GPR55

Summary

GPR55 (G protein-coupled receptor 55, HGNC:4511) is a protein-coding gene on chromosome 2q37.1, encoding G-protein coupled receptor 55 (Q9Y2T6). G-protein coupled receptor that binds to several ligands including 2-arachidonoyl lysophosphatidylinositol or lysophosphatidylglucoside with high affinity, leading to rapid and transient activation of numerous intracellular signaling pathways.

This gene belongs to the G-protein-coupled receptor superfamily. The encoded integral membrane protein is a likely cannabinoid receptor. It may be involved in several physiological and pathological processes by activating a variety of signal transduction pathways.

Source: NCBI Gene 9290 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 54 total
• Druggable target: yes — 8 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_005683

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4511
Approved symbol	GPR55
Name	G protein-coupled receptor 55
Location	2q37.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000135898
Ensembl biotype	protein_coding
OMIM	604107
Entrez	9290

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 7 protein_coding, 1 nonsense_mediated_decay

ENST00000392039, ENST00000392040, ENST00000438398, ENST00000444078, ENST00000622008, ENST00000650999, ENST00000886145, ENST00000886146

RefSeq mRNA: 1 — MANE Select: NM_005683 NM_005683

CCDS: CCDS2480

Canonical transcript exons

ENST00000650999 — 2 exons

Exon	Start	End
ENSE00001510514	230907328	230911096
ENSE00003843317	230925168	230925242

Expression profiles

Bgee: expression breadth ubiquitous, 102 present calls, max score 76.42.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.4728 / max 47.8392, expressed in 112 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
34467	0.4504	107
34471	0.0164	3
34470	0.0060	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	76.42	gold quality
leukocyte	CL:0000738	76.23	gold quality
pancreatic ductal cell	CL:0002079	73.73	silver quality
granulocyte	CL:0000094	71.19	gold quality
upper arm skin	UBERON:0004263	69.24	gold quality
nucleus accumbens	UBERON:0001882	68.47	gold quality
lymph node	UBERON:0000029	68.37	gold quality
epithelial cell of pancreas	CL:0000083	67.78	gold quality
spleen	UBERON:0002106	67.61	gold quality
putamen	UBERON:0001874	67.10	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	66.40	gold quality
caudate nucleus	UBERON:0001873	66.08	gold quality
left ventricle myocardium	UBERON:0006566	65.90	gold quality
parotid gland	UBERON:0001831	65.73	gold quality
myocardium	UBERON:0002349	65.43	gold quality
cardiac muscle of right atrium	UBERON:0003379	65.37	gold quality
right testis	UBERON:0004534	65.34	gold quality
vermiform appendix	UBERON:0001154	65.16	gold quality
blood	UBERON:0000178	64.83	gold quality
bone marrow cell	CL:0002092	63.65	silver quality
quadriceps femoris	UBERON:0001377	63.33	gold quality
left testis	UBERON:0004533	63.24	gold quality
caecum	UBERON:0001153	62.93	gold quality
vastus lateralis	UBERON:0001379	62.72	gold quality
superficial temporal artery	UBERON:0001614	62.63	gold quality
testis	UBERON:0000473	62.58	gold quality
mucosa of transverse colon	UBERON:0004991	61.15	gold quality
colonic epithelium	UBERON:0000397	60.95	gold quality
ileal mucosa	UBERON:0000331	60.61	silver quality
tonsil	UBERON:0002372	60.61	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.23

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

96 targeting GPR55, 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-6873-3P	100.00	71.42	2626
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-7152-3P	99.97	67.47	849
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-4778-3P	99.93	70.40	1818
HSA-MIR-6753-3P	99.93	66.57	637
HSA-MIR-7107-3P	99.93	66.73	627
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-182-5P	99.87	74.03	2589
HSA-MIR-130B-5P	99.83	68.50	1888
HSA-MIR-6875-3P	99.82	70.26	2983
HSA-MIR-3180-5P	99.82	69.12	2422
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-3059-5P	99.70	69.93	2491
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-6887-3P	99.66	67.83	1778
HSA-MIR-4527	99.66	67.43	714
HSA-MIR-3175	99.65	66.30	2031
HSA-MIR-6503-5P	99.62	66.96	597
HSA-MIR-1260A	99.61	66.67	1098
HSA-MIR-1260B	99.61	66.67	1098
HSA-MIR-4276	99.56	67.66	2514
HSA-MIR-3678-3P	99.31	67.10	1432
HSA-MIR-6731-5P	99.28	67.42	2375
HSA-MIR-8085	99.28	67.56	2362
HSA-MIR-4667-3P	99.26	65.45	1608

Literature-anchored findings (GeneRIF, showing 40)

• These results strongly suggest that GPR55 is a specific and functional receptor for lysophosphatidylinositol. (PMID:17765871)
• The GPR55 is a novel cannabinoid receptor, it binds to and is activated by the cannabinoid ligand CP55940 and couples to Galpha13 and can mediate activation of rhoA, cdc42 and rac1. (PMID:17876302)
• establish GPR55 as a cannabinoid receptor with signaling distinct from CB(1) and CB(2). (PMID:18263732)
• in endothelial cells, two receptors for anandamide were found, which were characterized as cannabinoid 1 receptor & and G-protein-coupled receptor 55; integrin clustering enables anandamide-induced Ca2+ signaling in endothelial cells via GPR55 (PMID:18445684)
• Treatment with lysophosphatidylinositol induces marked GPR55 internalization and stimulates a sustained, oscillatory calcium release pathway, which is dependent on Galpha13 and requires RhoA activation. (PMID:18757503)
• GPR55 is an atypical cannabinoid responder. (PMID:19723626)
• Data reveal a role of GPR55 in bone physiology by regulating osteoclast number and function. (PMID:19805329)
• results suggest that GPR55 and its endogenous ligand LPI play essential roles in the homoeostatic responses to stress signals in several mammalian tissues and cells including certain types of immune cells (PMID:20051382)
• this study demonistrated that low-functioning Val195 allele of GPR55 appears to be a risk factor for anorexia nervosa. (PMID:20506567)
• HIV-infected human cells injected into immunodeficient mice to observe expression levels of CB1R, CB2R and GPR55. (PMID:20549374)
• GPR55 expression in human tumors from different origins correlates with tumor aggressiveness. Moreover, GPR55 promotes cancer cell proliferation through the overactivation of the extracellular signal-regulated kinase cascade. (PMID:20818416)
• GPR55 is expressed in several prostate and ovarian cancer cell lines and has a critical role in regulating proliferation and anchorage-independent growth. GPR55 mediates the effects of lysophosphatidylinositol in prostate and ovarian cancer cells. (PMID:20838378)
• GPR55 is expressed in human tumours and drives proliferation and its expression correlates with tumour aggressiveness (PMID:21367464)
• GPR55 limits the tissue-injuring inflammatory responses mediated by CB(2)R, while it synergizes with CB(2)R in recruiting neutrophils to sites of inflammation. (PMID:21467997)
• The chemical diversity provided by three lead compounds combined with the identification of key GPR55 receptor interaction sites should provide a basis for the design of more efficacious second-generation GPR55 ligands that retain GPR55 selectivity. (PMID:21534610)
• New blood brothers: the GPR55 and CB2 partnership (PMID:21537344)
• GASP-1 is a key regulator of the trafficking and, by extension, functional expression of GPR55 (PMID:21718301)
• alpha-lysophosphatidylinositol(LPI)/GPR55 system is positively associated with obesity in humans. (PMID:22179809)
• Studies suggest the lysophosphatidylinositol (LPI)/orphan G protein-coupled receptor GPR55 axis plays an important role in different physiological and pathological contexts. (PMID:22285325)
• GPR55 drives skin carcinogenesis and is upregulated in human squamous cell carcinomas. (PMID:22751111)
• This review presents a summary of what is known about the G-protein coupled receptors GPR35 and GPR55 and their potential characterization as lysophospholipid or cannabinoid receptors, respectively–{REVIEW} (PMID:22820167)
• This article reviews current data about GPR55 pharmacology and signalling, highlighting its involvement in several pathophysiological conditions. [review] (PMID:23151004)
• CB1 modulates the signaling properties of the lysophosphatidylinositol receptor GPR55. (PMID:23161546)
• Data (including data from tissue bank samples) suggest that GPR55 is strongly expressed on myenteric neurons of the colon. (PMID:23603203)
• Data suggest that GPR55 is functionally expressed in vascular endothelium/platelets and is involved in regulation of calcium signaling; as suspected, lysophosphatidylinositol is a ligand/agonist for GPR55. (PMID:23639801)
• GPR55 antagonists occupies a horizontal binding pocket extending into the extracellular loop region, a central ligand portion that fits vertically in the receptor binding pocket. (PMID:24274581)
• GPR55 receptors were expressed in urothelial cell lines and interact with CB1 receptors. (PMID:24652077)
• CB2R and GPR55 form heteromers in cancer cells, these structures possess unique signaling properties, and modulation of these heteromers can modify the antitumoral activity of cannabinoids in vivo (PMID:24942731)
• This review summarizes our current knowledge of expression and function of GPR55 in tissues involved in metabolic regulation and the signaling cascades through which GPR55 is reported to act. (PMID:24972076)
• Heteromerization of GPR55 and cannabinoid CB2 receptors modulates signalling (PMID:25048571)
• Data suggest GPR55 (G-protein coupled receptor 55), ABCC1 (ATP-binding cassette sub-family C), and MPR1/ABCB1 (multidrug resistance protein 1) participate/cooperate in autocrine communication/tumorigenesis involving lysophosphatidylinositol. [REVIEW] (PMID:25233417)
• proinflammatory role in innate immunity (PMID:25344934)
• expression of CB1 and GPR55 in proximal tubules is altered in response to elevated levels of glucose and albumin (PMID:25545857)
• GPR55 is expressed in placenta,located solely at the placental endothelium; L-alpha-lysophosphatidylinositol (LPI), the endogenous ligand of GPR55, increases migratory activity of venous but not arterial placental endothelial cells suggesting a role of LPI-GPR55 axis in placental venous endothelium function (PMID:25869640)
• GPR55 was a direct target gene of miR-675-5p. (PMID:25889562)
• GPR55 could play deleterious role in ox-LDL-induced foam cells and could be a novel pharmacological target to manage atherosclerosis and other related cardiovascular diseases. (PMID:25970609)
• Inhibiting the pro-angiogenic L-alpha-lysophosphatidylinositol /GPR55 pathway appears a promising target against angiogenesis in ovarian carcinoma (PMID:25989290)
• GPR55 is involved in the migratory behaviour of colon carcinoma cells. (PMID:26436760)
• The signalling pathways activated by lysophosphatidylinositol through its receptor GPR55 play a pivotal role in different cancer. [review] (PMID:26588872)
• Inhibition of GPR55 activity produces antitumor effects via attenuation of the MEK/ERK and PI3K-AKT pathways leading to a reduction in the expression and function of MDR proteins. (PMID:27423937)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	gpr55a	ENSDARG00000043447
mus_musculus	Gpr55	ENSMUSG00000049608
rattus_norvegicus	Gpr55	ENSRNOG00000017521

Paralogs (16): P2RY10 (ENSG00000078589), GPR18 (ENSG00000125245), F2RL3 (ENSG00000127533), LPAR6 (ENSG00000139679), GPR65 (ENSG00000140030), GPR17 (ENSG00000144230), LPAR4 (ENSG00000147145), CYSLTR2 (ENSG00000152207), F2RL2 (ENSG00000164220), F2RL1 (ENSG00000164251), CYSLTR1 (ENSG00000173198), GPR4 (ENSG00000177464), GPR35 (ENSG00000178623), F2R (ENSG00000181104), P2RY8 (ENSG00000182162), GPR20 (ENSG00000204882)

Protein

Protein identifiers

G-protein coupled receptor 55 — Q9Y2T6 (reviewed: Q9Y2T6)

All UniProt accessions (3): A8K858, C9J1P7, Q9Y2T6

UniProt curated annotations — full annotation on UniProt →

Function. G-protein coupled receptor that binds to several ligands including 2-arachidonoyl lysophosphatidylinositol or lysophosphatidylglucoside with high affinity, leading to rapid and transient activation of numerous intracellular signaling pathways. Induces the Ca(2+) release from intracellular stores via ERK, the heterotrimeric G protein GNA13 and RHOA leading to morphological changes including cell rounding and stress fiber formation. In macrophages, acts downstream of lysophosphatidylglucoside to inhibit the translocation of the phospholipid-transporting ABCA1 to plasma membrane and subsequent cholesterol efflux leading to lipid accumulation and foam cell formation.

Subcellular location. Cell membrane.

Tissue specificity. Expressed in the caudate nucleus and putamen, but not detected in the hippocampus, thalamus, pons cerebellum, frontal cortex of the brain or in the liver. Expressed in osteoclasts and osteoblasts. Highly expressed in macrophages and B-cells.

Miscellaneous. The classification of this protein as a cannabinoid receptor remains a contentious issue due to conflicting pharmacological results.

Similarity. Belongs to the G-protein coupled receptor 1 family.

RefSeq proteins (1): NP_005674* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000276	GPCR_Rhodpsn	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain

Pfam: PF00001

UniProt features (35 total): helix 12, topological domain 8, transmembrane region 7, glycosylation site 2, sequence variant 2, turn 2, chain 1, strand 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
9GE2	ELECTRON MICROSCOPY	2.51
8ZX4	ELECTRON MICROSCOPY	2.85
9GE3	ELECTRON MICROSCOPY	2.87
9IY8	ELECTRON MICROSCOPY	3.01
8ZX5	ELECTRON MICROSCOPY	3.03
9IYA	ELECTRON MICROSCOPY	3.04

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y2T6-F1	87.36	0.58

Antibody-complex structures (SAbDab): 1 — 9IY8

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Glycosylation sites (2): 5, 171

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-373076	Class A/1 (Rhodopsin-like receptors)
R-HSA-418594	G alpha (i) signalling events

MSigDB gene sets: 104 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, GOBP_NEGATIVE_REGULATION_OF_CELL_DEVELOPMENT, GOBP_REGULATION_OF_OSTEOCLAST_DIFFERENTIATION, GOBP_POSITIVE_REGULATION_OF_RHO_PROTEIN_SIGNAL_TRANSDUCTION, GOBP_REGULATION_OF_SMALL_GTPASE_MEDIATED_SIGNAL_TRANSDUCTION, GOBP_POSITIVE_REGULATION_OF_MAPK_CASCADE, TGACCTY_ERR1_Q2, GOBP_MYELOID_LEUKOCYTE_DIFFERENTIATION, GOBP_REGULATION_OF_LEUKOCYTE_DIFFERENTIATION, GOBP_REGULATION_OF_HEMOPOIESIS, GOBP_NEGATIVE_REGULATION_OF_MULTICELLULAR_ORGANISMAL_PROCESS, ROZANOV_MMP14_TARGETS_UP, GOBP_NEGATIVE_REGULATION_OF_HEMOPOIESIS, GOBP_NEGATIVE_REGULATION_OF_MYELOID_LEUKOCYTE_DIFFERENTIATION, TGANTCA_AP1_C

GO Biological Process (8): G protein-coupled receptor signaling pathway (GO:0007186), phospholipase C-activating G protein-coupled receptor signaling pathway (GO:0007200), positive regulation of Rho protein signal transduction (GO:0035025), bone resorption (GO:0045453), negative regulation of osteoclast differentiation (GO:0045671), positive regulation of ERK1 and ERK2 cascade (GO:0070374), signal transduction (GO:0007165), cannabinoid signaling pathway (GO:0038171)

GO Molecular Function (2): G protein-coupled receptor activity (GO:0004930), cannabinoid receptor activity (GO:0004949)

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

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
GPCR ligand binding	1
GPCR downstream signalling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
G protein-coupled receptor signaling pathway	3
G protein-coupled receptor activity	2
signal transduction	1
phospholipase C activator activity	1
Rho protein signal transduction	1
regulation of Rho protein signal transduction	1
positive regulation of small GTPase mediated signal transduction	1
tissue homeostasis	1
bone remodeling	1
negative regulation of myeloid leukocyte differentiation	1
osteoclast differentiation	1
regulation of osteoclast differentiation	1
positive regulation of MAPK cascade	1
ERK1 and ERK2 cascade	1
regulation of ERK1 and ERK2 cascade	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
cannabinoid receptor activity	1
transmembrane signaling receptor activity	1
cannabinoid signaling pathway	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

708 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GPR55	GNA12	Q03113	982
GPR55	CNR1	P21554	974
GPR55	GPR119	Q8TDV5	923
GPR55	TRPV1	Q8NER1	922
GPR55	GNAQ	P50148	891
GPR55	GNA13	Q14344	854
GPR55	FAAH	O00519	848
GPR55	NAPEPLD	Q6IQ20	802
GPR55	HTR1A	P08908	782
GPR55	MGLL	Q99685	777
GPR55	TRPM8	Q7Z2W7	747
GPR55	PPARA	Q07869	746
GPR55	ARRB2	P32121	732
GPR55	ARRB1	P49407	725
GPR55	ABHD6	Q9BV23	717

IntAct

6 interactions, top by confidence:

A	B	Type	Score
GPR55	LGALS3	psi-mi:“MI:0914”(association)	0.530
GPR55	RAMP1	psi-mi:“MI:0915”(physical association)	0.400
RAMP2	GPR55	psi-mi:“MI:0915”(physical association)	0.400
GPR55	SCAMP3	psi-mi:“MI:0914”(association)	0.350

BioGRID (72): HOXD13 (Affinity Capture-MS), LGALS3 (Affinity Capture-MS), ARRB2 (Affinity Capture-MS), SPG7 (Affinity Capture-MS), ARRB2 (Affinity Capture-MS), LGALS3 (Affinity Capture-MS), ARRB2 (Affinity Capture-MS), HOXD13 (Affinity Capture-MS), LGALS3 (Affinity Capture-MS), RAB29 (Affinity Capture-MS), OXA1L (Affinity Capture-MS), AMFR (Affinity Capture-MS), NDUFA9 (Affinity Capture-MS), MISP (Affinity Capture-MS), PI4KA (Affinity Capture-MS)

ESM2 similar proteins: A7YY44, B0UXR0, B2GV46, E7FEL0, F8VQN3, O00398, O00590, O08707, O09027, O14843, O15529, O15552, O46685, P21556, P25105, P46002, P46093, P46094, P50132, P56484, Q00991, Q09QM4, Q13304, Q15743, Q1JQB3, Q3U507, Q3UFD7, Q3UJF0, Q4KLH9, Q6NS65, Q76EI6, Q86VZ1, Q8BFQ3, Q8BFU7, Q8BUD0, Q8BYC4, Q8C131, Q8TDS4, Q8TDS5, Q8VCK6

Diamond homologs: A0A6I8PUB9, B2GV46, E9QJ73, O00155, O14842, O14843, O15529, O35210, O77590, P21109, P25095, P25104, P29089, P29754, P29755, P30555, P30556, P34976, P35350, P43240, P70612, Q2YEF9, Q3UFD7, Q3UJF0, Q76EI6, Q76JU8, Q76JU9, Q76JV1, Q810W6, Q8K3T4, Q8VCK6, Q96G91, Q9GLN9, Q9NPB9, Q9P296, Q9TUE1, Q9WV26, Q9Y2T6, B0UXR0, B5X337

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
GPR55	“up-regulates activity”	GNA13	binding
“lysophosphatidylinositol 22:6”	“up-regulates activity”	GPR55	“chemical activation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	48
Likely benign	3
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

268 predictions. Top by Δscore:

Variant	Effect	Δscore
2:230911092:CACAA:C	acceptor_gain	0.9800
2:230911094:CAA:C	acceptor_gain	0.9800
2:230911097:C:CC	acceptor_gain	0.9600
2:230925162:TGTTA:T	donor_loss	0.9400
2:230925163:GTTAC:G	donor_loss	0.9400
2:230925164:TTACC:T	donor_loss	0.9400
2:230925165:TA:T	donor_loss	0.9400
2:230925166:ACCT:A	donor_loss	0.9400
2:230925167:CCT:C	donor_loss	0.9400
2:230925168:C:A	donor_loss	0.9400
2:230925161:CTGTT:C	donor_loss	0.9000
2:230911093:ACAA:A	acceptor_gain	0.8800
2:230911094:CAAC:C	acceptor_gain	0.8800
2:230915751:TGGAA:T	donor_gain	0.8200
2:230925169:T:C	donor_loss	0.8200
2:230914221:A:AT	donor_gain	0.8100
2:230924650:G:C	donor_gain	0.7800
2:230911095:AACTA:A	acceptor_loss	0.7500
2:230911096:AC:A	acceptor_loss	0.7500
2:230911097:CTA:C	acceptor_loss	0.7500
2:230911098:T:A	acceptor_loss	0.7500
2:230917135:A:C	donor_gain	0.7500
2:230911103:C:CT	acceptor_loss	0.7100
2:230925087:GAGTT:G	donor_loss	0.7000
2:230925088:AGTTA:A	donor_loss	0.7000
2:230925089:GTTAC:G	donor_loss	0.7000
2:230925090:TTAC:T	donor_loss	0.7000
2:230925091:TAC:T	donor_loss	0.7000
2:230925092:ACCTG:A	donor_loss	0.7000
2:230925093:C:A	donor_loss	0.7000

AlphaMissense

2138 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:230910651:G:C	S104R	0.991
2:230910651:G:T	S104R	0.991
2:230910653:T:G	S104R	0.991
2:230910246:G:C	F239L	0.990
2:230910246:G:T	F239L	0.990
2:230910248:A:G	F239L	0.990
2:230910639:G:C	S108R	0.990
2:230910639:G:T	S108R	0.990
2:230910641:T:G	S108R	0.990
2:230910393:G:C	F190L	0.989
2:230910393:G:T	F190L	0.989
2:230910395:A:G	F190L	0.989
2:230910456:G:C	F169L	0.989
2:230910456:G:T	F169L	0.989
2:230910458:A:G	F169L	0.989
2:230910504:G:C	S153R	0.989
2:230910504:G:T	S153R	0.989
2:230910506:T:G	S153R	0.989
2:230910615:G:C	S116R	0.988
2:230910615:G:T	S116R	0.988
2:230910617:T:G	S116R	0.988
2:230910768:G:C	N65K	0.987
2:230910768:G:T	N65K	0.987
2:230910258:G:C	F235L	0.986
2:230910258:G:T	F235L	0.986
2:230910260:A:G	F235L	0.986
2:230910527:A:G	W146R	0.985
2:230910527:A:T	W146R	0.985
2:230910607:C:G	R119P	0.984
2:230910241:G:C	P241R	0.983

dbSNP variants (sampled 300 via entrez): RS1000068457 (2:230906943 G>T), RS1000097878 (2:230958403 T>C), RS1000297241 (2:230909140 G>A,C), RS1000310941 (2:230933246 G>A), RS1000354946 (2:230915945 A>C), RS1000358358 (2:230942542 T>A), RS1000401786 (2:230907164 C>T), RS1000407550 (2:230915676 A>T), RS1000558957 (2:230957407 C>T), RS1000561291 (2:230921768 AC>A), RS1000662830 (2:230931022 A>C), RS1000691475 (2:230943831 C>A), RS1000725493 (2:230944033 C>T), RS1000753005 (2:230908919 G>A), RS1000903021 (2:230939187 A>G)

Disease associations

OMIM: gene MIM:604107 | disease phenotypes:

GenCC curated gene-disease

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

Orphanet (1): Familial prostate cancer (Orphanet:1331)

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST005175_4	Coronary artery calcified atherosclerotic plaque (90 or 130 HU threshold) in type 2 diabetes	6.000000e-07

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004723	coronary artery calcification

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D011471	Prostatic Neoplasms	C04.588.945.440.770; C12.100.500.260.750; C12.100.500.565.625; C12.200.294.260.750; C12.200.294.565.625; C12.200.758.409.750; C12.900.619.750

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1075322 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

8 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 187,344 (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
CHEMBL111	RIMONABANT	4	15,726
CHEMBL1334033	PERHEXILINE MALEATE	4	1,054
CHEMBL190461	CANNABIDIOL	4	26,379
CHEMBL465	DRONABINOL	4	62,107
CHEMBL63857	PHENOLPHTHALEIN	4	57,577
CHEMBL942	BISACODYL	4	14,654
CHEMBL2387541	TETRAHYDROCANNABIVARIN	2	4,884
CHEMBL2387742	CANNABIDIVARIN	2	4,963

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: gpcr — GPR18, GPR55 and GPR119

Most potent curated ligand interactions (31 total), top 25:

Ligand	Action	Affinity	Parameter
O-1602	Agonist	8.85	pEC50
2-arachidonoylglycerol	Agonist	8.52	pEC50
AM281	Antagonist	8.52	pIC50
JWH015	Agonist	8.4	pEC50
N-palmitoylethanolamine	Agonist	8.4	pEC50
CP55,244	Inverse agonist	8.3	pIC50
CP55940	Agonist	8.3	pEC50
GSK494581A	Agonist	8.19	pEC50
GSK575594A	Agonist	8.17	pEC50
Δ9-tetrahydrocannabinol	Agonist	8.1	pEC50
2-arachidonyl glyceryl ether	Agonist	8.0	pEC50
O-arachidonoyl ethanolamine	Agonist	7.92	pEC50
anandamide	Agonist	7.74	pEC50
HU-210	Agonist	7.59	pEC50
AM251	Agonist	7.41	pEC50
lysophosphatidylinositol	Agonist	7.31	pEC50
CID16020046	Antagonist	7.3	pA2
CID1792197	Agonist	6.96	pEC50
CID1172084	Agonist	6.8	pEC50
CP55,667	Inverse agonist	6.8	pIC50
CLUL1 (52-77)	Agonist	6.74	pEC50
ML193	Antagonist	6.66	pIC50
MSMB (91-114)	Agonist	6.65	pEC50
CID2440433	Agonist	6.6	pEC50
rimonabant	Antagonist	6.55	pEC50

Binding affinities (BindingDB)

440 measured of 561 human assays (623 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
SMR000230206	EC50	60 nM
SMR000013107	IC50	69 nM
SMR000198068	EC50	90.5 nM
cid_9581015	IC50	211 nM
(4E)-4-[[4-[ethyl(isopropyl)amino]anilino]methylene]-2-p-anisyl-isoquinoline-1,3-quinone	EC50	249 nM
MLS-0437442.0001	IC50	307 nM
methyl 5-[(E)-[(4-chlorophenyl)carbamothioylhydrazinylidene]methyl]-1-phenylpyrazole-4-carboxylate	IC50	319 nM
5-[(E)-[[anilino(sulfanylidene)methyl]hydrazinylidene]methyl]-1-(2,4-difluorophenyl)-4-pyrazolecarboxylic acid methyl ester	IC50	379 nM
sodium chloride	IC50	462 nM
MLS000409155	IC50	498 nM
(5Z)-3-(2-fluorophenyl)-5-[[5-(4-fluorophenyl)-1H-pyrazol-4-yl]methylidene]-2-imino-4-thiazolidinone	IC50	500 nM
tert-butyl 4-[3-[(3-chloro-4-methoxyphenyl)carbamoyl]-7-oxo-1H-pyrazolo[1,5-a]pyrimidin-5-yl]piperidine-1-carboxylate	IC50	500 nM
SMR000539567	EC50	500 nM
1-(4-azanyl-1,2,5-oxadiazol-3-yl)-N-[[(E)-2-methyl-3-phenyl-prop-2-enylidene]amino]-5-(piperidin-1-ylmethyl)-1,2,3-triazole-4-carboxamide	EC50	500 nM
MLS000590161	IC50	500 nM
4,5-dimethyl-2-[[[6-methyl-4-(4-methylphenyl)-2-sulfanylidene-3,4-dihydro-1H-pyrimidin-5-yl]-oxomethyl]amino]-3-thiophenecarboxylic acid ethyl ester	IC50	500 nM
2-[3-(2,6-dimethylphenyl)-4-oxidanylidene-5-(pyridin-4-ylmethylidene)-1,3-thiazolidin-2-ylidene]-3-(2-methyl-1H-indol-3-yl)-3-oxidanylidene-propanenitrile	IC50	500 nM
MLS000768286	IC50	500 nM
2-[bis(phenylmethyl)amino]-4-(dimethylamino)pyridine-3-carbonitrile;hydrochloride	IC50	509 nM
MLS000324873	EC50	523 nM
(5E)-1-prop-2-enyl-5-[[4-(pyridin-4-ylmethyl)anilino]methylidene]-2-sulfanylidene-1,3-diazinane-4,6-dione	IC50	543 nM
SMR000196687	IC50	552 nM
4,5-diphenyl-2-(1-pyrrolidinylmethylideneamino)-3-furancarbonitrile	IC50	558 nM
4-[[4-oxo-2-[2-oxo-2-(4-propan-2-ylanilino)ethyl]sulfanylthieno[3,2-d]pyrimidin-3-yl]methyl]benzoic acid	IC50	561 nM
cid_2467179	EC50	577 nM
SMR000199131	IC50	592 nM
cid_5014092	IC50	598 nM
cid_1981775	IC50	653 nM
SMR000497337	IC50	665 nM
SMR000015838	IC50	672 nM
N-[4-(tert-butylsulfamoyl)phenyl]-2-phenyl-2-phenylsulfanyl-ethanamide	IC50	678 nM
3-[1-[1-(4-chlorophenyl)cyclopropyl]carbonylpiperidin-4-yl]-5-phenyl-1,3,4-oxadiazol-2-one	IC50	680 nM
4-(2,3-dihydroindol-1-ylsulfonyl)-N,1-dimethyl-N-(4-methylphenyl)pyrrole-2-carboxamide	IC50	769 nM
MLS000336203	IC50	793 nM
SMR000186439	IC50	799 nM
5-chloro-2-methoxy-N-[(2-morpholin-4-ylphenyl)carbamothioyl]benzamide	IC50	825 nM
N-[3-(aminocarbonyl)-4,5-dimethyl-2-thienyl]-2-(3-methylphenyl)-4-quinolinecarboxamide	IC50	869 nM
1-[[(Z)-(5-phenylmethoxyindol-3-ylidene)methyl]amino]thiourea	EC50	874 nM
SMR000128269	IC50	894 nM
3-[(4-chlorophenyl)sulfonylamino]-N-(4-fluorophenyl)-4-methoxybenzenesulfonamide	IC50	908 nM
4-(3-bromophenyl)-2-(4-bromophenyl)-7-methyl-2H-pyrazolo[3,4-d]pyridazine	IC50	915 nM
MLS001151090	IC50	929 nM
3-(1,3-benzodioxol-5-yl)-N-[(4-methoxyphenyl)methyl]-3-phenyl-1-propanamine;hydrochloride	IC50	965 nM
SMR000294791	IC50	969 nM
methyl 1-phenyl-5-[(E)-(phenylcarbamothioylhydrazinylidene)methyl]pyrazole-4-carboxylate	IC50	1010 nM
cid_1172037	EC50	1030 nM
cid_16320697	EC50	1040 nM
SMR000025699	IC50	1060 nM
SMR000594884	IC50	1070 nM
cid_1291981	IC50	1080 nM

ChEMBL bioactivities

642 potent at pChembl≥5 of 736 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.64	EC50	0.227	nM	CHEMBL5414688
9.62	EC50	0.239	nM	CHEMBL5428306
9.40	EC50	0.4	nM	CHEMBL3781437
9.36	EC50	0.439	nM	CHEMBL5426486
9.29	EC50	0.51	nM	CHEMBL3781953
9.22	EC50	0.6	nM	CHEMBL3779969
9.16	EC50	0.69	nM	CHEMBL3781521
9.06	EC50	0.88	nM	CHEMBL3781158
8.89	EC50	1.28	nM	CHEMBL3779954
8.70	EC50	2	nM	CHEMBL3746228
8.70	EC50	2	nM	CHEMBL3746607
8.70	EC50	2	nM	CHEMBL499876
8.70	EC50	2	nM	CHEMBL3402654
8.55	EC50	2.82	nM	CHEMBL3780056
8.52	EC50	3.01	nM	CHEMBL5439124
8.43	EC50	3.76	nM	CHEMBL5427885
8.25	EC50	5.6	nM	CHEMBL3746316
8.21	EC50	6.2	nM	CHEMBL3745774
8.21	EC50	6.2	nM	CHEMBL5428306
8.20	EC50	6.36	nM	CHEMBL3780748
8.11	EC50	7.7	nM	CHEMBL3747608
8.09	EC50	8.2	nM	CHEMBL3781953
8.06	EC50	8.67	nM	CHEMBL3780020
7.99	EC50	10.2	nM	CHEMBL5428424
7.91	EC50	12.4	nM	CHEMBL3747626
7.86	EC50	13.8	nM	CHEMBL5424329
7.81	EC50	15.5	nM	CHEMBL3779969
7.74	EC50	18.2	nM	CHEMBL3779954
7.71	EC50	19.4	nM	CHEMBL3746874
7.71	EC50	19.6	nM	CHEMBL3781764
7.70	EC50	19.8	nM	CHEMBL3781158
7.69	EC50	20.24	nM	CHEMBL4299513
7.66	EC50	21.9	nM	CHEMBL3781521
7.61	EC50	24.6	nM	CHEMBL3781437
7.59	EC50	25.4	nM	CHEMBL3780020
7.56	EC50	27.3	nM	CHEMBL3781297
7.56	EC50	27.7	nM	CHEMBL3781210
7.55	EC50	28.4	nM	CHEMBL3780748
7.53	EC50	29.3	nM	CHEMBL3781224
7.52	EC50	30.4	nM	CHEMBL3780529
7.51	EC50	30.9	nM	CHEMBL3747083
7.50	EC50	31.5	nM	CHEMBL3781085
7.46	EC50	34.4	nM	CHEMBL5409272
7.41	EC50	39.2	nM	CHEMBL3745918
7.36	EC50	43.7	nM	CHEMBL5415218
7.26	EC50	54.7	nM	CHEMBL5430516
7.25	EC50	55.7	nM	CHEMBL3747718
7.19	EC50	64.8	nM	CHEMBL1722279
7.10	EC50	79.6	nM	CHEMBL5428111
7.07	EC50	85.1	nM	CHEMBL5416405

PubChem BioAssay actives

158 with measured affinity, of 853 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
5-methoxy-3-[(3-methoxyphenyl)methyl]-7-pentylchromen-2-one	750737: Antagonist activity at human GPR55 transfected in CHO cells assessed as inhibition of LPI-induced beta-arrestin recruitment incubated 60 mins prior to LPI addition by beta-arrestin translocation assay	kd	<0.0001	uM
N-[(1R)-1-(4-fluorophenyl)ethyl]-5-[5-(2,2,2-trifluoroethyl)-3-pyridinyl]pyrazin-2-amine	2014832: Agonist activity at human GPR55 expressed in human HEK293 cells assessed as effect on calcium flux incubated for 5 mins by FLIPR analysis	ec50	0.0002	uM
N-[(1R)-1-(4-fluorophenyl)ethyl]-6-[5-(2,2,2-trifluoroethyl)-3-pyridinyl]-1,2,4-triazin-3-amine	2014832: Agonist activity at human GPR55 expressed in human HEK293 cells assessed as effect on calcium flux incubated for 5 mins by FLIPR analysis	ec50	0.0002	uM
[4-[2-(7-methoxy-4,4-dimethylchromeno[4,3-c]pyrazol-2-yl)ethyl]piperazin-1-yl]-(oxolan-2-yl)methanone	1286526: Partial agonist activity at recombinant human GPR55 expressed in HEK293 cells after 5 mins by xCELLigence assay	ec50	0.0004	uM
5-[5-(2,2-difluoroethyl)-3-pyridinyl]-N-[(1R)-1-(4-fluorophenyl)ethyl]pyrazin-2-amine	2014832: Agonist activity at human GPR55 expressed in human HEK293 cells assessed as effect on calcium flux incubated for 5 mins by FLIPR analysis	ec50	0.0004	uM
[4-[2-(7-methoxy-4,4-dimethylchromeno[4,3-c]pyrazol-2-yl)ethyl]piperazin-1-yl]-thiophen-2-ylmethanone	1286526: Partial agonist activity at recombinant human GPR55 expressed in HEK293 cells after 5 mins by xCELLigence assay	ec50	0.0005	uM
[4-[2-(7-methoxy-4,4-dimethylchromeno[4,3-c]pyrazol-2-yl)ethyl]piperazin-1-yl]-phenylmethanone	1286526: Partial agonist activity at recombinant human GPR55 expressed in HEK293 cells after 5 mins by xCELLigence assay	ec50	0.0006	uM
1-[4-[2-(7-methoxy-4,4-dimethylchromeno[4,3-c]pyrazol-2-yl)ethyl]piperazin-1-yl]-2,2-dimethylpropan-1-one	1286526: Partial agonist activity at recombinant human GPR55 expressed in HEK293 cells after 5 mins by xCELLigence assay	ec50	0.0007	uM
furan-2-yl-[4-[2-(7-methoxy-4,4-dimethylchromeno[4,3-c]pyrazol-2-yl)ethyl]piperazin-1-yl]methanone	1286526: Partial agonist activity at recombinant human GPR55 expressed in HEK293 cells after 5 mins by xCELLigence assay	ec50	0.0009	uM
1-[4-[2-(7-methoxy-4,4-dimethylchromeno[4,3-c]pyrazol-2-yl)ethyl]piperazin-1-yl]-2-phenoxyethanone	1286526: Partial agonist activity at recombinant human GPR55 expressed in HEK293 cells after 5 mins by xCELLigence assay	ec50	0.0013	uM
N-[[4-[(4-fluorophenyl)methylsulfamoyl]phenyl]carbamothioyl]-4-phenylbenzamide	1267164: Agonist activity at human GPR55 expressed in HEK293 cells assessed as calcium signalling by fura 2-based digital epifluorescence microscopy	ec50	0.0020	uM
N-[[4-(furan-2-ylmethylsulfamoyl)phenyl]carbamothioyl]-4-phenylbenzamide	1267164: Agonist activity at human GPR55 expressed in HEK293 cells assessed as calcium signalling by fura 2-based digital epifluorescence microscopy	ec50	0.0020	uM
5-methyl-4-[(1R,6R)-3-methyl-6-prop-1-en-2-ylcyclohex-2-en-1-yl]benzene-1,3-diol	1692629: Activation of recombinant human GPR55 expressed in HEK293 cells assessed as increase in [35S]-GTPgammaS stimulation incubated for 60 min by scintillation counting method	ec50	0.0020	uM
4-[(1R,6R)-3-methyl-6-prop-1-en-2-ylcyclohex-2-en-1-yl]-5-pentylbenzene-1,3-diol	1692629: Activation of recombinant human GPR55 expressed in HEK293 cells assessed as increase in [35S]-GTPgammaS stimulation incubated for 60 min by scintillation counting method	ec50	0.0020	uM
[(2R)-2-hydroxy-3-[hydroxy-[(2R,3R,5S,6R)-2,3,4,5,6-pentahydroxycyclohexyl]oxyphosphoryl]oxypropyl] octadecanoate	1286527: Agonist activity at recombinant human GPR55 expressed in HEK293 cells after 5 mins by xCELLigence assay	ec50	0.0028	uM
5-(5-ethyl-3-pyridinyl)-N-[(1R)-1-(4-fluorophenyl)ethyl]pyrazin-2-amine	2014832: Agonist activity at human GPR55 expressed in human HEK293 cells assessed as effect on calcium flux incubated for 5 mins by FLIPR analysis	ec50	0.0030	uM
5-(5-ethyl-3-pyridinyl)-N-[(1R)-1-(4-fluorophenyl)ethyl]pyridin-2-amine	2014832: Agonist activity at human GPR55 expressed in human HEK293 cells assessed as effect on calcium flux incubated for 5 mins by FLIPR analysis	ec50	0.0038	uM
N-[[4-(benzylsulfamoyl)phenyl]carbamothioyl]-4-phenylbenzamide	1267164: Agonist activity at human GPR55 expressed in HEK293 cells assessed as calcium signalling by fura 2-based digital epifluorescence microscopy	ec50	0.0056	uM
4-phenyl-N-[[4-(phenylsulfamoyl)phenyl]carbamothioyl]benzamide	1267164: Agonist activity at human GPR55 expressed in HEK293 cells assessed as calcium signalling by fura 2-based digital epifluorescence microscopy	ec50	0.0062	uM
N-[(7-methoxy-4,4-dimethylchromeno[4,3-c]pyrazol-2-yl)methyl]-2-[4-(2-methoxyphenyl)piperazin-1-yl]acetamide	1286526: Partial agonist activity at recombinant human GPR55 expressed in HEK293 cells after 5 mins by xCELLigence assay	ec50	0.0064	uM
N-[[4-[(4-methoxyphenyl)methylsulfamoyl]phenyl]carbamothioyl]-4-phenylbenzamide	1267164: Agonist activity at human GPR55 expressed in HEK293 cells assessed as calcium signalling by fura 2-based digital epifluorescence microscopy	ec50	0.0077	uM
cyclohexyl-[4-[2-(7-methoxy-4,4-dimethylchromeno[4,3-c]pyrazol-2-yl)ethyl]piperazin-1-yl]methanone	1286526: Partial agonist activity at recombinant human GPR55 expressed in HEK293 cells after 5 mins by xCELLigence assay	ec50	0.0087	uM
N-[(1R)-1-(4-fluorophenyl)ethyl]-5-(5-methyl-3-pyridinyl)pyridin-2-amine	2014832: Agonist activity at human GPR55 expressed in human HEK293 cells assessed as effect on calcium flux incubated for 5 mins by FLIPR analysis	ec50	0.0102	uM
N-[[4-[(4-methylphenyl)methylsulfamoyl]phenyl]carbamothioyl]-4-phenylbenzamide	1267164: Agonist activity at human GPR55 expressed in HEK293 cells assessed as calcium signalling by fura 2-based digital epifluorescence microscopy	ec50	0.0124	uM
5-(5-cyclopropyl-3-pyridinyl)-N-[(1R)-1-(4-fluorophenyl)ethyl]pyridin-2-amine	2014832: Agonist activity at human GPR55 expressed in human HEK293 cells assessed as effect on calcium flux incubated for 5 mins by FLIPR analysis	ec50	0.0138	uM
4-phenyl-N-[[4-(prop-2-enylsulfamoyl)phenyl]carbamothioyl]benzamide	1267164: Agonist activity at human GPR55 expressed in HEK293 cells assessed as calcium signalling by fura 2-based digital epifluorescence microscopy	ec50	0.0194	uM
furan-2-yl-[4-[2-(7-methoxy-4,4-dimethylchromeno[3,4-d]pyrazol-1-yl)ethyl]piperazin-1-yl]methanone	1286530: Antagonist activity at recombinant human GPR55 expressed in HEK293 cells assessed as inhibition of LPI mediated receptor activation by measuring LPI EC50 after 5 mins by xCELLigence assay (Rvb = 1.6 to 4.1 nM)	ec50	0.0196	uM
[(2R)-2-hydroxy-3-[hydroxy-[(2S,3S,5R,6S)-2,3,4,5,6-pentahydroxycyclohexyl]oxyphosphoryl]oxypropyl] (5Z,8Z,11Z,14Z)-icosa-5,8,11,14-tetraenoate	1267164: Agonist activity at human GPR55 expressed in HEK293 cells assessed as calcium signalling by fura 2-based digital epifluorescence microscopy	ec50	0.0202	uM
N-[(7-methoxy-4,4-dimethylchromeno[3,4-d]pyrazol-1-yl)methyl]-2-[4-(4-methoxyphenyl)piperazin-1-yl]acetamide	1286530: Antagonist activity at recombinant human GPR55 expressed in HEK293 cells assessed as inhibition of LPI mediated receptor activation by measuring LPI EC50 after 5 mins by xCELLigence assay (Rvb = 1.6 to 4.1 nM)	ec50	0.0273	uM
N-[(7-methoxy-4,4-dimethylchromeno[3,4-d]pyrazol-1-yl)methyl]-2-(4-phenylpiperazin-1-yl)acetamide	1286530: Antagonist activity at recombinant human GPR55 expressed in HEK293 cells assessed as inhibition of LPI mediated receptor activation by measuring LPI EC50 after 5 mins by xCELLigence assay (Rvb = 1.6 to 4.1 nM)	ec50	0.0277	uM
[4-[2-(7-methoxy-4,4-dimethylchromeno[3,4-d]pyrazol-1-yl)ethyl]piperazin-1-yl]-thiophen-2-ylmethanone	1286530: Antagonist activity at recombinant human GPR55 expressed in HEK293 cells assessed as inhibition of LPI mediated receptor activation by measuring LPI EC50 after 5 mins by xCELLigence assay (Rvb = 1.6 to 4.1 nM)	ec50	0.0293	uM
2-[4-(2,3-dimethylphenyl)piperazin-1-yl]-N-[(7-methoxy-4,4-dimethylchromeno[4,3-c]pyrazol-2-yl)methyl]acetamide	1286530: Antagonist activity at recombinant human GPR55 expressed in HEK293 cells assessed as inhibition of LPI mediated receptor activation by measuring LPI EC50 after 5 mins by xCELLigence assay (Rvb = 1.6 to 4.1 nM)	ec50	0.0304	uM
N-[[4-(2-methylpropylsulfamoyl)phenyl]carbamothioyl]-4-phenylbenzamide	1267164: Agonist activity at human GPR55 expressed in HEK293 cells assessed as calcium signalling by fura 2-based digital epifluorescence microscopy	ec50	0.0309	uM
N-[(7-methoxy-4,4-dimethylchromeno[4,3-c]pyrazol-2-yl)methyl]-2-(4-phenylpiperazin-1-yl)acetamide	1286530: Antagonist activity at recombinant human GPR55 expressed in HEK293 cells assessed as inhibition of LPI mediated receptor activation by measuring LPI EC50 after 5 mins by xCELLigence assay (Rvb = 1.6 to 4.1 nM)	ec50	0.0315	uM
N-[(1R)-1-(4-fluorophenyl)ethyl]-5-pyridin-3-ylpyridin-2-amine	2014832: Agonist activity at human GPR55 expressed in human HEK293 cells assessed as effect on calcium flux incubated for 5 mins by FLIPR analysis	ec50	0.0344	uM
4-phenyl-N-[[4-(2-phenylethylsulfamoyl)phenyl]carbamothioyl]benzamide	1267164: Agonist activity at human GPR55 expressed in HEK293 cells assessed as calcium signalling by fura 2-based digital epifluorescence microscopy	ec50	0.0392	uM
N-[(1R)-1-(4-fluorophenyl)ethyl]-5-(5-methylsulfonyl-3-pyridinyl)pyrimidin-2-amine	2014832: Agonist activity at human GPR55 expressed in human HEK293 cells assessed as effect on calcium flux incubated for 5 mins by FLIPR analysis	ec50	0.0437	uM
N-[1-(4-fluorophenyl)ethyl]-5-pyridin-3-ylpyridin-2-amine	2014832: Agonist activity at human GPR55 expressed in human HEK293 cells assessed as effect on calcium flux incubated for 5 mins by FLIPR analysis	ec50	0.0547	uM
N-[[4-(dimethylsulfamoyl)phenyl]carbamothioyl]-4-phenylbenzamide	1267164: Agonist activity at human GPR55 expressed in HEK293 cells assessed as calcium signalling by fura 2-based digital epifluorescence microscopy	ec50	0.0557	uM
N-[(1R)-1-(4-fluorophenyl)ethyl]-5-(1,2-thiazol-4-yl)pyridin-2-amine	2014832: Agonist activity at human GPR55 expressed in human HEK293 cells assessed as effect on calcium flux incubated for 5 mins by FLIPR analysis	ec50	0.0796	uM
N-[(1R)-1-(4-fluorophenyl)ethyl]-5-(5-methylsulfonyl-3-pyridinyl)pyridin-2-amine	2014832: Agonist activity at human GPR55 expressed in human HEK293 cells assessed as effect on calcium flux incubated for 5 mins by FLIPR analysis	ec50	0.0851	uM
(E)-N-[[4-[[5-(hydroxymethyl)furan-2-yl]methyl-phenylsulfamoyl]phenyl]carbamothioyl]-3-(2-methoxyphenyl)prop-2-enamide	1487440: Agonist activity at beta-galactosidase enzyme fragment-fused GPR55 (unknown origin) expressed in CHOK1 cells assessed as increase in N-terminal deletion beta-galactosidase mutant-tagged beta arrestin recruitment measured for 1 sec by chemiluminescence based pathhunter assay	ec50	0.1000	uM
(E)-3-(2-methoxyphenyl)-N-[[4-[methyl(phenyl)sulfamoyl]phenyl]carbamothioyl]prop-2-enamide	1487441: Agonist activity at HA-epitope-tagged variant of GPR55E with serine enhanced C terminus (unknown origin) expressed in human U2OS cells assessed as increase in GFP-tagged beta arrestin2 recruitment after 75 mins by fluorescence assay	ec50	0.1100	uM
N-[(1R)-1-(4-fluorophenyl)ethyl]-5-[5-(trifluoromethyl)-3-pyridinyl]pyridin-2-amine	2014832: Agonist activity at human GPR55 expressed in human HEK293 cells assessed as effect on calcium flux incubated for 5 mins by FLIPR analysis	ec50	0.1110	uM
5-hydroxy-3-[(2-hydroxyphenyl)methyl]-7-(2-methylnonan-2-yl)chromen-2-one	750737: Antagonist activity at human GPR55 transfected in CHO cells assessed as inhibition of LPI-induced beta-arrestin recruitment incubated 60 mins prior to LPI addition by beta-arrestin translocation assay	ic50	0.1130	uM
5-[3-[[(1R)-1-(4-fluorophenyl)ethyl]amino]-1,2,4-triazin-6-yl]-3-methyl-1,3-benzoxazol-2-one	2014832: Agonist activity at human GPR55 expressed in human HEK293 cells assessed as effect on calcium flux incubated for 5 mins by FLIPR analysis	ec50	0.1310	uM
[4-(4-amino-2-fluorophenyl)piperazin-1-yl]-[2-(4-fluorophenyl)-5-methylsulfonylphenyl]methanone	1267178: Agonist activity at human GPR55 expressed in Saccharomyces cerevisiae by beta-galactosidase reporter assay	ec50	0.1580	uM
N-[4-(4-fluorophenyl)-1,3-thiazol-2-yl]-2-[(8-methoxy-4-methyl-[1,2,4]triazolo[4,3-a]quinolin-1-yl)sulfanyl]acetamide	1487441: Agonist activity at HA-epitope-tagged variant of GPR55E with serine enhanced C terminus (unknown origin) expressed in human U2OS cells assessed as increase in GFP-tagged beta arrestin2 recruitment after 75 mins by fluorescence assay	ec50	0.1600	uM
4-phenyl-N-[[4-(propylsulfamoyl)phenyl]carbamothioyl]benzamide	1267164: Agonist activity at human GPR55 expressed in HEK293 cells assessed as calcium signalling by fura 2-based digital epifluorescence microscopy	ec50	0.1757	uM
N-[[4-[2-hydroxyethyl(phenyl)sulfamoyl]phenyl]carbamothioyl]quinoline-7-carboxamide	1487440: Agonist activity at beta-galactosidase enzyme fragment-fused GPR55 (unknown origin) expressed in CHOK1 cells assessed as increase in N-terminal deletion beta-galactosidase mutant-tagged beta arrestin recruitment measured for 1 sec by chemiluminescence based pathhunter assay	ec50	0.2000	uM

CTD chemical–gene interactions

44 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
3-(2-hydroxy-4-(1,1-dimethylheptyl)phenyl)-4-(3-hydroxypropyl)cyclohexanol	decreases reaction, affects binding, decreases activity, increases activity, affects reaction	3
Benzo(a)pyrene	increases expression, affects methylation	2
Dronabinol	decreases reaction, increases activity, affects binding, decreases activity	2
aristolochic acid I	increases expression	1
1-(5-fluoropentyl)-3-(4-methyl-1-naphthoyl)indole	affects binding, decreases reaction, increases activity	1
N-(adamantan-1-yl)-1-(5-fluoropentyl)-1H-indole-3-carboxamide	affects binding, decreases reaction, increases activity	1
4’-methoxy-1-naphthylfenoterol	decreases reaction, increases activity, decreases activity	1
N-(1-adamantyl)-1-pentylindazole-3-carboxamide	increases activity, affects binding, decreases reaction	1
(4-ethyl-1-naphthalenyl)(1-(5-fluoropentyl)-1H-indol-3-yl)methanone	affects binding, decreases reaction, increases activity	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases methylation	1
terbufos	increases methylation	1
perfluorooctanoic acid	increases expression	1
lysophosphatidylinositol	affects binding, decreases reaction, increases activity	1
aflatoxin B2	decreases methylation	1
di-n-butylphosphoric acid	affects expression	1
AM 251	decreases reaction, increases activity	1
2-palmitoylglycerol	increases expression	1
4-(3-3,4-p-menthadien-(1,8)-yl)olivetol	increases activity	1
(1-(2-morpholin-4-yl-ethyl)-1H-indol-3-yl)-(2,2,3,3-tetramethylcyclopropyl)methanone	affects binding, decreases reaction, increases activity	1
1-pentyl-3-(1-naphthoyl)indole	increases activity, affects binding, decreases reaction	1
O-1602 compound	increases activity	1
4-(4-(3-hydroxyphenyl)-3-(4-methylphenyl)-6-oxo-1H,4H,5H,6H-pyrrolo(3,4-c)pyrazol-5-yl)benzoic acid	increases activity, decreases activity, decreases reaction	1
N-(adamtan-1-yl)-1-pentyl-1H-indole-3-carboxamide	affects binding, decreases reaction, increases activity	1
XLR-11	affects binding, decreases reaction, increases activity	1
(1-pentyl-1H-indol-3-yl)(2,2,3,3-tetramethylcyclopropyl)methanone	affects binding, decreases reaction, increases activity	1
Rimonabant	affects binding, increases activity	1
Air Pollutants	decreases expression, increases abundance	1
Arbutin	decreases expression	1
Ascorbic Acid	decreases reaction, increases expression	1

ChEMBL screening assays

92 unique, capped per target: 56 binding, 36 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1117885	Binding	Binding affinity to GPR55	Emerging targets in osteoporosis disease modification. — J Med Chem
CHEMBL1614165	Functional	PUBCHEM_BIOASSAY: Image-Based HTS for Selective Antagonists for GPR55. (Class of assay: confirmatory) [Related pubchem assays (depositor defined):AID2026, AID2809, AID2814, AID2815, AID2820, AID2822, AID2835, AID2836, AID485277, AID485278,	PubChem BioAssay data set

Cellosaurus cell lines

2 cell lines: 1 spontaneously immortalized cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_KX67	PathHunter CHO-K1 GPR55 beta-arrestin	Spontaneously immortalized cell line	Female
CVCL_ZC15	HEK293-hGPR55	Transformed cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00029224	PHASE4	COMPLETED	Treatment With Zoledronic Acid in Patients With Breast Cancer, Multiple Myeloma, and Prostate Cancer With Cancer Related Bone Lesions
NCT00035997	PHASE4	COMPLETED	Open-label Trial on the Effect of I.V. Zoledronic Acid 4 mg on Bone Density in Hormone Sensitive Prostate Cancer Patients With Bone Metastasis
NCT00063609	PHASE4	COMPLETED	The Effect of Zoledronic Acid on Bone Loss in Prostate Cancer Patients Undergoing Androgen Deprivation Therapy
NCT00103623	PHASE4	SUSPENDED	The Plenaxis® Experience Study
NCT00106392	PHASE4	COMPLETED	A Safety and Efficacy Study of Prograf in the Prevention of Erectile Dysfunction After Radical Prostatectomy
NCT00185029	PHASE4	UNKNOWN	MR-Lymphography and Lymph Node Staging in Prostate Cancer
NCT00199485	PHASE4	COMPLETED	Angelica Sinensis for the Treatment of Hot Flashes in Men Undergoing LHRH Therapy for Prostate Cancer
NCT00219219	PHASE4	COMPLETED	Zoledronic Acid in the Prevention of Skeletal-related Events in Hormone Refractory and Hormone-sensitive Prostate Cancer Patients With Bone Metastases
NCT00219271	PHASE4	COMPLETED	Effect Of Zoledronic Acid On Circulating And Bone Marrow-Residing Prostate Cancer Cells In Patients With Clinically Localized Prostate Cancer
NCT00237146	PHASE4	COMPLETED	Study to Evaluate Zoledronic Acid on Quality of Life and Skeletal-related Events as Adjuvant Treatment in Patients With Hormone-naïve Prostate Cancer and Bone Metastasis Who Have Undergone Orchiectomy
NCT00242554	PHASE4	COMPLETED	Open-label Phase IV Clinical Trial to Evaluate the Safety and Tolerability of Zoledronic Acid in Patients With Prostate Cancer and Bone Metastases
NCT00280098	PHASE4	COMPLETED	Docetaxel in the Treatment of Hormone Refractory Prostate Cancer
NCT00293696	PHASE4	COMPLETED	Casodex/Zoladex Biomarkers in Localised Prostate Cancer
NCT00334139	PHASE4	COMPLETED	Effect of Zoledronic Acid on Bone Metabolism in Patients With Bone Metastasis and Prostate or Breast Cancer
NCT00375765	PHASE4	COMPLETED	Effects On Dihydrotestosterone Regulated Gene Expression In Benign Prostatic Hyperplasia Or Prostate Cancer
NCT00391690	PHASE4	COMPLETED	Evaluation of Bone Markers as Diagnostic Tools for Early Detection of Bone Metastases in Patients With High Risk Prostate Cancer
NCT00422708	PHASE4	COMPLETED	Local Anesthesia for Prostate Biopsy
NCT00526331	PHASE4	COMPLETED	Evaluation of Arterial Pressure Based Cardiac Output for Goal-Directed Perioperative Therapy
NCT00590213	PHASE4	COMPLETED	Compare the Value of Prophylactic Versus Therapeutic Breast Radiotherapy in CASODEX
NCT00629330	PHASE4	TERMINATED	Dissemination of Prostate Cancer Screening to PCP’s in African American Communities
NCT00771966	PHASE4	COMPLETED	Radical Prostatectomy and Perioperative Fluid Therapy
NCT00805701	PHASE4	COMPLETED	Study Assessing The Efficacy And Safety Of Avodart (Dutasteride) At Improving Urinary Symptoms In Men With Prostate Cancer Who Are Undergoing Seed Implantation
NCT00859027	PHASE4	COMPLETED	Effect Of Risedronate On Bone Mass In Older Men Receiving Neoadjuvant Therapy For Prostate Cancer
NCT00906269	PHASE4	UNKNOWN	Can Hyperbaric Oxygen Improve Erectile Function Following Surgery for Prostate Cancer
NCT00953277	PHASE4	COMPLETED	Study of Nerve Reconstruction Using AVANCE in Subjects Who Undergo Robotic Assisted Prostatectomy for Treatment of Prostate Cancer
NCT00982800	PHASE4	COMPLETED	Does Postoperative Gabapentin Reduce Pain, Opioid Consumption and Anxiety and Have a Positive Effect on Health Related Quality of Life After Radical Prostatectomy?
NCT01083199	PHASE4	COMPLETED	Global Performance Evaluation of the AMS CONTINUUM™ Device
NCT01136226	PHASE4	COMPLETED	Evaluate Recovery of Testosterone for Patients Using Eligard
NCT01161563	PHASE4	COMPLETED	Randomized Crossover Trial to Assess the Tolerability of Gonadotropin Releasing Hormone (GnRH) Analogue Administration
NCT01230905	PHASE4	COMPLETED	Study to Monitor the Effects of Androgen Suppression Treatment on the Heart
NCT01296672	PHASE4	COMPLETED	3 Month Finasteride Challenge Test Can Significantly Improve the Performance of Screening for Prostate Cancer
NCT01365143	PHASE4	TERMINATED	Prospective Randomized Trial Comparing Robotic Versus Open Radical Prostatectomy
NCT01379742	PHASE4	UNKNOWN	Comparison of Between ThinSeed™ and OncoSeed™ for Permanent Prostate Brachytherapy
NCT01486563	PHASE4	COMPLETED	Hydroxyethyl Starch and Renal Function After Radical Prostatectomy
NCT01511874	PHASE4	COMPLETED	Efficacy and Safety Study of ELIGARD 22.5mg With Prostate Cancer
NCT01512472	PHASE4	TERMINATED	Firmagon (Degarelix) Intermittent Therapy
NCT01547416	PHASE4	COMPLETED	The Effect of Combined General/Epidural Anesthesia Versus General Anesthesia on Diaphragmatic Function
NCT01571544	PHASE4	COMPLETED	The Use of Thermal Suits as Preventing Hypothermia During Surgery
NCT01581749	PHASE4	UNKNOWN	Evaluation of Truebeam for Low-Intermediate Risk Prostate Cancer
NCT01649635	PHASE4	COMPLETED	Study of Cabazitaxel Combined With Prednisone and Prophylaxis of Neutropenia Complications in the Treatment of Patients With Metastatic Castration-resistant Prostate Cancer