FFAR4

Summary

FFAR4 (free fatty acid receptor 4, HGNC:19061) is a protein-coding gene on chromosome 10q23.33, encoding Free fatty acid receptor 4 (Q5NUL3). G-protein-coupled receptor for long-chain fatty acids (LCFAs) with a major role in adipogenesis, energy metabolism and inflammation.

This gene encodes a G protein-coupled receptor (GPR) which belongs to the rhodopsin family of GPRs. The encoded protein functions as a receptor for free fatty acids, including omega-3, and participates in suppressing anti-inflammatory responses and insulin sensitizing. Multiple transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 338557 — RefSeq curated summary.

At a glance

• GWAS associations: 16
• Clinical variants (ClinVar): 63 total
• Druggable target: yes — 8 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001195755

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19061
Approved symbol	FFAR4
Name	free fatty acid receptor 4
Location	10q23.33
Locus type	gene with protein product
Status	Approved
Aliases	PGR4
Ensembl gene	ENSG00000186188
Ensembl biotype	protein_coding
OMIM	609044
Entrez	338557

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 4 protein_coding

ENST00000371481, ENST00000371483, ENST00000604414, ENST00000944863

RefSeq mRNA: 2 — MANE Select: NM_001195755 NM_001195755, NM_181745

CCDS: CCDS31248, CCDS55720

Canonical transcript exons

ENST00000371481 — 3 exons

Exon	Start	End
ENSE00001334565	93576091	93576219
ENSE00003901935	93587220	93590072
ENSE00003902173	93566665	93567287

Expression profiles

Bgee: expression breadth ubiquitous, 132 present calls, max score 81.68.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.5467 / max 95.8970, expressed in 153 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
106283	0.5169	152
106284	0.0298	5

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mucosa of sigmoid colon	UBERON:0004993	81.68	gold quality
mucosa of transverse colon	UBERON:0004991	81.35	gold quality
rectum	UBERON:0001052	80.55	gold quality
colonic mucosa	UBERON:0000317	80.00	gold quality
adenohypophysis	UBERON:0002196	79.02	gold quality
pituitary gland	UBERON:0000007	76.76	gold quality
islet of Langerhans	UBERON:0000006	76.71	gold quality
transverse colon	UBERON:0001157	68.53	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	65.10	silver quality
adipose tissue	UBERON:0001013	63.89	gold quality
epithelial cell of pancreas	CL:0000083	63.88	gold quality
subcutaneous adipose tissue	UBERON:0002190	62.98	gold quality
granulocyte	CL:0000094	61.72	gold quality
prefrontal cortex	UBERON:0000451	61.59	gold quality
adipose tissue of abdominal region	UBERON:0007808	61.36	gold quality
omental fat pad	UBERON:0010414	61.13	gold quality
peritoneum	UBERON:0002358	61.07	gold quality
pancreas	UBERON:0001264	60.72	gold quality
Brodmann (1909) area 9	UBERON:0013540	60.07	gold quality
large intestine	UBERON:0000059	59.91	gold quality
right lung	UBERON:0002167	59.85	gold quality
colonic epithelium	UBERON:0000397	59.82	silver quality
visceral pleura	UBERON:0002401	59.71	gold quality
pancreatic ductal cell	CL:0002079	59.65	silver quality
right frontal lobe	UBERON:0002810	59.39	gold quality
colon	UBERON:0001155	59.32	gold quality
leukocyte	CL:0000738	59.31	gold quality
monocyte	CL:0000576	59.24	gold quality
Brodmann (1909) area 23	UBERON:0013554	58.87	silver quality
middle temporal gyrus	UBERON:0002771	58.83	silver quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-GEOD-125970	yes	19.25
E-MTAB-5061	yes	13.49
E-GEOD-81608	yes	7.68
E-ENAD-27	yes	4.76
E-GEOD-81547	yes	4.40
E-MTAB-7303	no	5.38
E-ANND-3	no	3.37

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

57 targeting FFAR4, 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-7110-3P	100.00	73.18	2486
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-489-3P	99.80	66.46	839
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-6817-3P	99.79	68.35	2126
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-7157-5P	99.66	69.33	1829
HSA-MIR-497-3P	99.61	69.71	1990
HSA-MIR-4310	99.59	68.84	2527
HSA-MIR-4762-5P	99.57	68.54	1424
HSA-MIR-5584-5P	99.49	68.22	2814
HSA-MIR-372-5P	99.41	69.11	2299
HSA-MIR-519D-5P	99.41	69.30	2057
HSA-MIR-5695	99.41	67.48	1047

Literature-anchored findings (GeneRIF, showing 40)

• possible significance of the alternate splice variant of GPR120 in human is discussed (PMID:19723586)
• These are the first results which demonstrate specific phosphorylation of GPR120 isoforms upon agonism by free fatty acids and the first which distinguish the phosphorylation profiles of the two GPR120 isoforms. (PMID:20471368)
• GPR120 may participate in human gustatory fatty acid perception. (PMID:21868624)
• agonist-stimulated GPR120S and GPR120L receptors both recruited beta-arrestin2 and underwent robust internalization. (PMID:22282525)
• GPR120 expression in adipose tissue is significantly higher in obese individuals than in lean controls; GPR120 exon sequencing in obese subjects reveals a deleterious non-synonymous mutation (p.R270H) that inhibits GPR120 signalling activity (PMID:22343897)
• Our data suggest that the combination of common genetic variations in the GPR120 gene and dietary fat intake is a possible determinant of body mass index. (PMID:23594480)
• Our results show that EPA, DHA and AA elicit the same signalling events, but with different kinetics and efficiency through GPR120 in Caco-2 cells. (PMID:23849180)
• these results demonstrate that GPR120 functions as a tumor-promoting receptor in colorectal carcinoma and, therefore, shows promise as a new potential target for cancer therapeutics. (PMID:23851494)
• this study demonstrates the expression of GPR120 in pancreas and shows the distribution of GPR120 in human and rat pancreas. (PMID:23993698)
• Free fatty acids and protein kinase C activation induce GPR120 phosphorylation. (PMID:24239485)
• Basal and heterologous phosphorylation of FFA4 is mediated by protein kinase C. (PMID:24412271)
• CD36 and GPR120 have nonoverlapping roles in taste bud cell signaling during orogustatory perception of dietary lipids; these are differentially regulated by obesity. (PMID:24412488)
• GPR120 is a nutrient sensor that is activated endogenously by both saturated and unsaturated long chain fatty acids. (PMID:24742677)
• G protein-coupled receptor 120 (GPR 120) levels are reduced in pediatric obstructive sleep apnea and obesity (particularly when both are present) and may play a role in modulating the degree of insulin resistance (PMID:24790272)
• Phosphorylation and structural elements within the C-terminal tail of FFA4 allow for the recruitment of arrestin-3. (PMID:24817122)
• GPR120 is predominantly expressed in the microvillous membrane (MVM) of placenta and the expression level of this receptor in MVM is not altered by maternal body mass index (PMID:24844436)
• detailed mode of binding of both long-chain fatty acid and synthetic agonist ligands at FFA4 by integrating molecular modeling, receptor mutagenesis, and ligand structure-activity relationship approaches in an iterative format (PMID:24860101)
• Authors show that oleic acid stimulates lipid droplet formation by activating the long-chain fatty acid receptor FFAR4, which signals through a pertussis-toxin-sensitive G-protein signalling pathway involving PI3-kinase, AKT and (PLD) activities. (PMID:24876224)
• Morbidly obese subjects had lower GPR120 mRNA and protein levels in visceral adipose tissue and a lower mRNA expression after a high-fat meal in peripheral blood mononuclear cells. (PMID:24913719)
• GPR120 may have a positive role in the management of diabetes;GPR120 activation supports metabolic homeostasis by inhibiting inflammation in macrophages and regulating glucose and/or lipid metabolism in adipose, liver, and muscle tissues (PMID:25114508)
• Characterizing pharmacological ligands to study the long-chain fatty acid receptors GPR40/FFA1 and GPR120/FFA4 (PMID:25131623)
• a significant interaction effect on alanine transaminase levels suggesting a driving effect of the PNPLA3 148M allele on liver injury in children with obesity carrying this variant. (PMID:25250621)
• TNFa decreases GLP-2 expression by up-regulating GPR120 in Crohn disease (PMID:25447053)
• Findings demonstrate the novel functional properties of GPR120 on human eosinophils and indicate the previously unrecognized link between nutrient metabolism and the immune system. (PMID:25790291)
• the low-frequency p.R270H variant which inhibits GPR120 activity might influence fasting glucose levels in a normal physiological range. (PMID:26025001)
• It promotes the secretion of glucagon-like peptide-1 (GLP-1) in the intestine, and also acts as a lipid sensor in adipose tissue to sense dietary fat and control energy balance.(review) (PMID:26028412)
• GPR120 functions as a receptor for omega-3 fatty acid, involving in regulating the secretion of gastrointestinal peptide hormone, adipogenesis, adipogenic differentiation and anti-inflammatory process. [review] (PMID:26230883)
• These results suggest that distinct effects of GPR120 and GPR40 are involved in the acquisition of malignant property in pancreatic cancer cells. (PMID:26282200)
• demonstrated a GPR120-mediated novel anti-inflammatory pathway in specific intestinal epithelial cell types that could be of therapeutic relevance to intestinal inflammatory disorders (PMID:26791484)
• Ligands for FFAR4 comprise the family of long chain polyunsaturated fatty acids, suggesting that many of the long-known beneficial effects of these fats may be receptor mediated. (Review) (PMID:26827942)
• GPR120 negatively and GPR40 positively regulate cellular functions during tumor progression in lung cancer cells. (PMID:26968637)
• P.R270H of FFAR4 impairs Gq and Gi signalling of FFAR4 in vitro. (PMID:27068006)
• p.R270H variant of GPR120 modulates the risk of type 2 diabetes in interaction with dietary fat intake. (PMID:27212621)
• Fatty acids are capable of directly acting on visceral adipocytes to modulate differently TNF-alpha, IL-6, IL-10 and adiponectin expression, with a different and greater effect in morbidly obese subjects. These effects are largely annulled when GPR120 expression was silenced, which suggests that they could be mediated by GPR120. (PMID:27299582)
• LPA1 plays a critical role in EGF responses and that FFA4 agonists inhibit proliferation by suppressing positive cross-talk between LPA1 and the EGF receptor (PMID:27474750)
• These results indicated that GPR120 enhanced and GPR40 inhibited the cell motile activity of highly migratory osteosarcoma cells. (PMID:28159555)
• G protein-coupled receptor 120 (GPR120) represents a promising target for the treatment of obesity-related metabolic disorders for its involvement in the regulation of adipogenesis, inflammation, glucose uptake, and insulin resistance. This review summarizes recent studies and advances regarding the systemic role of GPR120 in adipose tissue, including both white and brown adipocytes. [review] (PMID:28285320)
• Studied action of linoleic acid (LA) on cell migration and neoplasm invasiveness of breast cancer cells. Findings show Akt2 activation requires EGFR and PI3K activity, whereas migration and invasion are dependent on FFAR4, EGFR and PI3K/Akt activity. (PMID:28456993)
• Eicosapentaenoic acid prevents TNF-alpha-induced decrease of alpha-methylglucose uptake and AMPK phosphorylation in Caco-2 cells via GPR120 and AMPK activation. (PMID:28771713)
• 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)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Ffar4	ENSMUSG00000054200
rattus_norvegicus	Ffar4	ENSRNOG00000021763
drosophila_melanogaster	CrzR	FBGN0036278
caenorhabditis_elegans		WBGENE00013642

Paralogs (16): NPFFR2 (ENSG00000056291), GNRHR (ENSG00000109163), CCKBR (ENSG00000110148), HCRTR1 (ENSG00000121764), AVPR2 (ENSG00000126895), GALR3 (ENSG00000128310), HCRTR2 (ENSG00000137252), NPFFR1 (ENSG00000148734), CCKAR (ENSG00000163394), AVPR1A (ENSG00000166148), GALR1 (ENSG00000166573), GPR22 (ENSG00000172209), GPR150 (ENSG00000178015), OXTR (ENSG00000180914), QRFPR (ENSG00000186867), AVPR1B (ENSG00000198049)

Protein

Protein identifiers

Free fatty acid receptor 4 — Q5NUL3 (reviewed: Q5NUL3)

Alternative names: G-protein coupled receptor 120, G-protein coupled receptor 129, G-protein coupled receptor GT01, G-protein coupled receptor PGR4, Omega-3 fatty acid receptor 1

All UniProt accessions (2): Q5NUL3, S4R3L2

UniProt curated annotations — full annotation on UniProt →

Function. G-protein-coupled receptor for long-chain fatty acids (LCFAs) with a major role in adipogenesis, energy metabolism and inflammation. Signals via G-protein and beta-arrestin pathways. LCFAs sensing initiates activation of phosphoinositidase C-linked G proteins GNAQ and GNA11 (G(q)/G(11)), inducing a variety of cellular responses via second messenger pathways such as intracellular calcium mobilization, modulation of cyclic adenosine monophosphate (cAMP) production, and mitogen-activated protein kinases (MAPKs). After LCFAs binding, associates with beta-arrestin ARRB2 that acts as an adapter protein coupling the receptor to specific downstream signaling pathways, as well as mediating receptor endocytosis. In response to dietary fats, plays an important role in the regulation of adipocyte proliferation and differentiation. Acts as a receptor for omega-3 polyunsaturated fatty acids (PUFAs) at primary cilium of perivascular preadipocytes, initiating an adipogenic program via cAMP and CTCF-dependent chromatin remodeling that ultimately results in transcriptional activation of adipogenic genes and cell cycle entry. Induces differentiation of brown adipocytes probably via autocrine and endocrine functions of FGF21 hormone. Activates brown adipocytes by initiating intracellular calcium signaling that leads to mitochondrial depolarization and fission, and overall increased mitochondrial respiration. Consequently stimulates fatty acid uptake and oxidation in mitochondria together with UCP1-mediated thermogenic respiration, eventually reducing fat mass. Regulates bi-potential differentiation of bone marrow mesenchymal stem cells toward osteoblasts or adipocytes likely by up-regulating distinct integrins. In response to dietary fats regulates hormone secretion and appetite. Stimulates GIP and GLP1 secretion from enteroendocrine cells as well as GCG secretion in pancreatic alpha cells, thereby playing a role in the regulation of blood glucose levels. Negatively regulates glucose-induced SST secretion in pancreatic delta cells. Mediates LCFAs inhibition of GHRL secretion, an appetite-controlling hormone. In taste buds, contributes to sensing of dietary fatty acids by the gustatory system. During the inflammatory response, promotes anti-inflammatory M2 macrophage differentiation in adipose tissue. Mediates the anti-inflammatory effects of omega-3 PUFAs via inhibition of NLRP3 inflammasome activation. In this pathway, interacts with adapter protein ARRB2 and inhibits the priming step triggered by Toll-like receptors (TLRs) at the level of TAK1 and TAB1. Further inhibits the activation step when ARRB2 directly associates with NLRP3, leading to inhibition of pro-inflammatory cytokine release. Mediates LCFAs anti-apoptotic effects. Receptor for LCFAs decoupled from G-protein signaling. May signal through beta-arrestin pathway. After LCFAs binding, associates with beta-arrestin ARRB2 that may act as an adapter protein coupling the receptor to specific downstream signaling pathways, as well as mediating receptor endocytosis.

Subunit / interactions. Interacts (via C-terminus) with ARRB2 following LCFAs stimulation. Interacts (via C-terminus) with ARRB2 following LCFAs stimulation.

Subcellular location. Cell membrane. Endosome membrane. Lysosome membrane Cell membrane. Lysosome membrane. Cell projection. Cilium membrane.

Tissue specificity. The predominant isoform in human tissues. Expressed in adipose tissue, pancreatic islets, lung and brain. Expressed in alpha cells of pancreatic islets. Expressed in primary cilia of perivascular preadipocytes of white adipose tissue (at protein level). Abundant expression in the intestinal tract. Expressed in colonic intraepithelial neuroendocrine cells.

Post-translational modifications. Phosphorylated at two clusters of Ser and Thr residues located in the intracellular C-terminus, a prerequisite for FFAR4 internalization via an ARRB2-dependent pathway.

Polymorphism. Genetic variations in FFAR4 define the body mass index quantitative trait locus 10 (BMIQ10) [MIM:607514]. Variance in body mass index is a susceptibility factor for obesity.

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

Isoforms (2)

UniProt ID	Names	Canonical?
Q5NUL3-2	2	yes
Q5NUL3-1	1

RefSeq proteins (2): NP_001182684, NP_859529 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000276	GPCR_Rhodpsn	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain

Pfam: PF00001

UniProt features (50 total): helix 10, topological domain 8, transmembrane region 7, modified residue 5, turn 4, strand 4, mutagenesis site 3, sequence conflict 3, sequence variant 2, chain 1, glycosylation site 1, disulfide bond 1, splice variant 1

Structure

Experimental structures (PDB)

12 structures.

PDB	Method	Resolution (Å)
8G59	ELECTRON MICROSCOPY	2.64
8ID6	ELECTRON MICROSCOPY	2.8
8IYS	ELECTRON MICROSCOPY	2.95
8ID8	ELECTRON MICROSCOPY	3
8ID9	ELECTRON MICROSCOPY	3
8H4I	ELECTRON MICROSCOPY	3.06
8T3O	ELECTRON MICROSCOPY	3.06
8H4L	ELECTRON MICROSCOPY	3.07
8H4K	ELECTRON MICROSCOPY	3.1
8ID3	ELECTRON MICROSCOPY	3.1
8ID4	ELECTRON MICROSCOPY	3.1
8T3Q	ELECTRON MICROSCOPY	3.14

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5NUL3-F1	79.16	0.46

Antibody-complex structures (SAbDab): 12 — 8G59, 8H4I, 8H4K, 8H4L, 8ID3, 8ID4, 8ID6, 8ID8, 8ID9, 8IYS, 8T3O, 8T3Q

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 (5): 347, 349, 350, 357, 360

Disulfide bonds (1): 111–194

Glycosylation sites (1): 21

Mutagenesis-validated functional residues (3):

Position	Phenotype
99	impairs lcfa-induced intracellular calcium release.
178	has no effect on lcfa-induced intracellular calcium release.
347–360	impairs lcfa-mediated phosphorylation and interaction with arrb2.

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-381771	Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1)
R-HSA-416476	G alpha (q) signalling events
R-HSA-444209	Free fatty acid receptors

MSigDB gene sets: 184 (showing top): GSE45365_NK_CELL_VS_CD8_TCELL_DN, GSE37336_LY6C_POS_VS_NEG_NAIVE_CD4_TCELL_UP, GOBP_CARBOHYDRATE_TRANSPORT, GOBP_REGULATION_OF_FAT_CELL_DIFFERENTIATION, BENPORATH_ES_WITH_H3K27ME3, GOBP_NEGATIVE_REGULATION_OF_INTERLEUKIN_1_PRODUCTION, GOBP_INFLAMMATORY_RESPONSE, GOCC_VACUOLAR_MEMBRANE, GOBP_POSITIVE_REGULATION_OF_FAT_CELL_DIFFERENTIATION, GOBP_WHITE_FAT_CELL_DIFFERENTIATION, GOBP_POSITIVE_REGULATION_OF_MAPK_CASCADE, GOBP_REGULATION_OF_HORMONE_LEVELS, GOBP_NEGATIVE_REGULATION_OF_PEPTIDE_SECRETION, GOBP_OSTEOBLAST_DIFFERENTIATION, GOBP_SENSORY_PERCEPTION_OF_CHEMICAL_STIMULUS

GO Biological Process (24): negative regulation of cytokine production (GO:0001818), inflammatory response (GO:0006954), G protein-coupled receptor signaling pathway (GO:0007186), adenylate cyclase-activating G protein-coupled receptor signaling pathway (GO:0007189), phospholipase C-activating G protein-coupled receptor signaling pathway (GO:0007200), positive regulation of cytosolic calcium ion concentration (GO:0007204), regulation of D-glucose transmembrane transport (GO:0010827), negative regulation of interleukin-1 beta production (GO:0032691), ghrelin secretion (GO:0036321), negative regulation of apoptotic process (GO:0043066), positive regulation of osteoblast differentiation (GO:0045669), hormone secretion (GO:0046879), negative regulation of inflammatory response (GO:0050728), white fat cell differentiation (GO:0050872), brown fat cell differentiation (GO:0050873), positive regulation of glucagon secretion (GO:0070094), positive regulation of ERK1 and ERK2 cascade (GO:0070374), negative regulation of somatostatin secretion (GO:0090275), positive regulation of brown fat cell differentiation (GO:0090336), positive regulation of cold-induced thermogenesis (GO:0120162), signal transduction (GO:0007165), cell differentiation (GO:0030154), fat cell differentiation (GO:0045444), detection of chemical stimulus involved in sensory perception of taste (GO:0050912)

GO Molecular Function (6): G protein-coupled receptor activity (GO:0004930), fatty acid binding (GO:0005504), taste receptor activity (GO:0008527), arrestin family protein binding (GO:1990763), protein binding (GO:0005515), lipid binding (GO:0008289)

GO Cellular Component (11): lysosomal membrane (GO:0005765), plasma membrane (GO:0005886), cilium (GO:0005929), endosome membrane (GO:0010008), endocytic vesicle (GO:0030139), ciliary basal body (GO:0036064), ciliary membrane (GO:0060170), lysosome (GO:0005764), endosome (GO:0005768), membrane (GO:0016020), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Incretin synthesis, secretion, and inactivation	1
GPCR downstream signalling	1
Class A/1 (Rhodopsin-like receptors)	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
G protein-coupled receptor signaling pathway	2
fat cell differentiation	2
transmembrane signaling receptor activity	2
binding	2
bounding membrane of organelle	2
cytoplasmic vesicle	2
cilium	2
cellular anatomical structure	2
cytokine production	1
regulation of cytokine production	1
negative regulation of gene expression	1
negative regulation of multicellular organismal process	1
defense response	1
G protein-coupled receptor activity	1
signal transduction	1
adenylate cyclase-modulating G protein-coupled receptor signaling pathway	1
adenylate cyclase activator activity	1
phospholipase C activator activity	1
regulation of biological quality	1
regulation of transmembrane transport	1
D-glucose transmembrane transport	1
interleukin-1 beta production	1
regulation of interleukin-1 beta production	1
negative regulation of interleukin-1 production	1
peptide hormone secretion	1
apoptotic process	1
regulation of apoptotic process	1
negative regulation of programmed cell death	1
osteoblast differentiation	1
positive regulation of cell differentiation	1
regulation of osteoblast differentiation	1
hormone transport	1
signal release	1
inflammatory response	1
negative regulation of defense response	1
negative regulation of response to external stimulus	1
regulation of inflammatory response	1
glucagon secretion	1
regulation of glucagon secretion	1
positive regulation of peptide hormone secretion	1

Protein interactions and networks

STRING

1010 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FFAR4	FFAR1	O14842	938
FFAR4	ARRB2	P32121	903
FFAR4	GNAQ	P50148	884
FFAR4	FFAR2	O15552	867
FFAR4	FFAR3	O14843	860
FFAR4	GPR84	Q9NQS5	832
FFAR4	TAS1R3	Q7RTX0	802
FFAR4	TAS1R2	Q8TE23	791
FFAR4	GPR119	Q8TDV5	780
FFAR4	PYY	P10082	744
FFAR4	INS	P01308	728
FFAR4	SCARB2	Q14108	718
FFAR4	CD36	P16671	718
FFAR4	SCARB1	Q8WTV0	712
FFAR4	SLC5A1	P13866	706

IntAct

4 interactions, top by confidence:

A	B	Type	Score
RAMP1	FFAR4	psi-mi:“MI:0915”(physical association)	0.400
FFAR4	RAMP2	psi-mi:“MI:0915”(physical association)	0.400
FFAR4	RAMP3	psi-mi:“MI:0915”(physical association)	0.400

ESM2 similar proteins: C8YUV0, O19037, O77616, P31392, P43142, P55167, P56442, P56445, P56447, P56448, Q01726, Q29154, Q2AC31, Q5NUL3, Q6A155, Q7TMA4, Q7TQP3, Q80SS9, Q864F4, Q864F6, Q864F7, Q864F8, Q864H5, Q864H7, Q864H8, Q864H9, Q864I4, Q864I6, Q864I7, Q864J1, Q864J2, Q864J3, Q864J4, Q864J5, Q864J7, Q864J8, Q864J9, Q864K0, Q864K2, Q864K3

Diamond homologs: A0A287A2K5, C8YUV0, O00155, O02836, O08786, O15973, O18935, O19012, O19014, O19025, O19032, O19054, O19091, O62729, O77408, O77700, O77721, O77830, O97665, O97772, P04761, P08482, P0C5I1, P11229, P12657, P17200, P18089, P19328, P22270, P25021, P30545, P30551, P30552, P30553, P30796, P32211, P32238, P32239, P32302, P46627

SIGNOR signaling

9 interactions.

A	Effect	B	Mechanism
FFAR4	“up-regulates activity”	GNAS	binding
FFAR4	“up-regulates activity”	GNAL	binding
FFAR4	“up-regulates activity”	GNAI1	binding
FFAR4	“up-regulates activity”	GNAI3	binding
FFAR4	“up-regulates activity”	GNAO1	binding
FFAR4	“up-regulates activity”	GNAZ	binding
FFAR4	“up-regulates activity”	GNAQ	binding
FFAR4	“up-regulates activity”	GNA14	binding
“3-(4-{[5-Fluoro-2-(4-methylphenyl)phenyl]methoxy}phenyl)propanoic acid”	“up-regulates activity”	FFAR4	“chemical activation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	50
Likely benign	6
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

1100 predictions. Top by Δscore:

Variant	Effect	Δscore
10:93576215:TACAG:T	donor_loss	1.0000
10:93576216:ACAG:A	donor_loss	1.0000
10:93576217:CAG:C	donor_loss	1.0000
10:93576218:AG:A	donor_loss	1.0000
10:93576219:GG:G	donor_loss	1.0000
10:93576220:G:GC	donor_loss	1.0000
10:93576221:T:A	donor_loss	1.0000
10:93593819:TCA:T	donor_loss	1.0000
10:93593820:CA:C	donor_loss	1.0000
10:93593821:A:AC	donor_gain	1.0000
10:93593821:A:AG	donor_loss	1.0000
10:93593822:C:CC	donor_gain	1.0000
10:93594036:C:CC	acceptor_gain	1.0000
10:93600387:ACT:A	donor_loss	1.0000
10:93600388:CTC:C	donor_loss	1.0000
10:93600389:TCA:T	donor_loss	1.0000
10:93600390:CAC:C	donor_loss	1.0000
10:93600391:A:AC	donor_gain	1.0000
10:93600391:ACTT:A	donor_gain	1.0000
10:93600391:ACTTC:A	donor_gain	1.0000
10:93600392:C:CT	donor_gain	1.0000
10:93600392:C:G	donor_loss	1.0000
10:93600392:CT:C	donor_gain	1.0000
10:93600392:CTT:C	donor_gain	1.0000
10:93600392:CTTC:C	donor_gain	1.0000
10:93600392:CTTCC:C	donor_gain	1.0000
10:93600394:T:TA	donor_gain	1.0000
10:93600395:C:A	donor_gain	1.0000
10:93600429:T:TA	donor_gain	1.0000
10:93600497:TTA:T	acceptor_gain	1.0000

AlphaMissense

2313 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:93587355:A:C	S278R	0.997
10:93587357:C:A	S278R	0.997
10:93587357:C:G	S278R	0.997
10:93567117:A:C	S133R	0.995
10:93567119:C:A	S133R	0.995
10:93567119:C:G	S133R	0.995
10:93576117:G:C	W198C	0.994
10:93576117:G:T	W198C	0.994
10:93567032:G:C	W104C	0.993
10:93567032:G:T	W104C	0.993
10:93587340:T:C	F273L	0.992
10:93587342:C:A	F273L	0.992
10:93587342:C:G	F273L	0.992
10:93587352:T:A	W277R	0.992
10:93587352:T:C	W277R	0.992
10:93587359:C:G	P279R	0.992
10:93566960:C:A	N80K	0.991
10:93566960:C:G	N80K	0.991
10:93576103:T:A	C194S	0.991
10:93576104:G:C	C194S	0.991
10:93587359:C:A	P279H	0.991
10:93567030:T:A	W104R	0.990
10:93567030:T:C	W104R	0.990
10:93576104:G:A	C194Y	0.990
10:93576105:C:G	C194W	0.989
10:93567052:G:A	C111Y	0.988
10:93576199:A:C	S226R	0.988
10:93576201:T:A	S226R	0.988
10:93576201:T:G	S226R	0.988
10:93567081:A:C	S121R	0.987

dbSNP variants (sampled 300 via entrez): RS1000116072 (10:93572085 T>C), RS1000133083 (10:93586891 C>T), RS1000171727 (10:93570425 A>G), RS1000330755 (10:93568812 GTGTT>G), RS1000475310 (10:93568610 C>A,T), RS1000490479 (10:93576845 G>A), RS1000721106 (10:93570186 T>A,G), RS1000843470 (10:93580812 T>C), RS1000959924 (10:93586663 C>A), RS1001053151 (10:93575099 C>T), RS1001327033 (10:93586935 A>G,T), RS1001373533 (10:93581559 G>A), RS1001399927 (10:93586342 T>C), RS1001422060 (10:93575385 A>G), RS1001514076 (10:93565111 A>G)

Disease associations

OMIM: gene MIM:609044 | disease phenotypes: MIM:615147

GenCC curated gene-disease

Mondo (1): progressive retinal dystrophy due to retinol transport defect (MONDO:0014060)

Orphanet (1): Progressive retinal dystrophy due to retinol transport defect (Orphanet:352718)

HPO phenotypes

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

GWAS associations

16 associations (top):

Study	Trait	p-value
GCST009174_2	Response to (pegylated) interferon in chronic hepatitis B	1.000000e-06
GCST010242_26	HDL cholesterol levels	2.000000e-16
GCST010244_249	Triglyceride levels	2.000000e-23
GCST90002405_264	Reticulocyte count	2.000000e-09
GCST90020024_221	A body shape index	7.000000e-13
GCST90020025_559	Waist-to-hip ratio adjusted for BMI	2.000000e-10
GCST90020025_560	Waist-to-hip ratio adjusted for BMI	1.000000e-09
GCST90020025_561	Waist-to-hip ratio adjusted for BMI	7.000000e-11
GCST90020025_562	Waist-to-hip ratio adjusted for BMI	1.000000e-10
GCST90020025_563	Waist-to-hip ratio adjusted for BMI	8.000000e-15
GCST90020027_1638	Waist-hip index	7.000000e-11
GCST90020027_1639	Waist-hip index	1.000000e-10
GCST90020027_1640	Waist-hip index	1.000000e-14
GCST90020027_885	Waist-hip index	1.000000e-10
GCST90020027_886	Waist-hip index	7.000000e-10
GCST90020029_136	Waist circumference adjusted for body mass index	2.000000e-10

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0007859	response to interferon
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004530	triglyceride measurement
EFO:0007986	reticulocyte count
EFO:0007789	BMI-adjusted waist circumference
EFO:0007788	BMI-adjusted waist-hip ratio

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5339 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

8 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 394,176 (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
CHEMBL1200517	DIHYDROERGOTAMINE MESYLATE	4	2,704
CHEMBL1707	LOPERAMIDE HYDROCHLORIDE	4	59,532
CHEMBL1722209	TOLTERODINE TARTRATE	4	3,920
CHEMBL344159	TOLVAPTAN	4	3,645
CHEMBL502182	ELAGOLIX SODIUM	4	214
CHEMBL267476	LINOLEIC ACID	2	323,195
CHEMBL419667	RELCOVAPTAN	2	358
CHEMBL9506	DEVAZEPIDE	2	608

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: gpcr — Free fatty acid receptors

Most potent curated ligand interactions (11 total), top 11:

Ligand	Action	Affinity	Parameter
compound A [PMID 24997608]	Agonist	7.62	pEC50
TUG-891	Full agonist	7.0	pEC50
TUG-1197	Agonist	6.63	pEC50
NCG21	Full agonist	5.92	pEC50
linoleic acid	Full agonist	5.89	pEC50
α-linolenic acid	Full agonist	5.5	pEC50
GW9508	Partial agonist	5.46	pEC50
myristic acid	Full agonist	5.2	pEC50
grifolic acid methyl ether	Partial agonist	5.01	pA2
grifolic acid	Partial agonist	4.95	pA2
oleic acid	Full agonist	4.7	pEC50

Binding affinities (BindingDB)

418 measured of 420 human assays (420 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
Trans-(2-((2′-fluoro-5′-isopropoxy-[1,1′-biphenyl]-4-yl)methyl)cyclopropyl)acetic acid (Enantiomer 2)	EC50	60 nM	US-9938222: Cyclopropanecarboxylic acid GPR120 modulators
(1R)-2-[[2-fluoro-4-[2-fluoro-5-(3-fluorophenoxy)phenyl]phenoxy]methyl]cyclopropane-1-carboxylic acid	EC50	70 nM	US-9938222: Cyclopropanecarboxylic acid GPR120 modulators
(1R,2R)-2-(((2′,3-Difluoro-5′-phenoxy-[1,1′-biphenyl]-4-yl)oxy)methyl) cyclopropanecarboxylic acid (Enantiomer 1; absolute stereochemistry drawn in an arbitrary manner)	EC50	80 nM	US-9938222: Cyclopropanecarboxylic acid GPR120 modulators
2-[[4-[2,3-difluoro-5-(3-fluorophenoxy)phenyl]-2-fluorophenoxy]methyl]cyclopropane-1-carboxylic acid	EC50	90 nM	US-9938222: Cyclopropanecarboxylic acid GPR120 modulators
(1S)-2-[[4-[2-fluoro-5-[(6-methyl-3-pyridinyl)oxy]phenyl]phenoxy]methyl]cyclopropane-1-carboxylic acid	EC50	90 nM	US-9938222: Cyclopropanecarboxylic acid GPR120 modulators
2-[[4-(5-fluoro-2-phenoxyphenyl)phenoxy]methyl]cyclopropane-1-carboxylic acid	EC50	110 nM	US-9938222: Cyclopropanecarboxylic acid GPR120 modulators
(1S)-2-[[4-[2-chloro-5-(3-fluorophenoxy)-3-pyridinyl]phenoxy]methyl]cyclopropane-1-carboxylic acid	EC50	120 nM	US-9938222: Cyclopropanecarboxylic acid GPR120 modulators
2-[[2-fluoro-4-[2-fluoro-5-(3-fluoro-4-methylphenoxy)phenyl]phenoxy]methyl]cyclopropane-1-carboxylic acid	EC50	130 nM	US-9938222: Cyclopropanecarboxylic acid GPR120 modulators
2-[[4-(5-cyclobutyloxy-2-fluorophenyl)phenoxy]methyl]cyclopropane-1-carboxylic acid	EC50	140 nM	US-9938222: Cyclopropanecarboxylic acid GPR120 modulators
cis-(1S,2S)-2-[[4-[2,3-difluoro-5-(3-fluorophenoxy)phenyl]-2-fluorophenoxy]methyl]cyclopropane-1-carboxylic acid	EC50	140 nM	US-9938222: Cyclopropanecarboxylic acid GPR120 modulators
Trans-2-(((2′-fluoro-5′-((6-methylpyridin-3-yl)oxy)-[1,1′-biphenyl]-4-yl)oxy)methyl) cyclopropanecarboxylic acid (racemate)	EC50	140 nM	US-9938222: Cyclopropanecarboxylic acid GPR120 modulators
(Trans)-(+/−)-2-(((2′,3-difluoro-5′-phenoxy-[1,1′-biphenyl]-4-yl)oxy)methyl) cyclopropanecarboxylic acid	EC50	160 nM	US-9938222: Cyclopropanecarboxylic acid GPR120 modulators
4-[4-[[2-chloro-3-(trifluoromethyl)phenyl]methoxy]-1-bicyclo[2.2.1]heptanyl]butanoic acid	EC50	170 nM	US-9518000: Bicyclo [2.2.1] acid GPR120 modulators
2-[[2-fluoro-4-[2-fluoro-5-[(6-methyl-3-pyridinyl)oxy]phenyl]phenoxy]methyl]cyclopropane-1-carboxylic acid	EC50	170 nM	US-9938222: Cyclopropanecarboxylic acid GPR120 modulators
2-[[4-[2-fluoro-5-(3-fluorophenoxy)phenyl]phenoxy]methyl]cyclopropane-1-carboxylic acid	EC50	180 nM	US-9938222: Cyclopropanecarboxylic acid GPR120 modulators
cis-(1R,2R)-2-[[2-fluoro-4-(2-fluoro-5-propan-2-yloxyphenyl)phenoxy]methyl]cyclopropane-1-carboxylic acid	EC50	180 nM	US-9938222: Cyclopropanecarboxylic acid GPR120 modulators
2-[2-[4-(3-phenoxyphenyl)phenyl]ethyl]cyclopropane-1-carboxylic acid	EC50	180 nM	US-9938222: Cyclopropanecarboxylic acid GPR120 modulators
Trans-2-(((2′-fluoro-5′-isopropoxy-3-(trifluoromethyl)-[1,1′-biphenyl]-4-yl)oxy)methyl) cyclopropanecarboxylic acid (racemate)	EC50	180 nM	US-9938222: Cyclopropanecarboxylic acid GPR120 modulators
Trans-2-(((2′,3-difluoro-5′-(3-fluorophenoxy)-[1,1′-biphenyl]-4-yl)oxy)methyl) cyclopropanecarboxylic acid	EC50	180 nM	US-9938222: Cyclopropanecarboxylic acid GPR120 modulators
2-[2-[4-[(1R,3S)-3-phenoxycyclohexyl]phenyl]ethoxy]acetic acid	EC50	180 nM	US-10336684: Phenyl-(aza)cycloalkyl carboxylic acid GPR120 modulators
Trans-2-((4-(2-chloro-5-(3-fluorophenoxy)pyridin-3-yl)phenoxy)methyl) cyclopropanecarboxylic acid (racemate)	EC50	190 nM	US-9938222: Cyclopropanecarboxylic acid GPR120 modulators
(1R)-2-[[4-[2-fluoro-5-[(6-methyl-3-pyridinyl)oxy]phenyl]phenoxy]methyl]cyclopropane-1-carboxylic acid	EC50	190 nM	US-9938222: Cyclopropanecarboxylic acid GPR120 modulators
(1S,2R)-2-(2-(2′-Fluoro-5′-isopropoxy-[,1,1′-biphenyl]-4-yl)ethyl)cyclopropanecarboxylic acid (Enantiomer 2; absolute stereochemistry drawn in an arbitrary manner)	EC50	200 nM	US-9938222: Cyclopropanecarboxylic acid GPR120 modulators
(1S)-2-[[2-fluoro-4-[2-fluoro-5-(3-fluorophenoxy)phenyl]phenoxy]methyl]cyclopropane-1-carboxylic acid	EC50	200 nM	US-9938222: Cyclopropanecarboxylic acid GPR120 modulators
2-[8-(5-cyclobutyloxy-2-fluoro-4-methoxyphenyl)-8-azaspiro[4.5]decan-3-yl]ethyl formate	EC50	202 nM	US-9708270: Substituted spiropiperidinyl compounds useful as GPR120 agonists
Trans-2-(((2′-chloro-3-fluoro-5′-isopropoxy-[1,1′-biphenyl]-4yl)oxy)methyl) cyclopropanecarboxylic acid (racemate)	EC50	210 nM	US-9938222: Cyclopropanecarboxylic acid GPR120 modulators
(1R)-2-[[4-[2-chloro-5-(3-fluorophenoxy)-3-pyridinyl]phenoxy]methyl]cyclopropane-1-carboxylic acid	EC50	210 nM	US-9938222: Cyclopropanecarboxylic acid GPR120 modulators
2-[8-[2-cyano-5-(trifluoromethoxy)phenyl]-8-azaspiro[4.5]decan-3-yl]ethyl formate	EC50	220 nM	US-9708270: Substituted spiropiperidinyl compounds useful as GPR120 agonists
2-[[2-chloro-4-(2-fluoro-5-propan-2-yloxyphenyl)phenoxy]methyl]cyclopropane-1-carboxylic acid	EC50	220 nM	US-9938222: Cyclopropanecarboxylic acid GPR120 modulators
5-[4-[(3S)-3-phenoxypyrrolidin-1-yl]phenyl]pentanoic acid	EC50	220 nM	US-10336684: Phenyl-(aza)cycloalkyl carboxylic acid GPR120 modulators
4-[4-[[3-methyl-5-(trifluoromethoxy)phenyl]methoxy]-1-bicyclo[2.2.1]heptanyl]butanoic acid	EC50	230 nM	US-9518000: Bicyclo [2.2.1] acid GPR120 modulators
cis-(1S,2S)-2-[[4-(2,3-difluoro-5-propan-2-yloxyphenyl)-2-fluorophenoxy]methyl]cyclopropane-1-carboxylic acid	EC50	230 nM	US-9938222: Cyclopropanecarboxylic acid GPR120 modulators
4-[4-[[3-(4-fluorophenoxy)phenyl]methoxy]-1-bicyclo[2.2.1]heptanyl]butanoic acid	EC50	250 nM	US-9518000: Bicyclo [2.2.1] acid GPR120 modulators
4-[4-[[3-chloro-5-(trifluoromethoxy)phenyl]methoxy]-1-bicyclo[2.2.1]heptanyl]butanoic acid	EC50	250 nM	US-9518000: Bicyclo [2.2.1] acid GPR120 modulators
(METHOD A)	EC50	250 nM	US-9938222: Cyclopropanecarboxylic acid GPR120 modulators
4-[4-[[2-fluoro-5-(trifluoromethoxy)phenyl]methoxy]-1-bicyclo[2.2.1]heptanyl]butanoic acid	EC50	260 nM	US-9518000: Bicyclo [2.2.1] acid GPR120 modulators
4-(4-((2-(5-(1-Cyanocyclopropyl)thiophen-2-yl)-5-fluorobenzyl)oxy)phenyl)butanoic acid	EC50	260 nM	US-10227360: Compounds for use as GPR120 agonists
4-(4-((4-Fluoro-4’-(1-methylcyclopropyl)-[1,1’-biphenyl]-2-yl)methoxy)phenyl)butanoic acid	EC50	260 nM	US-10227360: Compounds for use as GPR120 agonists
4-(4-((4’-(1-Cyanocyclopropyl)-4-fluoro-[1,1’-biphenyl]-2-yl)methoxy)phenyl)butanoic acid	EC50	260 nM	US-10227360: Compounds for use as GPR120 agonists
3-(4-((4’-(1-Cyanocyclopropyl)-4-fluoro-[1,1’-biphenyl]-2-yl)methoxy)phenyl)propanoic acid	EC50	260 nM	US-10227360: Compounds for use as GPR120 agonists
4-(4-((4’-Cyclopropyl-4-fluoro-[1,1’-biphenyl]-2-yl)methoxy)phenyl)butanoic acid	EC50	260 nM	US-10227360: Compounds for use as GPR120 agonists
4-(4-((2-(2,3-Dihydro-1H-inden-5-yl)-5-fluorobenzyl)oxy)phenyl)butanoic acid	EC50	260 nM	US-10227360: Compounds for use as GPR120 agonists
4-(4-((5-Fluoro-2-(5,6,7,8-tetrahydronaphthalen-2-yl)benzyl)oxy)phenyl)butanoic acid	EC50	260 nM	US-10227360: Compounds for use as GPR120 agonists
4-(4-((2-(Bicyclo[4.2.0]octa-1(6),2,4-trien-3-yl)-5-fluorobenzyl)oxy)phenyl)butanoic acid	EC50	260 nM	US-10227360: Compounds for use as GPR120 agonists
4-(4-((2-(5-Cyclopropylthiophen-2-yl)-5-fluorobenzyl)oxy)phenyl)butanoic acid	EC50	260 nM	US-10227360: Compounds for use as GPR120 agonists
3-(5-((4’-(1-Cyanocyclopropyl)-4-fluoro-[1,1’-biphenyl]-2-yl)methoxy)pyridin-2-yl)propanoic acid	EC50	260 nM	US-10227360: Compounds for use as GPR120 agonists
4-(4-((2-(2,3-Dihydrobenzofuran-5-yl)-5-fluorobenzyl)oxy)phenyl)butanoic acid	EC50	260 nM	US-10227360: Compounds for use as GPR120 agonists
4-(4-((5-Fluoro-2-(4,5,6,7-tetrahydrobenzo[b]thiophen-2-yl)benzyl)oxy)phenyl)butanoic acid	EC50	260 nM	US-10227360: Compounds for use as GPR120 agonists
4-(4-((2-(6,7-Dihydro-5H-cyclopenta[b]pyridin-3-yl)-5-fluorobenzyl)oxy)phenyl)butanoic acid	EC50	260 nM	US-10227360: Compounds for use as GPR120 agonists
4-(4-((2-(Bicyclo[4.2.0]octa-1(6),2,4-trien-3-yl)benzyl)oxy)phenyl)butanoic acid	EC50	260 nM	US-10227360: Compounds for use as GPR120 agonists

ChEMBL bioactivities

1212 potent at pChembl≥5 of 1312 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.30	EC50	5	nM	CHEMBL3952043
8.28	EC50	5.3	nM	CHEMBL5286838
8.25	EC50	5.6	nM	CHEMBL3972870
8.22	EC50	6	nM	CHEMBL4637969
8.22	EC50	6	nM	CHEMBL4646784
8.22	EC50	6	nM	CHEMBL2386353
8.21	EC50	6.2	nM	CHEMBL3960738
8.11	EC50	7.8	nM	CHEMBL3898962
8.10	EC50	8	nM	CHEMBL3970166
8.08	EC50	8.3	nM	CHEMBL3909773
8.05	EC50	9	nM	CHEMBL3940429
8.00	EC50	10	nM	CHEMBL3970238
7.96	EC50	11	nM	CHEMBL3890089
7.89	EC50	13	nM	CHEMBL3943315
7.89	EC50	13	nM	CHEMBL3947070
7.85	EC50	14	nM	CHEMBL3972870
7.85	EC50	14	nM	CHEMBL3952043
7.82	EC50	15	nM	CHEMBL3960738
7.82	EC50	15	nM	CHEMBL3940429
7.80	EC50	16	nM	CHEMBL3896657
7.77	EC50	17	nM	CHEMBL3959068
7.77	EC50	17	nM	CHEMBL3959144
7.77	EC50	17	nM	CHEMBL3960231
7.75	EC50	18	nM	CHEMBL3898962
7.70	EC50	20	nM	CHEMBL3973101
7.68	EC50	21	nM	CHEMBL3946820
7.68	EC50	21	nM	CHEMBL3947070
7.62	EC50	24	nM	CHEMBL3980898
7.60	EC50	25	nM	CHEMBL3970166
7.60	EC50	25	nM	CHEMBL3890089
7.60	EC50	25	nM	CHEMBL4171724
7.55	EC50	28	nM	CHEMBL3970238
7.52	EC50	30	nM	CHEMBL3946820
7.51	EC50	31	nM	CHEMBL4162566
7.50	EC50	32	nM	CHEMBL3932664
7.48	EC50	33	nM	CHEMBL3971308
7.47	EC50	34	nM	CHEMBL4161536
7.46	EC50	35	nM	CHEMBL3980898
7.43	EC50	37	nM	CHEMBL3943315
7.41	EC50	38.9	nM	CHEMBL3910333
7.40	EC50	40	nM	CHEMBL3910333
7.40	EC50	40	nM	CHEMBL3909773
7.40	EC50	40	nM	CHEMBL4103243
7.40	EC50	39.81	nM	CHEMBL4103243
7.40	EC50	40	nM	CHEMBL4212409
7.38	EC50	42	nM	CHEMBL3941726
7.38	EC50	42	nM	CHEMBL4165366
7.37	EC50	43	nM	CHEMBL3907996
7.37	EC50	43	nM	CHEMBL4209308
7.36	EC50	43.65	nM	CHEMBL2058533

PubChem BioAssay actives

567 with measured affinity, of 1432 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
3-[(2R)-6-[3-fluoro-4-methoxy-6-(3-methoxycyclobutyl)oxy-2-pyridinyl]-3,4-dihydro-2H-chromen-2-yl]propanoic acid	1332302: Agonist activity at human GPR120 short isoform expressed in CHOK1 cells assessed as beta-arrestin recruitment after 90 mins by luminescence assay	ec50	0.0050	uM
2-(3-ethynyl-5-pyridin-3-yloxyphenyl)-3H-1,2-benzothiazole 1,1-dioxide	1924330: Agonist activity at human GPR120 expressed in CHO-K1 cells by beta-arrestin assay	ec50	0.0053	uM
3-[(2R)-6-[3-chloro-2-fluoro-5-[(5-methyl-1,3-thiazol-2-yl)oxy]phenyl]-3,4-dihydro-2H-chromen-2-yl]propanoic acid	1332302: Agonist activity at human GPR120 short isoform expressed in CHOK1 cells assessed as beta-arrestin recruitment after 90 mins by luminescence assay	ec50	0.0056	uM
(3S)-3-cyclopropyl-3-[4-[[5-(2-fluoro-5-methoxyphenyl)-6-(3,3,3-trifluoropropoxy)pyrazin-2-yl]methoxy]phenyl]propanoic acid	1662190: Agonist activity at GPR120 (unknown origin)	ec50	0.0060	uM
3-[4-[2-[2-(cyanomethyl)phenyl]ethynyl]-2-fluorophenyl]propanoic acid	2087778: Agonist activity at human GPR120 expressed in HEK293 cells by Fluo4-AM dye based intracellular calcium flux assay	ec50	0.0060	uM
3-[3-chloro-4-[[6-(cyclopropylmethylsulfanyl)-2-pyridinyl]methoxy]phenyl]propanoic acid	1662190: Agonist activity at GPR120 (unknown origin)	ec50	0.0060	uM
3-[(2R)-6-(6-cyclobutyloxy-3-fluoro-4-methoxy-2-pyridinyl)-3,4-dihydro-2H-chromen-2-yl]propanoic acid	1332302: Agonist activity at human GPR120 short isoform expressed in CHOK1 cells assessed as beta-arrestin recruitment after 90 mins by luminescence assay	ec50	0.0062	uM
cis-(1R,2R)-2-[(2R)-6-(6-cyclobutyloxy-3-fluoro-4-methoxy-2-pyridinyl)-3,4-dihydro-2H-chromen-2-yl]cyclopropane-1-carboxylic acid	1332302: Agonist activity at human GPR120 short isoform expressed in CHOK1 cells assessed as beta-arrestin recruitment after 90 mins by luminescence assay	ec50	0.0078	uM
cis-(1R,2R)-2-[(2R)-6-(5-cyclobutyloxy-2-fluoro-3-methoxyphenyl)-3,4-dihydro-2H-chromen-2-yl]cyclopropane-1-carboxylic acid	1332302: Agonist activity at human GPR120 short isoform expressed in CHOK1 cells assessed as beta-arrestin recruitment after 90 mins by luminescence assay	ec50	0.0080	uM
3-[(2R)-6-(3-chloro-5-cyclobutyloxy-2-fluorophenyl)-3,4-dihydro-2H-chromen-2-yl]propanoic acid	1332302: Agonist activity at human GPR120 short isoform expressed in CHOK1 cells assessed as beta-arrestin recruitment after 90 mins by luminescence assay	ec50	0.0083	uM
3-[(2R)-6-(5-cyclobutyloxy-2-fluoro-3-methoxyphenyl)-3,4-dihydro-2H-chromen-2-yl]propanoic acid	1332302: Agonist activity at human GPR120 short isoform expressed in CHOK1 cells assessed as beta-arrestin recruitment after 90 mins by luminescence assay	ec50	0.0090	uM
3-[(2R)-6-(5-cyclobutyloxy-2-fluorophenyl)-3,4-dihydro-2H-chromen-2-yl]propanoic acid	1332302: Agonist activity at human GPR120 short isoform expressed in CHOK1 cells assessed as beta-arrestin recruitment after 90 mins by luminescence assay	ec50	0.0100	uM
3-[(2R)-6-[2-fluoro-3-methoxy-5-(trifluoromethoxy)phenyl]-3,4-dihydro-2H-chromen-2-yl]propanoic acid	1332302: Agonist activity at human GPR120 short isoform expressed in CHOK1 cells assessed as beta-arrestin recruitment after 90 mins by luminescence assay	ec50	0.0110	uM
3-[(2R)-6-[2-fluoro-3-methoxy-5-[(5-methyl-1,3-thiazol-2-yl)oxy]phenyl]-3,4-dihydro-2H-chromen-2-yl]propanoic acid	1332302: Agonist activity at human GPR120 short isoform expressed in CHOK1 cells assessed as beta-arrestin recruitment after 90 mins by luminescence assay	ec50	0.0130	uM
3-[(2R)-6-(5-cyclobutyloxy-2,3-difluorophenyl)-3,4-dihydro-2H-chromen-2-yl]propanoic acid	1332302: Agonist activity at human GPR120 short isoform expressed in CHOK1 cells assessed as beta-arrestin recruitment after 90 mins by luminescence assay	ec50	0.0130	uM
3-[5-[2-fluoro-5-(trifluoromethoxy)phenyl]-1-benzofuran-2-yl]propanoic acid	1335045: Agonist activity at human GPR120 assessed as induction of beta-arrestin recruitment	ec50	0.0160	uM
3-[(2R)-6-[2-fluoro-5-(trifluoromethoxy)phenyl]-3,4-dihydro-2H-chromen-2-yl]propanoic acid	1332302: Agonist activity at human GPR120 short isoform expressed in CHOK1 cells assessed as beta-arrestin recruitment after 90 mins by luminescence assay	ec50	0.0170	uM
3-[(2R)-6-[3-chloro-2-fluoro-5-(trifluoromethoxy)phenyl]-3,4-dihydro-2H-chromen-2-yl]propanoic acid	1332302: Agonist activity at human GPR120 short isoform expressed in CHOK1 cells assessed as beta-arrestin recruitment after 90 mins by luminescence assay	ec50	0.0170	uM
cis-(1R,2R)-2-[(2R)-6-[2,3-difluoro-5-(3-methoxycyclobutyl)oxyphenyl]-3,4-dihydro-2H-chromen-2-yl]cyclopropane-1-carboxylic acid	1332302: Agonist activity at human GPR120 short isoform expressed in CHOK1 cells assessed as beta-arrestin recruitment after 90 mins by luminescence assay	ec50	0.0170	uM
4-[2,6-difluoro-4-[2-fluoro-5-(trifluoromethoxy)phenyl]phenoxy]butanoic acid	1328635: Agonist activity at human GPR120 expressed in CHOK1 cells measured after 60 mins by IP1-HTRF assay	ec50	0.0200	uM
3-[(2R)-6-(6-cyclobutyloxy-3-fluoro-2-pyridinyl)-3,4-dihydro-2H-chromen-2-yl]propanoic acid	1332302: Agonist activity at human GPR120 short isoform expressed in CHOK1 cells assessed as beta-arrestin recruitment after 90 mins by luminescence assay	ec50	0.0210	uM
3-[(2R)-6-[3,4-difluoro-6-(3-methoxycyclobutyl)oxy-2-pyridinyl]-3,4-dihydro-2H-chromen-2-yl]propanoic acid	1332302: Agonist activity at human GPR120 short isoform expressed in CHOK1 cells assessed as beta-arrestin recruitment after 90 mins by luminescence assay	ec50	0.0240	uM
3-[4-[[3-(4-chloro-3-fluorophenyl)-5-(trifluoromethyl)-1,2-thiazol-4-yl]methoxy]-3,5-difluorophenyl]propanoic acid	1502442: Agonist activity at human GPR120 short splice variant expressed in HEK293 cells assessed as increase in intracellular calcium flux incubated for 30 mins measured for 300 secs at 1 sec interval by Fluo-4 NW dye based FLIPR assay	ec50	0.0250	uM
3-[3-bromo-4-[[3-(4-chlorophenyl)-5-(trifluoromethyl)-1,2-thiazol-4-yl]methoxy]phenyl]propanoic acid	1502442: Agonist activity at human GPR120 short splice variant expressed in HEK293 cells assessed as increase in intracellular calcium flux incubated for 30 mins measured for 300 secs at 1 sec interval by Fluo-4 NW dye based FLIPR assay	ec50	0.0310	uM
5-[2-[(2R)-6-(5-cyclopropyloxy-2-fluoro-3-methoxyphenyl)-3,4-dihydro-2H-chromen-2-yl]ethyl]-2H-tetrazole	1332302: Agonist activity at human GPR120 short isoform expressed in CHOK1 cells assessed as beta-arrestin recruitment after 90 mins by luminescence assay	ec50	0.0320	uM
cis-(1R,2R)-2-[(2R)-6-[2-fluoro-5-(trifluoromethoxy)phenyl]-3,4-dihydro-2H-chromen-2-yl]cyclopropane-1-carboxylic acid	1332302: Agonist activity at human GPR120 short isoform expressed in CHOK1 cells assessed as beta-arrestin recruitment after 90 mins by luminescence assay	ec50	0.0330	uM
3-[4-[[3-(4-ethylphenyl)-5-(trifluoromethyl)-1,2-thiazol-4-yl]methoxy]-3,5-difluorophenyl]propanoic acid	1502442: Agonist activity at human GPR120 short splice variant expressed in HEK293 cells assessed as increase in intracellular calcium flux incubated for 30 mins measured for 300 secs at 1 sec interval by Fluo-4 NW dye based FLIPR assay	ec50	0.0340	uM
2-(3-chloro-5-pyridin-2-yloxyphenyl)-3H-1,2-benzothiazole 1,1-dioxide	1321312: Agonist activity at human FFA4 expressed in human Flp-In T-REx293 cells by Fura2-AM dye based calcium mobilization assay	ec50	0.0389	uM
3-[3-methyl-4-[(3-methyl-5-phenoxyphenyl)methoxy]phenyl]propanoic acid	1430002: Agonist activity at human FFA4 receptor expressed in human U2OS cells co-expressing Galpha16 assessed as calcium mobilization by Fluo-4 dye based FLIPR assay	ec50	0.0398	uM
3-[4-[[1-(4-ethylphenyl)-3-(trifluoromethyl)pyrrol-2-yl]methoxy]-2,3-difluorophenyl]propanoic acid	1374591: Agonist activity at recombinant human GPR120 short isoform expressed in HEK293 cells assessed as intracellular calcium flux measured for 300 secs at 1 sec time interval by Fluo-4 NW based FLIPR assay	ec50	0.0400	uM
3-[(2S)-6-[2-fluoro-5-(trifluoromethoxy)phenyl]-3,4-dihydro-2H-chromen-2-yl]propanoic acid	1332302: Agonist activity at human GPR120 short isoform expressed in CHOK1 cells assessed as beta-arrestin recruitment after 90 mins by luminescence assay	ec50	0.0420	uM
3-[4-[[3-(4-chloro-2-fluorophenyl)-5-(trifluoromethyl)-1,2-thiazol-4-yl]methoxy]-3,5-difluorophenyl]propanoic acid	1502442: Agonist activity at human GPR120 short splice variant expressed in HEK293 cells assessed as increase in intracellular calcium flux incubated for 30 mins measured for 300 secs at 1 sec interval by Fluo-4 NW dye based FLIPR assay	ec50	0.0420	uM
5-[2-[(2R)-6-[2-fluoro-3-methoxy-5-(3-methoxycyclobutyl)oxyphenyl]-3,4-dihydro-2H-chromen-2-yl]ethyl]-2H-tetrazole	1332302: Agonist activity at human GPR120 short isoform expressed in CHOK1 cells assessed as beta-arrestin recruitment after 90 mins by luminescence assay	ec50	0.0430	uM
3-[4-[[1-(4-chlorophenyl)-3-(trifluoromethyl)pyrrol-2-yl]methoxy]-3,5-difluorophenyl]propan-1-ol	1374591: Agonist activity at recombinant human GPR120 short isoform expressed in HEK293 cells assessed as intracellular calcium flux measured for 300 secs at 1 sec time interval by Fluo-4 NW based FLIPR assay	ec50	0.0430	uM
3-[4-[[5-fluoro-2-(4-methylphenyl)phenyl]methoxy]phenyl]propanoic acid	673111: Agonist activity at GPR120 expressed in HEK 293 cells assessed as beta-arrestin recruitment after 5 mins by BRET assay	ec50	0.0437	uM
3-[8-(2-chloro-5-cyclobutyloxyphenyl)-8-azaspiro[4.5]decan-3-yl]propanoic acid	1662190: Agonist activity at GPR120 (unknown origin)	ec50	0.0448	uM
4-[4-[[2-(5,6,7,8-tetrahydronaphthalen-2-yl)cyclohexen-1-yl]methoxy]phenyl]butanoic acid	1924333: Agonist activity at human GPR120 expressed in CHO-K1 cells by BRET assay	ec50	0.0500	uM
4-[4-[[2-(4-cyclopropylphenyl)cyclohexen-1-yl]methoxy]phenyl]butanoic acid	1662190: Agonist activity at GPR120 (unknown origin)	ec50	0.0500	uM
4-[4-[[2-(4-methylphenyl)cyclohexen-1-yl]methoxy]phenyl]butanoic acid	1924333: Agonist activity at human GPR120 expressed in CHO-K1 cells by BRET assay	ec50	0.0500	uM
3-[3,5-difluoro-4-[[1-(4-methylphenyl)-3-(trifluoromethyl)pyrrol-2-yl]methoxy]phenyl]propanoic acid	1374591: Agonist activity at recombinant human GPR120 short isoform expressed in HEK293 cells assessed as intracellular calcium flux measured for 300 secs at 1 sec time interval by Fluo-4 NW based FLIPR assay	ec50	0.0500	uM
3-[4-[(2-bromo-5-methylphenyl)methoxy]-3-methylphenyl]propanoic acid	1430002: Agonist activity at human FFA4 receptor expressed in human U2OS cells co-expressing Galpha16 assessed as calcium mobilization by Fluo-4 dye based FLIPR assay	ec50	0.0501	uM
3-[4-[[3-(4-chlorophenyl)-5-(trifluoromethyl)-1,2-thiazol-4-yl]methoxy]-3,5-difluorophenyl]propanoic acid	1502442: Agonist activity at human GPR120 short splice variant expressed in HEK293 cells assessed as increase in intracellular calcium flux incubated for 30 mins measured for 300 secs at 1 sec interval by Fluo-4 NW dye based FLIPR assay	ec50	0.0510	uM
3-[3,5-difluoro-4-[[5-(trifluoromethyl)-3-[4-(trifluoromethyl)phenyl]-1,2-thiazol-4-yl]methoxy]phenyl]propanoic acid	1502443: Agonist activity at PK-tagged human GPR120 long isoform expressed in CHOK1 cells co-expressing EA-tagged beta-arrestin assessed as beta-gal enzyme complex formation after 90 mins by enzyme fragment complementation assay	ec50	0.0510	uM
cis-(1R,2R)-2-[(2R)-6-[2-fluoro-3-methoxy-5-(3-methoxycyclobutyl)oxyphenyl]-3,4-dihydro-2H-chromen-2-yl]cyclopropane-1-carboxylic acid	1332301: Agonist activity at human GPR120 short isoform expressed in CHOK1 cells assessed as increase in IP1 accumulation after 60 mins by HTRF assay	ec50	0.0550	uM
3-[4-[[3-chloro-5-(4-ethylphenyl)-1,2-thiazol-4-yl]methoxy]-2,3-dimethylphenyl]propanoic acid	1502442: Agonist activity at human GPR120 short splice variant expressed in HEK293 cells assessed as increase in intracellular calcium flux incubated for 30 mins measured for 300 secs at 1 sec interval by Fluo-4 NW dye based FLIPR assay	ec50	0.0560	uM
4-[4-[2-chloro-5-(trifluoromethoxy)phenyl]phenoxy]butanoic acid	1328635: Agonist activity at human GPR120 expressed in CHOK1 cells measured after 60 mins by IP1-HTRF assay	ec50	0.0570	uM
3-[4-[[3-(4-ethylphenyl)-5-(trifluoromethyl)-1,2-oxazol-4-yl]methoxy]-3,5-difluorophenyl]propanoic acid	1486912: Agonist activity at human GPR120 short splice variant expressed in HEK293 cells assessed as increase in intracellular calcium flux by Fluo-4 NW dye based FLIPR assay	ec50	0.0570	uM
4-[4-[2-fluoro-5-(3-fluorophenoxy)phenyl]phenoxy]butanoic acid	1328635: Agonist activity at human GPR120 expressed in CHOK1 cells measured after 60 mins by IP1-HTRF assay	ec50	0.0600	uM
3-[4-[(3,5-dimethylphenyl)methoxy]-3-methylphenyl]propanoic acid	1430002: Agonist activity at human FFA4 receptor expressed in human U2OS cells co-expressing Galpha16 assessed as calcium mobilization by Fluo-4 dye based FLIPR assay	ec50	0.0600	uM
3-[3-methyl-4-[(3-methyl-5-propan-2-yloxyphenyl)methoxy]phenyl]propanoic acid	1430002: Agonist activity at human FFA4 receptor expressed in human U2OS cells co-expressing Galpha16 assessed as calcium mobilization by Fluo-4 dye based FLIPR assay	ec50	0.0600	uM

CTD chemical–gene interactions

12 total (human), top 12 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol F	increases methylation	1
sodium arsenite	increases expression	1
benzo(e)pyrene	decreases methylation	1
CGP 52608	affects binding, increases reaction	1
abrine	decreases expression	1
GW9508	affects binding, increases activity, increases reaction	1
Allergens	decreases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Methapyrilene	decreases methylation	1
Silicon Dioxide	decreases expression	1
Tretinoin	decreases expression	1
Endocannabinoids	affects binding, increases activity, increases reaction	1

ChEMBL screening assays

121 unique, capped per target: 71 functional, 50 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2060785	Functional	Agonist activity at GPR120 expressed in HEK 293 cells assessed as beta-arrestin recruitment after 5 mins by BRET assay	Discovery of a potent and selective GPR120 agonist. — J Med Chem
CHEMBL2320499	Binding	Agonist activity at GPR120 (unknown origin)	Discovery of a potent and selective free fatty acid receptor 1 agonist with low lipophilicity and high oral bioavailability. — J Med Chem

Cellosaurus cell lines

7 cell lines: 5 spontaneously immortalized cell line, 1 transformed cell line, 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_H443	CHO-K1/GPR120/Galpha15	Spontaneously immortalized cell line	Female
CVCL_KX25	PathHunter CHO-K1 GPR120L beta-arrestin	Spontaneously immortalized cell line	Female
CVCL_KX26	PathHunter CHO-K1 GPR120S beta-arrestin	Spontaneously immortalized cell line	Female
CVCL_KX27	PathHunter CHO-K1 GPR120S beta-arrestin-1	Spontaneously immortalized cell line	Female
CVCL_KZ51	PathHunter HEK 293 GPR120L Total GPCR Internalization	Transformed cell line	Female
CVCL_U007	CHO-GPR120	Spontaneously immortalized cell line	Female
CVCL_ZK31	Tango GPR120-bla U2OS	Cancer cell line	Female

Clinical trials (associated diseases)

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