GPR158

Summary

GPR158 (G protein-coupled receptor 158, HGNC:23689) is a protein-coding gene on chromosome 10p12.1, encoding Metabotropic glycine receptor (Q5T848). Metabotropic receptor for glycine that controls synapse formation and function in the brain.

Enables G protein-coupled glycine receptor activity and enzyme activator activity. Involved in G protein-coupled receptor signaling pathway; protein localization to plasma membrane; and regulation of G protein-coupled receptor signaling pathway. Is active in plasma membrane.

Source: NCBI Gene 57512 — RefSeq curated summary.

At a glance

• GWAS associations: 13
• Clinical variants (ClinVar): 190 total
• Druggable target: yes
• MANE Select transcript: NM_020752

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23689
Approved symbol	GPR158
Name	G protein-coupled receptor 158
Location	10p12.1
Locus type	gene with protein product
Status	Approved
Aliases	KIAA1136
Ensembl gene	ENSG00000151025
Ensembl biotype	protein_coding
OMIM	614573
Entrez	57512

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 2 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000376351, ENST00000482641, ENST00000490549, ENST00000650135

RefSeq mRNA: 1 — MANE Select: NM_020752 NM_020752

CCDS: CCDS31166

Canonical transcript exons

ENST00000376351 — 11 exons

Exon	Start	End
ENSE00001332774	25572649	25572887
ENSE00001332780	25550976	25551085
ENSE00001332787	25412250	25412473
ENSE00001332792	25395911	25396013
ENSE00001332803	25221052	25221157
ENSE00001332808	25175001	25176322
ENSE00001470266	25594292	25594397
ENSE00001470269	25589007	25589145
ENSE00003496521	25466651	25466719
ENSE00003515384	25596643	25596789
ENSE00003593581	25597772	25602229

Expression profiles

Bgee: expression breadth ubiquitous, 127 present calls, max score 99.01.

FANTOM5 (CAGE): breadth broad, TPM avg 2.7703 / max 184.2596, expressed in 391 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
104360	1.1188	191
104365	0.4721	114
104370	0.3344	151
104366	0.2732	96
104363	0.1621	74
205796	0.1488	93
104361	0.1292	75
104362	0.1072	56
104364	0.0246	17

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
endothelial cell	CL:0000115	99.01	gold quality
middle temporal gyrus	UBERON:0002771	98.53	gold quality
cerebellar vermis	UBERON:0004720	98.39	gold quality
Brodmann (1909) area 23	UBERON:0013554	98.26	gold quality
lateral nuclear group of thalamus	UBERON:0002736	95.28	gold quality
Brodmann (1909) area 46	UBERON:0006483	95.20	gold quality
pons	UBERON:0000988	94.87	gold quality
superior frontal gyrus	UBERON:0002661	94.06	gold quality
postcentral gyrus	UBERON:0002581	94.03	gold quality
primary visual cortex	UBERON:0002436	93.03	gold quality
parietal lobe	UBERON:0001872	93.02	gold quality
cerebellum	UBERON:0002037	92.28	gold quality
cerebellar cortex	UBERON:0002129	91.91	gold quality
occipital lobe	UBERON:0002021	91.83	gold quality
cerebellar hemisphere	UBERON:0002245	91.74	gold quality
entorhinal cortex	UBERON:0002728	90.90	gold quality
right hemisphere of cerebellum	UBERON:0014890	90.09	gold quality
lateral globus pallidus	UBERON:0002476	90.04	gold quality
prefrontal cortex	UBERON:0000451	89.02	gold quality
substantia nigra pars compacta	UBERON:0001965	88.88	gold quality
medulla oblongata	UBERON:0001896	88.04	gold quality
superior vestibular nucleus	UBERON:0007227	87.60	gold quality
frontal cortex	UBERON:0001870	87.31	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	86.93	gold quality
putamen	UBERON:0001874	86.64	gold quality
Brodmann (1909) area 9	UBERON:0013540	86.58	gold quality
dorsal plus ventral thalamus	UBERON:0001897	86.04	gold quality
substantia nigra pars reticulata	UBERON:0001966	85.67	gold quality
caudate nucleus	UBERON:0001873	85.40	gold quality
neocortex	UBERON:0001950	85.39	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-HCAD-35	yes	60.54
E-ANND-3	yes	4.55

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F1, TP63

miRNA regulators (miRDB)

238 targeting GPR158, 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-3163	100.00	77.23	8605
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-3646	100.00	73.56	5283
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-340-5P	100.00	72.50	4437
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-MIR-12121	99.99	66.64	255
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-33A-5P	99.99	68.62	1055
HSA-MIR-33B-5P	99.99	68.58	1062
HSA-MIR-4715-3P	99.98	66.03	670
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-25-3P	99.98	74.60	1817

Literature-anchored findings (GeneRIF, showing 10)

• Mutation of the NLS abrogates GPR158-mediated enhancement of cell proliferation. (PMID:23451275)
• expression and functional role of orphan receptor GPR158 in prostate cancer growth and progression (PMID:25693195)
• Our results suggest that common ethnic-specific variation in GPR158 may influence energy expenditure (EE) in Pima Indians. rs11014566 nominally associated with measures of EE and adiposity, where the G allele associated with lower 24-h EE, lower Resting Metabolic Rate, higher BMI, and higher percent body fat. But, the association of rs11014566 with BMI did not directionally replicate when assessed in other ethnic groups. (PMID:28476931)
• GPR158 is highly upregulated in the prefrontal cortex of human subjects with major depressive disorder. Exposure of mice to chronic stress also increased GPR158 protein levels in the prefrontal cortex in a glucocorticoid-dependent manner. (PMID:29419376)
• It findings implicate GPR158 as a homeostatic regulator of intraocular pressure and suggest GPR158 could be a pharmacological target for managing ocular hypertension. (PMID:30855200)
• Data observed that GPR158 interacted with and stabilized the amount of RGS7-beta5 through a 50-residue region downstream of its transmembrane domain and upstream of the VCPWE motifs. Also, two VCPWE motifs are involved in alphao binding. (PMID:31189666)
• Elevated GPR158 expression patterns in mucinous ovarian carcinoma patients with unfavorable overall survival. (PMID:31533654)
• Cryo-EM structure of human GPR158 receptor coupled to the RGS7-Gbeta5 signaling complex. (PMID:34793198)
• Structure of the class C orphan GPCR GPR158 in complex with RGS7-Gbeta5. (PMID:34815401)
• Orphan receptor GPR158 serves as a metabotropic glycine receptor: mGlyR. (PMID:36996198)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	gpr158a	ENSDARG00000077134
danio_rerio	gpr158b	ENSDARG00000079665
mus_musculus	Gpr158	ENSMUSG00000045967
rattus_norvegicus	Gpr158	ENSRNOG00000024832

Paralogs (1): GPR179 (ENSG00000277399)

Protein

Protein identifiers

Metabotropic glycine receptor — Q5T848 (reviewed: Q5T848)

Alternative names: G-protein coupled receptor 158

All UniProt accessions (2): Q5T848, A0A3B3IUC3

UniProt curated annotations — full annotation on UniProt →

Function. Metabotropic receptor for glycine that controls synapse formation and function in the brain. Acts as an atypical G-protein coupled receptor that recruits and regulates the RGS7-GNB5 complex instead of activating G proteins. In absence of glycine ligand, promotes the GTPase activator activity of RGS7, increasing the GTPase activity of G protein alpha subunits, thereby driving them into their inactive GDP-bound form. Glycine-binding changes the conformation of the intracellular surface, inhibiting the GTPase activator activity of the RGS7-GNB5 complex, promoting G protein alpha subunits into their active GTP-bound form and regulating cAMP levels. Also able to bind taurine, a compound closely related to glycine, but with a two-fold lower affinity. Glycine receptor-dependent regulation of cAMP controls key ion channels, kinases and neurotrophic factors involved in neuronal excitability and synaptic transmission. Plays a pivotal role in regulating mood and cognition via its ability to regulate neuronal excitability in L2/L3 pyramidal neurons of the prefrontal cortex. Also involved in spatial learning by regulating hippocampal CA1 neuronal excitability. Acts as a synaptic organizer in the hippocampus, required for proper mossy fiber-CA3 neurocircuitry establishment, structure and function: induces presynaptic differentiation in contacting axons via its interaction with GPC4. In addition to glycine, may also act as a receptor for osteocalcin (BGLAP) hormone: osteocalcin-binding initiates a signaling response that prevents neuronal apoptosis in the hippocampus and regulates the synthesis of neurotransmitters.

Subunit / interactions. Homodimer. Associates with the RGS7-GNB5 complex, promoting its localization to the cell membrane and regulating its GTPase activator activity. Interacts (via VCPWE motifs) with GNAO1. Interacts with GPC4. Interacts with EGFLAM.

Subcellular location. Cell membrane. Postsynaptic cell membrane. Presynaptic cell membrane. Nucleus.

Domain organisation. The Cache-like region shares similarity with the Cache domain, a well-known receptor for amino acids. It acts as a ligand-binding module that recognizes and binds glycine and taurine.

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

RefSeq proteins (1): NP_065803* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR017978	GPCR_3_C	Domain
IPR043458	GPR158/179	Family
IPR054714	GPR158_179_extracellular	Domain

Pfam: PF00003, PF22572

UniProt features (117 total): helix 21, strand 17, mutagenesis site 16, turn 10, topological domain 8, compositionally biased region 8, transmembrane region 7, modified residue 6, glycosylation site 5, region of interest 4, binding site 4, short sequence motif 3, disulfide bond 2, sequence variant 2, signal peptide 1, chain 1, cross-link 1, sequence conflict 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
7SHE	ELECTRON MICROSCOPY	3.4
7SHF	ELECTRON MICROSCOPY	3.4
9VOR	ELECTRON MICROSCOPY	3.47
7EWL	ELECTRON MICROSCOPY	3.52
7EWP	ELECTRON MICROSCOPY	4.3
7EWR	ELECTRON MICROSCOPY	4.7

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5T848-F1	58.71	0.14

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 (4): 172; 173; 271; 307

Post-translational modifications (7): 694, 705, 708, 865, 946, 1080, 774

Disulfide bonds (2): 99–272, 481–573

Glycosylation sites (5): 98, 143, 215, 274, 333

Mutagenesis-validated functional residues (16):

Position	Phenotype
135	does not affect ability to regulate camp levels; when associated with a-540 and a-578.
173	nearly abolished glycine-binding and ability to inhibit the gtpase activator activity of rgs7.
266	nearly abolished ability to inhibit the gtpase activator activity of rgs7 without affecting glycine-binding.
269	nearly abolished glycine-binding and ability to inhibit the gtpase activator activity of rgs7.
271	nearly abolished glycine-binding and ability to inhibit the gtpase activator activity of rgs7.
502	does not affect g protein alpha subunit activation.
505	does not affect g protein alpha subunit activation.
540	does not affect ability to regulate camp levels; when associated with a-135 and a-578.
578	does not affect ability to regulate camp levels; when associated with a-135 and a-540.
609	induces an increase of camp levels.
719–720	in m1 mutant; decreased localization to the nucleus.
731–732	in m2 mutant; decreased localization to the nucleus.
1007–1009	in mut1; decreased interaction with gnao1.
1072–1074	in mut2; does not affect interaction with gnao1.
1172–1174	in mut3; decreased interaction with gnao1.
1172–1174	in mut4; does not affect interaction with gnao1.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 210 (showing top): GSE37336_LY6C_POS_VS_NEG_NAIVE_CD4_TCELL_UP, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, GOBP_COGNITION, GCANCTGNY_MYOD_Q6, GOBP_NEUROTRANSMITTER_TRANSPORT, CHX10_01, GOBP_PROTEIN_LOCALIZATION_TO_CELL_PERIPHERY, GOBP_CELL_CELL_SIGNALING, GOBP_CELL_JUNCTION_ORGANIZATION, NF1_Q6_01, GGARNTKYCCA_UNKNOWN, GOBP_REGULATION_OF_NEUROTRANSMITTER_TRANSPORT, GOBP_SECRETION, TGANTCA_AP1_C, GOBP_POSITIVE_REGULATION_OF_NEUROTRANSMITTER_SECRETION

GO Biological Process (9): positive regulation of neurotransmitter secretion (GO:0001956), G protein-coupled receptor signaling pathway (GO:0007186), brain development (GO:0007420), regulation of G protein-coupled receptor signaling pathway (GO:0008277), regulation of synapse organization (GO:0050807), cognition (GO:0050890), protein localization to plasma membrane (GO:0072659), signal transduction (GO:0007165), negative regulation of G protein-coupled receptor signaling pathway (GO:0045744)

GO Molecular Function (4): transmembrane signaling receptor activity (GO:0004888), enzyme activator activity (GO:0008047), G protein-coupled glycine receptor activity (GO:0160079), G protein-coupled receptor activity (GO:0004930)

GO Cellular Component (9): nucleus (GO:0005634), plasma membrane (GO:0005886), presynaptic membrane (GO:0042734), postsynaptic membrane (GO:0045211), postsynaptic density membrane (GO:0098839), membrane (GO:0016020), cell projection (GO:0042995), neuron projection (GO:0043005), synapse (GO:0045202)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
G protein-coupled receptor signaling pathway	3
synaptic membrane	2
cellular anatomical structure	2
neurotransmitter secretion	1
regulation of neurotransmitter secretion	1
positive regulation of synaptic transmission	1
positive regulation of neurotransmitter transport	1
positive regulation of secretion by cell	1
G protein-coupled receptor activity	1
signal transduction	1
central nervous system development	1
animal organ development	1
head development	1
regulation of signal transduction	1
regulation of synapse structure or activity	1
synapse organization	1
regulation of cellular component organization	1
nervous system process	1
protein localization to membrane	1
protein localization to cell periphery	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
regulation of G protein-coupled receptor signaling pathway	1
negative regulation of signal transduction	1
signaling receptor activity	1
catalytic activity	1
enzyme regulator activity	1
molecular function activator activity	1
G protein-coupled neurotransmitter receptor activity	1
transmembrane signaling receptor activity	1
intracellular membrane-bounded organelle	1
membrane	1
cell periphery	1
presynapse	1
postsynapse	1
postsynaptic density	1
postsynaptic membrane	1

Protein interactions and networks

STRING

1426 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GPR158	RGS7	P49802	886
GPR158	GPRC6A	Q5T6X5	772
GPR158	BGLAP	P02818	756
GPR158	GNB5	O14775	675
GPR158	GPR156	Q8NFN8	667
GPR158	GPC4	O75487	656
GPR158	GPR137	Q96N19	624
GPR158	GPRC5B	Q9NZH0	564
GPR158	GNAQ	P50148	534
GPR158	GPRC5C	Q9NQ84	530
GPR158	GPR152	Q8TDT2	525
GPR158	RGS11	O94810	523
GPR158	GPR52	Q9Y2T5	513
GPR158	GPR171	O14626	501
GPR158	GPRC5A	Q8NFJ5	490

IntAct

3 interactions, top by confidence:

A	B	Type	Score
MYC		psi-mi:“MI:0914”(association)	0.350
PITX2	GPR158	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (8): GPR158 (Affinity Capture-RNA), GPR158 (Proximity Label-MS), GPR158 (Affinity Capture-RNA), GPR158 (Protein-RNA), GPR158 (Co-crystal Structure), GPR158 (Cross-Linking-MS (XL-MS)), PGAM1 (Cross-Linking-MS (XL-MS)), GPR158 (Affinity Capture-MS)

ESM2 similar proteins: A0A1B0GU71, A6QPI4, B2RV13, D4A6L0, E1BBQ2, F1LQY6, G3UW36, O08856, P15382, P53801, P55199, P56182, Q08CB3, Q0VF94, Q148E1, Q17RQ9, Q2KJ58, Q32Q90, Q4R5F9, Q4V8A6, Q4VA36, Q5I0I4, Q5NVI6, Q5R8Q2, Q5T6X4, Q5T848, Q5XII8, Q68EN5, Q6P767, Q8C419, Q8CHT6, Q8R143, Q8R1T1, Q8TBN0, Q8VDV3, Q8WUX9, Q90YH8, Q91WM6, Q91ZP9, Q96IL0

Diamond homologs: D4A6L0, E1BBQ2, E9PY61, Q54L53, Q5T848, Q6PRD1, Q8C419, Q1ZXQ7, Q54LG8, Q54QG7, Q54SH7, Q54SH8, Q54SW3, Q55AP1, Q75JP4, Q75JT4, Q86HH3, E4S1L1, P0CL55

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	167
Likely benign	8
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

3793 predictions. Top by Δscore:

Variant	Effect	Δscore
10:25221044:A:AG	acceptor_gain	1.0000
10:25221045:T:G	acceptor_gain	1.0000
10:25221048:CTA:C	acceptor_loss	1.0000
10:25221050:A:AG	acceptor_gain	1.0000
10:25221050:AG:A	acceptor_gain	1.0000
10:25221050:AGG:A	acceptor_gain	1.0000
10:25221050:AGGG:A	acceptor_gain	1.0000
10:25221051:G:GA	acceptor_gain	1.0000
10:25221051:GG:G	acceptor_gain	1.0000
10:25221051:GGG:G	acceptor_gain	1.0000
10:25221051:GGGG:G	acceptor_gain	1.0000
10:25221051:GGGGT:G	acceptor_gain	1.0000
10:25221154:AGAGG:A	donor_loss	1.0000
10:25221155:GAG:G	donor_gain	1.0000
10:25221155:GAGGT:G	donor_loss	1.0000
10:25221156:AGGTA:A	donor_loss	1.0000
10:25221157:GGT:G	donor_loss	1.0000
10:25221158:G:GG	donor_gain	1.0000
10:25221159:T:A	donor_loss	1.0000
10:25395909:A:AG	acceptor_gain	1.0000
10:25395910:G:GC	acceptor_gain	1.0000
10:25395910:GT:G	acceptor_gain	1.0000
10:25395910:GTGT:G	acceptor_gain	1.0000
10:25396009:TCGGA:T	donor_gain	1.0000
10:25396010:CGGA:C	donor_gain	1.0000
10:25396011:GGA:G	donor_gain	1.0000
10:25396011:GGAG:G	donor_gain	1.0000
10:25396012:GA:G	donor_gain	1.0000
10:25396012:GAG:G	donor_gain	1.0000
10:25396013:AGTA:A	donor_loss	1.0000

AlphaMissense

7935 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:25597779:T:C	L718P	1.000
10:25597788:T:C	L721P	1.000
10:25597800:T:C	L725P	1.000
10:25221137:T:A	C330S	0.999
10:25221138:G:C	C330S	0.999
10:25572662:T:C	F510L	0.999
10:25572664:T:A	F510L	0.999
10:25572664:T:G	F510L	0.999
10:25596739:A:C	S699R	0.999
10:25596741:T:A	S699R	0.999
10:25596741:T:G	S699R	0.999
10:25596754:T:A	W704R	0.999
10:25596754:T:C	W704R	0.999
10:25597779:T:A	L718Q	0.999
10:25597813:A:C	K729N	0.999
10:25597813:A:T	K729N	0.999
10:25597824:T:C	M733T	0.999
10:25597837:C:A	N737K	0.999
10:25597837:C:G	N737K	0.999
10:25221101:T:A	C318S	0.998
10:25221102:G:C	C318S	0.998
10:25395911:T:A	C337S	0.998
10:25395912:G:C	C337S	0.998
10:25551027:T:A	W486R	0.998
10:25551027:T:C	W486R	0.998
10:25596788:G:C	R715P	0.998
10:25597776:A:T	E717V	0.998
10:25597788:T:A	L721H	0.998
10:25597790:T:G	Y722D	0.998
10:25597800:T:A	L725Q	0.998

dbSNP variants (sampled 300 via entrez): RS1000000991 (10:25442104 A>T), RS1000014352 (10:25275767 T>A,C), RS1000017283 (10:25413074 A>G), RS1000028847 (10:25204648 G>A,T), RS1000037831 (10:25374112 C>A), RS1000040117 (10:25253002 G>A,T), RS1000056823 (10:25227158 G>A), RS1000060649 (10:25197973 T>A), RS1000061579 (10:25528622 TAA>T), RS1000062258 (10:25539418 T>G), RS1000092197 (10:25481376 A>G), RS1000093270 (10:25289860 G>C,T), RS1000093664 (10:25365669 A>C,G), RS1000095361 (10:25442402 A>G), RS1000118451 (10:25295648 C>A,T)

Disease associations

OMIM: gene MIM:614573 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

13 associations (top):

Study	Trait	p-value
GCST001491_36	Immune response to smallpox vaccine (IL-6)	4.000000e-09
GCST002284_26	QRS duration in Tripanosoma cruzi seropositivity	4.000000e-07
GCST004524_8	Energy expenditure (24h)	7.000000e-06
GCST005170_13	Intraocular pressure	5.000000e-08
GCST005316_64	Intelligence (MTAG)	9.000000e-09
GCST005351_12	Carboplatin disposition in epthelial ovarian cancer	6.000000e-06
GCST005580_316	Intraocular pressure	5.000000e-09
GCST005580_92	Intraocular pressure	5.000000e-11
GCST006479_107	Diverticular disease	5.000000e-16
GCST007631_3	Hepatitis C (spontaneous viral clearance)	2.000000e-07
GCST008105_2	Diverticular disease	2.000000e-22
GCST009254_8	Cerebellum white matter volume	2.000000e-06
GCST90000654_30	Central corneal thickness	1.000000e-08

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0004645	response to vaccine
EFO:0004695	intraocular pressure measurement
EFO:0004337	intelligence
EFO:0009959	diverticular disease
EFO:0009785	remission
EFO:0008320	white matter volume measurement
EFO:0005213	central corneal thickness

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4523874 (SINGLE PROTEIN)

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: gpcr — Class C Orphans

CTD chemical–gene interactions

20 total (human), top 20 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, decreases methylation	8
Aflatoxin B1	decreases methylation	2
FR900359	increases phosphorylation	1
bisphenol A	decreases expression	1
trichostatin A	increases expression	1
arsenite	increases methylation	1
aflatoxin B2	increases methylation	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
abrine	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
bisphenol S	affects cotreatment, decreases methylation	1
Sunitinib	increases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Benzo(a)pyrene	increases methylation	1
Cadmium	increases abundance, decreases expression	1
Folic Acid	decreases expression	1
Dihydrotestosterone	increases expression	1
Cyclosporine	increases expression	1
Cadmium Chloride	decreases expression, increases abundance	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4883425	Binding	PRESTO-Tango GPCRome screening (GPR158)	Data for DCP probe UCSF924

Clinical trials (associated diseases)

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