FFAR3

Summary

FFAR3 (free fatty acid receptor 3, HGNC:4499) is a protein-coding gene on chromosome 19q13.12, encoding Free fatty acid receptor 3 (O14843). G protein-coupled receptor that is activated by a major product of dietary fiber digestion, the short chain fatty acids (SCFAs), and that plays a role in the regulation of whole-body energy homeostasis and in intestinal immunity.

Enables G protein-coupled receptor activity. Involved in adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway and cellular response to fatty acid. Located in plasma membrane.

Source: NCBI Gene 2865 — automated summary from GO annotations (Alliance of Genome Resources).

At a glance

• Clinical variants (ClinVar): 86 total
• Regional missense constraint (gnomAD): 3 of 5 regions constrained (≈61% of expected missense variation)
• GTEx eGene: eQTL in 7 tissues, sQTL in 0 (q < 0.05)
• ChEMBL bioactivity: 4 clinical-phase molecules tested; no curated mechanism-of-action drug
• Constraint (gnomAD): pLI 0.31 (intermediate), LOEUF 1.87 (unconstrained)
• MANE Select transcript: NM_005304
• Notable: 86 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4499
Approved symbol	FFAR3
Name	free fatty acid receptor 3
Location	19q13.12
Locus type	gene with protein product
Status	Approved
Aliases	FFA3R
Ensembl gene	ENSG00000185897
Ensembl biotype	protein_coding
OMIM	603821
Entrez	2865

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

MANE Select: ENST00000327809

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

ENST00000327809, ENST00000594310, ENST00000965195

RefSeq mRNA: 1 — MANE Select: NM_005304 NM_005304

CCDS: CCDS12459

Canonical transcript exons

ENST00000327809 — 2 exons

Exon	Start	End
ENSE00001296125	35358460	35358649
ENSE00001298206	35358880	35360489

Expression profiles

Bgee: expression breadth ubiquitous, 108 present calls, max score 84.45.

Highest expression (Bgee): male germ line stem cell (sensu Vertebrata) in testis, blood, omental fat pad, islet of Langerhans, adipose tissue.

Genetic regulation across tissues (GTEx eQTL / sQTL)

FFAR3 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 7 tissues and its splicing (sQTL) in 0 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

7 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Adipose Subcutaneous	eqtl	2.3e-19	-0.36	19:35373433:G:C
Thyroid	eqtl	4.9e-15	-0.42	19:35373433:G:C
Adipose Visceral Omentum	eqtl	6.0e-10	-0.33	19:35373433:G:C
Colon Sigmoid	eqtl	6.2e-08	+0.51	19:35386182:G:C
Whole Blood	eqtl	2.4e-05	+0.18	19:35379878:A:T
Prostate	eqtl	1.5e-03	-0.46	19:35354837:A:T
Nerve Tibial	eqtl	4.9e-03	-0.21	19:35356501:G:A

Top tissues by expression

showing 100 of 126 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.45	silver quality
blood	UBERON:0000178	73.79	gold quality
omental fat pad	UBERON:0010414	69.57	gold quality
islet of Langerhans	UBERON:0000006	65.30	gold quality
adipose tissue	UBERON:0001013	65.14	gold quality
granulocyte	CL:0000094	63.63	gold quality
vermiform appendix	UBERON:0001154	62.63	gold quality
apex of heart	UBERON:0002098	61.79	gold quality
subcutaneous adipose tissue	UBERON:0002190	61.38	gold quality
monocyte	CL:0000576	59.61	gold quality
leukocyte	CL:0000738	59.51	gold quality
muscle layer of sigmoid colon	UBERON:0035805	57.83	gold quality
thoracic mammary gland	UBERON:0005200	55.72	gold quality
gall bladder	UBERON:0002110	54.50	gold quality
smooth muscle tissue	UBERON:0001135	53.43	gold quality
spleen	UBERON:0002106	52.84	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	52.51	gold quality
fundus of stomach	UBERON:0001160	52.48	gold quality
duodenum	UBERON:0002114	52.11	gold quality
pancreas	UBERON:0001264	51.40	gold quality
bone marrow	UBERON:0002371	50.85	gold quality
lymph node	UBERON:0000029	50.80	gold quality
colon	UBERON:0001155	50.00	gold quality
hindlimb stylopod muscle	UBERON:0004252	49.24	silver quality
intestine	UBERON:0000160	48.65	gold quality
placenta	UBERON:0001987	48.31	gold quality
right lobe of thyroid gland	UBERON:0001119	48.26	gold quality
body of stomach	UBERON:0001161	48.04	gold quality
urinary bladder	UBERON:0001255	47.26	gold quality
stomach	UBERON:0000945	47.03	gold quality
small intestine	UBERON:0002108	46.47	gold quality
left uterine tube	UBERON:0001303	46.22	gold quality
bone marrow cell	CL:0002092	45.36	gold quality
right uterine tube	UBERON:0001302	45.34	silver quality
left lobe of thyroid gland	UBERON:0001120	45.29	gold quality
substantia nigra	UBERON:0002038	45.25	gold quality
small intestine Peyer’s patch	UBERON:0003454	45.18	gold quality
descending thoracic aorta	UBERON:0002345	45.05	gold quality
upper lobe of left lung	UBERON:0008952	44.73	gold quality
thyroid gland	UBERON:0002046	44.54	gold quality
body of pancreas	UBERON:0001150	44.28	gold quality
transverse colon	UBERON:0001157	44.02	gold quality
heart left ventricle	UBERON:0002084	43.92	gold quality
mucosa of transverse colon	UBERON:0004991	43.25	silver quality
fallopian tube	UBERON:0003889	42.96	gold quality
muscle tissue	UBERON:0002385	42.29	gold quality
right lung	UBERON:0002167	42.18	gold quality
multicellular organism	UBERON:0000468	42.00	gold quality
putamen	UBERON:0001874	41.65	gold quality
colonic epithelium	UBERON:0000397	41.62	gold quality
lung	UBERON:0002048	41.11	gold quality
heart	UBERON:0000948	40.99	gold quality
Ammon’s horn	UBERON:0001954	40.91	gold quality
mucosa of stomach	UBERON:0001199	40.82	silver quality
left coronary artery	UBERON:0001626	40.74	gold quality
liver	UBERON:0002107	40.68	gold quality
ascending aorta	UBERON:0001496	40.12	gold quality
ovary	UBERON:0000992	40.08	gold quality
thoracic aorta	UBERON:0001515	39.93	gold quality
left ovary	UBERON:0002119	39.91	gold quality
right lobe of liver	UBERON:0001114	39.57	gold quality
right ovary	UBERON:0002118	39.30	gold quality
primary visual cortex	UBERON:0002436	39.13	silver quality
right coronary artery	UBERON:0001625	39.06	silver quality
lower esophagus muscularis layer	UBERON:0035833	38.90	gold quality
lower esophagus	UBERON:0013473	38.87	gold quality
Brodmann (1909) area 9	UBERON:0013540	38.63	gold quality
hypothalamus	UBERON:0001898	38.46	silver quality
caudate nucleus	UBERON:0001873	38.16	gold quality
nucleus accumbens	UBERON:0001882	38.16	gold quality
amygdala	UBERON:0001876	38.08	silver quality
skeletal muscle tissue	UBERON:0001134	38.02	gold quality
temporal lobe	UBERON:0001871	37.98	silver quality
left adrenal gland cortex	UBERON:0035825	37.82	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	37.62	gold quality
prostate gland	UBERON:0002367	37.40	gold quality
right atrium auricular region	UBERON:0006631	36.62	gold quality
ventricular zone	UBERON:0003053	36.48	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
prefrontal cortex	UBERON:0000451	36.46	gold quality
brain	UBERON:0000955	36.33	gold quality
tibial nerve	UBERON:0001323	36.21	gold quality
pituitary gland	UBERON:0000007	36.06	gold quality
cerebral cortex	UBERON:0000956	36.05	gold quality
sural nerve	UBERON:0015488	35.93	gold quality
rectum	UBERON:0001052	35.86	gold quality
frontal cortex	UBERON:0001870	35.60	gold quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
cortex of kidney	UBERON:0001225	35.47	gold quality
adenohypophysis	UBERON:0002196	35.47	gold quality
adrenal gland	UBERON:0002369	35.26	gold quality
left adrenal gland	UBERON:0001234	35.04	gold quality
tonsil	UBERON:0002372	34.96	silver quality
dorsolateral prefrontal cortex	UBERON:0009834	34.77	gold quality
right frontal lobe	UBERON:0002810	34.54	gold quality
anterior cingulate cortex	UBERON:0009835	34.05	gold quality
muscle of leg	UBERON:0001383	33.73	gold quality
tibial artery	UBERON:0007610	33.63	gold quality
popliteal artery	UBERON:0002250	33.58	gold quality
esophagus	UBERON:0001043	32.95	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.22

HPA expression

RNA tissue specificity: Tissue enhanced

60 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Appendix	tissue	2.4	low
Medulla oblongata	tissue	2.1
Adipose tissue	tissue	2.0	not detected
Smooth muscle	tissue	1.5	low
Midbrain	tissue	0.8
Bone marrow	tissue	0.8	low
Cerebral cortex	tissue	0.7	low
Pons	tissue	0.7
Basal ganglia	tissue	0.7	low
Choroid plexus	tissue	0.7
Hippocampal formation	tissue	0.7
Thalamus	tissue	0.6
Retrosplenial cortex	tissue	0.6
Stomach 1	tissue	0.5	low
Hypothalamus	tissue	0.5
Urinary bladder	tissue	0.4	low
Pancreas	tissue	0.4	low
Amygdala	tissue	0.4
Nucleus accumbens	tissue	0.4
Placenta	tissue	0.4	low
Cerebellum	tissue	0.4	low
Small intestine	tissue	0.4	low
Gallbladder	tissue	0.4	low
Spinal cord	tissue	0.4
Hippocampus	tissue	0.4	low
Pituitary gland	tissue	0.3
Substantia nigra	tissue	0.3
Duodenum	tissue	0.3	low
Locus coeruleus	tissue	0.3
Lymph node	tissue	0.2	low
Putamen	tissue	0.2
Spleen	tissue	0.2	low
Liver	tissue	0.2	low
Thymus	tissue	0.2
Ovary	tissue	0.1	low
Rectum	tissue	0.1	low
Parathyroid gland	tissue	0.1	low
Colon	tissue	0.1	low
Lung	tissue	0.1	low
Prostate	tissue	0.1	low
Occipital cortex	tissue	0.1
Cervix	tissue	0.0	low
Skin 1	tissue	0.0	low
Breast	tissue	0.0	low
Testis	tissue	0.0	low
Vagina	tissue	0.0	low
Seminal vesicle	tissue	0.0	low
Esophagus	tissue	0.0	low
Salivary gland	tissue	0.0	low
Endometrium 1	tissue	0.0	low
Epididymis	tissue	0.0	low
Thyroid gland	tissue	0.0	low
Kidney	tissue	0.0	low
Adrenal gland	tissue	0.0	low
Tonsil	tissue	0.0	low
Fallopian tube	tissue	0.0	low
Nasopharynx	tissue	-1.0	low
Bronchus	tissue	-1.0	low
Soft tissue 1	tissue	-1.0	low
Oral mucosa	tissue	-1.0	low

Brain sub-regions (HPA Brain Atlas): detected in 187; highest nTPM — Nucleus raphe pallidus (2.1), Parieto-temporal junction (white matter) (1.9), White matter (1.9), Temporal white matter (1.8), Area postrema (1.7).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting FFAR3 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

25 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-6748-5P	100.00	65.81	1057
HSA-MIR-3605-5P	99.96	67.12	932
HSA-MIR-1321	99.84	65.30	1811
HSA-MIR-4739	99.84	65.25	1832
HSA-MIR-4756-5P	99.84	64.98	1809
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-6745	99.74	65.33	1321
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-875-3P	99.63	69.47	2548
HSA-MIR-6861-3P	99.60	68.46	444
HSA-MIR-6081	99.48	66.07	1446
HSA-MIR-363-5P	99.46	64.51	1015
HSA-MIR-3182	99.40	68.15	2454
HSA-MIR-4667-3P	99.26	65.45	1608
HSA-MIR-593-3P	99.22	67.28	1327
HSA-MIR-2115-5P	98.66	68.07	1191
HSA-MIR-6865-3P	97.54	64.67	684
HSA-MIR-1913	97.07	66.20	1417
HSA-MIR-215-3P	97.02	68.01	1209
HSA-MIR-616-3P	96.82	66.99	784
HSA-MIR-4471	95.11	66.84	755
HSA-MIR-8059	95.11	66.30	646

Functional genomics

gnomAD constraint: pLI 0.311, LOEUF 1.87, missense Z 3.73 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000327809 splits into 5 regions with different missense tolerance; 3 are missense-constrained (≈61% of the expected missense variation). Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
19:35,358,891–35,359,084	53 / 83.6	0.63	no
19:35,359,085–35,359,444	33 / 154.2	0.21	yes (p 1.7e-22)
19:35,359,445–35,359,511	0 / 28.6	0.00	yes (p 8.9e-08)
19:35,359,512–35,359,704	37 / 91.2	0.41	no
19:35,359,705–35,359,928	13 / 88.9	0.15	yes (p 8.3e-16)

Literature-anchored findings (GeneRIF, showing 23)

• characterization of GP41 in human tissue as a receptor for short chain fatty acids (PMID:12711604)
• C2-C6 short-chain fatty acids, ligands of an orphan G protein-coupled receptor GPR41, stimulate leptin expression in both a mouse adipocyte cell line and mouse adipose tissue in primary culture (PMID:14722361)
• GPR41 and 43 mediate SCFA signaling in mammary epithelial cells and thereby play an important role in their stress management. (PMID:16887331)
• analysis of conserved polar residues in transmembrane domains V, VI, and VII of free fatty acid receptor 2 and free fatty acid receptor 3 are required for the binding and function of short chain fatty acids (PMID:18801738)
• Results suggest that GPR41 expressed in human colonic mucosa may function as a sensor for luminal short-chain fatty acids. (PMID:19574715)
• Study presents evidence showing that the six amino acid differences, including that R/W174 are polymorphisms rather than gene-specific differences between GPR41 and GPR42. (PMID:19630535)
• Selective orthosteric free fatty acid receptor 2 (FFA2) agonists: identification of the structural and chemical requirements for selective activation of FFA2 versus FFA3. (PMID:21220428)
• GPR41 gene expression is mediated by internal ribosome entry site (IRES)-dependent translation of bicistronic mRNA encoding GPR40 and GPR41 proteins (PMID:22493486)
• Propionate-stimulated GPR41 strongly coupled to ERK1/2 activation, while the coupling of linoleic acid-activated GPR40 and acetate-activated GPR43 was weaker. (PMID:22712802)
• GPR41 activation inhibits histone acetylation and cell growth. (PMID:22884094)
• Extracellular ionic locks determine variation in constitutive activity and ligand potency between species orthologs of the free fatty acid receptors FFA2 and FFA3 (PMID:23066016)
• a significant correlation between a higher body mass index and lower methylation in the promoter region of FFAR3 in type 2 diabetes and obesity patients (PMID:24325907)
• FFAR3 is expressed in pancreatic beta cells and mediates an inhibition of insulin secretion by coupling to Gi-type G proteins. (PMID:25581519)
• Our data suggest that GPR42 be reclassified as a functioning gene and that recognition of sequence and copy number polymorphism of the FFAR3/GPR42 complex be considered during genetic and pharmacological investigation of these receptors. (PMID:26260360)
• a single dose of soluble fibre was able to significantly reduce airway inflammation in stable asthma by downregulating GPR43 and GPR41 (PMID:28075383)
• Short-chain fatty acids lowered TNF-alpha-induced MCP-1 expression by reducing phosphorylation of p38 MAPK and JNK in a GPR41/GRP43-dependent manner in renal cortical epithelial cells. (PMID:28322790)
• 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)
• FFAR2 and FFAR3 interact to form a heteromer in primary monocytes and macrophages via proximity ligation assay, and during heterologous expression in HEK293 cells via bimolecular fluorescence complementation and fluorescence resonance energy transfer. FFAR2 and FFAR3 may interact to form a receptor heteromer with signaling that is distinct from the parent homomers. (PMID:28883043)
• Metabolic and physiological role of FFAR1 (GPR40), FFAR4 (GPR120), FFAR3 (GPR41) and FFAR2 (GPR43) is REVIEWED. (PMID:31487233)
• The short-chain free fatty acid receptor FFAR3 is expressed and potentiates contraction in human airway smooth muscle. (PMID:32209026)
• FFA2-, but not FFA3-agonists inhibit GSIS of human pseudoislets: a comparative study with mouse islets and rat INS-1E cells. (PMID:33020504)
• Genetic Inactivation of Free Fatty Acid Receptor 3 Impedes Behavioral Deficits and Pathological Hallmarks in the APPswe Alzheimer’s Disease Mouse Model. (PMID:35408893)
• Regulator of G-Protein Signaling-4 Attenuates Cardiac Adverse Remodeling and Neuronal Norepinephrine Release-Promoting Free Fatty Acid Receptor FFAR3 Signaling. (PMID:35628613)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	si:ch211-231m23.4	ENSDARG00000041292
danio_rerio	si:dkey-211g8.7	ENSDARG00000058535
danio_rerio	si:dkey-211g8.6	ENSDARG00000063088
danio_rerio		ENSDARG00000079661
danio_rerio	si:ch73-90p23.1	ENSDARG00000097901
mus_musculus	Ffar3	ENSMUSG00000019429
rattus_norvegicus	Ffar3	ENSRNOG00000037467

Paralogs (15): GPR31 (ENSG00000120436), GPR42 (ENSG00000126251), FFAR2 (ENSG00000126262), FFAR1 (ENSG00000126266), OXER1 (ENSG00000162881), OXGR1 (ENSG00000165621), P2RY1 (ENSG00000169860), P2RY6 (ENSG00000171631), GPR82 (ENSG00000171657), P2RY2 (ENSG00000175591), HCAR2 (ENSG00000182782), P2RY4 (ENSG00000186912), HCAR1 (ENSG00000196917), SUCNR1 (ENSG00000198829), HCAR3 (ENSG00000255398)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:2685324) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 30 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal liver morphology	1
small liver	1
small superior cervical ganglion	1
decreased body weight	1
microphthalmia	1
abnormal heart rate	1
abnormal digestion	1
increased circulating insulin level	1
abnormal eye morphology	1
abnormal kidney morphology	1
increased circulating ketone body level	1
enlarged kidney	1
abnormal feces composition	1
abnormal noradrenaline level	1
abnormal oxygen consumption	1
decreased oxygen consumption	1
impaired glucose tolerance	1
decreased heart rate	1
abnormal energy homeostasis	1
decreased body temperature	1
decreased circulating noradrenaline level	1
abnormal adipose tissue physiology	1
decreased circulating leptin level	1
abnormal intestinal transit time	1
decreased physiological sensitivity to xenobiotic	1

+5 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	Q76JV1	96.7%	Diamond
Sus scrofa	P50132	95.6%	Diamond
Mesocricetus auratus	Q76JU8	88.0%	Diamond
Bos taurus	Q3ZC80	78.0%	Diamond
Xenopus laevis	P47749	61.0%	Diamond
Xenopus tropicalis	A0A6I8PUB9	55.5%	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
FFAR1	protein-coding	2864
MAG	protein-coding	4099
HAMP	protein-coding	57817
CD22	protein-coding	933
LINC01531	ncRNA	100128682
GPR42	protein-coding	2866
MIR5196	ncRNA	100847070

Protein

Protein identifiers

Free fatty acid receptor 3 — O14843 (reviewed: O14843)

Alternative names: G protein-coupled receptor 41

All UniProt accessions (2): A0A0K0PUW7, O14843

UniProt curated annotations — full annotation on UniProt →

Function. G protein-coupled receptor that is activated by a major product of dietary fiber digestion, the short chain fatty acids (SCFAs), and that plays a role in the regulation of whole-body energy homeostasis and in intestinal immunity. In omnivorous mammals, the short chain fatty acids acetate, propionate and butyrate are produced primarily by the gut microbiome that metabolizes dietary fibers. SCFAs serve as a source of energy but also act as signaling molecules. That G protein-coupled receptor is probably coupled to the pertussis toxin-sensitive, G(i/o)-alpha family of G proteins. Its activation results in the formation of inositol 1,4,5-trisphosphate, the mobilization of intracellular calcium, the phosphorylation of the MAPK3/ERK1 and MAPK1/ERK2 kinases and the inhibition of intracellular cAMP accumulation. Activated by SCFAs and by beta-hydroxybutyrate, a ketone body produced by the liver upon starvation, it inhibits N-type calcium channels and modulates the activity of sympathetic neurons through a signaling cascade involving the beta and gamma subunits of its coupled G protein, phospholipase C and MAP kinases. Thereby, it may regulate energy expenditure through the control of the sympathetic nervous system that controls for instance heart rate. Upon activation by SCFAs accumulating in the intestine, it may also signal to the brain via neural circuits which in turn would regulate intestinal gluconeogenesis. May also control the production of hormones involved in whole-body energy homeostasis. May for instance, regulate blood pressure through renin secretion. May also regulate secretion of the PYY peptide by enteroendocrine cells and control gut motility, intestinal transit rate, and the harvesting of energy from SCFAs produced by gut microbiota. May also indirectly regulate the production of LEP/Leptin, a hormone acting on the CNS to inhibit food intake, in response to the presence of short-chain fatty acids in the intestine. Finally, may also play a role in glucose homeostasis. Besides its role in energy homeostasis, may play a role in intestinal immunity. May mediate the activation of the inflammatory and immune response by SCFAs in the gut, regulating the rapid production of chemokines and cytokines by intestinal epithelial cells. Among SCFAs, the fatty acids containing less than 6 carbons, the most potent activators are probably propionate, butyrate and pentanoate while acetate is a poor activator.

Subcellular location. Cell membrane.

Tissue specificity. Highest level in adipose tissue, and lower expression across all tissues tested. Expressed in sympathetic ganglia.

Polymorphism. The 6 amino acid differences at positions 44, 45, 174, 227, 256 and 346 between GPR42 and FFAR3, are polymorphic in the human population. The frequency of the probable inactive allele of FFAR3, with a Trp at position 174 was estimated to 1%.

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

RefSeq proteins (1): NP_005295* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000276	GPCR_Rhodpsn	Family
IPR013312	GPR40-rel_orph	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain

Pfam: PF00001

UniProt features (45 total): helix 11, topological domain 8, transmembrane region 7, sequence variant 6, mutagenesis site 5, turn 2, chain 1, region of interest 1, compositionally biased region 1, glycosylation site 1, disulfide bond 1, strand 1

Structure

Experimental structures (PDB)

2 structures by resolution:

PDB	Title	Method	Resolution (Å)
8J20	Cryo-EM structure of FFAR3 bound with valeric acid and AR420626	ELECTRON MICROSCOPY	3.2
8J21	Cryo-EM structure of FFAR3 complex bound with butyrate acid	ELECTRON MICROSCOPY	3.3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O14843-F1	86.90	0.66

Antibody-complex structures (SAbDab)

2 antibodies co-crystallized with this protein: 8J20, 8J21

Human Protein Atlas

Protein class: G-protein coupled receptors, GPCRs excl olfactory receptors, Predicted membrane proteins, GPCRHMM predicted membrane proteins

Protein evidence: Evidence at protein level

Antibody reliability (HPA): IH uncertain

Functional residue map

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

Disulfide bonds (1)

Type	Positions
Disulfide bond	88–169

Glycosylation sites (1)

Type	Positions
N-linked (glcnac…) asparagine	166

Mutagenesis-validated functional residues (5)

Position	Phenotype
146	partial loss of scfa-induced g protein-coupled receptor activity.
158	gain of scfa-independent constitutive g protein-coupled receptor activity.
185	loss of scfa-induced g protein-coupled receptor activity.
245	loss of scfa-induced g protein-coupled receptor activity.
258	loss of scfa-induced g protein-coupled receptor activity.

Function

Pathways and Gene Ontology

Reactome pathways

2 curated (TAS) of 7; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

7 pathways:

ID	Pathway	Evidence
R-HSA-444209	Free fatty acid receptors	curated
R-HSA-416476	G alpha (q) signalling events	curated
R-HSA-373076	Class A/1 (Rhodopsin-like receptors)	—
R-HSA-388396	GPCR downstream signalling	—
R-HSA-500792	GPCR ligand binding	—
R-HSA-162582	Signal Transduction	—
R-HSA-372790	Signaling by GPCR	—

MSigDB gene sets: 123 (showing top): GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_REGULATION_OF_BLOOD_PRESSURE, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_INFLAMMATORY_RESPONSE, GOBP_CELLULAR_RESPONSE_TO_LIPID, GOBP_POSITIVE_REGULATION_OF_CYTOKINE_PRODUCTION_INVOLVED_IN_IMMUNE_RESPONSE, GOBP_REGULATION_OF_HORMONE_LEVELS, GOBP_HORMONE_TRANSPORT, GOBP_POSITIVE_REGULATION_OF_CYTOKINE_PRODUCTION, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_POSITIVE_REGULATION_OF_ACUTE_INFLAMMATORY_RESPONSE, GOBP_CELLULAR_RESPONSE_TO_INSULIN_STIMULUS, GOBP_ORGAN_OR_TISSUE_SPECIFIC_IMMUNE_RESPONSE, GOBP_CELL_CELL_SIGNALING, GOBP_ORGANIC_HYDROXY_COMPOUND_TRANSPORT

GO Biological Process (15): mucosal immune response (GO:0002385), positive regulation of cytokine production involved in immune response (GO:0002720), positive regulation of acute inflammatory response to non-antigenic stimulus (GO:0002879), inflammatory response (GO:0006954), G protein-coupled receptor signaling pathway (GO:0007186), adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway (GO:0007193), regulation of norepinephrine secretion (GO:0014061), positive regulation of chemokine production (GO:0032722), negative regulation of blood pressure (GO:0045776), regulation of insulin receptor signaling pathway (GO:0046626), regulation of hormone biosynthetic process (GO:0046885), cellular response to fatty acid (GO:0071398), regulation of peptide hormone secretion (GO:0090276), immune system process (GO:0002376), signal transduction (GO:0007165)

GO Molecular Function (3): G protein-coupled receptor activity (GO:0004930), lipid binding (GO:0008289), protein binding (GO:0005515)

GO Cellular Component (2): plasma membrane (GO:0005886), membrane (GO:0016020)

Reactome top-level categories

5 top-level categories:

Category	Pathways
Signaling by GPCR	2
GPCR downstream signalling	1
Class A/1 (Rhodopsin-like receptors)	1
Signal Transduction	1
GPCR ligand binding	1

GO top-level categories

41 GO namespaces:

Category	Terms
positive regulation of cytokine production	2
binding	2
organ or tissue specific immune response	1
cytokine production involved in immune response	1
positive regulation of production of molecular mediator of immune response	1
regulation of cytokine production involved in immune response	1
acute inflammatory response to non-antigenic stimulus	1
positive regulation of acute inflammatory response	1
regulation of acute inflammatory response to non-antigenic stimulus	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 inhibitor activity	1
norepinephrine secretion	1
regulation of catecholamine secretion	1
chemokine production	1
regulation of chemokine production	1
regulation of blood pressure	1
insulin receptor signaling pathway	1
regulation of signal transduction	1
regulation of biosynthetic process	1
regulation of hormone metabolic process	1
hormone biosynthetic process	1
response to fatty acid	1
cellular response to lipid	1
cellular response to oxygen-containing compound	1
regulation of peptide secretion	1
peptide hormone secretion	1
regulation of hormone secretion	1
biological_process	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
transmembrane signaling receptor activity	1
G protein-coupled receptor signaling pathway	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 5 of 20 annotations. The rest are phylogenetic / computational / electronic (IEA).

5 experimentally-supported GO terms:

GO term	NS	Evidence
G protein-coupled receptor signaling pathway	BP	direct assay
adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway	BP	direct assay
cellular response to fatty acid	BP	direct assay
plasma membrane	CC	direct assay
G protein-coupled receptor activity	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 804 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FFAR3	CD22	P20273	837
FFAR3	GAL	P22466	837
FFAR3	PYY	P10082	800
FFAR3	FFAR4	Q5NUL3	779
FFAR3	GCG	P01275	719
FFAR3	GPR119	Q8TDV5	677
FFAR3	SLC5A8	Q8N695	676
FFAR3	GPR84	Q9NQS5	676
FFAR3	GPBAR1	Q8TDU6	675
FFAR3	HDAC9	Q9UKV0	655
FFAR3	ALDH18A1	P54886	610
FFAR3	NR1H4	Q96RI1	571
FFAR3	LEP	P41159	567
FFAR3	OR51E1	Q8TCB6	565
FFAR3	INS	P01308	547

IntAct

Human interaction partners of FFAR3 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

14 partners by confidence:

Partner	Interaction type	MIscore	Records
CD79A	physical association	0.560	3
COMT	physical association	0.560	3
CTXN3	physical association	0.560	3
EFNA5	physical association	0.560	3
KCNIP3	physical association	0.560	3
LAT	physical association	0.560	3
LTC4S	physical association	0.560	3
SERINC1	physical association	0.560	3
SLC41A1	physical association	0.560	3
TEX264	physical association	0.560	3
TOMM6	physical association	0.560	3
TREX1	physical association	0.560	3
UNC93B1	physical association	0.560	3
YIPF1	physical association	0.560	3

BioGRID (14 interactions; top human partners by supporting records): CD79A (Two-hybrid), COMT (Two-hybrid), CTXN3 (Two-hybrid), EFNA5 (Two-hybrid), KRAS (Synthetic Lethality), LAT (Two-hybrid), LTC4S (Two-hybrid), SERINC1 (Two-hybrid), SLC41A1 (Two-hybrid), TEX264 (Two-hybrid), TOMM6 (Two-hybrid), TREX1 (Two-hybrid), UNC93B1 (Two-hybrid), YIPF1 (Two-hybrid)

SIGNOR signaling

showing 7 of 9 signaling interactions:

A	Effect	B	Mechanism
FFAR3	“up-regulates activity”	GNAI1	binding
FFAR3	“up-regulates activity”	GNAI3	binding
FFAR3	“up-regulates activity”	GNA12	binding
“propionic acid”	“up-regulates activity”	FFAR3	“chemical activation”
FFAR3	“up-regulates activity”	GNAI2	binding
FFAR3	“up-regulates activity”	GNAZ	binding
FFAR3	“up-regulates activity”	GNAO1	binding

Disease & clinical

Genetic variants

Variant evidence for FFAR3: 86 ClinVar records (0 pathogenic / likely pathogenic).

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	73
Likely benign	10
Benign	2

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 19 predictions of 64):

Position(s)	Effect	Δscore	Sites
19:35358876	acceptor_gain	0.9900
19:35358878–35358879	acceptor_loss	0.9900	6
19:35358650–35358651	donor_loss	0.9700	5
19:35358881	acceptor_gain	0.9000
19:35358651	donor_loss	0.8500
19:35358967	acceptor_gain	0.8200
19:35358613	donor_gain	0.6500
19:35358554	donor_gain	0.6300
19:35358647	donor_gain	0.6300
19:35358525	donor_gain	0.6200

AlphaMissense

474 missense substitutions predicted likely pathogenic (of 2,232 scored), across 166 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
D272	8	0.872	0.928
D61	8	0.839	0.908
F173	7	0.875	0.961
C88	7	0.858	0.918
W81	7	0.849	0.960
C169	7	0.845	0.873
W257	7	0.833	0.959
F234	7	0.818	0.941
N32	7	0.810	0.922
F238	7	0.800	0.950
F39	7	0.765	0.878
F96	7	0.751	0.927
D51	7	0.658	0.732
N56	6	0.818	0.964
F193	6	0.816	0.952
P196	6	0.752	0.937
G28	5	0.912	0.949
S110	5	0.902	0.986
F283	5	0.875	0.939
S136	5	0.857	0.986

HPA cancer prognostics

RNA cancer specificity: Not detected

Disease associations

OMIM: gene MIM:603821 | disease phenotypes:

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5201 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 4,833,499 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

4 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL539	ACETIC ACID	4	3,642,061
CHEMBL14227	BUTYRIC ACID	2	428,661
CHEMBL14021	PROPIONIC ACID	2	738,019
CHEMBL62381	SODIUM BUTYRATE	2	24,758

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 (8 total), top 8:

Ligand	Action	Affinity	Parameter
(S)-4-CMTB	Agonist	6.4	pKi
propanoic acid	Full agonist	5.7	pEC50
FHQC	Agonist	5.65	pEC50
pentanoic acid	Full agonist	5.4	pEC50
butyric acid	Full agonist	4.9	pEC50
isobutyric acid	Full agonist	4.8	pEC50
acetic acid	Full agonist	3.9	pEC50
1-methylcyclopropanecarboxylic acid	Full agonist	3.9	pEC50

Binding affinities (BindingDB)

80 measured of 82 human assays (83 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
CHEMBL4859651	EC50	0.04 nM
CHEMBL4847662	EC50	0.417 nM
CHEMBL3963542	EC50	55 nM
CHEMBL3600993	EC50	58 nM
CHEMBL3926143	EC50	77 nM
CHEMBL4564389	EC50	129 nM
CHEMBL4436229	EC50	145 nM
CHEMBL4530642	EC50	162 nM
CHEMBL4567723	EC50	191 nM
5-ethyl-2-mercapto-3H-pyrano[2,3-d]pyrimidine-4,7-dione	EC50	220 nM
CHEMBL2036813	EC50	220 nM
CHEMBL5281556	EC50	220 nM
CHEMBL5277000	EC50	220 nM
CHEMBL4547569	EC50	245 nM
CHEMBL4581781	EC50	251 nM
CHEMBL4442868	EC50	251 nM
CHEMBL4098843	EC50	260 nM
CHEMBL3893207	EC50	280 nM
CHEMBL4513816	EC50	288 nM
CHEMBL3601001	EC50	300 nM
CHEMBL4473184	EC50	355 nM
CHEMBL5284951	EC50	380 nM
CHEMBL3941821	EC50	410 nM
CHEMBL4569482	EC50	537 nM
CHEMBL3601003	EC50	540 nM
CHEMBL3805888	EC50	580 nM
CHEMBL3805952	EC50	580 nM
CHEMBL4567938	EC50	589 nM
CHEMBL4547759	EC50	603 nM
CHEMBL4470725	EC50	617 nM
CHEMBL4440835	EC50	646 nM
CHEMBL4515057	EC50	692 nM
CHEMBL5270112	EC50	740 nM
CHEMBL3805328	EC50	760 nM
CHEMBL4592426	EC50	871 nM
CHEMBL4439667	EC50	1000 nM
CHEMBL4450056	EC50	1070 nM
CHEMBL4449702	EC50	1100 nM
CHEMBL4476587	EC50	1100 nM
CHEMBL4570341	EC50	1200 nM
CHEMBL4457531	EC50	1200 nM
CHEMBL4578663	EC50	1230 nM
CHEMBL3805879	EC50	1280 nM
CHEMBL4574477	EC50	1350 nM
CHEMBL4584743	EC50	1380 nM
CHEMBL4471380	EC50	1380 nM
CHEMBL4470372	EC50	1580 nM
CHEMBL4517214	EC50	1620 nM
CHEMBL4443263	EC50	1660 nM
CHEMBL4470404	EC50	1780 nM

ChEMBL bioactivities

85 potent at pChembl≥5 of 103 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.89	EC50	128.8	nM	CHEMBL4564389
6.84	EC50	144.5	nM	CHEMBL4436229
6.79	EC50	162.2	nM	CHEMBL4530642
6.72	EC50	190.6	nM	CHEMBL4567723
6.66	EC50	220	nM	CHEMBL5270112
6.66	EC50	220	nM	CHEMBL5275861
6.66	EC50	220	nM	CHEMBL5284951
6.66	EC50	220	nM	CHEMBL5281556
6.66	EC50	220	nM	CHEMBL1672755
6.66	EC50	220	nM	CHEMBL5277000
6.66	EC50	220	nM	CHEMBL2036813
6.61	EC50	245.5	nM	CHEMBL4547569
6.60	EC50	251.2	nM	CHEMBL4581781
6.60	EC50	251.2	nM	CHEMBL4442868
6.58	EC50	263	nM	CHEMBL4584743
6.54	EC50	288.4	nM	CHEMBL4513816
6.45	EC50	354.8	nM	CHEMBL4473184
6.43	EC50	371.5	nM	CHEMBL4567192
6.42	EC50	380.2	nM	CHEMBL4560915
6.40	EC50	398.1	nM	CHEMBL4516265
6.35	EC50	447	nM	CHEMBL5574528
6.30	EC50	501.2	nM	CHEMBL4447610
6.28	EC50	524.8	nM	CHEMBL4448591
6.28	EC50	524.8	nM	CHEMBL4470184
6.27	EC50	537	nM	CHEMBL4569482
6.27	EC50	537	nM	CHEMBL4448591
6.23	EC50	588.8	nM	CHEMBL4567938
6.22	EC50	602.6	nM	CHEMBL4547759
6.21	EC50	616.6	nM	CHEMBL4470725
6.19	EC50	645.6	nM	CHEMBL4440835
6.17	EC50	679	nM	CHEMBL5594815
6.16	EC50	691.8	nM	CHEMBL4545039
6.16	EC50	691.8	nM	CHEMBL4515057
6.16	EC50	691.8	nM	CHEMBL4457531
6.15	EC50	708	nM	CHEMBL4452922
6.14	EC50	724.4	nM	CHEMBL4443269
6.13	EC50	741	nM	CHEMBL4564389
6.06	EC50	871	nM	CHEMBL4592426
6.00	EC50	1000	nM	CHEMBL4439667
5.97	EC50	1072	nM	CHEMBL4450056
5.96	EC50	1096	nM	CHEMBL4449702
5.96	EC50	1096	nM	CHEMBL4476587
5.92	EC50	1202	nM	CHEMBL4457531
5.92	EC50	1202	nM	CHEMBL4570341
5.91	EC50	1230	nM	CHEMBL4578663
5.87	EC50	1349	nM	CHEMBL4574477
5.86	EC50	1380	nM	CHEMBL4584743
5.86	EC50	1380	nM	CHEMBL4471380
5.80	EC50	1585	nM	CHEMBL4470372
5.79	EC50	1622	nM	CHEMBL4570341

PubChem BioAssay actives

84 with measured affinity, of 358 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
N-(2,5-dichlorophenyl)-4-(furan-2-yl)-2-methyl-5-oxo-4,6,7,8-tetrahydro-1H-quinoline-3-carboxamide	1605673: Agonist activity at human FFA3 receptor stably expressed in Flp-In T-Rex HEK293 cells cotransfected with eYFP assessed as inhibition of forskolin-induced cAMP production measured after 1 hr by fluorescence plate reader assay	ec50	0.1288	uM
N-(2,5-dichlorophenyl)-2-methyl-5-oxo-4-propyl-4,6,7,8-tetrahydro-1H-quinoline-3-carboxamide	1605673: Agonist activity at human FFA3 receptor stably expressed in Flp-In T-Rex HEK293 cells cotransfected with eYFP assessed as inhibition of forskolin-induced cAMP production measured after 1 hr by fluorescence plate reader assay	ec50	0.1445	uM
4-cyclopentyl-N-(2,5-dichlorophenyl)-2-methyl-5-oxo-4,6,7,8-tetrahydro-1H-quinoline-3-carboxamide	1605673: Agonist activity at human FFA3 receptor stably expressed in Flp-In T-Rex HEK293 cells cotransfected with eYFP assessed as inhibition of forskolin-induced cAMP production measured after 1 hr by fluorescence plate reader assay	ec50	0.1622	uM
N-(2,5-dichlorophenyl)-2-methyl-4-(1,3-oxazol-2-yl)-5-oxo-4,6,7,8-tetrahydro-1H-quinoline-3-carboxamide	1605673: Agonist activity at human FFA3 receptor stably expressed in Flp-In T-Rex HEK293 cells cotransfected with eYFP assessed as inhibition of forskolin-induced cAMP production measured after 1 hr by fluorescence plate reader assay	ec50	0.1905	uM
5-butyl-1H-pyrano[2,3-d]pyrimidine-2,4,7-trione	1939798: Agonist activity at FFA3 (unknown origin) expressed in human Flp-In-293 cells assessed as inhibition of forskolin-stimulated cAMP accumulation incubated for 30 mins by Lance cAMP assay	ec50	0.2200	uM
5-butyl-2-sulfanylidene-1H-pyrano[2,3-d]pyrimidine-4,7-dione	1939798: Agonist activity at FFA3 (unknown origin) expressed in human Flp-In-293 cells assessed as inhibition of forskolin-stimulated cAMP accumulation incubated for 30 mins by Lance cAMP assay	ec50	0.2200	uM
5-(4-chlorobutyl)-1H-pyrano[2,3-d]pyrimidine-2,4,7-trione	1939798: Agonist activity at FFA3 (unknown origin) expressed in human Flp-In-293 cells assessed as inhibition of forskolin-stimulated cAMP accumulation incubated for 30 mins by Lance cAMP assay	ec50	0.2200	uM
5-(4-chlorobutyl)-2-sulfanylidene-1H-pyrano[2,3-d]pyrimidine-4,7-dione	1939798: Agonist activity at FFA3 (unknown origin) expressed in human Flp-In-293 cells assessed as inhibition of forskolin-stimulated cAMP accumulation incubated for 30 mins by Lance cAMP assay	ec50	0.2200	uM
5-propyl-2-sulfanylidene-1H-pyrano[2,3-d]pyrimidine-4,7-dione	1939798: Agonist activity at FFA3 (unknown origin) expressed in human Flp-In-293 cells assessed as inhibition of forskolin-stimulated cAMP accumulation incubated for 30 mins by Lance cAMP assay	ec50	0.2200	uM
5-ethyl-2-sulfanylidene-1H-pyrano[2,3-d]pyrimidine-4,7-dione	1939798: Agonist activity at FFA3 (unknown origin) expressed in human Flp-In-293 cells assessed as inhibition of forskolin-stimulated cAMP accumulation incubated for 30 mins by Lance cAMP assay	ec50	0.2200	uM
5-methyl-2-sulfanylidene-1H-pyrano[2,3-d]pyrimidine-4,7-dione	1939798: Agonist activity at FFA3 (unknown origin) expressed in human Flp-In-293 cells assessed as inhibition of forskolin-stimulated cAMP accumulation incubated for 30 mins by Lance cAMP assay	ec50	0.2200	uM
4-(5-bromofuran-2-yl)-2-methyl-N-(2-methylphenyl)-5-oxo-4,6,7,8-tetrahydro-1H-quinoline-3-carboxamide	1605673: Agonist activity at human FFA3 receptor stably expressed in Flp-In T-Rex HEK293 cells cotransfected with eYFP assessed as inhibition of forskolin-induced cAMP production measured after 1 hr by fluorescence plate reader assay	ec50	0.2455	uM
4-cyclopropyl-N-(2,5-dichlorophenyl)-2-methyl-5-oxo-4,6,7,8-tetrahydro-1H-quinoline-3-carboxamide	1605673: Agonist activity at human FFA3 receptor stably expressed in Flp-In T-Rex HEK293 cells cotransfected with eYFP assessed as inhibition of forskolin-induced cAMP production measured after 1 hr by fluorescence plate reader assay	ec50	0.2512	uM
N-(2,5-dichlorophenyl)-2-methyl-5-oxo-4-(1,3-thiazol-2-yl)-4,6,7,8-tetrahydro-1H-quinoline-3-carboxamide	1605673: Agonist activity at human FFA3 receptor stably expressed in Flp-In T-Rex HEK293 cells cotransfected with eYFP assessed as inhibition of forskolin-induced cAMP production measured after 1 hr by fluorescence plate reader assay	ec50	0.2512	uM
4-butyl-2-methyl-N-(2-methylphenyl)-5-oxo-4,6,7,8-tetrahydro-1H-quinoline-3-carboxamide	1605675: Positive allosteric modulation at human FFA3 receptor stably expressed in Flp-In T-Rex HEK293 cells cotransfected with eYFP assessed as inhibition of forskolin-induced cAMP production measured after 1 hr in presence of 1 uM propionate by fluorescence plate reader assay	ec50	0.2630	uM
4-cyclopentyl-2-methyl-N-(2-methylphenyl)-5-oxo-4,6,7,8-tetrahydro-1H-quinoline-3-carboxamide	1605673: Agonist activity at human FFA3 receptor stably expressed in Flp-In T-Rex HEK293 cells cotransfected with eYFP assessed as inhibition of forskolin-induced cAMP production measured after 1 hr by fluorescence plate reader assay	ec50	0.2884	uM
4-ethyl-2-methyl-N-(2-methylphenyl)-5-oxo-4,6,7,8-tetrahydro-1H-quinoline-3-carboxamide	1605675: Positive allosteric modulation at human FFA3 receptor stably expressed in Flp-In T-Rex HEK293 cells cotransfected with eYFP assessed as inhibition of forskolin-induced cAMP production measured after 1 hr in presence of 1 uM propionate by fluorescence plate reader assay	ec50	0.3548	uM
4-(furan-2-yl)-N-(2-methoxyphenyl)-2-methyl-5-oxo-4,6,7,8-tetrahydro-1H-quinoline-3-carboxamide	1605673: Agonist activity at human FFA3 receptor stably expressed in Flp-In T-Rex HEK293 cells cotransfected with eYFP assessed as inhibition of forskolin-induced cAMP production measured after 1 hr by fluorescence plate reader assay	ec50	0.3715	uM
5-cyano-2,6-dimethyl-N-(2-methylphenyl)-4-(2-methylpropyl)-1,4-dihydropyridine-3-carboxamide	1605675: Positive allosteric modulation at human FFA3 receptor stably expressed in Flp-In T-Rex HEK293 cells cotransfected with eYFP assessed as inhibition of forskolin-induced cAMP production measured after 1 hr in presence of 1 uM propionate by fluorescence plate reader assay	ec50	0.3802	uM
2-methyl-N-(2-methylphenyl)-5-oxo-4-pentyl-4,6,7,8-tetrahydro-1H-quinoline-3-carboxamide	1605675: Positive allosteric modulation at human FFA3 receptor stably expressed in Flp-In T-Rex HEK293 cells cotransfected with eYFP assessed as inhibition of forskolin-induced cAMP production measured after 1 hr in presence of 1 uM propionate by fluorescence plate reader assay	ec50	0.3981	uM
N-(2,5-dichlorophenyl)-2-methyl-5-oxo-4-[5-(2,3,4-trifluorophenyl)furan-2-yl]-4,6,7,8-tetrahydro-1H-quinoline-3-carboxamide	2107868: Agonist activity at doxycyclin-induced GPR41 (unknown origin) overexpressed in HEK293 cells assessed as decrease in forskolin-induced cAMP level	ec50	0.4470	uM
4-butan-2-yl-2-methyl-N-(2-methylphenyl)-5-oxo-4,6,7,8-tetrahydro-1H-quinoline-3-carboxamide	1605675: Positive allosteric modulation at human FFA3 receptor stably expressed in Flp-In T-Rex HEK293 cells cotransfected with eYFP assessed as inhibition of forskolin-induced cAMP production measured after 1 hr in presence of 1 uM propionate by fluorescence plate reader assay	ec50	0.5012	uM
4-(furan-2-yl)-2-methyl-N-(2-methylphenyl)-5-oxo-4,6,7,8-tetrahydro-1H-quinoline-3-carboxamide	1605673: Agonist activity at human FFA3 receptor stably expressed in Flp-In T-Rex HEK293 cells cotransfected with eYFP assessed as inhibition of forskolin-induced cAMP production measured after 1 hr by fluorescence plate reader assay	ec50	0.5248	uM
2-methyl-N-(2-methylphenyl)-4-(2-methylpropyl)-5-oxo-4,6,7,8-tetrahydro-1H-quinoline-3-carboxamide	1605675: Positive allosteric modulation at human FFA3 receptor stably expressed in Flp-In T-Rex HEK293 cells cotransfected with eYFP assessed as inhibition of forskolin-induced cAMP production measured after 1 hr in presence of 1 uM propionate by fluorescence plate reader assay	ec50	0.5248	uM
4-(furan-3-yl)-2-methyl-N-(2-methylphenyl)-5-oxo-4,6,7,8-tetrahydro-1H-quinoline-3-carboxamide	1605673: Agonist activity at human FFA3 receptor stably expressed in Flp-In T-Rex HEK293 cells cotransfected with eYFP assessed as inhibition of forskolin-induced cAMP production measured after 1 hr by fluorescence plate reader assay	ec50	0.5370	uM
2-methyl-N-(2-methylphenyl)-5-oxo-4-(2-phenylethyl)-4,6,7,8-tetrahydro-1H-quinoline-3-carboxamide	1605675: Positive allosteric modulation at human FFA3 receptor stably expressed in Flp-In T-Rex HEK293 cells cotransfected with eYFP assessed as inhibition of forskolin-induced cAMP production measured after 1 hr in presence of 1 uM propionate by fluorescence plate reader assay	ec50	0.5888	uM
4-cyclopropyl-2-methyl-N-(2-methylphenyl)-5-oxo-4,6,7,8-tetrahydro-1H-quinoline-3-carboxamide	1605673: Agonist activity at human FFA3 receptor stably expressed in Flp-In T-Rex HEK293 cells cotransfected with eYFP assessed as inhibition of forskolin-induced cAMP production measured after 1 hr by fluorescence plate reader assay	ec50	0.6026	uM
methyl 2-methyl-4-(2-methylpropyl)-5-oxo-4,6,7,8-tetrahydro-1H-quinoline-3-carboxylate	1605675: Positive allosteric modulation at human FFA3 receptor stably expressed in Flp-In T-Rex HEK293 cells cotransfected with eYFP assessed as inhibition of forskolin-induced cAMP production measured after 1 hr in presence of 1 uM propionate by fluorescence plate reader assay	ec50	0.6166	uM
N-(2-chloro-5-methylphenyl)-2-methyl-5-oxo-4-propyl-4,6,7,8-tetrahydro-1H-quinoline-3-carboxamide	1605673: Agonist activity at human FFA3 receptor stably expressed in Flp-In T-Rex HEK293 cells cotransfected with eYFP assessed as inhibition of forskolin-induced cAMP production measured after 1 hr by fluorescence plate reader assay	ec50	0.6456	uM
4-[5-(3,5-difluorophenyl)furan-2-yl]-2-methyl-N-(2-methylphenyl)-5-oxo-4,6,7,8-tetrahydro-1H-quinoline-3-carboxamide	2107868: Agonist activity at doxycyclin-induced GPR41 (unknown origin) overexpressed in HEK293 cells assessed as decrease in forskolin-induced cAMP level	ec50	0.6790	uM
2-methyl-N-(2-methylphenyl)-5-oxo-4-propyl-4,6,7,8-tetrahydro-1H-quinoline-3-carboxamide	1605675: Positive allosteric modulation at human FFA3 receptor stably expressed in Flp-In T-Rex HEK293 cells cotransfected with eYFP assessed as inhibition of forskolin-induced cAMP production measured after 1 hr in presence of 1 uM propionate by fluorescence plate reader assay	ec50	0.6918	uM
methyl 2,6-dimethyl-5-[(2-methylphenyl)carbamoyl]-4-(2-methylpropyl)-1,4-dihydropyridine-3-carboxylate	1605675: Positive allosteric modulation at human FFA3 receptor stably expressed in Flp-In T-Rex HEK293 cells cotransfected with eYFP assessed as inhibition of forskolin-induced cAMP production measured after 1 hr in presence of 1 uM propionate by fluorescence plate reader assay	ec50	0.6918	uM
4-(furan-2-yl)-2-methyl-N-(4-methylphenyl)-5-oxo-4,6,7,8-tetrahydro-1H-quinoline-3-carboxamide	1605673: Agonist activity at human FFA3 receptor stably expressed in Flp-In T-Rex HEK293 cells cotransfected with eYFP assessed as inhibition of forskolin-induced cAMP production measured after 1 hr by fluorescence plate reader assay	ec50	0.6918	uM
N-(2-chlorophenyl)-2-methyl-4-(2-methylpropyl)-5-oxo-4,6,7,8-tetrahydro-1H-quinoline-3-carboxamide	1605673: Agonist activity at human FFA3 receptor stably expressed in Flp-In T-Rex HEK293 cells cotransfected with eYFP assessed as inhibition of forskolin-induced cAMP production measured after 1 hr by fluorescence plate reader assay	ec50	0.7079	uM
2-methyl-N-(2-methylphenyl)-5-oxo-4-[(E)-2-phenylethenyl]-4,6,7,8-tetrahydro-1H-quinoline-3-carboxamide	1605675: Positive allosteric modulation at human FFA3 receptor stably expressed in Flp-In T-Rex HEK293 cells cotransfected with eYFP assessed as inhibition of forskolin-induced cAMP production measured after 1 hr in presence of 1 uM propionate by fluorescence plate reader assay	ec50	0.7244	uM
N-(2-chlorophenyl)-2-methyl-5-oxo-4-propyl-4,6,7,8-tetrahydro-1H-quinoline-3-carboxamide	1605673: Agonist activity at human FFA3 receptor stably expressed in Flp-In T-Rex HEK293 cells cotransfected with eYFP assessed as inhibition of forskolin-induced cAMP production measured after 1 hr by fluorescence plate reader assay	ec50	0.8710	uM
4-(1-benzofuran-2-yl)-2-methyl-N-(2-methylphenyl)-5-oxo-4,6,7,8-tetrahydro-1H-quinoline-3-carboxamide	1605673: Agonist activity at human FFA3 receptor stably expressed in Flp-In T-Rex HEK293 cells cotransfected with eYFP assessed as inhibition of forskolin-induced cAMP production measured after 1 hr by fluorescence plate reader assay	ec50	1.0000	uM
N-(3-chlorophenyl)-2-methyl-5-oxo-4-propyl-4,6,7,8-tetrahydro-1H-quinoline-3-carboxamide	1605673: Agonist activity at human FFA3 receptor stably expressed in Flp-In T-Rex HEK293 cells cotransfected with eYFP assessed as inhibition of forskolin-induced cAMP production measured after 1 hr by fluorescence plate reader assay	ec50	1.0715	uM
N-(2-chloro-5-methoxyphenyl)-2-methyl-5-oxo-4-propyl-4,6,7,8-tetrahydro-1H-quinoline-3-carboxamide	1605673: Agonist activity at human FFA3 receptor stably expressed in Flp-In T-Rex HEK293 cells cotransfected with eYFP assessed as inhibition of forskolin-induced cAMP production measured after 1 hr by fluorescence plate reader assay	ec50	1.0965	uM
2-methyl-4-(5-methylfuran-2-yl)-N-(2-methylphenyl)-5-oxo-4,6,7,8-tetrahydro-1H-quinoline-3-carboxamide	1605673: Agonist activity at human FFA3 receptor stably expressed in Flp-In T-Rex HEK293 cells cotransfected with eYFP assessed as inhibition of forskolin-induced cAMP production measured after 1 hr by fluorescence plate reader assay	ec50	1.0965	uM
2-methyl-N-(2-methylphenyl)-5-oxo-4-thiophen-2-yl-4,6,7,8-tetrahydro-1H-quinoline-3-carboxamide	1605675: Positive allosteric modulation at human FFA3 receptor stably expressed in Flp-In T-Rex HEK293 cells cotransfected with eYFP assessed as inhibition of forskolin-induced cAMP production measured after 1 hr in presence of 1 uM propionate by fluorescence plate reader assay	ec50	1.2023	uM
2-methyl-N-(2-methylphenyl)-5-oxo-4-phenyl-4,6,7,8-tetrahydro-1H-quinoline-3-carboxamide	1605673: Agonist activity at human FFA3 receptor stably expressed in Flp-In T-Rex HEK293 cells cotransfected with eYFP assessed as inhibition of forskolin-induced cAMP production measured after 1 hr by fluorescence plate reader assay	ec50	1.2303	uM
4-(3-bromophenyl)-2-methyl-N-(2-methylphenyl)-5-oxo-4,6,7,8-tetrahydro-1H-quinoline-3-carboxamide	1605673: Agonist activity at human FFA3 receptor stably expressed in Flp-In T-Rex HEK293 cells cotransfected with eYFP assessed as inhibition of forskolin-induced cAMP production measured after 1 hr by fluorescence plate reader assay	ec50	1.3490	uM
2-methyl-N-(2-methylphenyl)-4-(4-methylthiophen-2-yl)-5-oxo-4,6,7,8-tetrahydro-1H-quinoline-3-carboxamide	1605673: Agonist activity at human FFA3 receptor stably expressed in Flp-In T-Rex HEK293 cells cotransfected with eYFP assessed as inhibition of forskolin-induced cAMP production measured after 1 hr by fluorescence plate reader assay	ec50	1.3804	uM
4-(furan-2-yl)-2-methyl-N-(3-methylphenyl)-5-oxo-4,6,7,8-tetrahydro-1H-quinoline-3-carboxamide	1605673: Agonist activity at human FFA3 receptor stably expressed in Flp-In T-Rex HEK293 cells cotransfected with eYFP assessed as inhibition of forskolin-induced cAMP production measured after 1 hr by fluorescence plate reader assay	ec50	1.5849	uM
4-(4-bromophenyl)-2-methyl-N-(2-methylphenyl)-5-oxo-4,6,7,8-tetrahydro-1H-quinoline-3-carboxamide	1605673: Agonist activity at human FFA3 receptor stably expressed in Flp-In T-Rex HEK293 cells cotransfected with eYFP assessed as inhibition of forskolin-induced cAMP production measured after 1 hr by fluorescence plate reader assay	ec50	1.6218	uM
N-(2,5-dichlorophenyl)-2-methyl-4-(1,3-oxazol-4-yl)-5-oxo-4,6,7,8-tetrahydro-1H-quinoline-3-carboxamide	1605673: Agonist activity at human FFA3 receptor stably expressed in Flp-In T-Rex HEK293 cells cotransfected with eYFP assessed as inhibition of forskolin-induced cAMP production measured after 1 hr by fluorescence plate reader assay	ec50	1.6596	uM
N-(2,5-dichlorophenyl)-2-methyl-5-oxo-4-(1,3-thiazol-5-yl)-4,6,7,8-tetrahydro-1H-quinoline-3-carboxamide	1605673: Agonist activity at human FFA3 receptor stably expressed in Flp-In T-Rex HEK293 cells cotransfected with eYFP assessed as inhibition of forskolin-induced cAMP production measured after 1 hr by fluorescence plate reader assay	ec50	1.7783	uM
N-(2,5-dichlorophenyl)-2-methyl-5-oxo-4-(1,3-thiazol-4-yl)-4,6,7,8-tetrahydro-1H-quinoline-3-carboxamide	1605673: Agonist activity at human FFA3 receptor stably expressed in Flp-In T-Rex HEK293 cells cotransfected with eYFP assessed as inhibition of forskolin-induced cAMP production measured after 1 hr by fluorescence plate reader assay	ec50	1.9498	uM
2-methyl-N-(2-methylphenyl)-5-oxo-4-[3-(trifluoromethyl)phenyl]-4,6,7,8-tetrahydro-1H-quinoline-3-carboxamide	1605673: Agonist activity at human FFA3 receptor stably expressed in Flp-In T-Rex HEK293 cells cotransfected with eYFP assessed as inhibition of forskolin-induced cAMP production measured after 1 hr by fluorescence plate reader assay	ec50	2.8184	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, increases methylation	2
2-palmitoylglycerol	increases expression	1
gardiquimod	decreases reaction, increases expression	1
Resveratrol	decreases expression, affects cotreatment	1
Air Pollutants	increases abundance, increases expression	1
Amiodarone	increases expression	1
Benzo(a)pyrene	affects methylation	1
Hydralazine	affects cotreatment, increases expression	1
Ozone	increases abundance, increases expression	1
Plant Extracts	decreases expression, affects cotreatment	1
Tretinoin	increases expression	1
Protein Kinase Inhibitors	decreases reaction, increases expression	1

ChEMBL screening assays

56 unique, capped per target: 43 functional, 13 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1069234	Functional	Agonist activity at FFA3 receptor up to 30 uM	The first synthetic agonists of FFA2: Discovery and SAR of phenylacetamides as allosteric modulators. — *Bioorg Med Chem Lett*
CHEMBL2320490	Binding	Agonist activity at human FFA3 in expressed in HEK293 cells assessed as cellular mass movement by dynamic mass redistribution assay	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

2 cell lines: 2 spontaneously immortalized cell line

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

Cellosaurus	Name	Category	Sex
CVCL_KV14	cAMP Hunter CHO-K1 FFAR3 Gi	Spontaneously immortalized cell line	Female
CVCL_U014	CHO-FFAR3	Spontaneously immortalized cell line	Female

Clinical trials (associated diseases)

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

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for FFAR3 across ~30M SureChEMBL compounds — explore on Sugi Predict.