GPR183

Summary

GPR183 (G protein-coupled receptor 183, HGNC:3128) is a protein-coding gene on chromosome 13q32.3, encoding G-protein coupled receptor 183 (P32249). G-protein coupled receptor expressed in lymphocytes that acts as a chemotactic receptor for B-cells, T-cells, splenic dendritic cells, monocytes/macrophages and astrocytes.

This gene was identified by the up-regulation of its expression upon Epstein-Barr virus infection of primary B lymphocytes. This gene is predicted to encode a G protein-coupled receptor that is most closely related to the thrombin receptor. Expression of this gene was detected in B-lymphocyte cell lines and lymphoid tissues but not in T-lymphocyte cell lines or peripheral blood T lymphocytes. The function of this gene is unknown.

Source: NCBI Gene 1880 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 41 total — 1 pathogenic
• Druggable target: yes — 21 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_004951

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3128
Approved symbol	GPR183
Name	G protein-coupled receptor 183
Location	13q32.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000169508
Ensembl biotype	protein_coding
OMIM	605741
Entrez	1880

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000376414, ENST00000858905

RefSeq mRNA: 1 — MANE Select: NM_004951 NM_004951

CCDS: CCDS9492

Canonical transcript exons

ENST00000376414 — 2 exons

Exon	Start	End
ENSE00001470499	99294539	99296163
ENSE00001470505	99307340	99307399

Expression profiles

Bgee: expression breadth ubiquitous, 241 present calls, max score 95.44.

FANTOM5 (CAGE): breadth broad, TPM avg 65.3994 / max 8941.4940, expressed in 724 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
138001	43.5480	698
138002	16.1643	450
138000	5.6871	399

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
vermiform appendix	UBERON:0001154	95.44	gold quality
gall bladder	UBERON:0002110	93.62	gold quality
lymph node	UBERON:0000029	93.04	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	92.89	gold quality
epithelium of nasopharynx	UBERON:0001951	92.38	gold quality
blood	UBERON:0000178	90.40	gold quality
granulocyte	CL:0000094	90.04	gold quality
spleen	UBERON:0002106	89.26	gold quality
rectum	UBERON:0001052	89.22	gold quality
caecum	UBERON:0001153	88.62	gold quality
superficial temporal artery	UBERON:0001614	87.13	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	87.08	gold quality
bone marrow	UBERON:0002371	86.18	gold quality
lower lobe of lung	UBERON:0008949	86.14	gold quality
tibial nerve	UBERON:0001323	85.96	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.93	gold quality
mucosa of urinary bladder	UBERON:0001259	85.79	gold quality
leukocyte	CL:0000738	85.68	gold quality
right lung	UBERON:0002167	85.43	gold quality
muscle layer of sigmoid colon	UBERON:0035805	84.96	gold quality
mononuclear cell	CL:0000842	84.84	gold quality
spinal cord	UBERON:0002240	84.84	gold quality
small intestine Peyer’s patch	UBERON:0003454	84.76	gold quality
upper lobe of left lung	UBERON:0008952	84.73	gold quality
omental fat pad	UBERON:0010414	84.72	gold quality
monocyte	CL:0000576	84.66	gold quality
peritoneum	UBERON:0002358	84.63	gold quality
amniotic fluid	UBERON:0000173	84.48	gold quality
upper lobe of lung	UBERON:0008948	84.39	gold quality
sigmoid colon	UBERON:0001159	84.01	gold quality

Single-cell (SCXA)

Detected in 30 experiment(s), a significant marker in 28.

Experiment	Marker?	Max mean expression
E-HCAD-36	yes	5900.39
E-CURD-126	yes	4304.01
E-GEOD-89232	yes	3897.19
E-GEOD-75688	yes	3831.76
E-GEOD-135922	yes	3694.77
E-CURD-79	yes	3171.57
E-MTAB-6308	yes	3045.52
E-CURD-46	yes	3023.56
E-MTAB-8322	yes	2708.56
E-GEOD-84465	yes	2279.51
E-MTAB-8142	yes	2268.11
E-HCAD-15	yes	1935.25
E-CURD-88	yes	1348.48
E-CURD-112	yes	511.39
E-MTAB-6701	yes	77.18

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

31 targeting GPR183, 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-3646	100.00	73.56	5283
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-6079	99.84	68.54	1170
HSA-MIR-6885-3P	99.75	70.36	3187
HSA-MIR-2681-5P	99.75	67.64	1655
HSA-MIR-8084	99.73	69.57	1760
HSA-MIR-7156-5P	99.64	68.81	1369
HSA-MIR-1287-3P	99.63	66.93	492
HSA-MIR-567	99.63	68.57	1219
HSA-MIR-497-3P	99.61	69.71	1990
HSA-MIR-1290	99.59	69.90	2079
HSA-MIR-5004-3P	99.54	68.27	1371
HSA-MIR-3128	99.50	67.85	1258
HSA-MIR-4273	99.45	67.93	1206
HSA-MIR-887-5P	98.82	65.90	1347
HSA-MIR-31-5P	98.58	68.35	1239
HSA-MIR-2117	98.48	67.97	1307
HSA-MIR-876-5P	97.99	68.49	1345
HSA-MIR-1910-5P	97.42	66.36	844
HSA-MIR-6834-5P	96.25	64.88	823
HSA-MIR-4694-5P	94.62	65.39	532
HSA-MIR-371B-3P	94.48	66.59	345

Literature-anchored findings (GeneRIF, showing 24)

• Based on the constitutive signaling and cellular expression pattern of EBI2, it is suggested that it may function in conjunction with BILF1 in the reprogramming of the cell during EBV infection (PMID:16540462)
• Structural motifs of importance for the constitutive activity of EBI2: analysis of receptor activation in the absence of an agonist. (PMID:18628402)
• REVIEW: functional properties and in vivo biology (PMID:21261596)
• Molecular characterization of oxysterol binding to the Epstein-Barr virus-induced gene 2 (GPR183). (PMID:22875855)
• Data indicate that EBI2 expression modulates CXCL13 binding affinity to CXCR5. (PMID:22913878)
• This model of ligand docking yields important structural insight into the molecular mechanisms mediating EBI2 function. (PMID:22930711)
• Chronic rhinosinusitis with nasal polyps is characterized by B-cell inflammation and EBV-induced protein 2 expression. (PMID:23473835)
• EBI2 is expressed in primary human monocytes and macrophages. (PMID:24480442)
• These results demonstrate a role for EBI2 in astrocyte function and suggest that modulation of this receptor may be beneficial in neuroinflammatory disorders. (PMID:25297897)
• Studies provide evidence that EBI2 and oxysterols are important players not only in the immune system but also in the central nervous system. Proper functioning of the EBI2/oxysterol system seems crucial for healthy physiology and prevention of the onset or progression of several neurodegenerative diseases. [review] (PMID:26898310)
• this study concludes that EBI2 expression is directly influenced by EBV infection and that BRRF1 is necessary and sufficient for EBI2 upregulation during infection. (PMID:27902324)
• Human EBI2 (GPR183) expression in mice leads to an abnormally expanded CD5+ B1a B-cell subset and chronic lymphocytic leukemia-like B-cell malignancies. (PMID:28003273)
• These data suggest a significant role for EBI2 in human CD4(+) T cell migration, notably in patients with multiple sclerosis. (PMID:28052250)
• On ligand engagement, EBI2 typically signals via inhibitory G-protein subunit alpha to induce intracellular calcium mobilization, mitogen-activated protein kinase (MAPK) activation, and cell proliferation. (PMID:28125291)
• these data implicate the EBI2-oxysterol axis in inflammatory bowel disease pathogenesis (PMID:30742043)
• Orphan G-protein coupled receptor 183 (GPR183) potentiates insulin secretion and prevents glucotoxicity-induced beta-cell dysfunction. (PMID:31550518)
• GPR183 Regulates Interferons, Autophagy, and Bacterial Growth During Mycobacterium tuberculosis Infection and Is Associated With TB Disease Severity. (PMID:33240287)
• A single nucleotide polymorphism in the gene for GPR183 increases its surface expression on blood lymphocytes of patients with inflammatory bowel disease. (PMID:33511653)
• EBI2-expressing B cells in neuromyelitis optica spectrum disorder with AQP4-IgG: Association with acute attacks and serum cytokines. (PMID:34229205)
• EBI2 is a negative modulator of brown adipose tissue energy expenditure in mice and human brown adipocytes. (PMID:35351968)
• Abnormal lower expression of GPR183 in peripheral blood T and B cell subsets of systemic lupus erythematosus patients. (PMID:35875859)
• The Oxysterol Receptor EBI2 Links Innate and Adaptive Immunity to Limit IFN Response and Systemic Lupus Erythematosus. (PMID:37469011)
• The EBI2 receptor is coexpressed with CCR5 in CD4 + T cells and boosts HIV-1 R5 replication. (PMID:38770825)
• Exploring the Activation Mechanism of the GPR183 Receptor. (PMID:38877985)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	gpr183a	ENSDARG00000010317
danio_rerio	gpr183b	ENSDARG00000074302
mus_musculus	Gpr183	ENSMUSG00000051212
rattus_norvegicus	Gpr183	ENSRNOG00000025094

Paralogs (7): GPR174 (ENSG00000147138), GPR146 (ENSG00000164849), GPR151 (ENSG00000173250), RXFP3 (ENSG00000182631), GPR132 (ENSG00000183484), GPR141 (ENSG00000187037), P2RY11 (ENSG00000244165)

Protein

Protein identifiers

G-protein coupled receptor 183 — P32249 (reviewed: P32249)

Alternative names: Epstein-Barr virus-induced G-protein coupled receptor 2

All UniProt accessions (1): P32249

UniProt curated annotations — full annotation on UniProt →

Function. G-protein coupled receptor expressed in lymphocytes that acts as a chemotactic receptor for B-cells, T-cells, splenic dendritic cells, monocytes/macrophages and astrocytes. Receptor for oxysterol 7-alpha,25-dihydroxycholesterol (7-alpha,25-OHC) and other related oxysterols. Mediates cell positioning and movement of a number of cells by binding the 7-alpha,25-OHC ligand that forms a chemotactic gradient. Binding of 7-alpha,25-OHC mediates the correct localization of B-cells during humoral immune responses. Guides B-cell movement along the B-cell zone-T-cell zone boundary and later to interfollicular and outer follicular regions. Its specific expression during B-cell maturation helps position B-cells appropriately for mounting T-dependent antibody responses. Collaborates with CXCR5 to mediate B-cell migration; probably by forming a heterodimer with CXCR5 that affects the interaction between of CXCL13 and CXCR5. Also acts as a chemotactic receptor for some T-cells upon binding to 7-alpha,25-OHC ligand. Promotes follicular helper T (Tfh) cells differentiation by positioning activated T-cells at the follicle-T-zone interface, promoting contact of newly activated CD4 T-cells with activated dendritic cells and exposing them to Tfh-cell-promoting inducible costimulator (ICOS) ligand. Expression in splenic dendritic cells is required for their homeostasis, localization and ability to induce B- and T-cell responses: GPR183 acts as a chemotactic receptor in dendritic cells that mediates the accumulation of CD4(+) dendritic cells in bridging channels. Regulates migration of astrocytes and is involved in communication between astrocytes and macrophages. Promotes osteoclast precursor migration to bone surfaces. Signals constitutively through G(i)-alpha, but not G(s)-alpha or G(q)-alpha. Signals constitutively also via MAPK1/3 (ERK1/2).

Subunit / interactions. Homodimer and heterodimer. Heterodimerizes with CXCR5; leading to modulate the interaction between of CXCL13 and CXCR5.

Subcellular location. Cell membrane.

Tissue specificity. Expressed abundantly in lymphoid tissues such as spleen and lymph node, and in B- and T-lymphocytes. Also highly expressed in lung, heart and gastrointestinal tract, and weakly expressed in the urogenital system and brain. Expressed in astrocytes.

Induction. Induced following Epstein-Barr virus (EBV) infection.

Miscellaneous. GSK682753A (8-[(2E)-3-(4-chlorophenyl)prop-2-enoyl]-3-[(3,4-dichlorophenyl)methyl]-1-oxa-3,8-diazaspiro[4.5]decan-2-one), an inverse agonist, selectively inhibits the constitutive activity of GPR183 with high potency and efficacy. Specifically inhibited by NIBR189 ((2E)-3-(4-Bromophenyl)-1-[4-(4-methoxybenzoyl)-1-piperazinyl]-2-propene-1-one).

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

RefSeq proteins (1): NP_004942* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000276	GPCR_Rhodpsn	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain
IPR047160	GP183-like	Family

Pfam: PF00001

UniProt features (80 total): mutagenesis site 30, helix 14, topological domain 8, transmembrane region 7, turn 5, binding site 4, sequence conflict 3, region of interest 2, strand 2, chain 1, compositionally biased region 1, modified residue 1, disulfide bond 1, sequence variant 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
7TUY	ELECTRON MICROSCOPY	2.98
7TUZ	ELECTRON MICROSCOPY	3.12

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P32249-F1	86.81	0.61

Antibody-complex structures (SAbDab): 2 — 7TUY, 7TUZ

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): 87; 112; 116; 260

Post-translational modifications (1): 328

Disulfide bonds (1): 104–181

Mutagenesis-validated functional residues (30):

Position	Phenotype
21	strongly reduced localization to the cell membrane and reduced protein expression levels.
77	loss of receptor activation without affecting oxysterol agonist-binding.
77	strong decrease in oxysterol agonist-binding and receptor activation.
85	strongly reduced localization to the cell membrane.
87	strong decrease in oxysterol agonist-binding and receptor activation.
87	slight decrease in oxysterol agonist-binding and receptor activation.
90	10-fold reduction in receptor activation. strongly reduced localization to the cell membrane.
104	abolishes localization to the cell membrane without affecting protein expression levels.
111	500-fold decrease of ic(50) for gsk682753a. no effect on oxysterol agonist-binding and receptor activation.
112	strong decrease in oxysterol agonist-binding and receptor activation.
114	strongly reduced localization to the cell membrane.
115	no effect.
116	strong decrease in oxysterol agonist-binding and receptor activation.
181	abolishes localization to the cell membrane without affecting protein expression levels.
183	strong reduction in ligand potency.
197	reduced localization to the cell membrane and reduced receptor function.
205	no effect.
256	increased receptor activation.
257	increased receptor activation. strongly reduced localization to the cell membrane.
260	strong decrease in oxysterol agonist-binding and receptor activation.
261	reduced localization to the cell membrane and reduced receptor function.
264	reduced localization to the cell membrane and reduced receptor function.
280	strongly reduced localization to the cell membrane and reduced protein expression levels.
287	10-fold reduction in receptor activation.

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: 434 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_REGULATION_OF_LEUKOCYTE_PROLIFERATION, WALLACE_PROSTATE_CANCER_RACE_UP, GOBP_DENDRITIC_CELL_MIGRATION, YAGI_AML_WITH_INV_16_TRANSLOCATION, GOBP_CELL_CHEMOTAXIS, GOBP_B_CELL_ACTIVATION, GOBP_T_CELL_ACTIVATION_INVOLVED_IN_IMMUNE_RESPONSE, MODULE_64, GOBP_ALPHA_BETA_T_CELL_DIFFERENTIATION, GOBP_POSITIVE_REGULATION_OF_MAPK_CASCADE, GOBP_B_CELL_PROLIFERATION, GOBP_NEUROGENESIS, GOBP_MYELOID_LEUKOCYTE_DIFFERENTIATION

GO Biological Process (18): adaptive immune response (GO:0002250), B cell activation involved in immune response (GO:0002312), mature B cell differentiation involved in immune response (GO:0002313), dendritic cell chemotaxis (GO:0002407), immune response (GO:0006955), humoral immune response (GO:0006959), G protein-coupled receptor signaling pathway (GO:0007186), T cell chemotaxis (GO:0010818), osteoclast differentiation (GO:0030316), leukocyte chemotaxis (GO:0030595), positive regulation of B cell proliferation (GO:0030890), dendritic cell homeostasis (GO:0036145), T follicular helper cell differentiation (GO:0061470), positive regulation of ERK1 and ERK2 cascade (GO:0070374), regulation of astrocyte chemotaxis (GO:2000458), immune system process (GO:0002376), signal transduction (GO:0007165), cell chemotaxis (GO:0060326)

GO Molecular Function (2): G protein-coupled receptor activity (GO:0004930), oxysterol binding (GO:0008142)

GO Cellular Component (3): nucleoplasm (GO:0005654), 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
immune response	4
cellular anatomical structure	2
lymphocyte activation involved in immune response	1
B cell activation	1
B cell activation involved in immune response	1
mature B cell differentiation	1
leukocyte chemotaxis	1
dendritic cell migration	1
immune system process	1
response to stimulus	1
G protein-coupled receptor activity	1
signal transduction	1
lymphocyte chemotaxis	1
T cell migration	1
myeloid leukocyte differentiation	1
leukocyte migration	1
cell chemotaxis	1
regulation of B cell proliferation	1
B cell proliferation	1
positive regulation of lymphocyte proliferation	1
positive regulation of B cell activation	1
leukocyte homeostasis	1
T-helper cell differentiation	1
positive regulation of MAPK cascade	1
ERK1 and ERK2 cascade	1
regulation of ERK1 and ERK2 cascade	1
astrocyte chemotaxis	1
regulation of chemotaxis	1
regulation of glial cell migration	1
biological_process	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
chemotaxis	1
cell migration	1
cellular response to chemical stimulus	1
transmembrane signaling receptor activity	1
G protein-coupled receptor signaling pathway	1

Protein interactions and networks

STRING

2000 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GPR183	ARRB1	P49407	697
GPR183	CXCL13	O43927	681
GPR183	CH25H	O95992	669
GPR183	BCL6	P41182	606
GPR183	CYP7B1	O75881	600
GPR183	PRDM1	O75626	598
GPR183	CCL19	Q99731	582
GPR183	HSD3B7	Q9H2F3	571
GPR183	CD69	Q07108	544
GPR183	CCL21	O00585	543
GPR183	IRF7	Q92985	534
GPR183	MS4A1	P08984	526
GPR183	CXCR5	P32302	514
GPR183	S1PR2	O95136	514
GPR183	CD38	P28907	506

IntAct

16 interactions, top by confidence:

A	B	Type	Score
GPR183	NRP1	psi-mi:“MI:0914”(association)	0.530
GPR183	GPC1	psi-mi:“MI:0914”(association)	0.530
GPR183	RAMP1	psi-mi:“MI:0915”(physical association)	0.400
RAMP1	GPR183	psi-mi:“MI:0915”(physical association)	0.400
GPR183	RAMP2	psi-mi:“MI:0915”(physical association)	0.400
RAMP2	GPR183	psi-mi:“MI:0915”(physical association)	0.400
GPR183	RAMP3	psi-mi:“MI:0915”(physical association)	0.400
RAMP3	GPR183	psi-mi:“MI:0915”(physical association)	0.400
GPR183	fldB	psi-mi:“MI:0915”(physical association)	0.000
GPR183	MTA1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (93): TSHZ3 (Affinity Capture-MS), EIF2B5 (Affinity Capture-MS), EIF2B1 (Affinity Capture-MS), BZW2 (Affinity Capture-MS), EIF2B4 (Affinity Capture-MS), ITPRIPL1 (Affinity Capture-MS), EIF2B2 (Affinity Capture-MS), NID2 (Affinity Capture-MS), FAM193B (Affinity Capture-MS), ARHGAP29 (Affinity Capture-MS), TMED8 (Affinity Capture-MS), SEC63 (Affinity Capture-MS), SDC2 (Affinity Capture-MS), STAG1 (Affinity Capture-MS), STAG2 (Affinity Capture-MS)

ESM2 similar proteins: A1A5S3, A5PLE7, B0UXR0, B5X337, F5HDK1, F5HF62, F8VQN3, O00421, O18982, O97663, P09703, P32249, P35351, P35374, P46002, P49685, P50052, P51676, P56412, P69332, P69333, Q01035, Q0II78, Q0VDU3, Q14330, Q1RMI1, Q28929, Q3T0E9, Q3U507, Q4R613, Q6IYF9, Q75ZH0, Q83207, Q89609, Q8BZR0, Q8IYL9, Q8K1Z6, Q95N03, Q96P67, Q98146

Diamond homologs: A0A4W3GG95, A0A6I8PUB9, A6QLE7, D4A7K7, E7FEL0, E9QJ73, O00254, O08675, O46685, P0C0W8, P0C5J4, P32246, P32249, P32250, P34996, P35366, P35383, P41231, P41232, P46093, P47900, P48042, P49650, P49651, P49652, P50132, P56482, P58826, P59902, P79928, P97266, Q149R9, Q15743, Q1JQB3, Q2Y2P0, Q3U6B2, Q3ZC80, Q4G072, Q4KLH9, Q5E9H8

SIGNOR signaling

6 interactions.

A	Effect	B	Mechanism
GPR183	“up-regulates activity”	GNAI1	binding
GPR183	“up-regulates activity”	GNAI3	binding
GPR183	“up-regulates activity”	GNAO1	binding
GPR183	“up-regulates activity”	GNAZ	binding
GPR183	“up-regulates activity”	GNA12	binding
7alpha,25-dihydroxycholesterol	“up-regulates activity”	GPR183	“chemical activation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	38
Likely benign	1
Benign	1

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
4755345	GRCh38/hg38 13q31.3-34(chr13:89779269-114338054)x1	Pathogenic

SpliceAI

189 predictions. Top by Δscore:

Variant	Effect	Δscore
13:99296159:GGTGT:G	acceptor_gain	1.0000
13:99296160:GTGT:G	acceptor_gain	1.0000
13:99296160:GTGTC:G	acceptor_loss	1.0000
13:99296161:TGT:T	acceptor_gain	1.0000
13:99296162:GT:G	acceptor_gain	1.0000
13:99296162:GTCT:G	acceptor_loss	1.0000
13:99296163:TC:T	acceptor_loss	1.0000
13:99296164:C:CC	acceptor_gain	1.0000
13:99296165:T:A	acceptor_loss	1.0000
13:99307336:TTACA:T	donor_loss	1.0000
13:99307338:A:AC	donor_gain	1.0000
13:99307339:C:CT	donor_gain	1.0000
13:99307339:CA:C	donor_gain	1.0000
13:99307339:CAT:C	donor_gain	1.0000
13:99307339:CATA:C	donor_gain	1.0000
13:99307339:CATAT:C	donor_gain	1.0000
13:99296176:C:CT	acceptor_gain	0.9900
13:99296176:C:T	acceptor_gain	0.9900
13:99296785:CATGA:C	acceptor_gain	0.9900
13:99296787:TGA:T	acceptor_gain	0.9900
13:99296790:C:CC	acceptor_gain	0.9900
13:99307334:ACTT:A	donor_loss	0.9900
13:99307334:A:AC	donor_gain	0.9800
13:99307335:C:CC	donor_gain	0.9800
13:99307343:T:C	donor_gain	0.9800
13:99296177:A:T	acceptor_gain	0.9700
13:99296788:GA:G	acceptor_gain	0.9600
13:99296719:AGT:A	donor_gain	0.9500
13:99307332:GTACT:G	donor_loss	0.9500
13:99307333:TACTT:T	donor_loss	0.9500

AlphaMissense

2409 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
13:99295680:A:G	W156R	0.998
13:99295680:A:T	W156R	0.998
13:99295760:C:G	R129P	0.998
13:99295768:A:C	S126R	0.998
13:99295768:A:T	S126R	0.998
13:99295770:T:G	S126R	0.998
13:99295835:C:G	C104S	0.998
13:99295836:A:T	C104S	0.998
13:99295855:C:A	W97C	0.998
13:99295855:C:G	W97C	0.998
13:99295603:G:C	C181W	0.997
13:99295604:C:G	C181S	0.997
13:99295604:C:T	C181Y	0.997
13:99295605:A:T	C181S	0.997
13:99295776:A:G	C124R	0.997
13:99295834:A:C	C104W	0.997
13:99295886:C:G	R87P	0.997
13:99295892:G:C	P85R	0.997
13:99295370:G:C	P259R	0.996
13:99295370:G:T	P259H	0.996
13:99295523:G:C	P208R	0.996
13:99295605:A:G	C181R	0.996
13:99295835:C:T	C104Y	0.996
13:99295836:A:G	C104R	0.996
13:99295857:A:G	W97R	0.996
13:99295857:A:T	W97R	0.996
13:99295916:T:A	D77V	0.996
13:99295916:T:G	D77A	0.996
13:99295928:A:G	L73S	0.996
13:99295930:A:C	N72K	0.996

dbSNP variants (sampled 300 via entrez): RS1000040063 (13:99306387 A>G), RS1000131742 (13:99300252 C>T), RS1000549481 (13:99300411 A>G), RS1000978804 (13:99308865 G>T), RS1001444901 (13:99305957 G>A), RS1001522678 (13:99299827 G>A), RS1001536803 (13:99301988 A>G), RS1001590367 (13:99305637 C>T), RS1001951107 (13:99294152 C>T), RS1002056912 (13:99300049 C>T), RS1002209329 (13:99298848 G>A), RS1002251629 (13:99301299 T>C), RS1002296223 (13:99294103 A>G), RS1002596985 (13:99300613 T>A), RS1002656508 (13:99298666 T>C)

Disease associations

OMIM: gene MIM:605741 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST001725_21	Inflammatory bowel disease	2.000000e-14
GCST004131_117	Inflammatory bowel disease	1.000000e-06
GCST005536_29	Type 1 diabetes	3.000000e-08
GCST008916_6	Asthma	4.000000e-13
GCST009798_86	Asthma	3.000000e-16
GCST90014325_56	Asthma	1.000000e-16

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3259470 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

21 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 250,272 (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
CHEMBL1200681	MONTELUKAST SODIUM	4	10,913
CHEMBL1200776	CINACALCET HYDROCHLORIDE	4	1,220
CHEMBL1201082	FLUOXETINE HYDROCHLORIDE	4	18,871
CHEMBL1263	SALMETEROL	4	40,383
CHEMBL1471	APREPITANT	4	901
CHEMBL1615374	VILAZODONE HYDROCHLORIDE	4	432
CHEMBL1707	LOPERAMIDE HYDROCHLORIDE	4	59,532
CHEMBL2105737	SONIDEGIB	4	3,859
CHEMBL2105760	BREXPIPRAZOLE	4	1,755
CHEMBL2111101	PIMAVANSERIN	4	1,357
CHEMBL314854	FINGOLIMOD	4	16,015
CHEMBL3707247	OZANIMOD	4	1,588
CHEMBL398435	TICAGRELOR	4	2,956
CHEMBL465	DRONABINOL	4	62,107
CHEMBL493982	VORAPAXAR	4	1,021
CHEMBL567	PERPHENAZINE	4	21,883
CHEMBL506981	REMINERTANT	3	235
CHEMBL1230609	FORETINIB	2	3,096
CHEMBL3187503	GSK-1292263	2	346
CHEMBL405355	NIGULDIPINE	2	1,802
CHEMBL79834	SPIRAMIDE	2

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: gpcr — Class A Orphans with emerging pharmacology

Most potent curated ligand interactions (12 total), top 12:

Ligand	Action	Affinity	Parameter
7α,25-dihydroxycholesterol	Full agonist	9.62	pIC50
7α,27-dihydroxycholesterol	Agonist	8.89	pEC50
7β, 25-dihydroxycholesterol	Agonist	8.68	pEC50
compound 32 [PMID: 38047891]	Antagonist	8.07	pIC50
NIBR189	Antagonist	7.96	pIC50
7β, 27-dihydroxycholesterol	Agonist	7.29	pEC50
GSK682753A	Inverse agonist	7.27	pIC50
7α-hydroxycholesterol	Agonist	7.09	pEC50
25-hydroxycholesterol	Agonist	6.9	pEC50
7β-hydroxycholesterol	Agonist	5.75	pEC50
NIBR51	Agonist	5.65	pEC50
27-hydroxycholesterol	Agonist	5.52	pEC50

ChEMBL bioactivities

320 potent at pChembl≥5 of 320 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.49	EC50	0.032	nM	CHEMBL4788348
9.99	EC50	0.102	nM	CHEMBL4779254
9.85	EC50	0.14	nM	CHEMBL4788348
9.82	EC50	0.15	nM	CHEMBL5574852
9.65	IC50	0.2239	nM	CHEMBL3262896
9.52	IC50	0.3	nM	CHEMBL3262896
9.39	IC50	0.409	nM	CHEMBL3560809
9.25	IC50	0.564	nM	CHEMBL3262896
9.21	IC50	0.62	nM	CHEMBL3560864
9.21	Kd	0.6166	nM	CHEMBL5567610
9.09	IC50	0.82	nM	CHEMBL5567610
9.06	IC50	0.88	nM	CHEMBL5567610
8.99	IC50	1.03	nM	CHEMBL3560331
8.99	IC50	1.02	nM	CHEMBL3560888
8.96	IC50	1.083	nM	CHEMBL3262896
8.94	IC50	1.15	nM	CHEMBL3560117
8.93	IC50	1.17	nM	CHEMBL3561364
8.89	EC50	1.3	nM	CHEMBL4788277
8.82	IC50	1.5	nM	CHEMBL3561756
8.78	IC50	1.66	nM	CHEMBL3561399
8.76	IC50	1.72	nM	CHEMBL3560041
8.76	IC50	1.74	nM	CHEMBL3560453
8.75	IC50	1.77	nM	CHEMBL3561255
8.74	IC50	1.83	nM	CHEMBL5567610
8.73	IC50	1.88	nM	CHEMBL3560732
8.68	IC50	2.1	nM	CHEMBL3560464
8.68	EC50	2.1	nM	CHEMBL3311219
8.66	IC50	2.21	nM	CHEMBL3560573
8.65	IC50	2.23	nM	CHEMBL3561798
8.60	IC50	2.54	nM	CHEMBL5570287
8.58	IC50	2.61	nM	CHEMBL3560897
8.55	IC50	2.8	nM	CHEMBL1704801
8.54	IC50	2.86	nM	CHEMBL3262896
8.52	IC50	3.05	nM	CHEMBL5594301
8.49	EC50	3.22	nM	CHEMBL5574852
8.48	IC50	3.27	nM	CHEMBL3560820
8.46	IC50	3.43	nM	CHEMBL3561859
8.45	IC50	3.59	nM	CHEMBL1580410
8.44	IC50	3.64	nM	CHEMBL3560415
8.39	EC50	4.1	nM	CHEMBL4757291
8.36	IC50	4.41	nM	CHEMBL3560365
8.33	EC50	4.63	nM	CHEMBL5574852
8.31	IC50	4.898	nM	CHEMBL3262876
8.30	IC50	5	nM	CHEMBL3262895
8.30	IC50	5.012	nM	CHEMBL3262895
8.28	IC50	5.3	nM	CHEMBL3262876
8.28	IC50	5.23	nM	CHEMBL3561495
8.26	IC50	5.48	nM	CHEMBL3561390
8.25	IC50	5.62	nM	CHEMBL3561208
8.24	IC50	5.7	nM	CHEMBL5573697

PubChem BioAssay actives

145 with measured affinity, of 182 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
(3S,7S,8S,9S,10R,13R,14S,17R)-17-[(2R)-6-hydroxy-6-methylheptan-2-yl]-10,13-dimethyl-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthrene-3,7-diol	1713552: Agonist activity at Go2-q-coupled human EBI2 expressed in COS7 cell membranes assessed as stimulation of [35S]GTPgammaS binding preincubated for 20 mins followed by [35S]GTPgammaS addition and measured after 1 hr by scintillation counting analysis	ec50	<0.0001	uM
(3S,7S,8S,9S,10R,13R,14S,17R)-17-[(2R)-6-hydroxy-6-methylheptan-2-yl]-10,13-dimethyl-7-(trifluoromethyl)-1,2,3,4,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthrene-3,7-diol	1713552: Agonist activity at Go2-q-coupled human EBI2 expressed in COS7 cell membranes assessed as stimulation of [35S]GTPgammaS binding preincubated for 20 mins followed by [35S]GTPgammaS addition and measured after 1 hr by scintillation counting analysis	ec50	0.0001	uM
(3S,7S,10R,13R,17R)-17-[(2R)-6-hydroxy-6-methylheptan-2-yl]-10,13-dimethyl-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthrene-3,7-diol	2090697: Agonist activity at GPR183 (unknown origin) transfected in HEK293 cells assessed as reduction in forskolin induced cAMP generation incubated for 30 mins by Glosensor cAMP assay	ec50	0.0001	uM
(E)-3-(4-bromophenyl)-1-[4-(4-methoxybenzoyl)piperazin-1-yl]prop-2-en-1-one	1138883: Antagonist activity at EBI2 receptor in human U937 cells assessed as inhibition of 7-alpha,25-OHC-induced cell migration after 3 hrs by flow cytometric analysis	ic50	0.0002	uM
(E)-1-[4-(2-amino-1,3-benzothiazole-6-carbonyl)piperazin-1-yl]-3-(4-bromophenyl)prop-2-en-1-one	2090703: Antagonist potency at GPR183 (unknown origin) transfected in HEK293 cells by schild plot analysis	kd	0.0006	uM
(3S,7S,8S,9S,10R,13R,14S,17R)-17-[(2R)-7-hydroxy-6-methylheptan-2-yl]-10,13-dimethyl-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthrene-3,7-diol	1713568: Agonist activity at Go2-q-coupled EBI2 (unknown origin) expressed in COS7 cell membranes assessed as stimulation of [35S]GTPgammaS binding preincubated for 20 mins followed by [35S]GTPgammaS addition and measured after 1 hr by scintillation counting analysis	ec50	0.0013	uM
(3S,7R,8S,9S,10R,13R,14S,17R)-17-[(2R)-6-hydroxy-6-methylheptan-2-yl]-10,13-dimethyl-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthrene-3,7-diol	1713568: Agonist activity at Go2-q-coupled EBI2 (unknown origin) expressed in COS7 cell membranes assessed as stimulation of [35S]GTPgammaS binding preincubated for 20 mins followed by [35S]GTPgammaS addition and measured after 1 hr by scintillation counting analysis	ec50	0.0021	uM
(E)-3-(4-bromophenyl)-1-[4-[2-(trifluoromethyl)-1,3-benzothiazole-6-carbonyl]piperazin-1-yl]prop-2-en-1-one	2090682: Antagonist activity at GPR183 (unknown origin) transfected in HEK293 cells incubated for 30 mins by Glosensor cAMP assay	ic50	0.0025	uM
(E)-1-[4-(1,3-benzothiazole-6-carbonyl)piperazin-1-yl]-3-(4-bromophenyl)prop-2-en-1-one	2090682: Antagonist activity at GPR183 (unknown origin) transfected in HEK293 cells incubated for 30 mins by Glosensor cAMP assay	ic50	0.0031	uM
(3S,7R,8S,9S,10R,13R,14S,17R)-17-[(2R)-6-hydroxy-6-methylheptan-2-yl]-10,13-dimethyl-7-(trifluoromethyl)-1,2,3,4,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthrene-3,7-diol	1713552: Agonist activity at Go2-q-coupled human EBI2 expressed in COS7 cell membranes assessed as stimulation of [35S]GTPgammaS binding preincubated for 20 mins followed by [35S]GTPgammaS addition and measured after 1 hr by scintillation counting analysis	ec50	0.0041	uM
1-[4-(2-naphthalen-2-yloxyacetyl)piperazin-1-yl]-2-phenylethanone	1138883: Antagonist activity at EBI2 receptor in human U937 cells assessed as inhibition of 7-alpha,25-OHC-induced cell migration after 3 hrs by flow cytometric analysis	ic50	0.0049	uM
(E)-3-(4-bromophenyl)-1-[4-(2,3-dihydro-1-benzofuran-5-carbonyl)piperazin-1-yl]prop-2-en-1-one	1138853: Antagonist activity at recombinant human EBI2 receptor expressed in CHO cells assessed as inhibition of NIBR51-induced intracellular calcium release measured for 3 mins by FLIPR assay	ic50	0.0050	uM
2-[1-[(E)-3-(4-bromophenyl)prop-2-enoyl]piperidin-4-yl]-2,2-difluoro-N-(4-methoxyphenyl)acetamide	2090682: Antagonist activity at GPR183 (unknown origin) transfected in HEK293 cells incubated for 30 mins by Glosensor cAMP assay	ic50	0.0057	uM
(E)-3-(4-bromophenyl)-1-[4-[2-(methylamino)-1,3-benzothiazole-6-carbonyl]piperazin-1-yl]prop-2-en-1-one	2090682: Antagonist activity at GPR183 (unknown origin) transfected in HEK293 cells incubated for 30 mins by Glosensor cAMP assay	ic50	0.0062	uM
(E)-3-(4-bromophenyl)-1-[4-(2-methyl-1H-indole-6-carbonyl)piperazin-1-yl]prop-2-en-1-one	2090682: Antagonist activity at GPR183 (unknown origin) transfected in HEK293 cells incubated for 30 mins by Glosensor cAMP assay	ic50	0.0076	uM
(E)-3-(4-bromophenyl)-1-[4-(1-methylindole-6-carbonyl)piperazin-1-yl]prop-2-en-1-one	2090682: Antagonist activity at GPR183 (unknown origin) transfected in HEK293 cells incubated for 30 mins by Glosensor cAMP assay	ic50	0.0079	uM
2-(2,4-dimethyl-6-oxo-1H-pyrimidin-5-yl)-N-[1-(3,4,5-trimethoxyphenyl)ethyl]acetamide	2090740: Antagonist activity at GPR183 (unknown origin) incubated for 30 mins by calcium mobilization assay	ic50	0.0083	uM
(E)-1-[4-(4-chloro-3-methylbenzoyl)piperazin-1-yl]-3-(4-methoxyphenyl)prop-2-en-1-one	1138853: Antagonist activity at recombinant human EBI2 receptor expressed in CHO cells assessed as inhibition of NIBR51-induced intracellular calcium release measured for 3 mins by FLIPR assay	ic50	0.0129	uM
6,7-dimethoxy-N-phenylmethoxy-3,4-dihydro-1H-isoquinoline-2-carboxamide	2090740: Antagonist activity at GPR183 (unknown origin) incubated for 30 mins by calcium mobilization assay	ic50	0.0139	uM
(E)-3-(4-chlorophenyl)-1-[4-(2,3-dihydro-1-benzofuran-5-carbonyl)piperazin-1-yl]prop-2-en-1-one	1138853: Antagonist activity at recombinant human EBI2 receptor expressed in CHO cells assessed as inhibition of NIBR51-induced intracellular calcium release measured for 3 mins by FLIPR assay	ic50	0.0158	uM
(E)-1-[4-(2-amino-1,3-benzothiazole-6-carbonyl)piperazin-1-yl]-3-(4-chlorophenyl)prop-2-en-1-one	2090682: Antagonist activity at GPR183 (unknown origin) transfected in HEK293 cells incubated for 30 mins by Glosensor cAMP assay	ic50	0.0159	uM
(E)-1-[4-(1-benzofuran-5-carbonyl)piperazin-1-yl]-3-(4-bromophenyl)prop-2-en-1-one	2024330: Antagonist activity at human GPR183 expressed in CHO-K1 cells co-expressing Gqi5 assessed as inhibition of 7alpha,25-OHC induced calcium mobilization incubated for 30 mins by FLIPR Calcium 6 dye based assay	ic50	0.0160	uM
(E)-3-(3-fluoro-4-methylphenyl)-1-[4-(2-phenylacetyl)piperazin-1-yl]prop-2-en-1-one	1138853: Antagonist activity at recombinant human EBI2 receptor expressed in CHO cells assessed as inhibition of NIBR51-induced intracellular calcium release measured for 3 mins by FLIPR assay	ic50	0.0170	uM
methyl 4-[4-[(E)-3-(4-methoxyphenyl)prop-2-enoyl]piperazine-1-carbonyl]benzoate	1138853: Antagonist activity at recombinant human EBI2 receptor expressed in CHO cells assessed as inhibition of NIBR51-induced intracellular calcium release measured for 3 mins by FLIPR assay	ic50	0.0170	uM
(E)-1-[4-(2,3-dihydro-1-benzofuran-5-carbonyl)piperazin-1-yl]-3-(4-methoxyphenyl)prop-2-en-1-one	1138853: Antagonist activity at recombinant human EBI2 receptor expressed in CHO cells assessed as inhibition of NIBR51-induced intracellular calcium release measured for 3 mins by FLIPR assay	ic50	0.0180	uM
(E)-3-(4-bromophenyl)-1-[4-(3-methyl-1H-indole-6-carbonyl)piperazin-1-yl]prop-2-en-1-one	2090682: Antagonist activity at GPR183 (unknown origin) transfected in HEK293 cells incubated for 30 mins by Glosensor cAMP assay	ic50	0.0189	uM
N-[6-[4-[(E)-3-(4-bromophenyl)prop-2-enoyl]piperazine-1-carbonyl]-1,3-benzothiazol-2-yl]acetamide	2090682: Antagonist activity at GPR183 (unknown origin) transfected in HEK293 cells incubated for 30 mins by Glosensor cAMP assay	ic50	0.0189	uM
(E)-3-(4-methylphenyl)-1-[4-(2-phenylacetyl)piperazin-1-yl]prop-2-en-1-one	1138853: Antagonist activity at recombinant human EBI2 receptor expressed in CHO cells assessed as inhibition of NIBR51-induced intracellular calcium release measured for 3 mins by FLIPR assay	ic50	0.0190	uM
(E)-1-[4-[4-(dimethylamino)benzoyl]piperazin-1-yl]-3-(4-methoxyphenyl)prop-2-en-1-one	1138853: Antagonist activity at recombinant human EBI2 receptor expressed in CHO cells assessed as inhibition of NIBR51-induced intracellular calcium release measured for 3 mins by FLIPR assay	ic50	0.0190	uM
2-[1-[(E)-3-(4-bromophenyl)prop-2-enoyl]piperidin-4-yl]-N-(4-methoxyphenyl)acetamide	2090682: Antagonist activity at GPR183 (unknown origin) transfected in HEK293 cells incubated for 30 mins by Glosensor cAMP assay	ic50	0.0197	uM
(E)-3-(2,2-difluoro-1,3-benzodioxol-5-yl)-1-[4-(6-methoxypyridine-3-carbonyl)piperazin-1-yl]prop-2-en-1-one	2024330: Antagonist activity at human GPR183 expressed in CHO-K1 cells co-expressing Gqi5 assessed as inhibition of 7alpha,25-OHC induced calcium mobilization incubated for 30 mins by FLIPR Calcium 6 dye based assay	ic50	0.0207	uM
(E)-3-(4-bromophenyl)-1-[4-(2-phenylacetyl)piperazin-1-yl]prop-2-en-1-one	1138853: Antagonist activity at recombinant human EBI2 receptor expressed in CHO cells assessed as inhibition of NIBR51-induced intracellular calcium release measured for 3 mins by FLIPR assay	ic50	0.0209	uM
(E)-3-(2,2-difluoro-1,3-benzodioxol-5-yl)-1-[4-(1H-indazole-5-carbonyl)piperazin-1-yl]prop-2-en-1-one	2024330: Antagonist activity at human GPR183 expressed in CHO-K1 cells co-expressing Gqi5 assessed as inhibition of 7alpha,25-OHC induced calcium mobilization incubated for 30 mins by FLIPR Calcium 6 dye based assay	ic50	0.0220	uM
(E)-3-(3,4-dichlorophenyl)-1-[4-(2-phenylacetyl)piperazin-1-yl]prop-2-en-1-one	1138853: Antagonist activity at recombinant human EBI2 receptor expressed in CHO cells assessed as inhibition of NIBR51-induced intracellular calcium release measured for 3 mins by FLIPR assay	ic50	0.0240	uM
(E)-1-[4-(azetidine-1-carbonyl)piperazin-1-yl]-3-(2,2-difluoro-1,3-benzodioxol-5-yl)prop-2-en-1-one	2024330: Antagonist activity at human GPR183 expressed in CHO-K1 cells co-expressing Gqi5 assessed as inhibition of 7alpha,25-OHC induced calcium mobilization incubated for 30 mins by FLIPR Calcium 6 dye based assay	ic50	0.0257	uM
1-[4-[2-(4-bromophenoxy)acetyl]piperazin-1-yl]-2-phenylethanone	1138853: Antagonist activity at recombinant human EBI2 receptor expressed in CHO cells assessed as inhibition of NIBR51-induced intracellular calcium release measured for 3 mins by FLIPR assay	ic50	0.0280	uM
3-(3,4-difluorophenyl)-N-(3-fluoro-5-morpholin-4-ylphenyl)propanamide	2090740: Antagonist activity at GPR183 (unknown origin) incubated for 30 mins by calcium mobilization assay	ic50	0.0285	uM
(E)-3-(4-methoxyphenyl)-1-[4-(2-phenylacetyl)piperazin-1-yl]prop-2-en-1-one	1138853: Antagonist activity at recombinant human EBI2 receptor expressed in CHO cells assessed as inhibition of NIBR51-induced intracellular calcium release measured for 3 mins by FLIPR assay	ic50	0.0288	uM
(E)-3-(4-bromophenyl)-1-[4-(2-methoxypyrimidine-5-carbonyl)piperazin-1-yl]prop-2-en-1-one	2024330: Antagonist activity at human GPR183 expressed in CHO-K1 cells co-expressing Gqi5 assessed as inhibition of 7alpha,25-OHC induced calcium mobilization incubated for 30 mins by FLIPR Calcium 6 dye based assay	ic50	0.0294	uM
(E)-3-(4-methoxyphenyl)-1-[4-(3-methylbenzoyl)piperazin-1-yl]prop-2-en-1-one	1138853: Antagonist activity at recombinant human EBI2 receptor expressed in CHO cells assessed as inhibition of NIBR51-induced intracellular calcium release measured for 3 mins by FLIPR assay	ic50	0.0295	uM
(E)-3-(4-bromophenyl)-1-[4-(6-methoxypyridine-3-carbonyl)piperazin-1-yl]prop-2-en-1-one	2024330: Antagonist activity at human GPR183 expressed in CHO-K1 cells co-expressing Gqi5 assessed as inhibition of 7alpha,25-OHC induced calcium mobilization incubated for 30 mins by FLIPR Calcium 6 dye based assay	ic50	0.0300	uM
(E)-1-[4-(2-amino-1,3-benzothiazole-6-carbonyl)piperazin-1-yl]-3-[4-(trifluoromethyl)phenyl]prop-2-en-1-one	2090682: Antagonist activity at GPR183 (unknown origin) transfected in HEK293 cells incubated for 30 mins by Glosensor cAMP assay	ic50	0.0301	uM
(E)-3-(2,2-difluoro-1,3-benzodioxol-5-yl)-1-[4-(2-methoxypyrimidine-5-carbonyl)piperazin-1-yl]prop-2-en-1-one	2024330: Antagonist activity at human GPR183 expressed in CHO-K1 cells co-expressing Gqi5 assessed as inhibition of 7alpha,25-OHC induced calcium mobilization incubated for 30 mins by FLIPR Calcium 6 dye based assay	ic50	0.0313	uM
(E)-1-[4-(4-methoxybenzoyl)piperazin-1-yl]-3-(4-methoxyphenyl)prop-2-en-1-one	1138853: Antagonist activity at recombinant human EBI2 receptor expressed in CHO cells assessed as inhibition of NIBR51-induced intracellular calcium release measured for 3 mins by FLIPR assay	ic50	0.0320	uM
cyclopropyl 4-[(E)-3-(2,2-difluoro-1,3-benzodioxol-5-yl)prop-2-enoyl]piperazine-1-carboxylate	2024330: Antagonist activity at human GPR183 expressed in CHO-K1 cells co-expressing Gqi5 assessed as inhibition of 7alpha,25-OHC induced calcium mobilization incubated for 30 mins by FLIPR Calcium 6 dye based assay	ic50	0.0333	uM
dronabinol	2065420: Agonist activity at human GPR183 expressed in PathHunter CHO-K1 cells assessed as activation by measuring beta-arrestin2 recruitment	ec50	0.0380	uM
(E)-3-(4-bromophenyl)-1-[4-(oxane-4-carbonyl)piperazin-1-yl]prop-2-en-1-one	2024330: Antagonist activity at human GPR183 expressed in CHO-K1 cells co-expressing Gqi5 assessed as inhibition of 7alpha,25-OHC induced calcium mobilization incubated for 30 mins by FLIPR Calcium 6 dye based assay	ic50	0.0390	uM
(E)-3-(4-methoxyphenyl)-1-[4-(4-methylbenzoyl)piperazin-1-yl]prop-2-en-1-one	1138853: Antagonist activity at recombinant human EBI2 receptor expressed in CHO cells assessed as inhibition of NIBR51-induced intracellular calcium release measured for 3 mins by FLIPR assay	ic50	0.0398	uM
(E)-1-[4-(2-amino-1,3-benzothiazole-6-carbonyl)piperazin-1-yl]-3-(2,2-difluoro-1,3-benzodioxol-5-yl)prop-2-en-1-one	2090682: Antagonist activity at GPR183 (unknown origin) transfected in HEK293 cells incubated for 30 mins by Glosensor cAMP assay	ic50	0.0436	uM
(E)-1-[4-(3,4-dimethylbenzoyl)piperazin-1-yl]-3-(4-methoxyphenyl)prop-2-en-1-one	1138853: Antagonist activity at recombinant human EBI2 receptor expressed in CHO cells assessed as inhibition of NIBR51-induced intracellular calcium release measured for 3 mins by FLIPR assay	ic50	0.0437	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases methylation, increases expression	2
Estradiol	affects cotreatment, decreases expression, increases expression	2
Lipopolysaccharides	decreases reaction, increases expression, affects response to substance, affects cotreatment, decreases expression	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
GSK-J4	increases expression	1
bisphenol A	affects methylation, affects cotreatment, decreases methylation	1
2-methyl-4-isothiazolin-3-one	increases expression	1
ascorbate-2-phosphate	affects binding, affects cotreatment, increases expression	1
trichostatin A	decreases expression	1
sodium arsenite	decreases expression	1
HC toxin	decreases expression	1
4-(2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)-1-propenyl)benzoic acid	affects cotreatment, increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment, decreases expression	1
tacedinaline	decreases expression	1
pentabromodiphenyl ether	decreases expression	1
entinostat	decreases expression	1
scriptaid	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
Chir 99021	affects cotreatment, increases expression, affects binding	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
mocetinostat	decreases expression	1
suberoyl bis-hydroxamic acid	decreases expression	1
XAV939	affects binding, affects cotreatment, increases expression	1
incobotulinumtoxinA	decreases expression	1
LDN 193189	increases expression, affects cotreatment	1
(+)-JQ1 compound	decreases expression	1
3-(4-pyridyl)-1H-indole	affects cotreatment, increases expression	1
Rosuvastatin Calcium	decreases reaction, increases expression	1
Irinotecan	increases expression	1
Pioglitazone	decreases expression	1

ChEMBL screening assays

36 unique, capped per target: 28 functional, 8 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3266156	Binding	Displacement of [3H]-7-alpha,25-OHC from recombinant human EBI2 receptor expressed in CHO cells after 10 mins by scintillation counting analysis	Identification and characterization of small molecule modulators of the Epstein-Barr virus-induced gene 2 (EBI2) receptor. — J Med Chem
CHEMBL3266157	Functional	Antagonist activity at recombinant human EBI2 receptor expressed in CHO cells assessed as inhibition of NIBR51-induced intracellular calcium release measured for 3 mins by FLIPR assay	Identification and characterization of small molecule modulators of the Epstein-Barr virus-induced gene 2 (EBI2) receptor. — J Med Chem

Cellosaurus cell lines

3 cell lines: 2 spontaneously immortalized cell line, 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_KV11	cAMP Hunter CHO-K1 EBI2 Gi	Spontaneously immortalized cell line	Female
CVCL_KW91	PathHunter CHO-K1 EBI2 beta-arrestin	Spontaneously immortalized cell line	Female
CVCL_LA21	PathHunter U2OS EBI2 Total GPCR Internalization	Cancer cell line	Female

Clinical trials (associated diseases)

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