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): 64 total — 1 likely-pathogenic
• GTEx eGene: eQTL in 20 tissues, sQTL in 0 (q < 0.05)
• ChEMBL bioactivity: 8 clinical-phase molecules tested; no curated mechanism-of-action drug
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.03 (unconstrained)
• MANE Select transcript: NM_001195755
• Notable: 64 clinical variants but no curated precision-oncology (CIViC) evidence yet

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: 5 — 4 protein_coding, 1 nonsense_mediated_decay

MANE Select: ENST00000371481

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 2, TSL 3: 1

ENST00000371481, ENST00000371483, ENST00000604414, ENST00000944863, ENST00001001553

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.

Highest expression (Bgee): mucosa of sigmoid colon, mucosa of transverse colon, rectum, colonic mucosa, adenohypophysis.

Genetic regulation across tissues (GTEx eQTL / sQTL)

FFAR4 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 20 tissues and its splicing (sQTL) in 0 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

20 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Pancreas	eqtl	3.7e-25	-0.80	10:93573306:A:G
Adipose Subcutaneous	eqtl	9.6e-18	-0.27	10:93557908:G:C
Lung	eqtl	2.7e-12	+0.26	10:93573306:A:G
Brain Nucleus accumbens basal ganglia	eqtl	1.3e-09	+0.48	10:93687720:C:G
Whole Blood	eqtl	6.4e-09	-0.24	10:93515215:C:A
Breast Mammary Tissue	eqtl	3.1e-07	+0.28	10:93573062:C:T
Adipose Visceral Omentum	eqtl	4.8e-06	+0.18	10:93550782:T:C
Brain Frontal Cortex BA9	eqtl	1.4e-04	+0.22	10:93573306:A:G
Esophagus Muscularis	eqtl	2.1e-04	-0.24	10:93516137:C:G
Esophagus Gastroesophageal Junction	eqtl	8.7e-04	-0.29	10:93519084:C:T
Brain Cortex	eqtl	2.7e-03	+0.20	10:93564746:C:A
Brain Caudate basal ganglia	eqtl	4.2e-03	+0.26	10:93687720:C:G
Spleen	eqtl	1.0e-02	-0.35	10:93526960:C:A
Skin Sun Exposed Lower leg	eqtl	1.1e-02	+0.82	10:93802258:G:A
Testis	eqtl	1.3e-02	+0.35	10:93571844:C:T
Brain Anterior cingulate cortex BA24	eqtl	2.1e-02	-0.47	10:93833357:G:A
Brain Substantia nigra	eqtl	2.5e-02	-0.35	10:93546920:C:T
Artery Tibial	eqtl	2.6e-02	+0.29	10:93514704:A:G
Brain Putamen basal ganglia	eqtl	2.7e-02	+0.37	10:93581054:T:G
Nerve Tibial	eqtl	3.4e-02	-0.15	10:93550955:T:C

FANTOM5 promoters

2 alternative TSS:

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

Top tissues by expression

showing 100 of 238 tissues 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
ileal mucosa	UBERON:0000331	58.64	silver quality
dorsolateral prefrontal cortex	UBERON:0009834	58.47	gold quality
frontal cortex	UBERON:0001870	57.89	gold quality
anterior cingulate cortex	UBERON:0009835	57.49	gold quality
lower lobe of lung	UBERON:0008949	57.39	silver quality
neocortex	UBERON:0001950	56.90	gold quality
intestine	UBERON:0000160	56.62	gold quality
upper lobe of lung	UBERON:0008948	55.94	gold quality
upper lobe of left lung	UBERON:0008952	55.86	gold quality
vermiform appendix	UBERON:0001154	55.08	gold quality
parietal pleura	UBERON:0002400	54.66	gold quality
cerebral cortex	UBERON:0000956	54.44	gold quality
right testis	UBERON:0004534	54.41	gold quality
cardiac muscle of right atrium	UBERON:0003379	54.34	gold quality
left ventricle myocardium	UBERON:0006566	54.23	gold quality
lung	UBERON:0002048	54.19	gold quality
gall bladder	UBERON:0002110	54.07	gold quality
skin of hip	UBERON:0001554	53.94	gold quality
kidney epithelium	UBERON:0004819	53.93	gold quality
upper arm skin	UBERON:0004263	53.52	gold quality
buccal mucosa cell	CL:0002336	53.38	gold quality
layer of synovial tissue	UBERON:0007616	53.36	silver quality
body of pancreas	UBERON:0001150	53.26	gold quality
left testis	UBERON:0004533	53.03	gold quality
thoracic mammary gland	UBERON:0005200	52.39	gold quality
mammary gland	UBERON:0001911	52.24	gold quality
testis	UBERON:0000473	52.11	gold quality
hypothalamus	UBERON:0001898	51.99	gold quality
forebrain	UBERON:0001890	51.93	gold quality
caecum	UBERON:0001153	51.76	gold quality
endothelial cell	CL:0000115	51.55	gold quality
primary visual cortex	UBERON:0002436	51.14	silver quality
tibialis anterior	UBERON:0001385	50.57	silver quality
myocardium	UBERON:0002349	50.25	gold quality
tendon of biceps brachii	UBERON:0008188	49.33	gold quality
brain	UBERON:0000955	49.31	gold quality
upper leg skin	UBERON:0004262	49.20	silver quality
cerebellar vermis	UBERON:0004720	48.93	gold quality
right adrenal gland cortex	UBERON:0035827	48.52	gold quality
occipital lobe	UBERON:0002021	48.30	silver quality
small intestine Peyer’s patch	UBERON:0003454	48.03	gold quality
left coronary artery	UBERON:0001626	47.96	gold quality
small intestine	UBERON:0002108	47.64	gold quality
superior frontal gyrus	UBERON:0002661	47.52	gold quality
lymph node	UBERON:0000029	47.37	gold quality
coronary artery	UBERON:0001621	47.10	gold quality
nasal cavity epithelium	UBERON:0005384	47.03	gold quality
right lobe of liver	UBERON:0001114	47.01	gold quality
quadriceps femoris	UBERON:0001377	46.87	gold quality
left adrenal gland cortex	UBERON:0035825	46.86	gold quality
sural nerve	UBERON:0015488	46.82	gold quality
deltoid	UBERON:0001476	46.80	gold quality
left adrenal gland	UBERON:0001234	46.77	gold quality
adrenal cortex	UBERON:0001235	46.70	gold quality
right adrenal gland	UBERON:0001233	46.69	gold quality
skin of abdomen	UBERON:0001416	46.62	gold quality
duodenum	UBERON:0002114	46.16	gold quality
Ammon’s horn	UBERON:0001954	46.01	gold quality
multicellular organism	UBERON:0000468	46.00	gold quality
material anatomical entity	UBERON:0000465	45.99	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	45.94	gold quality
adrenal gland	UBERON:0002369	45.84	gold quality
zone of skin	UBERON:0000014	45.83	gold quality
skin of leg	UBERON:0001511	45.74	gold quality
nucleus accumbens	UBERON:0001882	45.60	gold quality
germinal epithelium of ovary	UBERON:0001304	45.59	gold quality
anatomical system	UBERON:0000467	45.57	gold quality
liver	UBERON:0002107	45.47	silver quality
amygdala	UBERON:0001876	45.43	gold quality
spinal cord	UBERON:0002240	45.43	gold 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

HPA expression

RNA tissue specificity: Group enriched

showing 60 of 66 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM
Rectum	tissue	10.7
Pituitary gland	tissue	10.4
Olfactory bulb	tissue	9.6
Prefrontal cortex	tissue	9.3
Cerebral cortex	tissue	9.3
Retrosplenial cortex	tissue	9.3
Retrosplenial and cingulate cortex	tissue	9.2
Insular cortex	tissue	9.2
Hippocampal formation	tissue	9.1
Entorhinal cortex	tissue	9.1
Cerebellum	tissue	9.0
Temporal cortex	tissue	8.8
Amygdala	tissue	8.1
Colon	tissue	7.8
Corpus callosum	tissue	7.5
Motor cortex	tissue	7.3
Occipital cortex	tissue	7.2
Ventral forebrain	tissue	7.1
Basal ganglia	tissue	7.0
Somatosensory cortex	tissue	6.9
Septum	tissue	6.5
Periaqueductal gray	tissue	6.2
Putamen	tissue	6.1
Substantia nigra	tissue	6.0
Hypothalamus	tissue	5.4
Midbrain	tissue	4.9
Medulla oblongata	tissue	4.8
Spinal cord	tissue	4.8
Superior colliculi	tissue	4.3
Thalamus	tissue	4.1
Pons	tissue	3.9
Adipose tissue	tissue	3.8
Lung	tissue	3.4
Hippocampus	tissue	2.5
Postcentral gyrus	tissue	2.4
Nucleus accumbens	tissue	2.3
Locus coeruleus	tissue	2.3
Choroid plexus	tissue	2.2
Fallopian tube	tissue	0.9
Skin 1	tissue	0.8
Appendix	tissue	0.6
Stomach 1	tissue	0.5
Pancreas	tissue	0.5
Testis	tissue	0.4
Liver	tissue	0.4
Small intestine	tissue	0.4
Gallbladder	tissue	0.4
Duodenum	tissue	0.4
Adrenal gland	tissue	0.4
Breast	tissue	0.3
Skeletal muscle	tissue	0.3
Lymph node	tissue	0.2
Heart muscle	tissue	0.2
Esophagus	tissue	0.2
Smooth muscle	tissue	0.2
Thymus	tissue	0.2
Retina	tissue	0.1
Salivary gland	tissue	0.1
Parathyroid gland	tissue	0.1
Urinary bladder	tissue	0.1

Brain sub-regions (HPA Brain Atlas): detected in 189; highest nTPM — White matter (7.5), Subiculum (7.1), Ventromedial nucleus (7.1), Ventral hippocampus (6.8), Dorsal hippocampus (6.7).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting FFAR4 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 57 miRNAs:

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

Functional genomics

gnomAD constraint: pLI 2.43e-05, LOEUF 1.03, missense Z -0.128 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000371481 — one region, missense o/e 0.99.

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	CCKLR-17D3	FBGN0030954
drosophila_melanogaster	CCKLR-17D1	FBGN0259231

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)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:2147577) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 34 distinct phenotype terms.

Mouse phenotype (MP)	Records
increased white adipose tissue amount	1
increased circulating LDL cholesterol level	1
abnormal lipid level	1
increased circulating HDL cholesterol level	1
abnormal gustatory system physiology	1
abnormal taste sensitivity	1
increased circulating insulin level	1
hepatic steatosis	1
increased circulating alanine transaminase level	1
abnormal white adipose tissue morphology	1
increased liver weight	1
abnormal insulin secretion	1
decreased energy expenditure	1
increased circulating cholesterol level	1
decreased oxygen consumption	1
impaired glucose tolerance	1
insulin resistance	1
increased circulating glucose level	1
increased susceptibility to diet-induced obesity	1
increased circulating leptin level	1
abnormal white adipose tissue physiology	1
decreased physiological sensitivity to xenobiotic	1
abnormal pancreatic somatostatin secretion	1
increased white fat cell size	1
enlarged pancreatic islets	1

+9 more (showing top 25).

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
Macaca fascicularis	C8YUV0	97.8%	Diamond
Sus scrofa	A0A287A2K5	94.9%	Diamond
Bos taurus	P79266	94.9%	Diamond
Canis lupus familiaris	P30552	91.2%	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
MYOF	protein-coding	26509
CEP55	protein-coding	55165
RBP4	protein-coding	5950
PDE6C	protein-coding	5146
FRA10AC1	protein-coding	118924

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. Mediates VLCFAs-dependent liver-to-adipose tissue signaling and adipose tissue thermogenesis. 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 (54 total): helix 14, topological domain 8, transmembrane region 7, modified residue 5, turn 5, mutagenesis site 3, sequence conflict 3, strand 3, sequence variant 2, chain 1, glycosylation site 1, disulfide bond 1, splice variant 1

Structure

Experimental structures (PDB)

16 structures by resolution:

PDB	Title	Method	Resolution (Å)
8G59	Cryo-EM structure of the TUG891 bound GPR120-Giq complex	ELECTRON MICROSCOPY	2.64
24XB	Cryo-EM Structure of the Apo FFAR4-Gq Complex	ELECTRON MICROSCOPY	2.65
24QH	Cryo-EM Structure of the FFAR4-Gi complex with unknown density	ELECTRON MICROSCOPY	2.74
8ID6	Cryo-EM structure of the oleic acid bound GPR120-Gi complex	ELECTRON MICROSCOPY	2.8
8IYS	TUG891-bound FFAR4 in complex with Gq	ELECTRON MICROSCOPY	2.95
9XFI	Cryo-EM structure of the Bavachalcone bound FFAR4-Giq complex	ELECTRON MICROSCOPY	2.99
8ID8	Cryo-EM structure of the TUG891 bound GPR120-Gi complex	ELECTRON MICROSCOPY	3
8ID9	Cryo-EM structure of the eicosapentaenoic acid bound GPR120-Gi complex	ELECTRON MICROSCOPY	3
8H4I	DHA-bound FFAR4 in complex with Gs	ELECTRON MICROSCOPY	3.06
8T3O	Cryo-EM structure of the TUG-891 bound FFA4-Gq complex	ELECTRON MICROSCOPY	3.06
8H4L	DHA-bound FFAR4 in complex with Gq	ELECTRON MICROSCOPY	3.07
8H4K	GW9508-bound FFAR4 in complex with Gq	ELECTRON MICROSCOPY	3.1
8ID3	Cryo-EM structure of the 9-hydroxystearic acid bound GPR120-Gi complex	ELECTRON MICROSCOPY	3.1
8ID4	Cryo-EM structure of the linoleic acid bound GPR120-Gi complex	ELECTRON MICROSCOPY	3.1
8T3Q	Cryo-EM structure of the DHA bound FFA4-Gq complex	ELECTRON MICROSCOPY	3.14
9XFJ	Cryo-EM structure of the Bavachalcone bound GPR120-Giq complex (local refinement)	ELECTRON MICROSCOPY	3.25

Predicted structure (AlphaFold)

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

Antibody-complex structures (SAbDab)

12 antibodies co-crystallized with this protein: 8G59, 8H4I, 8H4K, 8H4L, 8ID3, 8ID4, 8ID6, 8ID8, 8ID9, 8IYS, 8T3O, 8T3Q

Human Protein Atlas

Protein class: Transporters, G-protein coupled receptors, GPCRs excl olfactory receptors, Predicted membrane proteins, GPCRHMM predicted membrane proteins, FDA approved drug targets, Biotech drugs, Human disease related genes

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): plasma membrane; basal body; vesicles

Antibody reliability (HPA): IF supported

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)

Type	Positions
Phosphothreonine	347, 349
Phosphoserine	350, 357, 360

Disulfide bonds (1)

Type	Positions
Disulfide bond	111–194

Glycosylation sites (1)

Type	Positions
N-linked (glcnac…) asparagine	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

2 curated (TAS) of 11; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

11 pathways:

ID	Pathway	Evidence
R-HSA-416476	G alpha (q) signalling events	curated
R-HSA-381771	Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1)	curated
R-HSA-373076	Class A/1 (Rhodopsin-like receptors)	—
R-HSA-444209	Free fatty acid receptors	electronic
R-HSA-388396	GPCR downstream signalling	—
R-HSA-500792	GPCR ligand binding	—
R-HSA-400508	Incretin synthesis, secretion, and inactivation	—
R-HSA-392499	Metabolism of proteins	—
R-HSA-2980736	Peptide hormone metabolism	—
R-HSA-162582	Signal Transduction	—
R-HSA-372790	Signaling by GPCR	—

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 (7): lysosomal membrane (GO:0005765), plasma membrane (GO:0005886), cilium (GO:0005929), endosome membrane (GO:0010008), endocytic vesicle (GO:0030139), ciliary membrane (GO:0060170), membrane (GO:0016020)

Reactome top-level categories

8 top-level categories:

Category	Pathways
Signaling by GPCR	2
Incretin synthesis, secretion, and inactivation	1
GPCR downstream signalling	1
Class A/1 (Rhodopsin-like receptors)	1
Metabolism of proteins	1
Signal Transduction	1
GPCR ligand binding	1
Peptide hormone metabolism	1

GO top-level categories

showing 60 of 66 GO namespaces:

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
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
positive regulation of MAPK cascade	1
ERK1 and ERK2 cascade	1
regulation of ERK1 and ERK2 cascade	1
somatostatin secretion	1
regulation of somatostatin secretion	1
negative regulation of peptide hormone secretion	1
positive regulation of fat cell differentiation	1
brown fat cell differentiation	1
regulation of brown fat cell differentiation	1
positive regulation of multicellular organismal process	1
cold-induced thermogenesis	1
regulation of cold-induced thermogenesis	1
lipid binding	1
monocarboxylic acid binding	1
detection of chemical stimulus involved in sensory perception of taste	1
protein binding	1
lysosome	1
lytic vacuole membrane	1
membrane	1
cell periphery	1
intraciliary transport particle	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 9 of 37 annotations. The rest are phylogenetic / computational / electronic (IEA).

9 experimentally-supported GO terms:

GO term	NS	Evidence
negative regulation of interleukin-1 beta production	BP	mutant phenotype
phospholipase C-activating G protein-coupled receptor signaling pathway	BP	mutant phenotype
positive regulation of cytosolic calcium ion concentration	BP	direct assay
white fat cell differentiation	BP	direct assay
cilium	CC	direct assay
endosome membrane	CC	direct assay
lysosomal membrane	CC	direct assay
plasma membrane	CC	direct assay
arrestin family protein binding	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 954 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FFAR4	FFAR1	O14842	891
FFAR4	TAS1R3	Q7RTX0	791
FFAR4	FFAR2	O15552	787
FFAR4	FFAR3	O14843	779
FFAR4	TAS1R2	Q8TE23	775
FFAR4	GPR119	Q8TDV5	773
FFAR4	PYY	P10082	731
FFAR4	GPR84	Q9NQS5	725
FFAR4	SLC5A1	P13866	701
FFAR4	GCG	P01275	679
FFAR4	MC3R	P41968	677
FFAR4	GLP1R	P43220	668
FFAR4	PCSK1	P29120	661
FFAR4	GLP2R	O95838	659
FFAR4	FTO	Q9C0B1	653

IntAct

Human interaction partners of FFAR4 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

3 partners by confidence:

Partner	Interaction type	MIscore	Records
RAMP1	physical association	0.400	1
RAMP2	physical association	0.400	1
RAMP3	physical association	0.400	1

SIGNOR signaling

9 signaling 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

Genetic variants

Variant evidence for FFAR4: 64 ClinVar records (1 pathogenic / likely pathogenic); 16 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	50
Likely benign	6
Benign	2

Top pathogenic / likely-pathogenic (1)

Showing all 1 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
13068	NM_006744.4(RBP4):c.278G>A (p.Gly93Asp)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	3

Per-variant reference — Sugi Variant

Explore FFAR4’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 27 predictions of 201):

Position(s)	Effect	Δscore	Sites
10:93576220–93576221	donor_loss	1.0000	4
10:93576089–93576090	acceptor_loss	0.9900	6
10:93576220	donor_loss	0.9900
10:93567288–93567289	donor_loss	0.9800	5
10:93576086	acceptor_gain	0.9800
10:93587218–93587219	acceptor_loss	0.9800	6
10:93567289	donor_loss	0.9600
10:93576221	donor_loss	0.9600
10:93587217	acceptor_loss	0.9500
10:93576082	acceptor_gain	0.9400

AlphaMissense

702 missense substitutions predicted likely pathogenic (of 2,313 scored), across 204 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
D85	8	0.962	0.980
N58	8	0.905	0.985
F88	8	0.894	0.970
N317	8	0.889	0.976
D259	8	0.814	0.887
C194	7	0.982	0.991
W104	7	0.974	0.993
C111	7	0.973	0.988
W198	7	0.962	0.994
F25	7	0.956	0.984
W277	7	0.945	0.992
F177	7	0.937	0.979
W207	7	0.935	0.983
F27	7	0.933	0.979
F28	7	0.932	0.968
F273	7	0.922	0.992
E43	7	0.904	0.958
W163	7	0.896	0.984
F303	7	0.883	0.939
S133	7	0.872	0.995

HPA cancer prognostics

RNA cancer specificity: Cancer enhanced (Colon Adenocarcinoma, Rectum Adenocarcinoma)

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)

GWAS associations

16 associations:

Study	Trait	p-value
GCST010244_84	Triglyceride levels	2e-23
GCST010242_201	HDL cholesterol levels	2e-16
GCST90020025_1071	Waist-to-hip ratio adjusted for BMI	8e-15
GCST90020027_597	Waist-hip index	1e-14
GCST90020024_819	A body shape index	7e-13
GCST90020025_1069	Waist-to-hip ratio adjusted for BMI	7e-11
GCST90020027_595	Waist-hip index	7e-11
GCST90020025_1070	Waist-to-hip ratio adjusted for BMI	1e-10
GCST90020027_576	Waist-hip index	1e-10
GCST90020027_596	Waist-hip index	1e-10
GCST90020025_1067	Waist-to-hip ratio adjusted for BMI	2e-10
GCST90020029_1491	Waist circumference adjusted for body mass index	2e-10
GCST90020027_577	Waist-hip index	7e-10
GCST90020025_1068	Waist-to-hip ratio adjusted for BMI	1e-9
GCST90002405_537	Reticulocyte count	2e-9
GCST009174_2	Response to (pegylated) interferon in chronic hepatitis B	1e-6

EFO canonical traits (from GWAS)

6 canonical traits:

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

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 396,972 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

8 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL1200517	DIHYDROERGOTAMINE MESYLATE	4	2,721
CHEMBL502182	ELAGOLIX SODIUM	4	219
CHEMBL1707	LOPERAMIDE HYDROCHLORIDE	4	59,642
CHEMBL1722209	TOLTERODINE TARTRATE	4	3,939
CHEMBL344159	TOLVAPTAN	4	3,719
CHEMBL9506	DEVAZEPIDE	2	613
CHEMBL267476	LINOLEIC ACID	2	325,752
CHEMBL419667	RELCOVAPTAN	2	367

PharmGKB: 1 entry (CPIC guideline: no)

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)

772 measured of 896 human assays (926 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
CHEMBL4859651	EC50	0.04 nM
CHEMBL4847662	EC50	0.417 nM
CHEMBL4637969	EC50	6 nM
CHEMBL4646784	EC50	6 nM
CHEMBL2164239	EC50	9.33 nM
3-(4(2’-Methylbiphenyl-3-ylmethylamino)phenyl)propanoic acid	EC50	11 nM
3-{4-[(2’,6’-Dimethylbiphenyl-3-yl)methoxy]-2-fluorophenyl}propanoic Acid	EC50	14 nM
CHEMBL2164242	EC50	14 nM
3-{4-[(2’-Methylbiphenyl-3-yl)methoxy]phenyl}propanic Acid	EC50	16.6 nM
CHEMBL2386363	EC50	17 nM
CHEMBL2163924	EC50	17.4 nM
CHEMBL2164241	EC50	17.8 nM
CHEMBL2386355	EC50	18 nM
CHEMBL2386364	EC50	18 nM
CHEMBL2386353	EC50	19 nM
CHEMBL3785637	EC50	20 nM
CHEMBL2315528	EC50	20 nM
CHEMBL5268316	EC50	20 nM
CHEMBL2386362	EC50	22 nM
CHEMBL2164240	EC50	23.4 nM
CHEMBL4162566	EC50	31 nM
CHEMBL3288346	EC50	32 nM
3-(4-(o-Tolylethynyl)phenyl)propanoic acid	EC50	32 nM
CHEMBL2386361	EC50	33 nM
CHEMBL4161536	EC50	34 nM
3-{4-[(3-Phenoxybenzyl)oxy]phenyl}propanoic Acid	EC50	34 nM
CHEMBL2386359	EC50	35 nM
CHEMBL3785764	EC50	37 nM
CHEMBL2386365	EC50	38 nM
CHEMBL4212409	EC50	40 nM
CHEMBL4209308	EC50	43 nM
CHEMBL4639009	EC50	45 nM
CHEMBL3787072	EC50	48 nM
CHEMBL4091723	EC50	50 nM
CHEMBL5272316	EC50	50 nM
CHEMBL4205429	EC50	50 nM
CHEMBL4159180	EC50	51 nM
CHEMBL3963542	EC50	55 nM
CHEMBL4086174	EC50	57 nM
CHEMBL3600993	EC50	58 nM
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
CHEMBL4646553	EC50	61 nM
(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
CHEMBL4164509	EC50	71 nM
CHEMBL4642324	EC50	71 nM
CHEMBL2386354	EC50	74 nM
CHEMBL4169851	EC50	75 nM
CHEMBL1773254	EC50	75.9 nM
CHEMBL3926143	EC50	77 nM
(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

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 1436 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	increases reaction, affects binding, increases activity	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

8 cell lines: 5 spontaneously immortalized cell line, 2 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_F4SA	HyCyte A-549 stable cell line for hFFAR4 overexpression	Cancer cell line	Male
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)

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

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for FFAR4 across ~30M SureChEMBL compounds — explore on Sugi Predict.