation on UniProt →

Function. G-protein coupled receptor for glutamate. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Signaling inhibits adenylate cyclase activity. Signaling stimulates TRPM1 channel activity and Ca(2+) uptake. Required for normal vision.

Subunit / interactions. Homodimer. Interacts with GPR179. Interacts with photoreceptor synaptic protein LRIT1 (via its N-terminal extracellular domain). Interacts with NYX and TRPM1.

Subcellular location. Cell membrane. Endoplasmic reticulum membrane. Golgi apparatus membrane. Cell projection. Dendrite.

Tissue specificity. Detected in melanocytes.

Disease relevance. Night blindness, congenital stationary, 1B (CSNB1B) [MIM:257270] A non-progressive retinal disorder characterized by impaired night vision. Congenital stationary night blindness type 1B is an autosomal recessive form associated with a negative electroretinogram waveform. Patients are night blind from an early age, and when maximally dark-adapted, they could perceive lights only with an intensity equal to or slightly dimmer than that normally detected by the cone system. ERGs in response to single brief flashes of light have clearly detectable a-waves, which are derived from photoreceptors, and greatly reduced b-waves, which are derived from the second-order inner retinal neurons. ERGs in response to sawtooth flickering light indicate a markedly reduced on response and a nearly normal OFF response. There is no subjective delay in the perception of suddenly appearing white vs black objects on a gray background. The disease is caused by variants affecting the gene represented in this entry.

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

RefSeq proteins (1): NP_000834* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000112	GPCR_3__mGluR6	Family
IPR000162	GPCR_3_mtglu_rcpt	Family
IPR000337	GPCR_3	Family
IPR001828	ANF_lig-bd_rcpt	Domain
IPR011500	GPCR_3_9-Cys_dom	Domain
IPR017978	GPCR_3_C	Domain
IPR017979	GPCR_3_CS	Conserved_site
IPR028082	Peripla_BP_I	Homologous_superfamily
IPR038550	GPCR_3_9-Cys_sf	Homologous_superfamily
IPR050726	mGluR	Family

Pfam: PF00003, PF01094, PF07562

UniProt features (48 total): sequence variant 13, topological domain 8, disulfide bond 8, transmembrane region 7, binding site 5, glycosylation site 4, signal peptide 1, chain 1, region of interest 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
9LLZ	ELECTRON MICROSCOPY	3.2
9UYQ	ELECTRON MICROSCOPY	3.27
9UYO	ELECTRON MICROSCOPY	3.39
9UYP	ELECTRON MICROSCOPY	3.51
9LM0	ELECTRON MICROSCOPY	3.82

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O15303-F1	85.90	0.57

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): 154; 175–177; 225; 307; 400

Disulfide bonds (8): 57–99, 244–536, 367–383, 423–430, 518–537, 522–540, 543–555, 558–571

Glycosylation sites (4): 296, 451, 479, 567

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: 168 (showing top): GOBP_POSITIVE_REGULATION_OF_CALCIUM_ION_TRANSPORT, BENPORATH_ES_WITH_H3K27ME3, GOBP_BEHAVIOR, GOBP_SYNAPSE_ASSEMBLY, GOBP_REGULATION_OF_SYNAPTIC_TRANSMISSION_GLUTAMATERGIC, XU_HGF_TARGETS_REPRESSED_BY_AKT1_DN, GOBP_G_PROTEIN_COUPLED_GLUTAMATE_RECEPTOR_SIGNALING_PATHWAY, GOBP_POSITIVE_REGULATION_OF_TRANSMEMBRANE_TRANSPORT, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_CELL_CELL_SIGNALING, GOBP_ADENYLATE_CYCLASE_MODULATING_G_PROTEIN_COUPLED_RECEPTOR_SIGNALING_PATHWAY, GOBP_CELL_JUNCTION_ORGANIZATION, GOBP_REGULATION_OF_CALCIUM_ION_TRANSMEMBRANE_TRANSPORT, GOBP_CALCIUM_ION_IMPORT, GOBP_POSITIVE_REGULATION_OF_MONOATOMIC_ION_TRANSPORT

GO Biological Process (15): G protein-coupled glutamate receptor signaling pathway (GO:0007216), chemical synaptic transmission (GO:0007268), synapse assembly (GO:0007416), locomotory behavior (GO:0007626), detection of visible light (GO:0009584), gene expression (GO:0010467), detection of light stimulus involved in visual perception (GO:0050908), regulation of synaptic transmission, glutamatergic (GO:0051966), retina development in camera-type eye (GO:0060041), positive regulation of calcium ion import across plasma membrane (GO:1905665), signal transduction (GO:0007165), G protein-coupled receptor signaling pathway (GO:0007186), adenylate cyclase-inhibiting G protein-coupled glutamate receptor signaling pathway (GO:0007196), visual perception (GO:0007601), sensory perception of light stimulus (GO:0050953)

GO Molecular Function (5): adenylate cyclase inhibiting G protein-coupled glutamate receptor activity (GO:0001640), G protein-coupled receptor activity (GO:0004930), glutamate receptor activity (GO:0008066), protein homodimerization activity (GO:0042803), protein binding (GO:0005515)

GO Cellular Component (11): Golgi membrane (GO:0000139), endoplasmic reticulum membrane (GO:0005789), plasma membrane (GO:0005886), dendrite (GO:0030425), new growing cell tip (GO:0035841), synapse (GO:0045202), endoplasmic reticulum (GO:0005783), Golgi apparatus (GO:0005794), membrane (GO:0016020), cell projection (GO:0042995), cell tip (GO:0051286)

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
G protein-coupled receptor signaling pathway	2
G protein-coupled glutamate receptor activity	2
transmembrane signaling receptor activity	2
cytoplasm	2
endomembrane system	2
intracellular membrane-bounded organelle	2
cellular anatomical structure	2
glutamate receptor signaling pathway	1
anterograde trans-synaptic signaling	1
nervous system development	1
cell junction assembly	1
synapse organization	1
behavior	1
detection of light stimulus	1
macromolecule biosynthetic process	1
visual perception	1
detection of light stimulus involved in sensory perception	1
synaptic transmission, glutamatergic	1
modulation of chemical synaptic transmission	1
camera-type eye development	1
anatomical structure development	1
positive regulation of calcium ion import	1
calcium ion import across plasma membrane	1
positive regulation of calcium ion transmembrane transport	1
regulation of calcium ion import across plasma membrane	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
adenylate cyclase inhibiting G protein-coupled glutamate receptor activity	1
adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway	1
G protein-coupled glutamate receptor signaling pathway	1
sensory perception of light stimulus	1
sensory perception	1
adenylate cyclase-inhibiting G protein-coupled glutamate receptor signaling pathway	1
glutamate binding	1
identical protein binding	1

Protein interactions and networks

STRING

1612 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GRM6	TRPM1	Q7Z4N2	974
GRM6	NYX	Q9GZU5	959
GRM6	GRIK1	P39086	759
GRM6	CACNA1F	O60840	732
GRM6	LRIT3	Q3SXY7	723
GRM6	GPR179	Q6PRD1	713
GRM6	GRIA1	P42261	688
GRM6	CABP4	P57796	662
GRM6	ELFN1	P0C7U0	653
GRM6	RHO	P08100	648
GRM6	GRIA4	P48058	605
GRM6	GNAO1	P09471	604
GRM6	GNAT1	P11488	585
GRM6	OPN4	Q9UHM6	577
GRM6	GRIK4	Q16099	575

IntAct

0 interactions, top by confidence:

BioGRID (2): GRM6 (Biochemical Activity), GRM6 (Co-fractionation)

ESM2 similar proteins: A0A3Q2HW92, A2AIG8, A4FV98, A5PK45, A6NDV4, A6QLK4, A6QQ24, D3YWP0, F1PZV2, O09009, O15303, O35790, O55240, P04180, P35349, Q08758, Q0P5C0, Q1JPJ0, Q3T0A0, Q3T9M1, Q3U481, Q501J2, Q5E9V4, Q5SX19, Q6AYG0, Q6NUT3, Q863I4, Q86VF5, Q86VU5, Q8BVM4, Q8K297, Q8NBJ5, Q8R2H9, Q8TCT0, Q8TCT1, Q8TCT7, Q8VCE6, Q92781, Q96AZ1, Q96FB5

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”	GRM6	“chemical activation”
GRM6	“up-regulates activity”	GNAS	binding
GRM6	up-regulates	Excitatory_synaptic_transmission
GRM6	“up-regulates quantity”	calcium(2+)	relocalization

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	42
Likely pathogenic	12
Uncertain significance	407
Likely benign	292
Benign	63

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1072852	NM_000843.4(GRM6):c.1336C>T (p.Arg446Ter)	Pathogenic
1073427	NC_000005.10:g.178991560del	Pathogenic
1073858	NM_000843.4(GRM6):c.1864G>T (p.Glu622Ter)	Pathogenic
1074889	NM_000843.4(GRM6):c.208G>T (p.Glu70Ter)	Pathogenic
1075435	NM_000843.4(GRM6):c.165_177del (p.Arg55_Ala56insTer)	Pathogenic
1075954	NM_000843.4(GRM6):c.152_174dup (p.Gln59fs)	Pathogenic
1323038	NM_000843.4(GRM6):c.722-1G>T	Pathogenic
1409749	NM_000843.4(GRM6):c.3G>T (p.Met1Ile)	Pathogenic
1419812	NM_000843.4(GRM6):c.222C>G (p.Tyr74Ter)	Pathogenic
1432797	NM_000843.4(GRM6):c.1357del (p.Ser453fs)	Pathogenic
1433743	NM_000843.4(GRM6):c.1036C>T (p.Arg346Ter)	Pathogenic
1437040	NM_000843.4(GRM6):c.2119dup (p.Leu707fs)	Pathogenic
1438097	NM_000843.4(GRM6):c.1256_1257del (p.His419fs)	Pathogenic
1449932	NM_000843.4(GRM6):c.222C>A (p.Tyr74Ter)	Pathogenic
1924679	NM_000843.4(GRM6):c.1466dup (p.Val490fs)	Pathogenic
198438	NM_000843.4(GRM6):c.1462C>T (p.Gln488Ter)	Pathogenic
2013348	NM_000843.4(GRM6):c.2129del (p.Val710fs)	Pathogenic
2017346	NM_000843.4(GRM6):c.1465_1466insAAGTGGGC (p.Ala489fs)	Pathogenic
2032299	NM_000843.4(GRM6):c.1236_1243dup (p.Leu415fs)	Pathogenic
2048110	NM_000843.4(GRM6):c.1576G>T (p.Glu526Ter)	Pathogenic
2083365	NM_000843.4(GRM6):c.1123C>T (p.Gln375Ter)	Pathogenic
2103349	NM_000843.4(GRM6):c.597C>A (p.Tyr199Ter)	Pathogenic
2107991	NM_000843.4(GRM6):c.86_87del (p.Ala29fs)	Pathogenic
2111268	NM_000843.4(GRM6):c.208del (p.Glu70fs)	Pathogenic
2423425	NC_000005.9:g.(?178409993)(178416072_?)del	Pathogenic
2444850	NM_000843.4(GRM6):c.1478G>A (p.Trp493Ter)	Pathogenic
2788741	NM_000843.4(GRM6):c.768_789dup (p.Ile264fs)	Pathogenic
2860839	NM_000843.4(GRM6):c.2144G>A (p.Trp715Ter)	Pathogenic
2869949	NM_000843.4(GRM6):c.824dup (p.Ile276fs)	Pathogenic
3249080	NM_000843.4(GRM6):c.1551dup (p.Cys518fs)	Pathogenic

SpliceAI

2277 predictions. Top by Δscore:

Variant	Effect	Δscore
5:178982906:TTACC:T	donor_loss	1.0000
5:178982907:TA:T	donor_loss	1.0000
5:178982908:ACCTT:A	donor_loss	1.0000
5:178982909:C:CG	donor_loss	1.0000
5:178989401:AAATC:A	acceptor_gain	1.0000
5:178989402:AATC:A	acceptor_gain	1.0000
5:178989403:ATC:A	acceptor_gain	1.0000
5:178989404:TC:T	acceptor_gain	1.0000
5:178989405:CC:C	acceptor_gain	1.0000
5:178989414:A:T	acceptor_gain	1.0000
5:178990587:CTCA:C	donor_loss	1.0000
5:178990588:TCA:T	donor_loss	1.0000
5:178990589:CA:C	donor_loss	1.0000
5:178990590:A:AC	donor_gain	1.0000
5:178990590:A:AT	donor_loss	1.0000
5:178990591:C:CT	donor_gain	1.0000
5:178990591:CCGT:C	donor_gain	1.0000
5:178990742:CCCGC:C	acceptor_gain	1.0000
5:178990743:CCGCC:C	acceptor_gain	1.0000
5:178990746:CCT:C	acceptor_loss	1.0000
5:178982904:CATTA:C	donor_loss	0.9900
5:178983218:CCAC:C	acceptor_gain	0.9900
5:178983219:CACC:C	acceptor_gain	0.9900
5:178986208:G:A	donor_gain	0.9900
5:178987058:C:CT	acceptor_gain	0.9900
5:178987059:A:T	acceptor_gain	0.9900
5:178988931:TCA:T	donor_loss	0.9900
5:178988932:CA:C	donor_loss	0.9900
5:178989136:CTGTC:C	acceptor_gain	0.9900
5:178989139:TCCTA:T	acceptor_loss	0.9900

AlphaMissense

5639 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:178990679:A:G	W309R	1.000
5:178990679:A:T	W309R	1.000
5:178992069:G:C	S173R	1.000
5:178992069:G:T	S173R	1.000
5:178992071:T:G	S173R	1.000
5:178983009:G:C	F779L	0.999
5:178983009:G:T	F779L	0.999
5:178983011:A:G	F779L	0.999
5:178986640:C:A	W538C	0.999
5:178986640:C:G	W538C	0.999
5:178986689:C:G	C522S	0.999
5:178986689:C:T	C522Y	0.999
5:178986690:A:T	C522S	0.999
5:178986701:C:G	C518S	0.999
5:178986701:C:T	C518Y	0.999
5:178986702:A:G	C518R	0.999
5:178986702:A:T	C518S	0.999
5:178986859:C:A	W493C	0.999
5:178986859:C:G	W493C	0.999
5:178989270:C:G	C383S	0.999
5:178989271:A:T	C383S	0.999
5:178989318:C:G	C367S	0.999
5:178989319:A:T	C367S	0.999
5:178989335:C:A	W361C	0.999
5:178989335:C:G	W361C	0.999
5:178989337:A:G	W361R	0.999
5:178989337:A:T	W361R	0.999
5:178989348:A:C	F357C	0.999
5:178989356:G:C	N354K	0.999
5:178989356:G:T	N354K	0.999

dbSNP variants (sampled 300 via entrez): RS1000585564 (5:178980133 A>C), RS1000690897 (5:178984653 T>C), RS1001188778 (5:178981303 G>A), RS1001512493 (5:178993543 G>A), RS1001559369 (5:178993499 GC>G), RS1001643125 (5:178981527 C>A,T), RS1001701778 (5:178984825 G>A), RS1001846187 (5:178995155 C>T), RS1001952128 (5:178988059 C>A,T), RS1002092880 (5:178988579 C>T), RS1002113850 (5:178985813 T>C), RS1002144977 (5:178985906 C>T), RS1002245844 (5:178982531 C>A,G), RS1002600008 (5:178982247 C>T), RS1002619282 (5:178995021 G>A,C)

Disease associations

OMIM: gene MIM:604096 | disease phenotypes: MIM:257270, MIM:310500, MIM:613216, MIM:204000

GenCC curated gene-disease

Disease	Classification	Inheritance
congenital stationary night blindness 1B	Definitive	Autosomal recessive
congenital stationary night blindness	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
GRM6-related retinopathy	Definitive	AR

Mondo (6): inherited retinal dystrophy (MONDO:0019118), congenital stationary night blindness 1B (MONDO:0009758), congenital stationary night blindness (MONDO:0016293), congenital stationary night blindness 1C (MONDO:0013183), Leber congenital amaurosis (MONDO:0018998), optic atrophy (MONDO:0003608)

Orphanet (3): OBSOLETE: Inherited retinal disorder (Orphanet:71862), Congenital stationary night blindness (Orphanet:215), Leber congenital amaurosis (Orphanet:65)

HPO phenotypes

8 total (9 of 8 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000545	Myopia
HP:0000662	Nyctalopia
HP:0000666	Horizontal nystagmus
HP:0007642	Early-onset non-progressive night blindness
HP:0007737	Spicular pigmentation of the retina
HP:0011463	Childhood onset
HP:0012047	Hemeralopia
HP:0000556	Retinal dystrophy

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST001875_9	Pubertal anthropometrics	6.000000e-07
GCST009269_7	Dental caries (decayed and filled deciduous teeth)	3.000000e-06
GCST010002_45	Refractive error	9.000000e-17
GCST010605_4	Parent of origin effect on receptive language ability (paternal)	2.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0005686	receptive language perception
EFO:0005939	parental genotype effect measurement

MeSH disease descriptors (5)

Descriptor	Name	Tree numbers
D057130	Leber Congenital Amaurosis	C11.270.516; C11.768.364
D009896	Optic Atrophy	C10.292.700.225; C11.640.451
D058499	Retinal Dystrophies	C11.768.585.658
C567704	CSNB1C (supp.)
C536122	Night blindness, congenital stationary (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4573 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

3 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 975,751 (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
CHEMBL91	MICONAZOLE	4	45,914
CHEMBL575060	GLUTAMIC ACID	3	929,756
CHEMBL8759	EGLUMETAD	2	81

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

PharmGKB variants

5 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs17078853	GRM6		0.00	0
rs2071247	GRM6		0.00	0
rs17078877	GRM6		0.00	0
rs11746675	GRM6		0.00	0
rs2067011	GRM6		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 (20 total), top 20:

Ligand	Action	Affinity	Parameter
L-AP4	Full agonist	7.3	pEC50
LY379268	Full agonist	6.4	pIC50
L-serine-O-phosphate	Full agonist	6.4	pEC50
L-CCG-I	Full agonist	6.2	pEC50
LSP1-2111	Agonist	5.77	pEC50
DCG-IV	Antagonist	5.6	pEC50
eglumegad	Full agonist	5.5	pIC50
(S)-3,4-DCPG	Full agonist	5.4	pEC50
LSP4-2022	Agonist	5.36	pEC50
(R,S)-4-PPG	Full agonist	5.3	pEC50
L-glutamic acid	Agonist	4.8	pEC50
PHCCC	Positive	4.8	pEC50
(1S,3R)-ACPD	Full agonist	4.7	pEC50
ACPT-I	Full agonist	4.7	pIC50
1-benzyl-APDC	Full agonist	4.7	pEC50
[3H]LY341495	Antagonist	4.5	pEC50
α-methylserine-O-phosphate	Antagonist	4.1	pEC50
homo-AMPA	Agonist	4.1	pEC50
MAP4	Antagonist	3.5	pIC50
MPPG	Antagonist	3.3	pIC50

Binding affinities (BindingDB)

3 measured of 4 human assays (9 total across all organisms); most potent 3 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
(2S,4aR,6aR,7R,9S,10aS,10bR)-9-(acetyloxy)-2-(furan-3-yl)dodecahydro-6a,10b-dimethyl-4,10-dioxo-2H-naphtho-[2,1-c]pyran-7-carboxylic acid methyl ester	EC50	0.3 nM
2-amino-3-(3,5-dioxo[1,2,4]oxadiazolidin-2-yl)propionic acid	IC50	9500 nM
L-serine O-phosphate	IC50	523000 nM

ChEMBL bioactivities

76 potent at pChembl≥5 of 103 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.26	EC50	55	nM	CHEMBL33567
6.57	IC50	267	nM	CHEMBL2381641
6.55	EC50	280	nM	CHEMBL285843
6.40	EC50	401	nM	LY-379268
6.40	Ki	400	nM	LY-379268
6.15	EC50	709	nM	CHEMBL2381649
6.12	EC50	760	nM	CHEMBL4101970
6.12	IC50	750	nM	CHEMBL566136
6.11	EC50	780	nM	CHEMBL2381644
6.05	Ki	900	nM	CHEMBL33567
6.00	EC50	1000	nM	CHEMBL33567
5.97	EC50	1070	nM	CHEMBL4077705
5.96	EC50	1100	nM	CHEMBL4081842
5.90	EC50	1270	nM	CHEMBL2381650
5.86	IC50	1380	nM	CHEMBL2381640
5.85	EC50	1410	nM	CHEMBL2381652
5.77	EC50	1700	nM	CHEMBL3114672
5.72	IC50	1890	nM	CHEMBL2381645
5.71	EC50	1950	nM	CHEMBL4081453
5.71	EC50	1950	nM	CHEMBL229697
5.62	EC50	2400	nM	CHEMBL33567
5.62	EC50	2400	nM	CHEMBL4072781
5.62	EC50	2400	nM	CHEMBL4085558
5.62	IC50	2400	nM	CHEMBL568515
5.62	Ki	2400	nM	CHEMBL88999
5.61	EC50	2430	nM	LY-389795
5.54	EC50	2900	nM	CHEMBL4078629
5.52	IC50	3040	nM	CHEMBL2381643
5.52	EC50	2990	nM	EGLUMETAD
5.52	Ki	3000	nM	EGLUMETAD
5.50	EC50	3200	nM	CHEMBL143210
5.50	EC50	3200	nM	CHEMBL4085750
5.50	EC50	3200	nM	CHEMBL3114672
5.50	EC50	3200	nM	CHEMBL4064187
5.49	EC50	3250	nM	CHEMBL2381651
5.48	IC50	3300	nM	CHEMBL3947221
5.47	EC50	3360	nM	EGLUMETAD
5.47	EC50	3410	nM	CHEMBL227288
5.46	EC50	3450	nM	CHEMBL3616847
5.46	IC50	3500	nM	CHEMBL579009
5.44	EC50	3600	nM	CHEMBL4061423
5.44	EC50	3600	nM	CHEMBL4072316
5.44	IC50	3600	nM	CHEMBL577069
5.41	EC50	3900	nM	CHEMBL4085327
5.40	EC50	4000	nM	CHEMBL4101241
5.40	EC50	4000	nM	CHEMBL4091029
5.40	IC50	4010	nM	CHEMBL4751065
5.40	IC50	4000	nM	2S,4R-4-METHYLGLUTAMATE
5.39	IC50	4100	nM	CHEMBL568300
5.38	EC50	4200	nM	CHEMBL3114673

PubChem BioAssay actives

76 with measured affinity, of 375 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
(2S)-2-amino-4-phosphonobutanoic acid	1573601: Activation of human metabotropic glutamate 6 receptor expressed in golden hamster AV12-664 cells	ec50	0.0550	uM
(1S,2S,5R,6S)-2-amino-4-methylidenebicyclo[3.1.0]hexane-2,6-dicarboxylic acid	748161: Antagonist activity at human mGlu6 receptor expressed in golden Syrian hamster AV12 cells coexpressing EAAT1 assessed as inhibition of forskolin-stimulated cAMP production after 20 mins by FLIPR assay	ic50	0.2670	uM
2-amino-4-phosphonobutanoic acid	107253: Compound was tested for the inhibition of Metabotropic glutamate receptor 6	ec50	0.2800	uM
(1R,4R,5S,6R)-4-amino-2-oxabicyclo[3.1.0]hexane-4,6-dicarboxylic acid	107093: Agonist potency against cloned Metabotropic glutamate receptor 6 (mGluR-6).	ki	0.4000	uM
(1S,2S,4S,5R,6S)-4-acetamido-2-aminobicyclo[3.1.0]hexane-2,6-dicarboxylic acid	748163: Agonist activity at human mGlu6 receptor expressed in golden Syrian hamster AV12 cells coexpressing EAAT1 after 20 mins by FLIPR assay	ec50	0.7090	uM
ethyl 2-amino-4-methyl-5-phenylthiophene-3-carboxylate	439881: Antagonist activity at human recombinant GluR6 expressed in HEK cells coexpressing aequorine assessed as inhibition of glutamate-induced Ca2+ influx at 10 uM by luminescence reporter assay	ic50	0.7500	uM
(2S)-2-amino-4-[[(S)-(3-fluoro-4-hydroxy-5-nitrophenyl)-hydroxymethyl]-hydroxyphosphoryl]butanoic acid	1455162: Agonist activity at mGlu6 (unknown origin) expressed in HEK293 cells coexpressing chimeric Gq/i protein assessed as increase in intracellular calcium accumulation by Fluo-4 AM dye based fluorescence assay	ec50	0.7600	uM
(1S,2S,4R,5R,6S)-2-amino-4-azidobicyclo[3.1.0]hexane-2,6-dicarboxylic acid	748163: Agonist activity at human mGlu6 receptor expressed in golden Syrian hamster AV12 cells coexpressing EAAT1 after 20 mins by FLIPR assay	ec50	0.7800	uM
(2S)-2-amino-4-[[(3-fluoro-4-hydroxy-5-nitrophenyl)-hydroxymethyl]-hydroxyphosphoryl]butanoic acid	1455162: Agonist activity at mGlu6 (unknown origin) expressed in HEK293 cells coexpressing chimeric Gq/i protein assessed as increase in intracellular calcium accumulation by Fluo-4 AM dye based fluorescence assay	ec50	1.0700	uM
(2S)-2-amino-4-[hydroxy-[(S)-hydroxy-(4-hydroxy-3-methoxy-5-nitrophenyl)methyl]phosphoryl]butanoic acid	1455162: Agonist activity at mGlu6 (unknown origin) expressed in HEK293 cells coexpressing chimeric Gq/i protein assessed as increase in intracellular calcium accumulation by Fluo-4 AM dye based fluorescence assay	ec50	1.1000	uM
(1R,2S,4R,5R,6R)-2-amino-4-phenylsulfanylbicyclo[3.1.0]hexane-2,6-dicarboxylic acid	748163: Agonist activity at human mGlu6 receptor expressed in golden Syrian hamster AV12 cells coexpressing EAAT1 after 20 mins by FLIPR assay	ec50	1.2700	uM
(1S,2S,5R,6R)-2-amino-4-oxobicyclo[3.1.0]hexane-2,6-dicarboxylic acid	748161: Antagonist activity at human mGlu6 receptor expressed in golden Syrian hamster AV12 cells coexpressing EAAT1 assessed as inhibition of forskolin-stimulated cAMP production after 20 mins by FLIPR assay	ic50	1.3800	uM
(1R,2S,4R,5R,6R)-2-amino-4-fluorobicyclo[3.1.0]hexane-2,6-dicarboxylic acid	748163: Agonist activity at human mGlu6 receptor expressed in golden Syrian hamster AV12 cells coexpressing EAAT1 after 20 mins by FLIPR assay	ec50	1.4100	uM
(2S)-2-amino-4-[hydroxy-[hydroxy-(4-hydroxy-3-methoxy-5-nitrophenyl)methyl]phosphoryl]butanoic acid	1455158: Agonist activity at mGlu6 (unknown origin) expressed in HEK293 cells coexpressing chimeric Gq/i protein assessed as [3H]inositol phosphate accumulation after 30 mins by scintillation and luminescence counting method	ec50	1.7000	uM
(1S,2S,4S,5R,6S)-2-amino-4-azidobicyclo[3.1.0]hexane-2,6-dicarboxylic acid	748161: Antagonist activity at human mGlu6 receptor expressed in golden Syrian hamster AV12 cells coexpressing EAAT1 assessed as inhibition of forskolin-stimulated cAMP production after 20 mins by FLIPR assay	ic50	1.8900	uM
cis-(1S,2R)-1-amino-2-(phosphonomethyl)cyclopropane-1-carboxylic acid	292379: Agonist activity at mGlu6 receptor expressed in HEK 293 cells assessed as effect on inositol phosphate production	ec50	1.9500	uM
(1S,2S,4S,5R,6S)-2-amino-4-[(3-methoxybenzoyl)amino]bicyclo[3.1.0]hexane-2,6-dicarboxylic acid	1468316: Agonist activity at human mGlu6 receptor expressed in hamster AV12 cells co-expressing rat EAAT1 assessed as inhibition of forskolin-stimulated cAMP formation after 20 mins by HTRF assay	ec50	1.9500	uM
(4S,6S)-4-amino-2-thiabicyclo[3.1.0]hexane-4,6-dicarboxylic acid	107093: Agonist potency against cloned Metabotropic glutamate receptor 6 (mGluR-6).	ki	2.4000	uM
(2S)-2-amino-4-[hydroxy-[(R)-hydroxy-(4-hydroxy-3-methoxy-5-nitrophenyl)methyl]phosphoryl]butanoic acid	1455162: Agonist activity at mGlu6 (unknown origin) expressed in HEK293 cells coexpressing chimeric Gq/i protein assessed as increase in intracellular calcium accumulation by Fluo-4 AM dye based fluorescence assay	ec50	2.4000	uM
(2S)-2-amino-4-[hydroxy-[(S)-hydroxy-(3-nitrophenyl)methyl]phosphoryl]butanoic acid	1455162: Agonist activity at mGlu6 (unknown origin) expressed in HEK293 cells coexpressing chimeric Gq/i protein assessed as increase in intracellular calcium accumulation by Fluo-4 AM dye based fluorescence assay	ec50	2.4000	uM
propyl 2-amino-4-methyl-5-phenylthiophene-3-carboxylate	439881: Antagonist activity at human recombinant GluR6 expressed in HEK cells coexpressing aequorine assessed as inhibition of glutamate-induced Ca2+ influx at 10 uM by luminescence reporter assay	ic50	2.4000	uM
(1R,4S,5S,6S)-4-amino-2-thiabicyclo[3.1.0]hexane-4,6-dicarboxylic acid	221690: Inhibition of forskolin stimulated cAMP production in RGT cells expressing recombinant human mGluR6	ec50	2.4300	uM
(2S)-2-amino-4-[hydroxy-[hydroxy-[4-nitro-3-(trifluoromethyl)phenyl]methyl]phosphoryl]butanoic acid	1455162: Agonist activity at mGlu6 (unknown origin) expressed in HEK293 cells coexpressing chimeric Gq/i protein assessed as increase in intracellular calcium accumulation by Fluo-4 AM dye based fluorescence assay	ec50	2.9000	uM
(1S,2S,5R,6S)-2-aminobicyclo[3.1.0]hexane-2,6-dicarboxylic acid	221690: Inhibition of forskolin stimulated cAMP production in RGT cells expressing recombinant human mGluR6	ec50	2.9900	uM
(1S,2S,4S,5R,6R)-2-amino-4-hydroxybicyclo[3.1.0]hexane-2,6-dicarboxylic acid	748161: Antagonist activity at human mGlu6 receptor expressed in golden Syrian hamster AV12 cells coexpressing EAAT1 assessed as inhibition of forskolin-stimulated cAMP production after 20 mins by FLIPR assay	ic50	3.0400	uM
(2S)-2-amino-4-[hydroxy-[(R)-hydroxy-(3-nitrophenyl)methyl]phosphoryl]butanoic acid	1455162: Agonist activity at mGlu6 (unknown origin) expressed in HEK293 cells coexpressing chimeric Gq/i protein assessed as increase in intracellular calcium accumulation by Fluo-4 AM dye based fluorescence assay	ec50	3.2000	uM
4-[(S)-amino(carboxy)methyl]phthalic acid	1455162: Agonist activity at mGlu6 (unknown origin) expressed in HEK293 cells coexpressing chimeric Gq/i protein assessed as increase in intracellular calcium accumulation by Fluo-4 AM dye based fluorescence assay	ec50	3.2000	uM
(2S)-2-amino-4-[hydroxy-[(3-nitrophenyl)methyl]phosphoryl]butanoic acid	1455162: Agonist activity at mGlu6 (unknown origin) expressed in HEK293 cells coexpressing chimeric Gq/i protein assessed as increase in intracellular calcium accumulation by Fluo-4 AM dye based fluorescence assay	ec50	3.2000	uM
(1R,2S,4S,5R,6R)-2-amino-4-phenylsulfanylbicyclo[3.1.0]hexane-2,6-dicarboxylic acid	748163: Agonist activity at human mGlu6 receptor expressed in golden Syrian hamster AV12 cells coexpressing EAAT1 after 20 mins by FLIPR assay	ec50	3.2500	uM
(1S,2R,3S,4S,5R,6R)-2-amino-3-[(3,4-dichlorophenyl)methoxy]-4-hydroxybicyclo[3.1.0]hexane-2,6-dicarboxylic acid	1329865: Antagonist activity at recombinant human mGlu6 receptor expressed in hamster AV12 cells co-expressing human EAAT1 assessed as inhibition of L-AP4-inhibited forskolin-stimulated cAMP formation after 20 mins by HTRF assay	ic50	3.3000	uM
trans-(1S,2S)-1-amino-2-(phosphonomethyl)cyclopropane-1-carboxylic acid	292379: Agonist activity at mGlu6 receptor expressed in HEK 293 cells assessed as effect on inositol phosphate production	ec50	3.4100	uM
(1R,2S,4R,5R,6R)-2-amino-4-(1H-1,2,4-triazol-5-ylsulfanyl)bicyclo[3.1.0]hexane-2,6-dicarboxylic acid	1247536: Agonist activity at human recombinant mGlu6 receptor expressed in AV12 cells assessed as inhibition of forskolin-stimulated cAMP production after 1 hr by fluorescence assay	ec50	3.4500	uM
ethyl 2-isothiocyanato-4-methyl-5-phenylthiophene-3-carboxylate	439881: Antagonist activity at human recombinant GluR6 expressed in HEK cells coexpressing aequorine assessed as inhibition of glutamate-induced Ca2+ influx at 10 uM by luminescence reporter assay	ic50	3.5000	uM
(2S)-2-amino-4-[hydroxy-[(S)-hydroxy-(4-hydroxy-3-nitrophenyl)methyl]phosphoryl]butanoic acid	1455162: Agonist activity at mGlu6 (unknown origin) expressed in HEK293 cells coexpressing chimeric Gq/i protein assessed as increase in intracellular calcium accumulation by Fluo-4 AM dye based fluorescence assay	ec50	3.6000	uM
tert-butyl 2-amino-4-methyl-5-phenylthiophene-3-carboxylate	439881: Antagonist activity at human recombinant GluR6 expressed in HEK cells coexpressing aequorine assessed as inhibition of glutamate-induced Ca2+ influx at 10 uM by luminescence reporter assay	ic50	3.6000	uM
(2S)-2-amino-4-[hydroxy-[hydroxy-(5-nitrothiophen-3-yl)methyl]phosphoryl]butanoic acid	1455158: Agonist activity at mGlu6 (unknown origin) expressed in HEK293 cells coexpressing chimeric Gq/i protein assessed as [3H]inositol phosphate accumulation after 30 mins by scintillation and luminescence counting method	ec50	3.6000	uM
(2S)-2-amino-4-[hydroxy-[(R)-hydroxy-(4-methoxy-3-nitrophenyl)methyl]phosphoryl]butanoic acid	1455162: Agonist activity at mGlu6 (unknown origin) expressed in HEK293 cells coexpressing chimeric Gq/i protein assessed as increase in intracellular calcium accumulation by Fluo-4 AM dye based fluorescence assay	ec50	3.9000	uM
(2S)-2-amino-4-[hydroxy-[hydroxy-(4-methyl-3-nitrophenyl)methyl]phosphoryl]butanoic acid	1455162: Agonist activity at mGlu6 (unknown origin) expressed in HEK293 cells coexpressing chimeric Gq/i protein assessed as increase in intracellular calcium accumulation by Fluo-4 AM dye based fluorescence assay	ec50	4.0000	uM
(2S)-2-amino-4-[[(4-fluoro-3-nitrophenyl)-hydroxymethyl]-hydroxyphosphoryl]butanoic acid	1455162: Agonist activity at mGlu6 (unknown origin) expressed in HEK293 cells coexpressing chimeric Gq/i protein assessed as increase in intracellular calcium accumulation by Fluo-4 AM dye based fluorescence assay	ec50	4.0000	uM
(2S,4R)-2-amino-4-methylpentanedioic acid	439881: Antagonist activity at human recombinant GluR6 expressed in HEK cells coexpressing aequorine assessed as inhibition of glutamate-induced Ca2+ influx at 10 uM by luminescence reporter assay	ic50	4.0000	uM
(1S,2R,3S,4S,5R,6R)-2-amino-3-[(3,4-difluorophenyl)sulfanylmethyl]-4-hydroxybicyclo[3.1.0]hexane-2,6-dicarboxylic acid;hydrochloride	1714580: Antagonist activity at human recombinant mGlu6 stably expressed in golden hamster AV12 cell membrane co-expressing Galpha15 assessed as reduction in glutamate-induced calcium influx incubated for 90 to 120 min by Fluo-4-AM dye based FLIPR assay	ic50	4.0100	uM
methyl 2-amino-4-methyl-5-phenylthiophene-3-carboxylate	439881: Antagonist activity at human recombinant GluR6 expressed in HEK cells coexpressing aequorine assessed as inhibition of glutamate-induced Ca2+ influx at 10 uM by luminescence reporter assay	ic50	4.1000	uM
(2S)-2-amino-4-[hydroxy-[hydroxy-(5-nitrothiophen-2-yl)methyl]phosphoryl]butanoic acid	1455162: Agonist activity at mGlu6 (unknown origin) expressed in HEK293 cells coexpressing chimeric Gq/i protein assessed as increase in intracellular calcium accumulation by Fluo-4 AM dye based fluorescence assay	ec50	4.2000	uM
(2S)-2-amino-4-[[[4-(carboxymethoxy)phenyl]-hydroxymethyl]-hydroxyphosphoryl]butanoic acid	1455162: Agonist activity at mGlu6 (unknown origin) expressed in HEK293 cells coexpressing chimeric Gq/i protein assessed as increase in intracellular calcium accumulation by Fluo-4 AM dye based fluorescence assay	ec50	4.2000	uM
(1S,2S,4R,5R,6R)-2-amino-4-hydroxybicyclo[3.1.0]hexane-2,6-dicarboxylic acid	748163: Agonist activity at human mGlu6 receptor expressed in golden Syrian hamster AV12 cells coexpressing EAAT1 after 20 mins by FLIPR assay	ec50	4.3700	uM
(2S)-2-amino-4-[hydroxy-[(S)-hydroxy-(4-methoxy-3-nitrophenyl)methyl]phosphoryl]butanoic acid	1455162: Agonist activity at mGlu6 (unknown origin) expressed in HEK293 cells coexpressing chimeric Gq/i protein assessed as increase in intracellular calcium accumulation by Fluo-4 AM dye based fluorescence assay	ec50	4.5000	uM
ethyl 2-amino-4,5-diphenylthiophene-3-carboxylate	439881: Antagonist activity at human recombinant GluR6 expressed in HEK cells coexpressing aequorine assessed as inhibition of glutamate-induced Ca2+ influx at 10 uM by luminescence reporter assay	ic50	4.5000	uM
(2S)-2-amino-4-[hydroxy-[hydroxy-(4-nitrophenyl)methyl]phosphoryl]butanoic acid	1455162: Agonist activity at mGlu6 (unknown origin) expressed in HEK293 cells coexpressing chimeric Gq/i protein assessed as increase in intracellular calcium accumulation by Fluo-4 AM dye based fluorescence assay	ec50	4.6000	uM
2-amino-2-(4-phosphonophenyl)acetic acid	107093: Agonist potency against cloned Metabotropic glutamate receptor 6 (mGluR-6).	ki	4.7000	uM
glutamic acid	107253: Compound was tested for the inhibition of Metabotropic glutamate receptor 6	ec50	4.9000	uM

CTD chemical–gene interactions

9 total (human), top 9 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
arsenite	increases methylation	1
2-palmitoylglycerol	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Amphotericin B	increases expression	1
Arsenic	affects methylation	1
Copper	affects cotreatment, decreases expression	1
Hydrogen Peroxide	affects cotreatment, increases expression	1
Theophylline	affects cotreatment, increases expression	1
Tobacco Smoke Pollution	decreases expression	1

ChEMBL screening assays

103 unique, capped per target: 55 functional, 48 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1004113	Functional	Antagonist activity at cloned mGluR6 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
CHEMBL1109168	Binding	Inhibition of mGluR6 expressed in CHO cells at 10 uM	Structure-activity relationships in a novel series of 7-substituted-aryl quinolines and 5-substituted-aryl benzothiazoles at the metabotropic glutamate receptor subtype 5. — Bioorg Med Chem

Cellosaurus cell lines

1 cell lines: 1 spontaneously immortalized cell line

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

Cellosaurus	Name	Category	Sex
CVCL_KV35	cAMP Hunter CHO-K1 GRM6 Gi	Spontaneously immortalized cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04224207	PHASE3	COMPLETED	Management of Retinitis Pigmentosa by Mesenchymal Stem Cells by Wharton’s Jelly Derived Mesenchymal Stem Cells
NCT07082855	PHASE3	NOT_YET_RECRUITING	A Multicenter, Randomized, Double-Blind, Controlled Clinical Study of Minocycline for the Treatment of Retinitis Pigmentosa
NCT00999609	PHASE3	ACTIVE_NOT_RECRUITING	Safety and Efficacy Study in Subjects With Leber Congenital Amaurosis
NCT06891443	PHASE3	RECRUITING	Study to Evaluate Sepofarsen in Subjects With Leber Congenital Amaurosis (LCA) Type 10 (HYPERION)
NCT03763227	PHASE2	COMPLETED	Intravitreal Ranibizumab (Lucentis®) in the Treatment of Non-leaking Macular Cysts in Retinal Dystrophy
NCT04068207	PHASE2	COMPLETED	Minocycline Treatment in Retinitis Pigmentosa
NCT04945772	PHASE2	COMPLETED	Efficacy and Safety of MCO-010 Optogenetic Therapy in Adults With Retinitis Pigmentosa [RESTORE]
NCT05902962	PHASE1	COMPLETED	SAD of IVT VP-001 in PRPF31 Mutation-Associated Retinal Dystrophy Subjects
NCT06319872	PHASE1	RECRUITING	The Effects of Disulfiram (Antabuse®) on Visual Acuity in Patients With Retinal Degeneration
NCT06455826	PHASE1	COMPLETED	MAD of IVT VP-001 in PRPF31 Mutation-Associated Retinal Dystrophy Subjects (Wallaby)
NCT00516477	PHASE1	COMPLETED	Safety Study in Subjects With Leber Congenital Amaurosis
NCT00821340	PHASE1	COMPLETED	Clinical Trial of Gene Therapy for Leber Congenital Amaurosis Caused by RPE65 Mutations
NCT01064505	PHASE1	COMPLETED	Safety Study of a Single IVT Injection of QPI-1007 in Chronic Optic Nerve Atrophy and Recent Onset NAION Patients
NCT05147701	PHASE1	RECRUITING	Safety of Cultured Allogeneic Adult Umbilical Cord Derived Mesenchymal Stem Cells for NAION
NCT02435940	Not specified	RECRUITING	Inherited Retinal Degenerative Disease Registry
NCT02909985	Not specified	COMPLETED	Visual Activity Evoked by Infrared in Humans After Dark Adaptation
NCT04855045	PHASE2/PHASE3	UNKNOWN	An Open-label, Dose Escalation and Double-masked, Randomized, Controlled Trial Evaluating Safety and Tolerability of Sepofarsen in Children (<8 Years of Age) With LCA10 Caused by Mutations in the CEP290 Gene.
NCT03872479	PHASE1/PHASE2	UNKNOWN	Single Ascending Dose Study in Participants With LCA10
NCT04123626	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	A Study to Evaluate the Safety and Tolerability of QR-1123 in Subjects With Autosomal Dominant Retinitis Pigmentosa Due to the P23H Mutation in the RHO Gene
NCT04545736	PHASE1/PHASE2	RECRUITING	Oral Metformin for Treatment of ABCA4 Retinopathy
NCT06212297	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Fellow-eye Study (FE) of LX101 in Subjects With Inherited Retinal Dystrophy
NCT06852963	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	A Repeat-Dose, Open-Label, Two Arm Safety and Efficacy Study of Two Doses of VP-001 Administered Intravitreally in Participants With Confirmed PRPF31 Mutation-Associated Retinal Dystrophy, Including Participants Previously Treated With VP001
NCT07177196	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Personalized Antisense Oligonucleotide Therapy for a Single Participant With PRPH2 Mutation Associated With Retinal Dystrophy
NCT07063030	EARLY_PHASE1	RECRUITING	A Study of LX107 Gene Therapy in AIPL1-IRD Patients
NCT01546181	Not specified	COMPLETED	Retinal Imaging by Adaptive Optics in Healthy Eyes and During Retinal and General Diseases
NCT01876147	Not specified	COMPLETED	Visual and Functional Assessment in Low Vision Patients
NCT01920867	Not specified	UNKNOWN	Stem Cell Ophthalmology Treatment Study
NCT02014389	Not specified	RECRUITING	Evaluation of Objective Perimetry Using Chromatic Multifocal Pupillometer
NCT02983305	Not specified	COMPLETED	Optical Head-Mounted Display Technology for Low Vision Rehabilitation
NCT03592017	Not specified	COMPLETED	Performance of Long-wavelength Autofluorescence Imaging
NCT03662386	Not specified	TERMINATED	Prospective Analysis of Genotype-phenotype Correlations Observed in a Large Cohort of Patients With Hereditary Retinal Dystrophies - GEPHIRD
NCT03691168	Not specified	UNKNOWN	Multi-center Observation of the Natural Course of Inherited Retinal Dystrophies
NCT03843840	Not specified	COMPLETED	Dual Wavelength OCT
NCT03853252	Not specified	COMPLETED	iPS Cells of Patients for Models of Retinal Dystrophies
NCT05130385	Not specified	UNKNOWN	High Resolution Optical Coherence Tomography
NCT05294978	Not specified	RECRUITING	EyeConic: Qualification for Cone-Optogenetics
NCT05573984	Not specified	ACTIVE_NOT_RECRUITING	Natural History of PRPF31 Mutation-Associated Retinal Dystrophy
NCT05793515	Not specified	COMPLETED	Mechanisms of Inherited Retinal Dystrophies Using Whole Genome Sequencing and in Vitro and in Vivo Models
NCT05820100	Not specified	COMPLETED	Observational Study to Assess the Reliability and Validity of the MLYMT and MLSDT
NCT05976139	Not specified	RECRUITING	Micropulsed Laser in Patients With Macular Oedema in Retinal Dystrophies