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 signaling receptor complex.

Source: NCBI Gene 53831 — automated summary from GO annotations (Alliance of Genome Resources).

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 44 total
• GTEx eGene: eQTL in 14 tissues, sQTL in 0 (q < 0.05)
• Drug target: yes — 2 curated mechanism-of-action drugs; 5 molecules with ChEMBL bioactivity
• Constraint (gnomAD): pLI 0.02 (LoF-tolerant), LOEUF 0.88 (unconstrained)
• 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: 4 — 4 protein_coding

MANE Select: ENST00000267015

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1

ENST00000267015, ENST00000551809, ENST00000879277, ENST00001143817

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.

Highest expression (Bgee): bone marrow, male germ line stem cell (sensu Vertebrata) in testis, bone marrow cell, trabecular bone tissue, monocyte.

Genetic regulation across tissues (GTEx eQTL / sQTL)

GPR84 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 14 tissues and its splicing (sQTL) in 0 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

14 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Whole Blood	eqtl	2.2e-10	-0.14	12:54364546:A:G
Cells Cultured fibroblasts	eqtl	2.9e-06	-0.29	12:54367040:A:G
Artery Tibial	eqtl	4.2e-06	+0.20	12:54368147:T:C
Adipose Subcutaneous	eqtl	2.3e-04	-0.16	12:54362018:T:A
Nerve Tibial	eqtl	2.5e-03	-0.17	12:54364546:A:G
Artery Aorta	eqtl	2.8e-03	-0.20	12:54367040:A:G
Artery Coronary	eqtl	4.1e-03	-0.20	12:54367040:A:G
Heart Atrial Appendage	eqtl	5.2e-03	+0.94	12:53979713:C:T
Uterus	eqtl	1.7e-02	-1.26	12:54996568:C:G
Adrenal Gland	eqtl	2.1e-02	-0.23	12:54367040:A:G
Adipose Visceral Omentum	eqtl	2.4e-02	-0.13	12:54367040:A:G
Thyroid	eqtl	3.7e-02	+0.19	12:53448688:T:C
Spleen	eqtl	4.3e-02	-0.14	12:54367040:A:G
Cells EBV-transformed lymphocytes	eqtl	4.7e-02	+0.15	12:54364546:A:G

FANTOM5 promoters

1 alternative TSS:

Promoter ID	TPM avg	Samples expressed
131327	12.1034	372

Top tissues by expression

showing 100 of 252 tissues 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
placenta	UBERON:0001987	57.80	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	57.80	gold quality
omental fat pad	UBERON:0010414	57.13	gold quality
peritoneum	UBERON:0002358	57.09	gold quality
adipose tissue of abdominal region	UBERON:0007808	56.26	gold quality
spinal cord	UBERON:0002240	56.23	gold quality
right lung	UBERON:0002167	55.65	gold quality
aorta	UBERON:0000947	55.49	gold quality
smooth muscle tissue	UBERON:0001135	55.17	gold quality
rectum	UBERON:0001052	55.13	gold quality
superficial temporal artery	UBERON:0001614	55.00	gold quality
lung	UBERON:0002048	54.93	gold quality
left uterine tube	UBERON:0001303	54.89	gold quality
germinal epithelium of ovary	UBERON:0001304	54.68	gold quality
cardiac muscle of right atrium	UBERON:0003379	54.34	gold quality
left ventricle myocardium	UBERON:0006566	54.23	gold quality
kidney epithelium	UBERON:0004819	53.93	gold quality
upper arm skin	UBERON:0004263	53.52	gold quality
epithelial cell of pancreas	CL:0000083	53.07	gold quality
right lobe of thyroid gland	UBERON:0001119	52.92	gold quality
deltoid	UBERON:0001476	52.38	gold quality
right atrium auricular region	UBERON:0006631	51.87	gold quality
cardiac atrium	UBERON:0002081	51.86	gold quality
left lobe of thyroid gland	UBERON:0001120	51.84	gold quality
tibial artery	UBERON:0007610	51.74	gold quality
popliteal artery	UBERON:0002250	51.71	gold quality
lymph node	UBERON:0000029	51.51	gold quality
adenohypophysis	UBERON:0002196	51.45	gold quality
esophagus mucosa	UBERON:0002469	51.33	gold quality
hypothalamus	UBERON:0001898	51.12	gold quality
decidua	UBERON:0002450	51.11	gold quality
thyroid gland	UBERON:0002046	51.09	gold quality
metanephros cortex	UBERON:0010533	51.02	gold quality
amygdala	UBERON:0001876	50.77	gold quality
substantia nigra	UBERON:0002038	50.67	gold quality
myocardium	UBERON:0002349	50.25	gold quality
islet of Langerhans	UBERON:0000006	50.16	gold quality
adipose tissue	UBERON:0001013	49.70	gold quality
skin of abdomen	UBERON:0001416	49.70	gold quality
corpus epididymis	UBERON:0004359	49.68	gold quality
heart	UBERON:0000948	49.55	gold quality
midbrain	UBERON:0001891	49.41	gold quality
skin of leg	UBERON:0001511	49.34	gold quality
minor salivary gland	UBERON:0001830	49.27	gold quality
tonsil	UBERON:0002372	49.13	gold quality
metanephros	UBERON:0000081	49.04	gold quality
anatomical system	UBERON:0000467	49.03	gold quality
subcutaneous adipose tissue	UBERON:0002190	48.94	gold quality
multicellular organism	UBERON:0000468	48.86	gold quality
material anatomical entity	UBERON:0000465	48.85	gold quality
myometrium	UBERON:0001296	48.80	gold quality
lower lobe of lung	UBERON:0008949	48.60	silver quality
heart left ventricle	UBERON:0002084	48.52	gold quality
zone of skin	UBERON:0000014	48.51	gold quality
saliva-secreting gland	UBERON:0001044	48.44	gold quality
pancreas	UBERON:0001264	48.38	gold quality
cardiac ventricle	UBERON:0002082	48.23	gold quality
mouth mucosa	UBERON:0003729	48.07	gold quality
adult mammalian kidney	UBERON:0000082	48.03	gold quality
endocervix	UBERON:0000458	47.98	gold quality
pituitary gland	UBERON:0000007	47.95	gold quality
Brodmann (1909) area 9	UBERON:0013540	47.83	gold quality
esophagus	UBERON:0001043	47.55	gold quality
quadriceps femoris	UBERON:0001377	47.53	gold quality
apex of heart	UBERON:0002098	47.48	gold quality
nasal cavity epithelium	UBERON:0005384	47.48	gold quality
body of stomach	UBERON:0001161	47.36	gold quality
urinary bladder	UBERON:0001255	47.35	gold quality
right ovary	UBERON:0002118	47.35	gold quality
anterior cingulate cortex	UBERON:0009835	47.32	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

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 73 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Bone marrow	tissue	21.5	high
Urinary bladder	tissue	14.6	low
Appendix	tissue	7.8	medium
Adipose tissue	tissue	4.2	low
Hypothalamus	tissue	3.0
Placenta	tissue	2.9	not detected
Periaqueductal gray	tissue	2.9
Spinal cord	tissue	2.6
Retina	tissue	2.5
Medulla oblongata	tissue	2.4
Substantia nigra	tissue	2.4
Pons	tissue	2.3
Corpus callosum	tissue	2.2
Septum	tissue	2.0
Smooth muscle	tissue	1.8	not detected
Midbrain	tissue	1.8
Choroid plexus	tissue	1.7
Thalamus	tissue	1.7
Ventral pallidum	tissue	1.3
Amygdala	tissue	1.2
Superior colliculi	tissue	1.2
Putamen	tissue	1.1
Hippocampal formation	tissue	1.1
Basal ganglia	tissue	0.9	medium
Gallbladder	tissue	0.9	not detected
Locus coeruleus	tissue	0.9
Adrenal gland	tissue	0.9	low
Lung	tissue	0.8	not detected
Hippocampus	tissue	0.8	low
Pituitary gland	tissue	0.7
Skin 1	tissue	0.7	low
Tonsil	tissue	0.7	not detected
Prefrontal cortex	tissue	0.6
Cerebral cortex	tissue	0.6	low
Rectum	tissue	0.6	low
Olfactory bulb	tissue	0.6
Insular cortex	tissue	0.6
Nucleus accumbens	tissue	0.5
Retrosplenial cortex	tissue	0.5
Temporal cortex	tissue	0.5
Stomach 1	tissue	0.4	not detected
Vagina	tissue	0.4	not detected
Pancreas	tissue	0.4	not detected
Motor cortex	tissue	0.4
Thymus	tissue	0.4
Postcentral gyrus	tissue	0.4
Entorhinal cortex	tissue	0.4
Cingulate cortex	tissue	0.4
Somatosensory cortex	tissue	0.4
Occipital cortex	tissue	0.4
Lymph node	tissue	0.3	not detected
Salivary gland	tissue	0.3	not detected
Colon	tissue	0.3	not detected
Epididymis	tissue	0.3	not detected
Spleen	tissue	0.3	not detected
Prostate	tissue	0.3	not detected
Cervix	tissue	0.2	not detected
Testis	tissue	0.2	not detected
Seminal vesicle	tissue	0.2	low
Liver	tissue	0.2	not detected

Brain sub-regions (HPA Brain Atlas): detected in 188; highest nTPM — Lateral funiculus (white matter) (4.9), Nucleus raphe pallidus (3.9), Peritrigeminal nucleus (3.2), Anterior funiculus (white matter) (2.6), Ventral spinal cord (2.6).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting GPR84 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 35 miRNAs:

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

Functional genomics

gnomAD constraint: pLI 0.0206, LOEUF 0.878, missense Z 1.63 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000267015 — one region, missense o/e 0.85.

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)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1934129) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 5 distinct phenotype terms.

Mouse phenotype (MP)	Records
increased circulating alanine transaminase level	1
abnormal T-helper 2 physiology	1
increased interleukin-13 secretion	1
increased interleukin-4 secretion	1
increased interleukin-5 secretion	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Mus musculus	Q8BUD0	99.2%	Diamond
Sus scrofa	O02835	99.1%	Diamond
Canis lupus familiaris	Q9TUP7	98.4%	Diamond
Bos taurus	Q0GBZ5	95.3%	Diamond
Oryctolagus cuniculus	P79217	81.9%	Diamond
Callorhinchus milii	A0A4W3GG95	73.4%	Diamond
Xenopus tropicalis	B3DM66	72.8%	Diamond
Drosophila melanogaster	Q9VNM1	37.3%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
GTSF1	protein-coding	121355
COPZ1	protein-coding	22818
ZNF385A	protein-coding	25946
NCKAP1L	protein-coding	3071
ITGA5	protein-coding	3678
MIR148B	ncRNA	442892
PDE1B	protein-coding	5153
GPR84-AS1	ncRNA	102724050
NFE2	protein-coding	4778

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 18, topological domain 8, transmembrane region 7, modified residue 4, turn 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)

9 structures by resolution:

PDB	Title	Method	Resolution (Å)
8J18	Cryo-EM structure of the 3-OH-C12-bound GPR84 receptor-Gi complex	ELECTRON MICROSCOPY	2.89
8G05	Cryo-EM structure of an orphan GPCR-Gi protein signaling complex	ELECTRON MICROSCOPY	3
9PT4	Cryo-EM structure of GPR84-Gi complex bound to OX04529	ELECTRON MICROSCOPY	3.03
9WIJ	Cryo-EM structure of GPR84 with GLPG1205	ELECTRON MICROSCOPY	3.05
10JB	Cryo-EM structure of Gi-coupled GPR84 in complex with OX04539 and PSB-16671	ELECTRON MICROSCOPY	3.22
8J19	Cryo-EM structure of the LY237-bound GPR84 receptor-Gi complex	ELECTRON MICROSCOPY	3.23
8J1A	Cryo-EM structure of the GPR84 receptor-Gi complex with no ligand modeled	ELECTRON MICROSCOPY	3.24
9WIK	Cryo-EM structure of GPR84-Gi complex with DL-175	ELECTRON MICROSCOPY	3.3
10JA	Cryo-EM structure of Gi-coupled GPR84 in complex with OX04539	ELECTRON MICROSCOPY	3.43

Predicted structure (AlphaFold)

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

Antibody-complex structures (SAbDab)

4 antibodies co-crystallized with this protein: 8G05, 8J18, 8J19, 8J1A

Human Protein Atlas

Protein class: G-protein coupled receptors, GPCRs excl olfactory receptors, Predicted membrane proteins, GPCRHMM predicted membrane proteins, UniProt - Evidence at transcript level

Protein evidence: Evidence at protein level

Antibody reliability (HPA): IH enhanced

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)

Type	Positions
Phosphoserine	221, 224
Phosphothreonine	263, 264

Glycosylation sites (2)

Type	Positions
N-linked (glcnac…) asparagine	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 curated (TAS) of 7; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

7 pathways:

ID	Pathway	Evidence
R-HSA-418555	G alpha (s) signalling events	curated
R-HSA-6798695	Neutrophil degranulation	curated
R-HSA-388396	GPCR downstream signalling	—
R-HSA-168256	Immune System	—
R-HSA-168249	Innate Immune System	—
R-HSA-162582	Signal Transduction	—
R-HSA-372790	Signaling by GPCR	—

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

5 top-level categories:

Category	Pathways
GPCR downstream signalling	1
Innate Immune System	1
Immune System	1
Signal Transduction	1
Signaling by GPCR	1

GO top-level categories

18 GO namespaces:

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

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 1 of 11 annotations. The rest are phylogenetic / computational / electronic (IEA).

1 experimentally-supported GO terms:

GO term	NS	Evidence
signaling receptor complex	CC	direct assay

Protein interactions and networks

STRING

showing 15 of 1,090 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GPR84	FFAR1	O14842	756
GPR84	FFAR4	Q5NUL3	725
GPR84	FFAR2	O15552	704
GPR84	GPR119	Q8TDV5	685
GPR84	FFAR3	O14843	676
GPR84	GPR82	Q96P67	563
GPR84	HCAR2	Q8TDS4	533
GPR84	CASR	P41180	498
GPR84	GPR62	Q9BZJ7	486
GPR84	GPR35	Q9HC97	482
GPR84	HCAR3	P49019	471
GPR84	GPR61	Q9BZJ8	428
GPR84	GPR142	Q7Z601	397
GPR84	GPRC6A	Q5T6X5	391
GPR84	GPR132	Q9UNW8	385

IntAct

Human interaction partners of GPR84 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

5 partners by confidence:

Partner	Interaction type	MIscore	Records
CERS6	physical association	0.560	1
RAMP3	physical association	0.400	3
RAMP2	physical association	0.400	1
EI24	association	0.350	1
LGALS3	association	0.350	1

BioGRID (26 interactions; top human partners by supporting records): CERS6 (Affinity Capture-MS; 3 records), ATP12A (Affinity Capture-MS), ATP1A3 (Affinity Capture-MS), COG1 (Affinity Capture-MS), DYM (Affinity Capture-MS), ECHDC1 (Affinity Capture-MS), EI24 (Affinity Capture-MS), FANCD2 (Affinity Capture-MS), FLOT2 (Affinity Capture-MS), GEMIN4 (Affinity Capture-MS), IPO11 (Affinity Capture-MS), LGALS3 (Affinity Capture-MS), LMBR1 (Affinity Capture-MS), MPDU1 (Affinity Capture-MS), RAB29 (Affinity Capture-MS)

SIGNOR signaling

showing 6 of 8 signaling 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”
GPR84	“up-regulates activity”	GNAI2	binding

Disease & clinical

Genetic variants

Variant evidence for GPR84: 44 ClinVar records (0 pathogenic / likely pathogenic); 1 GWAS association.

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

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 19 predictions of 217):

Position(s)	Effect	Δscore	Sites
12:54363860–54363861	acceptor_loss	0.8700	6
12:54363870	acceptor_loss	0.8600
12:54363875	acceptor_loss	0.8600
12:54364391–54364392	donor_loss	0.8600	5
12:54364391	donor_loss	0.8100
12:54363360	acceptor_gain	0.7800
12:54363862	acceptor_loss	0.7700
12:54363359	acceptor_gain	0.7500
12:54363370	acceptor_gain	0.7400
12:54364393	donor_loss	0.6800

AlphaMissense

790 missense substitutions predicted likely pathogenic (of 2,558 scored), across 221 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
D66	8	0.970	0.985
N38	8	0.930	0.989
F328	8	0.927	0.990
F101	8	0.916	0.984
F335	8	0.912	0.985
N366	8	0.911	0.987
F325	8	0.900	0.981
F187	8	0.878	0.977
F170	8	0.874	0.968
D342	8	0.841	0.895
F152	8	0.813	0.942
C93	7	0.983	0.993
C168	7	0.982	0.991
C166	7	0.971	0.991
F377	7	0.961	0.987
C11	7	0.960	0.977
W86	7	0.959	0.993
W360	7	0.940	0.990
S169	7	0.916	0.993
W145	7	0.904	0.992

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

1 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	unfavorable	5.24e-06

Disease associations

OMIM: gene MIM:606383 | disease phenotypes:

GWAS associations

1 associations:

Study	Trait	p-value
GCST005962_45	Waist-to-hip ratio adjusted for BMI x sex x age interaction (4df test)	7e-13

EFO canonical traits (from GWAS)

3 canonical traits:

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)

Drugs by curated mechanism of action (ChEMBL)

Drugs whose curated ChEMBL mechanism of action targets the GPR84 protein itself — single-protein targets only (drugs acting on a protein family or complex that merely includes it are excluded). Includes antibodies and oligonucleotides that bioactivity screening does not capture.

2 curated-mechanism drugs:

Drug	Modality	Max phase
GLPG-1205	Small molecule	2
SETOGEPRAM	Small molecule	2

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 364,973 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

5 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL446452	ARUNDINE	3	2,864
CHEMBL108030	UNDECANOATE	3	82,720
CHEMBL3716365	GLPG-1205	2	219
CHEMBL324846	OCTANOIC ACID	2	259,372
CHEMBL107874	TRIDECANOATE	2	19,798

PharmGKB: 1 entry (CPIC guideline: no)

GtoPdb / IUPHAR curated pharmacology

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

Target class: gpcr — GPR42, GPR84

Most potent curated ligand interactions (17 total), top 17:

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
GPR84 antagonist 42E2	Antagonist	6.6	pIC50
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)

286 measured of 393 human assays (395 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
CHEMBL3828298	EC50	0.189 nM
6-(4-Phenyl-butylamino)-1H-pyrimidine-2,4-dione	KI	0.58 nM
CHEMBL4547165	KI	0.582 nM
CHEMBL3718309	IC50	0.6 nM
CHEMBL125436	KI	0.726 nM
CHEMBL3827756	EC50	0.79 nM
CHEMBL4468895	KI	0.866 nM
CHEMBL3715656	IC50	0.9 nM
CHEMBL4521587	KI	1.1 nM
CHEMBL3827638	EC50	1.3 nM
CHEMBL13302	EC50	1.3 nM
CHEMBL4439640	KI	1.3 nM
CHEMBL4580884	KI	1.3 nM
CHEMBL221598	EC50	1.6 nM
CHEMBL4528940	KI	2.1 nM
CHEMBL4571353	KI	2.3 nM
CHEMBL4438595	KI	2.6 nM
CHEMBL4528577	KI	3.1 nM
CHEMBL4562761	KI	3.2 nM
CHEMBL4534827	KI	3.3 nM
CHEMBL4568775	KI	3.6 nM
CHEMBL4467630	KI	3.8 nM
CHEMBL4468678	KI	4 nM
CHEMBL5205352	IC50	4.6 nM
CHEMBL5170226	IC50	4.7 nM
CHEMBL4473999	KI	4.8 nM
CHEMBL4794652	IC50	5 nM
CHEMBL5186088	IC50	5 nM
CHEMBL5180818	IC50	5.2 nM
CHEMBL3716446	IC50	6 nM
CHEMBL3828303	EC50	6.1 nM
CHEMBL5191944	IC50	6.7 nM
CHEMBL4451909	KI	6.9 nM
CHEMBL5171669	IC50	7.2 nM
CHEMBL5207823	IC50	8.5 nM
CHEMBL5172567	IC50	8.7 nM
CHEMBL5176994	IC50	9.4 nM
CHEMBL4474487	KI	9.5 nM
CHEMBL5172502	IC50	9.8 nM
CHEMBL4103552	IC50	10 nM
CHEMBL4082477	IC50	10 nM
CHEMBL4060589	IC50	10 nM
CHEMBL4069275	IC50	10 nM
CHEMBL4098028	IC50	10 nM
CHEMBL4080004	IC50	10 nM
CHEMBL4085616	IC50	10 nM
CHEMBL4090321	IC50	10 nM
CHEMBL5181240	IC50	10 nM
6-Phenethylamino-1H-pyrimidine-2,4-dione	KI	11 nM
CHEMBL3827580	EC50	11 nM

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

830 with measured affinity, of 1650 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
2-[2-(4-ethylphenyl)ethyl]-6-(oxan-2-ylmethoxy)-1H-pyridin-4-one	2261416: Inverse agonist activity at human GPR84 expressed in HTLA cells co-expressing GPR84-tango plasmid assessed as beta-arrestin recruitment incubated for 30 mins by PRESTO-Tango assay	ec50	0.0035	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

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	affects cotreatment, decreases methylation	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)

Via MONDO — disease-level, not drug-specific.

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for GPR84 across ~30M SureChEMBL compounds — explore on Sugi Predict.