GPR84

Summary

GPR84 (G protein-coupled receptor 84, HGNC:4535) is a protein-coding gene on chromosome 12q13.13, encoding G-protein coupled receptor 84 (Q9NQS5). G protein-coupled receptor that responds endogenously to dietary fatty acids or nutrient, specifically medium-chain free fatty acid (FFA) with carbon chain lengths of C9 to C14.

Predicted to enable urotensin II receptor activity. Predicted to be involved in neuropeptide signaling pathway. Part of receptor complex.

Source: NCBI Gene 53831 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 44 total
• Druggable target: yes — 5 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_020370

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4535
Approved symbol	GPR84
Name	G protein-coupled receptor 84
Location	12q13.13
Locus type	gene with protein product
Status	Approved
Aliases	EX33
Ensembl gene	ENSG00000139572
Ensembl biotype	protein_coding
OMIM	606383
Entrez	53831

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000267015, ENST00000551809, ENST00000879277

RefSeq mRNA: 1 — MANE Select: NM_020370 NM_020370

CCDS: CCDS8878

Canonical transcript exons

ENST00000267015 — 2 exons

Exon	Start	End
ENSE00001147936	54364393	54364486
ENSE00001253419	54362445	54363859

Expression profiles

Bgee: expression breadth ubiquitous, 147 present calls, max score 87.25.

FANTOM5 (CAGE): breadth broad, TPM avg 12.1034 / max 1083.0675, expressed in 372 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
131327	12.1034	372

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
bone marrow	UBERON:0002371	87.25	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.51	gold quality
bone marrow cell	CL:0002092	81.75	gold quality
trabecular bone tissue	UBERON:0002483	81.46	gold quality
monocyte	CL:0000576	74.10	gold quality
leukocyte	CL:0000738	73.94	gold quality
blood	UBERON:0000178	72.83	gold quality
vermiform appendix	UBERON:0001154	72.59	gold quality
granulocyte	CL:0000094	69.74	gold quality
caecum	UBERON:0001153	65.62	gold quality
amniotic fluid	UBERON:0000173	65.61	gold quality
spleen	UBERON:0002106	64.13	gold quality
right coronary artery	UBERON:0001625	63.82	gold quality
tibialis anterior	UBERON:0001385	62.20	silver quality
descending thoracic aorta	UBERON:0002345	61.86	gold quality
ileal mucosa	UBERON:0000331	61.70	silver quality
left adrenal gland	UBERON:0001234	61.22	gold quality
left adrenal gland cortex	UBERON:0035825	61.17	gold quality
thoracic aorta	UBERON:0001515	60.74	gold quality
cartilage tissue	UBERON:0002418	60.65	silver quality
gall bladder	UBERON:0002110	60.54	gold quality
ascending aorta	UBERON:0001496	60.51	gold quality
upper lobe of left lung	UBERON:0008952	60.49	gold quality
right adrenal gland	UBERON:0001233	60.03	gold quality
left coronary artery	UBERON:0001626	59.74	gold quality
upper lobe of lung	UBERON:0008948	59.67	gold quality
adrenal cortex	UBERON:0001235	59.14	gold quality
coronary artery	UBERON:0001621	59.00	gold quality
right adrenal gland cortex	UBERON:0035827	58.27	gold quality
adrenal gland	UBERON:0002369	57.81	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.48

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

35 targeting GPR84, 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-4534	99.99	66.58	1907
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-8082	99.95	67.27	1170
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-4760-3P	99.93	70.50	2385
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-1273H-5P	99.77	66.32	2471
HSA-MIR-11181-3P	99.75	66.38	2205
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-494-3P	99.70	71.45	2795
HSA-MIR-30B-3P	99.70	65.76	2325
HSA-MIR-3689A-3P	99.70	65.73	2306
HSA-MIR-3689B-3P	99.70	65.71	2311
HSA-MIR-3689C	99.70	65.71	2311
HSA-MIR-6779-5P	99.70	65.76	2363
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-3175	99.65	66.30	2031
HSA-MIR-365A-3P	99.43	70.02	836
HSA-MIR-365B-3P	99.43	70.02	836
HSA-MIR-3140-5P	99.39	69.04	1136
HSA-MIR-185-5P	99.35	68.60	2497
HSA-MIR-4644	99.35	69.12	2514
HSA-MIR-8085	99.28	67.56	2362
HSA-MIR-6731-5P	99.28	67.42	2375
HSA-MIR-133A-3P	99.27	71.53	1270
HSA-MIR-133B	99.27	71.53	1270
HSA-MIR-4477A	98.83	69.75	2952

Literature-anchored findings (GeneRIF, showing 16)

• Medium-chain fatty acid-sensing receptor, GPR84, is a proinflammatory receptor. (PMID:23449982)
• A previously unrecognized role of GPR84 in maintaining fully developed acute myeloid leukemia by sustaining aberrant beta-catenin signaling in leukemic stem cells. (PMID:25293777)
• concluded that diindolylmethane was a positive allosteric modulator for GPR84 (PMID:25425658)
• GPR84 modulates TNFalpha mRNA expression in the LPS tolerant monocytes. (PMID:28404994)
• Data suggest that cytokines TNFalpha and interleukin-1b markedly reduce GPR120/FFAR4 expression in adipocytes; in contrast, these cytokines induce expression of GPR84 and GPR41/FFAR3 in adipocytes. These studies were conducted in adipocytes cultured from subcutaneous adipose tissue. (GPR = G-protein coupled receptor; FFAR = free fatty acid receptor) (PMID:28835131)
• we show functional similarities but also some important differences between GPR84 and FFA2R in human phagocytes, thus providing some mechanistic insights into GPR84 regulation in blood neutrophils and cells recruited to an aseptic inflammatory site in vivo. (PMID:29477577)
• Has a strong stimulatory effect on the expression of cytokine and chemokine genes, particularly CSF3, and on the expression of GPR84, a pro-inflammatory fatty acid receptor. (PMID:29775920)
• Natural biased signaling of hydroxycarboxylic acid receptor 3 and G protein-coupled receptor 84. (PMID:32102673)
• 20 Years an Orphan: Is GPR84 a Plausible Medium-Chain Fatty Acid-Sensing Receptor? (PMID:33001759)
• The Two Formyl Peptide Receptors Differently Regulate GPR84-Mediated Neutrophil NADPH Oxidase Activity. (PMID:33789297)
• Inter-cellular CRISPR screens reveal regulators of cancer cell phagocytosis. (PMID:34497417)
• Hydroxycarboxylic acid receptor 3 and GPR84 - Two metabolite-sensing G protein-coupled receptors with opposing functions in innate immune cells. (PMID:34968686)
• Function and regulation of GPR84 in human neutrophils. (PMID:36869866)
• Regulation of the pro-inflammatory G protein-coupled receptor GPR84. (PMID:37085331)
• GPR84 in physiology-Many functions in many tissues. (PMID:37533166)
• Kinetic insights into agonist-dependent signalling bias at the pro-inflammatory G-protein coupled receptor GPR84. (PMID:37543157)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	gpr84	ENSDARG00000077308
rattus_norvegicus	Gpr84	ENSRNOG00000036834
caenorhabditis_elegans		WBGENE00001052

Paralogs (25): DRD4 (ENSG00000069696), HRH3 (ENSG00000101180), HRH2 (ENSG00000113749), CHRM3 (ENSG00000133019), HRH4 (ENSG00000134489), TAAR5 (ENSG00000135569), GPR161 (ENSG00000143147), TAAR2 (ENSG00000146378), TAAR6 (ENSG00000146383), TAAR8 (ENSG00000146385), TAAR1 (ENSG00000146399), DRD3 (ENSG00000151577), HTR4 (ENSG00000164270), CHRM1 (ENSG00000168539), DRD5 (ENSG00000169676), HTR1A (ENSG00000178394), HTR1D (ENSG00000179546), CHRM4 (ENSG00000180720), CHRM2 (ENSG00000181072), DRD1 (ENSG00000184845), CHRM5 (ENSG00000184984), GPR21 (ENSG00000188394), HRH1 (ENSG00000196639), GPR52 (ENSG00000203737), TAAR9 (ENSG00000237110)

Protein

Protein identifiers

G-protein coupled receptor 84 — Q9NQS5 (reviewed: Q9NQS5)

Alternative names: Inflammation-related G-protein coupled receptor EX33

All UniProt accessions (1): Q9NQS5

UniProt curated annotations — full annotation on UniProt →

Function. G protein-coupled receptor that responds endogenously to dietary fatty acids or nutrient, specifically medium-chain free fatty acid (FFA) with carbon chain lengths of C9 to C14. Capric acid (C10:0), undecanoic acid (C11:0) and lauric acid (C12:0) are the most potent agonists. In immune cells, functions as a pro-inflammatory receptor via 6-OAU and promotes the expression of pro-inflammatory mediators such as TNFalpha, IL-6 and IL-12B as well as stimulating chemotactic responses through activation of signaling mediators AKT, ERK and NF-kappa-B. In addition, triggers increased bacterial adhesion and phagocytosis in macrophages and regulates pro-inflammatory function via enhancing NLRP3 inflammasome activation. Also plays an important role in inflammation by modulating neutrophil functions. Mechanistically, promotes neutrophil chemotaxis, reactive oxygen species (ROS) production and degranulation via LYN-AKT/ERK pathway. To regulate ROS, communicates with the two formyl peptide receptors FPR2 and FPR1 to control the NADPH oxidase activity in neutrophils.

Subunit / interactions. Interacts with ARRB2 and ARR3.

Subcellular location. Cell membrane.

Tissue specificity. Expressed predominantly in hematopoietic tissues. High levels detected in the bone marrow and lower levels in the peripheral leukocytes and lung. Also expressed in brain, heart, muscle, colon, thymus, spleen, kidney, liver, placenta and intestine. Within the leukocyte population expression is higher in neutrophils and eosinophils relative to T- or B-lymphocytes.

Post-translational modifications. Phosphorylated by a subset of GPR84-activating ligands. Constitutively phosphorylated at Ser-221 and Ser-224 in the absence of 2-HTP. By contrast, Thr-263 and Thr-264 are phosphorylated only following prior cell treatment with 2-HTP.

Induction. By bacterial lipopolysaccharides (LPS) in the monocytic leukemia cell line THP-1.

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

RefSeq proteins (1): NP_065103* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000276	GPCR_Rhodpsn	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain

Pfam: PF00001

UniProt features (54 total): helix 16, topological domain 8, transmembrane region 7, turn 6, modified residue 4, strand 4, glycosylation site 2, sequence variant 2, mutagenesis site 2, chain 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
8J18	ELECTRON MICROSCOPY	2.89
8G05	ELECTRON MICROSCOPY	3
8J19	ELECTRON MICROSCOPY	3.23
8J1A	ELECTRON MICROSCOPY	3.24

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NQS5-F1	81.40	0.69

Antibody-complex structures (SAbDab): 4 — 8G05, 8J18, 8J19, 8J1A

Functional residue map

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

Post-translational modifications (4): 221, 224, 263, 264

Glycosylation sites (2): 3, 8

Mutagenesis-validated functional residues (2):

Position	Phenotype
263	more than 50% loss of interaction with arr3.
264	more than 50% loss of interaction with arr3.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-418555	G alpha (s) signalling events
R-HSA-6798695	Neutrophil degranulation

MSigDB gene sets: 135 (showing top): REACTOME_INNATE_IMMUNE_SYSTEM, GOCC_SECRETORY_GRANULE, FOSTER_TOLERANT_MACROPHAGE_UP, GOMF_PEPTIDE_RECEPTOR_ACTIVITY, AFFAR_YY1_TARGETS_DN, IZADPANAH_STEM_CELL_ADIPOSE_VS_BONE_UP, GOCC_SECRETORY_VESICLE, GOCC_SPECIFIC_GRANULE, GOCC_SECRETORY_GRANULE_MEMBRANE, GOCC_RECEPTOR_COMPLEX, KRIGE_RESPONSE_TO_TOSEDOSTAT_24HR_UP, MGGAAGTG_GABP_B, GOMF_TRANSMEMBRANE_SIGNALING_RECEPTOR_ACTIVITY, ZHOU_INFLAMMATORY_RESPONSE_LIVE_UP, GOMF_G_PROTEIN_COUPLED_RECEPTOR_ACTIVITY

GO Biological Process (3): neuropeptide signaling pathway (GO:0007218), signal transduction (GO:0007165), G protein-coupled receptor signaling pathway (GO:0007186)

GO Molecular Function (3): urotensin II receptor activity (GO:0001604), G protein-coupled receptor activity (GO:0004930), protein binding (GO:0005515)

GO Cellular Component (5): plasma membrane (GO:0005886), specific granule membrane (GO:0035579), signaling receptor complex (GO:0043235), tertiary granule membrane (GO:0070821), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
GPCR downstream signalling	1
Innate Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
G protein-coupled receptor signaling pathway	2
secretory granule membrane	2
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
G protein-coupled receptor activity	1
signal transduction	1
G protein-coupled peptide receptor activity	1
transmembrane signaling receptor activity	1
binding	1
membrane	1
cell periphery	1
specific granule	1
protein-containing complex	1
tertiary granule	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1354 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GPR84	FFAR4	Q5NUL3	832
GPR84	FFAR1	O14842	831
GPR84	FFAR2	O15552	823
GPR84	FFAR3	O14843	814
GPR84	GPR119	Q8TDV5	732
GPR84	ARRB2	P32121	578
GPR84	HCAR1	Q9BXC0	527
GPR84	HCAR2	Q8TDS4	518
GPR84	SAG	P10523	493
GPR84	HCAR3	P49019	467
GPR84	GPR35	Q9HC97	446
GPR84	CSRNP2	Q9H175	420
GPR84	GPRC6A	Q5T6X5	410
GPR84	S1PR4	O95977	409
GPR84	GPR65	Q8IYL9	392

IntAct

9 interactions, top by confidence:

A	B	Type	Score
GPR84	CERS6	psi-mi:“MI:0915”(physical association)	0.560
RAMP3	GPR84	psi-mi:“MI:0915”(physical association)	0.400
RAMP2	GPR84	psi-mi:“MI:0915”(physical association)	0.400
ATG16L1		psi-mi:“MI:0914”(association)	0.350
GPR84	LGALS3	psi-mi:“MI:0914”(association)	0.350
GPR84	EI24	psi-mi:“MI:0914”(association)	0.350

BioGRID (26): REEP5 (Affinity Capture-MS), CERS6 (Affinity Capture-MS), LMBR1 (Affinity Capture-MS), CERS6 (Affinity Capture-MS), CERS6 (Affinity Capture-MS), LGALS3 (Affinity Capture-MS), TUBGCP2 (Affinity Capture-MS), GEMIN4 (Affinity Capture-MS), TNFAIP2 (Affinity Capture-MS), RER1 (Affinity Capture-MS), ECHDC1 (Affinity Capture-MS), TTI2 (Affinity Capture-MS), DYM (Affinity Capture-MS), MPDU1 (Affinity Capture-MS), WFS1 (Affinity Capture-MS)

ESM2 similar proteins: A0A084B9Z2, A0A0A2JY25, A0A0D1E6B3, A0A0R8YXT5, A0A142I738, A0A2I1CSG1, A0A2L0P0K0, A0A348HAY3, A1CIM4, B2KWI0, G1X9E2, G1X9H9, G1XJN1, G5EDW2, I1RLA6, O13780, O13880, O42579, O60353, P0DUT8, P13773, P31302, P31303, P31397, P49190, P70555, P78741, P9WEL3, P9WEU1, P9WEV3, Q05659, Q09460, Q0CRW7, Q0V6Q8, Q12256, Q2KI97, Q4D3E8, Q4G2T3, Q4WR17, Q54ET0

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

5 interactions.

A	Effect	B	Mechanism
GPR84	“up-regulates activity”	GNAI1	binding
GPR84	“up-regulates activity”	GNAI3	binding
GPR84	“up-regulates activity”	GNAO1	binding
GPR84	“up-regulates activity”	GNAZ	binding
“decanoic acid”	“up-regulates activity”	GPR84	“chemical activation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	42
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

374 predictions. Top by Δscore:

Variant	Effect	Δscore
12:54363860:C:CC	acceptor_gain	0.9700
12:54363856:GAGG:G	acceptor_gain	0.9500
12:54363858:GG:G	acceptor_gain	0.9300
12:54363358:ACT:A	acceptor_gain	0.9000
12:54363869:C:CT	acceptor_gain	0.9000
12:54363855:AGAGG:A	acceptor_gain	0.8900
12:54363857:AGG:A	acceptor_gain	0.8900
12:54364387:GCTTA:G	donor_loss	0.8700
12:54364388:CTTA:C	donor_loss	0.8700
12:54364389:TTA:T	donor_loss	0.8700
12:54364390:TACCT:T	donor_loss	0.8700
12:54364391:ACC:A	donor_loss	0.8700
12:54364392:C:G	donor_loss	0.8700
12:54363858:GGCT:G	acceptor_loss	0.8600
12:54363859:GCTAA:G	acceptor_loss	0.8600
12:54363860:C:G	acceptor_loss	0.8600
12:54363861:T:C	acceptor_loss	0.8600
12:54363870:A:T	acceptor_gain	0.8400
12:54363359:C:CA	acceptor_gain	0.8300
12:54363875:G:GC	acceptor_gain	0.8200
12:54363875:G:C	acceptor_gain	0.8100
12:54363359:C:CC	acceptor_gain	0.8000
12:54363360:T:A	acceptor_gain	0.7900
12:54363280:AGCCC:A	acceptor_gain	0.7800
12:54363369:C:CT	acceptor_gain	0.7800
12:54363862:A:C	acceptor_loss	0.7700
12:54363357:GACT:G	acceptor_gain	0.7600
12:54363370:A:T	acceptor_gain	0.7400
12:54363279:GAGCC:G	acceptor_gain	0.7100
12:54363356:AGACT:A	acceptor_gain	0.7100

AlphaMissense

2558 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:54363399:G:C	S151R	0.998
12:54363399:G:T	S151R	0.998
12:54363401:T:G	S151R	0.998
12:54363276:G:C	S192R	0.993
12:54363276:G:T	S192R	0.993
12:54363278:T:G	S192R	0.993
12:54363345:G:C	S169R	0.993
12:54363345:G:T	S169R	0.993
12:54363347:T:G	S169R	0.993
12:54363574:C:T	C93Y	0.993
12:54363594:C:A	W86C	0.993
12:54363594:C:G	W86C	0.993
12:54363669:G:C	N61K	0.993
12:54363669:G:T	N61K	0.993
12:54363419:A:G	W145R	0.992
12:54363419:A:T	W145R	0.992
12:54362859:G:C	S331R	0.991
12:54362859:G:T	S331R	0.991
12:54362861:T:G	S331R	0.991
12:54363349:C:T	C168Y	0.991
12:54363354:G:C	C166W	0.991
12:54362774:A:G	W360R	0.990
12:54362774:A:T	W360R	0.990
12:54362868:A:C	F328L	0.990
12:54362868:A:T	F328L	0.990
12:54362870:A:G	F328L	0.990
12:54363273:A:C	S193R	0.990
12:54363273:A:T	S193R	0.990
12:54363275:T:G	S193R	0.990
12:54363355:C:T	C166Y	0.990

dbSNP variants (sampled 300 via entrez): RS1000481052 (12:54356493 G>A), RS1000624901 (12:54360573 C>T), RS1000751762 (12:54353737 G>A), RS1000900413 (12:54361610 A>T), RS1001211370 (12:54363426 C>T), RS1001472042 (12:54356942 A>G), RS1001631451 (12:54356705 G>A), RS1001642103 (12:54355844 G>A), RS1002213561 (12:54361653 G>A), RS1002231398 (12:54355264 G>A), RS1002588033 (12:54354702 C>T), RS1002951924 (12:54365196 C>T), RS1003039606 (12:54350866 T>C,G), RS1003105912 (12:54358301 T>C), RS1003314061 (12:54351500 A>G)

Disease associations

OMIM: gene MIM:606383 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST005962_20	Waist-to-hip ratio adjusted for BMI x sex x age interaction (4df test)	7.000000e-13

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3714079 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

5 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 361,026 (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
CHEMBL108030	UNDECANOATE	3	81,591
CHEMBL446452	ARUNDINE	3	2,826
CHEMBL107874	TRIDECANOATE	2	19,569
CHEMBL324846	OCTANOIC ACID	2	256,830
CHEMBL3716365	GLPG-1205	2	210

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: gpcr — GPR42, GPR84

Most potent curated ligand interactions (16 total), top 16:

Ligand	Action	Affinity	Parameter
GLPG1205	Antagonist	11.0	pIC50
OX04529	Biased agonist	10.74	pEC50
PSB-17365	Agonist	8.7	pEC50
PSB-1584	Agonist	8.3	pEC50
DL-175	Agonist	7.91	pEC50
TUG-2181	Inverse agonist	7.47	pIC50
6-n-octylaminouracil	Full agonist	7.0	pEC50
decanoic acid	Full agonist	5.4	pEC50
undecanoic acid	Agonist	5.1	pEC50
lauric acid	Agonist	5.05	pEC50
2-hydroxylauric acid	Full agonist	5.0	pEC50
3-hydroxylauric acid	Full agonist	4.9	pEC50
PBI-4547	Antagonist	4.77	pIC50
2-hydroxy capric acid	Full agonist	4.5	pEC50
3-hydroxy capric acid	Full agonist	3.6	pEC50
setogepram	Antagonist	3.4	pIC50

Binding affinities (BindingDB)

6 measured of 48 human assays (48 total across all organisms); most potent 6 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
CHEMBL5196041	IC50	604 nM
US20250340543, Compound I-25	IC50	7500 nM	US-20250340543: GPR84 ANTAGONISTS AND USES THEREOF
2-(1,4-dioxan-2-ylmethoxy)-10-(6-methyl-3-pyridinyl)-6,7-dihydropyrimido[1,6-d][1,4]benzoxazepin-4-one	IC50	7500 nM	US-20250340543: GPR84 ANTAGONISTS AND USES THEREOF
2-[2-(6-ethoxy-3-pyridinyl)ethyl]-6-(oxan-2-ylmethoxy)-1H-pyridin-4-one	IC50	7500 nM	US-20250340543: GPR84 ANTAGONISTS AND USES THEREOF
6-[4-(2-cyclopropylethynyl)phenyl]-4-[[(2R)-1,4-dioxan-2-yl]methoxy]-1-ethylpyridin-2-one	IC50	12500 nM	US-20250340543: GPR84 ANTAGONISTS AND USES THEREOF
1-[(1S)-1-[4-(2-cyclopropylethynyl)-3-fluorophenyl]ethyl]-6-methyl-4-(pyrimidin-2-ylmethoxy)pyridin-2-one	IC50	12500 nM	US-20250340543: GPR84 ANTAGONISTS AND USES THEREOF

ChEMBL bioactivities

1233 potent at pChembl≥5 of 1293 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
11.00	IC50	0.01	nM	CHEMBL3717600
11.00	IC50	0.01	nM	CHEMBL3716527
11.00	IC50	0.01	nM	CHEMBL3716889
11.00	IC50	0.01	nM	CHEMBL3716528
11.00	IC50	0.01	nM	CHEMBL3717809
11.00	IC50	0.01	nM	CHEMBL3714785
11.00	IC50	0.01	nM	CHEMBL3715088
11.00	IC50	0.01	nM	CHEMBL3716159
11.00	IC50	0.01	nM	CHEMBL3716561
11.00	IC50	0.01	nM	CHEMBL3718720
11.00	IC50	0.01	nM	GLPG-1205
11.00	IC50	0.01	nM	CHEMBL3714783
11.00	IC50	0.01	nM	CHEMBL3716784
11.00	IC50	0.01	nM	CHEMBL3715907
11.00	IC50	0.01	nM	CHEMBL3715064
11.00	IC50	0.01	nM	CHEMBL3717416
11.00	IC50	0.01	nM	CHEMBL3717753
11.00	IC50	0.01	nM	CHEMBL3715656
11.00	IC50	0.01	nM	CHEMBL3717743
11.00	IC50	0.01	nM	CHEMBL3717641
11.00	IC50	0.01	nM	CHEMBL3718005
11.00	IC50	0.01	nM	CHEMBL3716958
11.00	IC50	0.01	nM	CHEMBL3716024
11.00	IC50	0.01	nM	CHEMBL3717853
11.00	IC50	0.01	nM	CHEMBL3717201
11.00	IC50	0.01	nM	CHEMBL3717795
11.00	IC50	0.01	nM	CHEMBL3714904
11.00	IC50	0.01	nM	CHEMBL3715192
11.00	IC50	0.01	nM	CHEMBL3718497
11.00	IC50	0.01	nM	CHEMBL3719374
11.00	IC50	0.01	nM	CHEMBL3719101
11.00	IC50	0.01	nM	CHEMBL3718331
11.00	IC50	0.01	nM	CHEMBL3718192
11.00	IC50	0.01	nM	CHEMBL3718244
11.00	IC50	0.01	nM	CHEMBL3718528
11.00	IC50	0.01	nM	CHEMBL3715443
11.00	IC50	0.01	nM	CHEMBL3716722
11.00	IC50	0.01	nM	CHEMBL3717905
11.00	IC50	0.01	nM	CHEMBL3716728
11.00	IC50	0.01	nM	CHEMBL3717963
11.00	IC50	0.01	nM	CHEMBL3718080
11.00	IC50	0.01	nM	CHEMBL3718999
11.00	IC50	0.01	nM	CHEMBL3719258
11.00	IC50	0.01	nM	CHEMBL3715923
11.00	IC50	0.01	nM	CHEMBL3718350
11.00	IC50	0.01	nM	CHEMBL3719092
11.00	IC50	0.01	nM	CHEMBL3716446
11.00	IC50	0.01	nM	CHEMBL3719364
11.00	IC50	0.01	nM	CHEMBL3715817
11.00	IC50	0.01	nM	CHEMBL3719100

PubChem BioAssay actives

718 with measured affinity, of 1459 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
4-hydroxy-6-octyl-1H-pyridin-2-one	2090435: Agonist activity at GPR84 (unknown origin) expressed in HTLA cells assessed as beta-arrestin recruitment incubated for 1 day by PRESTO-Tango assay	ec50	<0.0001	uM
5-[3-[3,5-bis(trifluoromethyl)phenyl]propyl]-1-oxidopyridin-1-ium-3-ol	1992718: Agonist activity at human GPR84 expressed in CHO-K1 cells assessed as inhibition of forskolin induced cAMP production pretreated with forskolin for 30 mins followed by compound addition and measured after 18 to 24 hrs by DiscoverX HitHunter cAMP assay	ec50	<0.0001	uM
5-[3-[4-chloro-3-(trifluoromethyl)phenyl]propyl]-1-oxidopyridin-1-ium-3-ol	1992718: Agonist activity at human GPR84 expressed in CHO-K1 cells assessed as inhibition of forskolin induced cAMP production pretreated with forskolin for 30 mins followed by compound addition and measured after 18 to 24 hrs by DiscoverX HitHunter cAMP assay	ec50	<0.0001	uM
5-[3-(4-chloronaphthalen-1-yl)propyl]-1-oxidopyridin-1-ium-3-ol	1992718: Agonist activity at human GPR84 expressed in CHO-K1 cells assessed as inhibition of forskolin induced cAMP production pretreated with forskolin for 30 mins followed by compound addition and measured after 18 to 24 hrs by DiscoverX HitHunter cAMP assay	ec50	<0.0001	uM
6-(5-cyclohexylpentyl)-4-hydroxy-1H-pyridin-2-one	2090435: Agonist activity at GPR84 (unknown origin) expressed in HTLA cells assessed as beta-arrestin recruitment incubated for 1 day by PRESTO-Tango assay	ec50	<0.0001	uM
6-heptyl-4-hydroxy-1H-pyridin-2-one	2090435: Agonist activity at GPR84 (unknown origin) expressed in HTLA cells assessed as beta-arrestin recruitment incubated for 1 day by PRESTO-Tango assay	ec50	<0.0001	uM
4-hydroxy-6-nonyl-1H-pyridin-2-one	2090435: Agonist activity at GPR84 (unknown origin) expressed in HTLA cells assessed as beta-arrestin recruitment incubated for 1 day by PRESTO-Tango assay	ec50	0.0001	uM
6-decyl-4-hydroxy-1H-pyridin-2-one	2090435: Agonist activity at GPR84 (unknown origin) expressed in HTLA cells assessed as beta-arrestin recruitment incubated for 1 day by PRESTO-Tango assay	ec50	0.0002	uM
2-(2-pyrazin-2-yloxyethoxy)-9-[2-(3-tritiophenyl)ethyl]-6,7-dihydropyrimido[6,1-a]isoquinolin-4-one	1707066: Binding affinity to recombinant human N-terminal epitope tagged/eYFP-fused FLAG-tagged GPR84 expressed in Flp-In TREx 293 cell membrane incubated for 1 hr by liquid scintillation spectrometry	kd	0.0002	uM
2-hexylsulfanyl-4-hydroxy-1H-pyrimidin-6-one	1546369: Displacement of [3H]PSB-1584 from recombinant human GPR84 expressed in CHO cell membranes co-expressing beta-arrestin2 measured after 6 hrs by scintillation counting method	ki	0.0002	uM
4-hydroxy-2-(4-phenylbutylsulfanyl)-1H-pyrimidin-6-one	1546369: Displacement of [3H]PSB-1584 from recombinant human GPR84 expressed in CHO cell membranes co-expressing beta-arrestin2 measured after 6 hrs by scintillation counting method	ki	0.0003	uM
6-[2-(4-bromophenyl)ethylamino]-1H-pyrimidine-2,4-dione	1546369: Displacement of [3H]PSB-1584 from recombinant human GPR84 expressed in CHO cell membranes co-expressing beta-arrestin2 measured after 6 hrs by scintillation counting method	ki	0.0003	uM
4-hydroxy-6-[2-(4-propylphenyl)ethyl]-1H-pyridin-2-one	2090435: Agonist activity at GPR84 (unknown origin) expressed in HTLA cells assessed as beta-arrestin recruitment incubated for 1 day by PRESTO-Tango assay	ec50	0.0003	uM
6-dodecyl-4-hydroxy-1H-pyridin-2-one	2090435: Agonist activity at GPR84 (unknown origin) expressed in HTLA cells assessed as beta-arrestin recruitment incubated for 1 day by PRESTO-Tango assay	ec50	0.0003	uM
4-hydroxy-6-undecyl-1H-pyridin-2-one	2090435: Agonist activity at GPR84 (unknown origin) expressed in HTLA cells assessed as beta-arrestin recruitment incubated for 1 day by PRESTO-Tango assay	ec50	0.0004	uM
4-hydroxy-6-(5-phenylpentyl)-1H-pyridin-2-one	2090435: Agonist activity at GPR84 (unknown origin) expressed in HTLA cells assessed as beta-arrestin recruitment incubated for 1 day by PRESTO-Tango assay	ec50	0.0005	uM
6-[2-(4-butylphenyl)ethyl]-4-hydroxy-1H-pyridin-2-one	2090440: Agonist activity at GPR84 (unknown origin) expressed in doxycycline induced Flp-In-T-REx-293 cells transfected with GalphaI preincubated for 15 mins in presence of IBMX followed by forskolin stimulation for 45 mins by time-resolved fluorescence assay	ec50	0.0005	uM
6-(octylamino)-1H-pyrimidine-2,4-dione	1546369: Displacement of [3H]PSB-1584 from recombinant human GPR84 expressed in CHO cell membranes co-expressing beta-arrestin2 measured after 6 hrs by scintillation counting method	ki	0.0006	uM
6-[2-(4-chlorophenyl)ethylamino]-1H-pyrimidine-2,4-dione	1546369: Displacement of [3H]PSB-1584 from recombinant human GPR84 expressed in CHO cell membranes co-expressing beta-arrestin2 measured after 6 hrs by scintillation counting method	ki	0.0006	uM
6-[2-(4-ethylphenyl)ethylamino]-1H-pyrimidine-2,4-dione	1546369: Displacement of [3H]PSB-1584 from recombinant human GPR84 expressed in CHO cell membranes co-expressing beta-arrestin2 measured after 6 hrs by scintillation counting method	ki	0.0006	uM
4-hydroxy-6-tridecyl-1H-pyridin-2-one	2090435: Agonist activity at GPR84 (unknown origin) expressed in HTLA cells assessed as beta-arrestin recruitment incubated for 1 day by PRESTO-Tango assay	ec50	0.0006	uM
6-(4-phenylbutylamino)-1H-pyrimidine-2,4-dione	1546369: Displacement of [3H]PSB-1584 from recombinant human GPR84 expressed in CHO cell membranes co-expressing beta-arrestin2 measured after 6 hrs by scintillation counting method	ki	0.0006	uM
2-(2,3-dihydro-[1,4]dioxino[2,3-b]pyridin-2-ylmethoxy)-9-(3-hydroxy-3-phenylprop-1-ynyl)-6,7-dihydropyrimido[6,1-a]isoquinolin-4-one	1681251: Antagonist activity at recombinant human GPR84 stably overexpressed in HEK293T cell membranes co-expressing G-alpha assessed as inhibition of DIM-stimulated [35S]GTPgammaS binding after 90 mins by scintillation counting method	ic50	0.0006	uM
4-hydroxy-2-(3-phenylpropylsulfanyl)-1H-pyrimidin-6-one	1546369: Displacement of [3H]PSB-1584 from recombinant human GPR84 expressed in CHO cell membranes co-expressing beta-arrestin2 measured after 6 hrs by scintillation counting method	ki	0.0007	uM
6-(decylamino)-1H-pyrimidine-2,4-dione	1546369: Displacement of [3H]PSB-1584 from recombinant human GPR84 expressed in CHO cell membranes co-expressing beta-arrestin2 measured after 6 hrs by scintillation counting method	ki	0.0007	uM
6-(heptylamino)-1H-pyrimidine-2,4-dione	1546369: Displacement of [3H]PSB-1584 from recombinant human GPR84 expressed in CHO cell membranes co-expressing beta-arrestin2 measured after 6 hrs by scintillation counting method	ki	0.0009	uM
4-hydroxy-6-(4-phenoxyphenyl)-1H-pyridin-2-one	2090435: Agonist activity at GPR84 (unknown origin) expressed in HTLA cells assessed as beta-arrestin recruitment incubated for 1 day by PRESTO-Tango assay	ec50	0.0009	uM
9-(3-anilinoprop-1-ynyl)-2-(1,4-dioxan-2-ylmethoxy)-6,7-dihydropyrimido[6,1-a]isoquinolin-4-one	1707059: Antagonist activity at human Flag-tagged Gialpha-coupled GPR84 expressed in human Flp-In-T-REx-293 cell membrane assessed as reduction in PSB-16671-induced stimulation of [35S]GTPgammaS binding preincubated for 15 mins followed by PSB-16671 addition and subsequent addition of [35S]GTPgammaS measured after 60 mins by liquid scintillation spectroscopy	ic50	0.0009	uM
4-hydroxy-6-(6-phenoxy-3-pyridinyl)-1H-pyridin-2-one	2090435: Agonist activity at GPR84 (unknown origin) expressed in HTLA cells assessed as beta-arrestin recruitment incubated for 1 day by PRESTO-Tango assay	ec50	0.0010	uM
4-hydroxy-6-octoxy-1H-pyridin-2-one	2090435: Agonist activity at GPR84 (unknown origin) expressed in HTLA cells assessed as beta-arrestin recruitment incubated for 1 day by PRESTO-Tango assay	ec50	0.0010	uM
6-(nonylamino)-1H-pyrimidine-2,4-dione	1546369: Displacement of [3H]PSB-1584 from recombinant human GPR84 expressed in CHO cell membranes co-expressing beta-arrestin2 measured after 6 hrs by scintillation counting method	ki	0.0011	uM
6-[2-(4-methylphenyl)ethylamino]-1H-pyrimidine-2,4-dione	1546369: Displacement of [3H]PSB-1584 from recombinant human GPR84 expressed in CHO cell membranes co-expressing beta-arrestin2 measured after 6 hrs by scintillation counting method	ki	0.0013	uM
6-[2-(4-tert-butylphenyl)ethylamino]-1H-pyrimidine-2,4-dione	1546369: Displacement of [3H]PSB-1584 from recombinant human GPR84 expressed in CHO cell membranes co-expressing beta-arrestin2 measured after 6 hrs by scintillation counting method	ki	0.0013	uM
6-heptoxy-4-hydroxy-1H-pyridin-2-one	2090435: Agonist activity at GPR84 (unknown origin) expressed in HTLA cells assessed as beta-arrestin recruitment incubated for 1 day by PRESTO-Tango assay	ec50	0.0013	uM
2,5-dihydroxy-3-octylcyclohexa-2,5-diene-1,4-dione	1707054: Agonist activity at human GPR84 expressed in HEK293 cells assessed as reduction in forskolin-stimulated cAMP production incubated for 60 mins by HTRF assay	ec50	0.0016	uM
4-hydroxy-6-(4-phenylbutyl)-1H-pyridin-2-one	2090435: Agonist activity at GPR84 (unknown origin) expressed in HTLA cells assessed as beta-arrestin recruitment incubated for 1 day by PRESTO-Tango assay	ec50	0.0017	uM
6-(3-phenoxypropylamino)-1H-pyrimidine-2,4-dione	1546369: Displacement of [3H]PSB-1584 from recombinant human GPR84 expressed in CHO cell membranes co-expressing beta-arrestin2 measured after 6 hrs by scintillation counting method	ki	0.0021	uM
6-(heptylamino)-4-hydroxy-1H-pyridin-2-one	2090435: Agonist activity at GPR84 (unknown origin) expressed in HTLA cells assessed as beta-arrestin recruitment incubated for 1 day by PRESTO-Tango assay	ec50	0.0022	uM
6-[2-(2,4-dichlorophenyl)ethylamino]-1H-pyrimidine-2,4-dione	1546369: Displacement of [3H]PSB-1584 from recombinant human GPR84 expressed in CHO cell membranes co-expressing beta-arrestin2 measured after 6 hrs by scintillation counting method	ki	0.0023	uM
2-[2-(4-chlorophenyl)ethylsulfanyl]-4-hydroxy-1H-pyrimidin-6-one	1546369: Displacement of [3H]PSB-1584 from recombinant human GPR84 expressed in CHO cell membranes co-expressing beta-arrestin2 measured after 6 hrs by scintillation counting method	ki	0.0026	uM
6-(hexylamino)-4-hydroxy-1H-pyridin-2-one	2090435: Agonist activity at GPR84 (unknown origin) expressed in HTLA cells assessed as beta-arrestin recruitment incubated for 1 day by PRESTO-Tango assay	ec50	0.0029	uM
6-[2-(4-tert-butylphenyl)ethyl]-4-hydroxy-1H-pyridin-2-one	2090435: Agonist activity at GPR84 (unknown origin) expressed in HTLA cells assessed as beta-arrestin recruitment incubated for 1 day by PRESTO-Tango assay	ec50	0.0030	uM
6-(hexylamino)-1H-pyrimidine-2,4-dione	1546369: Displacement of [3H]PSB-1584 from recombinant human GPR84 expressed in CHO cell membranes co-expressing beta-arrestin2 measured after 6 hrs by scintillation counting method	ki	0.0030	uM
6-(2-phenoxyethylamino)-1H-pyrimidine-2,4-dione	1546369: Displacement of [3H]PSB-1584 from recombinant human GPR84 expressed in CHO cell membranes co-expressing beta-arrestin2 measured after 6 hrs by scintillation counting method	ki	0.0031	uM
2-[2-(4-bromophenyl)ethylsulfanyl]-4-hydroxy-1H-pyrimidin-6-one	1546369: Displacement of [3H]PSB-1584 from recombinant human GPR84 expressed in CHO cell membranes co-expressing beta-arrestin2 measured after 6 hrs by scintillation counting method	ki	0.0032	uM
4-hydroxy-6-[(4-propylphenyl)methoxy]-1H-pyridin-2-one	2090435: Agonist activity at GPR84 (unknown origin) expressed in HTLA cells assessed as beta-arrestin recruitment incubated for 1 day by PRESTO-Tango assay	ec50	0.0032	uM
4-hydroxy-2-[2-(4-methylphenyl)ethylsulfanyl]-1H-pyrimidin-6-one	1546369: Displacement of [3H]PSB-1584 from recombinant human GPR84 expressed in CHO cell membranes co-expressing beta-arrestin2 measured after 6 hrs by scintillation counting method	ki	0.0033	uM
4-hydroxy-6-(octylamino)-1H-pyridin-2-one	2090435: Agonist activity at GPR84 (unknown origin) expressed in HTLA cells assessed as beta-arrestin recruitment incubated for 1 day by PRESTO-Tango assay	ec50	0.0033	uM
6-[methyl(octyl)amino]-1H-pyrimidine-2,4-dione	1546369: Displacement of [3H]PSB-1584 from recombinant human GPR84 expressed in CHO cell membranes co-expressing beta-arrestin2 measured after 6 hrs by scintillation counting method	ki	0.0036	uM
2-[2-(4-fluorophenyl)ethylsulfanyl]-4-hydroxy-1H-pyrimidin-6-one	1546369: Displacement of [3H]PSB-1584 from recombinant human GPR84 expressed in CHO cell membranes co-expressing beta-arrestin2 measured after 6 hrs by scintillation counting method	ki	0.0038	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Endosulfan	increases expression	2
Nickel	increases expression	2
alpha phellandrene	decreases expression	1
bisphenol A	affects cotreatment, decreases methylation	1
sulforaphane	increases expression	1
CGP 52608	affects binding, increases reaction	1
Fulvestrant	decreases methylation, affects cotreatment	1
Air Pollutants	increases abundance, increases expression	1
Air Pollutants, Occupational	increases expression	1
Demecolcine	increases expression	1
Lipopolysaccharides	increases expression	1
Ozone	increases abundance, increases expression	1
Tetradecanoylphorbol Acetate	increases expression	1
Tretinoin	increases expression	1
Vincristine	increases expression	1
Aflatoxin B1	increases methylation	1
Antirheumatic Agents	decreases expression	1

ChEMBL screening assays

168 unique, capped per target: 127 functional, 41 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3720808	Functional	Antagonist activity against GPR84 (unknown origin) expressed in cell membranes incubated for 90 mins by [35S]GTPgammaS binding assay	Dihydropyrimidinoisoquinolinones and pharmaceutical compositions thereof for the treatment of inflammatory disorders
CHEMBL3830329	Binding	Potency index, ratio of 6-OAU EC50 to compound EC50 for GPR84 (unknown origin) expressed in HEK293 cells coexpressing Galpha16 protein	Design and Synthesis of 2-Alkylpyrimidine-4,6-diol and 6-Alkylpyridine-2,4-diol as Potent GPR84 Agonists. — ACS Med Chem Lett

Cellosaurus cell lines

2 cell lines: 2 spontaneously immortalized cell line

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

Cellosaurus	Name	Category	Sex
CVCL_KV31	cAMP Hunter CHO-K1 GPR84 Gi	Spontaneously immortalized cell line	Female
CVCL_KX75	PathHunter CHO-K1 GPR84 beta-arrestin	Spontaneously immortalized cell line	Female

Clinical trials (associated diseases)

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