FPR3

Summary

FPR3 (formyl peptide receptor 3, HGNC:3828) is a protein-coding gene on chromosome 19q13.41, encoding N-formyl peptide receptor 3 (P25089). May function as a pattern recognition G protein-coupled receptor (PRR/GPCR) involved in innate recognition of peptides derived from a specific set of bacterial pathogens or host mitochondria as pathogen- and damage-associated molecular patterns (PAMPs and DAMPs).

Predicted to enable N-formyl peptide receptor activity and complement receptor activity. Predicted to be involved in several processes, including complement receptor mediated signaling pathway; phospholipase C-activating G protein-coupled receptor signaling pathway; and positive regulation of cytosolic calcium ion concentration. Located in plasma membrane.

Source: NCBI Gene 2359 — automated summary from GO annotations (Alliance of Genome Resources).

At a glance

• GWAS associations: 20
• Clinical variants (ClinVar): 39 total
• GTEx eGene: eQTL in 17 tissues, sQTL in 0 (q < 0.05)
• ChEMBL bioactivity: 10 clinical-phase molecules tested; no curated mechanism-of-action drug
• Constraint (gnomAD): pLI 0.15 (intermediate), LOEUF 1.91 (unconstrained)
• MANE Select transcript: NM_002030

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3828
Approved symbol	FPR3
Name	formyl peptide receptor 3
Location	19q13.41
Locus type	gene with protein product
Status	Approved
Aliases	FPRH1, FMLPY, RMLP-R-I
Ensembl gene	ENSG00000187474
Ensembl biotype	protein_coding
OMIM	136539
Entrez	2359

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 6 protein_coding

MANE Select: ENST00000339223

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1, TSL 4: 1

ENST00000339223, ENST00000595991, ENST00000901092, ENST00000901093, ENST00000957103, ENST00001134669

RefSeq mRNA: 1 — MANE Select: NM_002030 NM_002030

CCDS: CCDS12841

Canonical transcript exons

ENST00000339223 — 2 exons

Exon	Start	End
ENSE00001379510	51823739	51826190
ENSE00001404479	51795157	51795331

Expression profiles

Bgee: expression breadth ubiquitous, 194 present calls, max score 87.17.

FANTOM5 (CAGE): breadth broad, TPM avg 6.1561 / max 293.8163, expressed in 319 samples.

Highest expression (Bgee): gall bladder, rectum, primordial germ cell in gonad, amniotic fluid, coronary artery.

Genetic regulation across tissues (GTEx eQTL / sQTL)

FPR3 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 17 tissues and its splicing (sQTL) in 0 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

17 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Testis	eqtl	5.1e-96	+1.26	19:51795028:T:C
Adipose Subcutaneous	eqtl	9.5e-06	+0.13	19:51790457:T:C
Whole Blood	eqtl	2.9e-05	-0.20	19:51793284:A:C
Adipose Visceral Omentum	eqtl	3.5e-05	-0.50	19:51739410:C:T
Breast Mammary Tissue	eqtl	6.6e-05	+0.19	19:51765591:T:C
Lung	eqtl	7.9e-05	+0.14	19:51796174:G:A
Skin Sun Exposed Lower leg	eqtl	2.7e-04	+0.17	19:51790844:T:C
Skin Not Sun Exposed Suprapubic	eqtl	5.7e-04	+0.17	19:51796100:A:G
Heart Atrial Appendage	eqtl	5.5e-03	+0.15	19:51797810:G:A
Artery Aorta	eqtl	8.7e-03	+0.12	19:51796174:G:A
Thyroid	eqtl	1.6e-02	-0.14	19:51797309:CTT:C
Muscle Skeletal	eqtl	1.7e-02	+0.13	19:51793039:C:T
Spleen	eqtl	1.7e-02	+0.93	19:51291181:A:G
Artery Tibial	eqtl	2.0e-02	+0.12	19:51795323:A:C
Nerve Tibial	eqtl	2.1e-02	+0.13	19:51789880:G:A
Minor Salivary Gland	eqtl	3.0e-02	+0.69	19:52621621:A:AACTT
Heart Left Ventricle	eqtl	4.8e-02	+0.14	19:51831208:A:C

FANTOM5 promoters

3 alternative TSS:

Promoter ID	TPM avg	Samples expressed
177269	5.4744	312
177268	0.5914	143
177270	0.0903	53

Top tissues by expression

showing 100 of 281 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
gall bladder	UBERON:0002110	87.17	gold quality
rectum	UBERON:0001052	85.53	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	84.57	gold quality
amniotic fluid	UBERON:0000173	83.01	gold quality
right coronary artery	UBERON:0001625	82.94	gold quality
synovial joint	UBERON:0002217	82.46	gold quality
layer of synovial tissue	UBERON:0007616	82.37	gold quality
mucosa of sigmoid colon	UBERON:0004993	82.32	gold quality
vermiform appendix	UBERON:0001154	81.31	gold quality
calcaneal tendon	UBERON:0003701	77.56	gold quality
caecum	UBERON:0001153	77.49	gold quality
descending thoracic aorta	UBERON:0002345	77.49	gold quality
lymph node	UBERON:0000029	77.43	gold quality
upper lobe of left lung	UBERON:0008952	77.05	gold quality
upper lobe of lung	UBERON:0008948	76.85	gold quality
palpebral conjunctiva	UBERON:0001812	76.69	gold quality
left adrenal gland	UBERON:0001234	76.26	gold quality
left adrenal gland cortex	UBERON:0035825	75.82	gold quality
right adrenal gland cortex	UBERON:0035827	75.62	gold quality
lower lobe of lung	UBERON:0008949	75.46	gold quality
smooth muscle tissue	UBERON:0001135	75.30	gold quality
decidua	UBERON:0002450	75.21	gold quality
left coronary artery	UBERON:0001626	75.01	gold quality
colonic mucosa	UBERON:0000317	74.88	gold quality
right adrenal gland	UBERON:0001233	74.82	gold quality
germinal epithelium of ovary	UBERON:0001304	74.56	gold quality
omental fat pad	UBERON:0010414	74.56	gold quality
coronary artery	UBERON:0001621	74.50	gold quality
peritoneum	UBERON:0002358	74.50	gold quality
adrenal cortex	UBERON:0001235	74.48	gold quality
colonic epithelium	UBERON:0000397	74.43	gold quality
thoracic aorta	UBERON:0001515	74.01	gold quality
adipose tissue of abdominal region	UBERON:0007808	73.98	gold quality
pericardium	UBERON:0002407	73.83	gold quality
visceral pleura	UBERON:0002401	73.79	gold quality
subcutaneous adipose tissue	UBERON:0002190	73.62	gold quality
adrenal gland	UBERON:0002369	73.53	gold quality
skin of hip	UBERON:0001554	73.46	gold quality
ascending aorta	UBERON:0001496	73.37	gold quality
lung	UBERON:0002048	73.34	gold quality
jejunal mucosa	UBERON:0000399	73.18	gold quality
adipose tissue	UBERON:0001013	73.18	gold quality
spleen	UBERON:0002106	73.09	gold quality
right lung	UBERON:0002167	72.66	gold quality
connective tissue	UBERON:0002384	72.63	gold quality
ileal mucosa	UBERON:0000331	72.48	silver quality
pleura	UBERON:0000977	72.26	gold quality
granulocyte	CL:0000094	72.20	gold quality
monocyte	CL:0000576	72.19	gold quality
leukocyte	CL:0000738	72.02	gold quality
pancreatic ductal cell	CL:0002079	71.95	silver quality
mononuclear cell	CL:0000842	71.87	gold quality
tendon	UBERON:0000043	71.56	gold quality
parietal pleura	UBERON:0002400	71.34	gold quality
small intestine Peyer’s patch	UBERON:0003454	70.84	gold quality
duodenum	UBERON:0002114	70.79	gold quality
small intestine	UBERON:0002108	70.67	gold quality
islet of Langerhans	UBERON:0000006	70.02	gold quality
large intestine	UBERON:0000059	69.81	gold quality
upper leg skin	UBERON:0004262	69.80	gold quality
intestine	UBERON:0000160	69.77	gold quality
transverse colon	UBERON:0001157	69.63	gold quality
mucosa of stomach	UBERON:0001199	69.48	gold quality
colon	UBERON:0001155	69.39	gold quality
aorta	UBERON:0000947	69.00	gold quality
sigmoid colon	UBERON:0001159	68.92	gold quality
superficial temporal artery	UBERON:0001614	68.04	silver quality
right atrium auricular region	UBERON:0006631	67.83	gold quality
urinary bladder	UBERON:0001255	67.68	gold quality
cardiac atrium	UBERON:0002081	67.27	gold quality
lower esophagus muscularis layer	UBERON:0035833	66.47	gold quality
lower esophagus	UBERON:0013473	66.39	gold quality
epithelium of nasopharynx	UBERON:0001951	66.21	silver quality
heart right ventricle	UBERON:0002080	66.16	silver quality
esophagogastric junction muscularis propria	UBERON:0035841	66.14	gold quality
muscle layer of sigmoid colon	UBERON:0035805	66.03	gold quality
liver	UBERON:0002107	65.71	gold quality
minor salivary gland	UBERON:0001830	65.65	gold quality
trabecular bone tissue	UBERON:0002483	65.60	gold quality
tibial artery	UBERON:0007610	65.40	gold quality
popliteal artery	UBERON:0002250	65.37	gold quality
heart	UBERON:0000948	65.36	gold quality
pancreas	UBERON:0001264	65.14	gold quality
tibial nerve	UBERON:0001323	65.08	gold quality
thoracic mammary gland	UBERON:0005200	65.03	gold quality
mammalian vulva	UBERON:0000997	64.95	silver quality
left uterine tube	UBERON:0001303	64.87	gold quality
jejunum	UBERON:0002115	64.82	gold quality
mucosa of transverse colon	UBERON:0004991	64.70	gold quality
mammary gland	UBERON:0001911	64.63	gold quality
mouth mucosa	UBERON:0003729	64.51	gold quality
saliva-secreting gland	UBERON:0001044	64.35	gold quality
bone marrow cell	CL:0002092	64.13	silver quality
oral cavity	UBERON:0000167	63.22	gold quality
esophagus	UBERON:0001043	63.16	gold quality
cardiac ventricle	UBERON:0002082	62.64	gold quality
heart left ventricle	UBERON:0002084	62.61	gold quality
right ovary	UBERON:0002118	62.46	gold quality
left ventricle myocardium	UBERON:0006566	62.24	gold quality
body of pancreas	UBERON:0001150	62.21	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-8410	yes	40.31
E-ANND-3	yes	18.91

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 61 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM
Lung	tissue	26.6
Appendix	tissue	22.6
Liver	tissue	19.9
Gallbladder	tissue	17.6
Rectum	tissue	17.1
Urinary bladder	tissue	16.3
Spleen	tissue	15.3
Thalamus	tissue	14.9
Small intestine	tissue	13.6
Lymph node	tissue	13.0
Colon	tissue	11.8
Adrenal gland	tissue	11.4
Duodenum	tissue	10.6
Tonsil	tissue	10.3
Adipose tissue	tissue	9.9
Smooth muscle	tissue	8.3
Thymus	tissue	7.6
Pons	tissue	7.3
Medulla oblongata	tissue	7.3
Stomach 1	tissue	6.7
Esophagus	tissue	5.4
Choroid plexus	tissue	5.4
Cervix	tissue	5.2
Placenta	tissue	5.2
Breast	tissue	5.0
Spinal cord	tissue	3.6
Heart muscle	tissue	3.5
Endometrium 1	tissue	3.5
Basal ganglia	tissue	3.2
Cerebral cortex	tissue	3.1
Midbrain	tissue	3.0
Substantia nigra	tissue	3.0
Kidney	tissue	3.0
Seminal vesicle	tissue	2.7
Skin 1	tissue	2.6
Testis	tissue	2.5
Hypothalamus	tissue	2.5
Amygdala	tissue	2.3
Prostate	tissue	2.3
Hippocampal formation	tissue	2.3
Pancreas	tissue	2.2
Putamen	tissue	2.1
Thyroid gland	tissue	2.1
Parathyroid gland	tissue	2.0
Cerebellum	tissue	2.0
Hippocampus	tissue	2.0
Tongue	tissue	1.9
Fallopian tube	tissue	1.9
Ovary	tissue	1.8
Locus coeruleus	tissue	1.8
Retrosplenial cortex	tissue	1.8
Nucleus accumbens	tissue	1.7
Salivary gland	tissue	1.4
Epididymis	tissue	1.4
Postcentral gyrus	tissue	1.3
Occipital cortex	tissue	1.3
Vagina	tissue	1.1
Pituitary gland	tissue	0.9
Skeletal muscle	tissue	0.8
Bone marrow	tissue	0.4

Brain sub-regions (HPA Brain Atlas): detected in 185; highest nTPM — Anterior thalamic nucleus, ventral (14.9), Lateral funiculus (white matter) (9.2), White matter (9.2), Dorsolateral tegmental area (7.3), Nucleus gracilis (7.3).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting FPR3 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 65 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-6759-5P	99.99	66.54	785
HSA-MIR-433-3P	99.98	69.37	1203
HSA-MIR-6755-5P	99.95	65.59	464
HSA-MIR-6772-5P	99.94	67.01	577
HSA-MIR-9718	99.94	68.91	918
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-374B-5P	99.90	69.98	2734
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-MIR-548AC	99.84	70.77	4351
HSA-MIR-548H-3P	99.84	70.80	4349
HSA-MIR-548Z	99.84	70.80	4349
HSA-MIR-4495	99.82	72.08	3080
HSA-MIR-4517	99.76	69.19	1867
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-7154-5P	99.69	70.52	1900
HSA-MIR-4470	99.66	69.35	1767
HSA-MIR-4804-3P	99.65	67.78	866
HSA-MIR-561-3P	99.64	70.90	3647
HSA-MIR-6757-3P	99.63	66.88	1089
HSA-MIR-217-5P	99.49	69.93	1419
HSA-MIR-12131	99.48	68.72	1673
HSA-MIR-766-5P	99.47	67.91	2225
HSA-MIR-20A-3P	99.44	69.10	1575
HSA-MIR-4735-5P	99.43	68.49	1780
HSA-MIR-548AV-3P	99.43	68.50	1721

Functional genomics

gnomAD constraint: pLI 0.148, LOEUF 1.91, missense Z 2.05 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000339223 — one region, missense o/e 0.78.

Literature-anchored findings (GeneRIF, showing 20)

• Human dendritic cells express functional FPRL2 throughout maturation. FPRL2 & its endogenous ligand may be involved in regulating DC trafficking during Ag uptake & processing s well as the T-cell-stimulating phase of the immune responses. (PMID:12223529)
• investigated the direct effect of LXA4 as well as the effect on agonist-induced biological responses using transfected HL-60 cells expressing FPR, FPRL1 or FPRL2 (PMID:12410796)
• an annexin 1 peptide can activate FPR, FPRL1, and FPRL2; results indicate that annexin 1 participates in regulating leukocyte emigration into inflamed tissue by activating and desensitizing different receptors of the FPR family. (PMID:15187149)
• Results show that humanin (HN) acts as a ligand for formyl peptide receptor-like 1 (FPRL1) and 2 (FPRL2). (PMID:15465011)
• Activation of FPRL2 inhibits lipopolysaccharide-induced dendritic cell maturation. (PMID:16002663)
• However, F2L inhibits formyl peptide receptor (FPR) and FPRL1 activities, resulting in the inhibition of intracellular calcium increases, and superoxide generation induced by N-formyl-Met-Leu-Phe, MMK-1, or Trp-Lys-Tyr-Met-Val-d-Met in neutrophils. (PMID:17577578)
• FPRL2 is expressed and functional in macrophages differentiated from monocytes in vitro in different conditions (PMID:19342677)
• Human monocytes express FPR1, FPR2, and FPR3; human neutrophils express FPR1 and FPR2, but not FPR3. (PMID:19843937)
• Results show that uPAR expression regulates the adhesive and migratory ability of CXCR4-expressing cells through a mechanism involving fMLP receptors and alpha-v integrins. (PMID:20972812)
• N-formyl peptide receptor 3 (FPR3) departs from the homologous FPR2/ALX receptor with regard to the major processes governing chemoattractant receptor regulation, expression at the cell surface, and phosphorylation. (PMID:21543323)
• F2L peptide, derived from the processing of nanomolar concentrations of heme-binding protein (HEBP)1, is active on FPR3 and able to induce recruitment of FPR3-expressing monocytes, macrophages, and mouse neutrophils (PMID:21709160)
• transcriptional variations of FPR3 occur by an alternative promoter during primate evolution. (PMID:21717223)
• The demonstrated proper folding and functionality of the cell-free produced human FPR3 opens a new avenue for the fast and efficient generation of human FPRs (and even other GPCRs) for structural and functional analysis. (PMID:23746112)
• The H. pylori-derived peptide Hp(2-20) stimulated eosinophil migration through the engagement of FPR2 and FPR3, and also induced production of VEGF-A and TGF-beta, two key mediators of tissue remodelling. (PMID:24067461)
• Taken together, our results suggest that intracellular FPR in naive CD4 T cells and surface FPRs in activated CD4 T cells might regulate immune responses by regulating CD4 T cell activity. (PMID:29427663)
• These findings provide evidence for defective FPR2/3 and annexin A1 expressions that, associated with decreased M2a polarization, might be involved in the development of cigarette smoking induced persistent airflow limitation in chronic obstructive pulmonary disease. (PMID:29544524)
• Low FPR3 expression is associated with obstructive sleep apnea. (PMID:31116781)
• D-Peptide analogues of Boc-Phe-Leu-Phe-Leu-Phe-COOH induce neovascularization via endothelial N-formyl peptide receptor 3. (PMID:32152757)
• Formyl peptide receptor 2 is an emerging modulator of inflammation in the liver. (PMID:36750693)
• FPR3 reprograms glycolytic metabolism and stemness in gastric cancer via calcium-NFATc1 pathway. (PMID:38614385)

Cross-species orthologs

0 orthologs

Paralogs (8): C5AR2 (ENSG00000134830), GPR32 (ENSG00000142511), FPR2 (ENSG00000171049), FPR1 (ENSG00000171051), C3AR1 (ENSG00000171860), CMKLR1 (ENSG00000174600), C5AR1 (ENSG00000197405), GPR33 (ENSG00000214943)

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
Pan paniscus	Q49SQ2	99.7%	Diamond
Pan troglodytes	Q49SQ3	99.7%	Diamond
Macaca mulatta	O97664	99.2%	Diamond
Macaca fascicularis	Q95LH1	99.2%	Diamond
Gorilla gorilla gorilla	P79177	98.9%	Diamond
Pongo pygmaeus	P79234	97.9%	Diamond
Pongo abelii	Q5REI5	96.5%	Diamond
Mus musculus	Q3SXG2	95.0%	Diamond
Rattus norvegicus	P46090	92.1%	Diamond
Rattus rattus	Q49SP8	89.4%	Diamond
Sus scrofa	B1PHQ8	87.4%	Diamond
Bos taurus	B9VR26	85.4%	Diamond
Oryctolagus cuniculus	Q05394	79.2%	Diamond
Canis lupus familiaris	P30992	69.8%	Diamond
Cavia porcellus	O70129	68.9%	Diamond
Danio rerio	P0C7U5	59.5%	Diamond
Oncorhynchus mykiss	Q6UNA4	59.5%	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
ZNF649-AS1	ncRNA	101928571
ZNF649	protein-coding	65251
ZNF577	protein-coding	84765
FPR1	protein-coding	2357
FPR2	protein-coding	2358

Protein

Protein identifiers

N-formyl peptide receptor 3 — P25089 (reviewed: P25089)

Alternative names: FMLP-related receptor II, Formyl peptide receptor-like 2

All UniProt accessions (2): P25089, Q6L5J4

UniProt curated annotations — full annotation on UniProt →

Function. May function as a pattern recognition G protein-coupled receptor (PRR/GPCR) involved in innate recognition of peptides derived from a specific set of bacterial pathogens or host mitochondria as pathogen- and damage-associated molecular patterns (PAMPs and DAMPs). Low affinity receptor for a restricted repertoire of bacterial N-formylated peptides including fMKKIML from L. monocytogenes and fMPKLNR from V. cholerae. Contrary to FPR1 and FPR2 does not act as a receptor for fMLF peptide. High affinity receptor for N-acetylated F2L peptide derived from the cleavage of heme-binding protein HEBP1. F2L peptide binding may trigger chemotaxis of monocytes and dendritic cells to facilitate tissue repair. Low affinity receptor for N-acetylated Ac2-26 peptide derived from ANXA1, an anti-inflammatory and pro-resolving agonist. Ac2-26 peptide binding can direct myeloid cell chemotaxis within the inflammatory site where ANXA1 is at high concentrations, but it can also lead to receptor desensitization to limit the inflammatory response. Receptor for MT-RNR2/humanin, a mitochondrial-derived peptide that has an anti-inflammatory role in resolution of inflammation. Peptide binding leads to conformational changes coupled to heterotrimeric G(i) protein signaling. Upon GDP to GTP conversion, G(i)-alpha subunit dissociates from G-beta and G-gamma subunits. Free G(i)-alpha subunit inhibits cyclic adenylate cyclase and cAMP synthesis whereas the G-beta and G-gamma dimer activates downstream phospholipase C-beta and phosphoinositide 3-kinase signaling cascades leading to Ca(2+) influx.

Subunit / interactions. Heterodimer with FPR1.

Subcellular location. Cell membrane.

Tissue specificity. Detected in various tissues with highest expression in lung. Expressed in immature dendritic cells (at protein level).

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

RefSeq proteins (1): NP_002021* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000276	GPCR_Rhodpsn	Family
IPR000826	Formyl_rcpt-rel	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain

Pfam: PF00001

UniProt features (24 total): topological domain 8, transmembrane region 7, sequence conflict 3, glycosylation site 2, chain 1, region of interest 1, compositionally biased region 1, disulfide bond 1

Structure

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P25089-F1	83.62	0.58

Human Protein Atlas

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

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): plasma membrane; primary cilium

Antibody reliability (HPA): IF approved

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	98–176

Glycosylation sites (2)

Type	Positions
N-linked (glcnac…) asparagine	4, 10

Function

Pathways and Gene Ontology

Reactome pathways

2 curated (TAS) of 8; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

8 pathways:

ID	Pathway	Evidence
R-HSA-444473	Formyl peptide receptors bind formyl peptides and many other ligands	curated
R-HSA-418594	G alpha (i) 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-375276	Peptide ligand-binding receptors	—
R-HSA-162582	Signal Transduction	—
R-HSA-372790	Signaling by GPCR	—

MSigDB gene sets: 146 (showing top): GOBP_INFLAMMATORY_RESPONSE, GOBP_TAXIS, REACTOME_PEPTIDE_LIGAND_BINDING_RECEPTORS, GOBP_REGULATION_OF_IMMUNE_RESPONSE, KEGG_NEUROACTIVE_LIGAND_RECEPTOR_INTERACTION, MODULE_123, DODD_NASOPHARYNGEAL_CARCINOMA_UP, GOMF_PEPTIDE_RECEPTOR_ACTIVITY, GOBP_PHOSPHOLIPASE_C_ACTIVATING_G_PROTEIN_COUPLED_RECEPTOR_SIGNALING_PATHWAY, PID_UPA_UPAR_PATHWAY, REACTOME_CLASS_A_1_RHODOPSIN_LIKE_RECEPTORS, GOMF_TRANSMEMBRANE_SIGNALING_RECEPTOR_ACTIVITY, GOMF_G_PROTEIN_COUPLED_RECEPTOR_ACTIVITY, GOBP_ACTIVATION_OF_IMMUNE_RESPONSE, VERHAAK_GLIOBLASTOMA_MESENCHYMAL

GO Biological Process (9): complement receptor mediated signaling pathway (GO:0002430), chemotaxis (GO:0006935), inflammatory response (GO:0006954), signal transduction (GO:0007165), phospholipase C-activating G protein-coupled receptor signaling pathway (GO:0007200), positive regulation of cytosolic calcium ion concentration (GO:0007204), cell communication (GO:0007154), G protein-coupled receptor signaling pathway (GO:0007186), signaling (GO:0023052)

GO Molecular Function (4): complement receptor activity (GO:0004875), N-formyl peptide receptor activity (GO:0004982), G protein-coupled receptor activity (GO:0004930), protein binding (GO:0005515)

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

Reactome top-level categories

6 top-level categories:

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

GO top-level categories

24 GO namespaces:

Category	Terms
cellular process	2
G protein-coupled receptor signaling pathway	2
transmembrane signaling receptor activity	2
immune response-activating cell surface receptor signaling pathway	1
response to chemical	1
taxis	1
defense response	1
cell communication	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
phospholipase C activator activity	1
regulation of biological quality	1
G protein-coupled receptor activity	1
signal transduction	1
regulation of biological process	1
complement binding	1
complement receptor mediated signaling pathway	1
immune receptor activity	1
G protein-coupled peptide receptor activity	1
binding	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 1 of 15 annotations. The rest are phylogenetic / computational / electronic (IEA).

1 experimentally-supported GO terms:

GO term	NS	Evidence
plasma membrane	CC	direct assay

Protein interactions and networks

STRING

showing 15 of 683 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FPR3	HEBP1	Q9NRV9	931
FPR3	ANXA1	P04083	779
FPR3	VSTM2L	Q96N03	351
FPR3	FKBP2	P26885	341
FPR3	PCDH11X	Q9BZA7	297
FPR3	CAMP	P49913	285
FPR3	HSH2D	Q96JZ2	272
FPR3	OR6K6	Q8NGW6	266
FPR3	SEMA6B	Q9H3T3	255
FPR3	COX6B1	P14854	249
FPR3	VSIG4	Q9Y279	243
FPR3	OC90	Q02509	236
FPR3	I6L893	I6L893	236
FPR3	SNAP91	O60641	235
FPR3	IL27RA	Q6UWB1	225

IntAct

Human interaction partners of FPR3 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	3
RAMP2	physical association	0.400	2
RAMP3	physical association	0.400	2

SIGNOR signaling

1 signaling interactions:

A	Effect	B	Mechanism
ANXA1	“up-regulates activity”	FPR3	binding

Ligand–receptor pairs (CellPhoneDB) (3)

Curated ligand–receptor partners (cell-cell communication), distinct from the protein–protein interactions above.

3 ligand–receptor pairs:

Partner	This gene’s role	Signaling class
MT-RNR2	receptor	Signaling by Humanin
ANXA1	receptor	Signaling by Annexin
HEBP1	receptor

Disease & clinical

Genetic variants

Variant evidence for FPR3: 39 ClinVar records (0 pathogenic / likely pathogenic); 20 GWAS associations.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	29
Likely benign	7
Benign	0

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 14 predictions of 215):

Position(s)	Effect	Δscore	Sites
19:51817767	acceptor_gain	1.0000
19:51795332–51795333	donor_loss	0.9900	5
19:51817762	acceptor_gain	0.9800
19:51795333	donor_loss	0.9100
19:51822801	donor_gain	0.9100
19:51795313	donor_gain	0.9000
19:51817773	acceptor_gain	0.8900
19:51822796	donor_gain	0.8800
19:51822848	donor_gain	0.8800
19:51822794	donor_gain	0.8400

AlphaMissense

538 missense substitutions predicted likely pathogenic (of 2,336 scored), across 182 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
N44	8	0.905	0.969
D71	8	0.889	0.962
D122	8	0.865	0.937
W91	7	0.967	0.993
C176	7	0.943	0.969
C98	7	0.942	0.975
F93	7	0.902	0.943
F210	7	0.855	0.977
N298	7	0.829	0.927
F250	7	0.828	0.973
W150	7	0.796	0.967
W254	7	0.772	0.902
F163	7	0.769	0.906
P299	6	0.875	0.926
G94	6	0.864	0.958
P213	6	0.821	0.948
G43	6	0.773	0.935
W132	6	0.767	0.889
N66	6	0.760	0.933
V47	6	0.753	0.896

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

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

1 prognostic cancer types:

Cancer	Prognostic	p-value
Lung Adenocarcinoma (validation)	unfavorable	0.000257

Disease associations

OMIM: gene MIM:136539 | disease phenotypes:

GWAS associations

20 associations:

Study	Trait	p-value
GCST008084_186	HDL cholesterol levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	1e-18
GCST90002382_444	Eosinophil percentage of white cells	1e-18
GCST90002381_205	Eosinophil count	3e-18
GCST010242_184	HDL cholesterol levels	8e-18
GCST008075_143	HDL cholesterol levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	8e-16
GCST008084_22	HDL cholesterol levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	9e-16
GCST010241_402	Apolipoprotein A1 levels	3e-14
GCST008075_108	HDL cholesterol levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	2e-12
GCST006611_152	HDL cholesterol	3e-11
GCST90002399_181	Neutrophil percentage of white cells	8e-10
GCST004623_4	Neutrophil percentage of granulocytes	7e-9
GCST008085_125	HDL cholesterol levels in current drinkers	1e-8
GCST010796_2706	Electrocardiogram morphology (amplitude at temporal datapoints)	1e-8
GCST005760_1	Dimensional psychopathology (Cognitive)	3e-8
GCST010043_150	Asthma	3e-8
GCST007277_24	Tourette syndrome	9e-7
GCST008070_107	HDL cholesterol levels	2e-6
GCST005531_87	Multiple sclerosis	3e-6
GCST008085_69	HDL cholesterol levels in current drinkers	4e-6
GCST004866_7	Alopecia areata	6e-6

EFO canonical traits (from GWAS)

9 canonical traits:

EFO ID	Trait name
EFO:0007994	neutrophil percentage of granulocytes
EFO:0009098	cognitive domain measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004329	alcohol drinking
EFO:0004614	apolipoprotein A 1 measurement
EFO:0004327	electrocardiography
EFO:0004842	eosinophil count
EFO:0007991	eosinophil percentage of leukocytes
EFO:0007990	neutrophil percentage of leukocytes

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5646 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 80,018 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

10 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL1200776	CINACALCET HYDROCHLORIDE	4	1,229
CHEMBL1200492	NEFAZODONE HYDROCHLORIDE	4	5,453
CHEMBL567	PERPHENAZINE	4	22,063
CHEMBL1263	SALMETEROL	4	40,637
CHEMBL398435	TICAGRELOR	4	3,116
CHEMBL1615374	VILAZODONE HYDROCHLORIDE	4	451
CHEMBL506981	REMINERTANT	3	251
CHEMBL232656	BX 471 FREE BASE	2	198
CHEMBL405355	NIGULDIPINE	2	1,809
CHEMBL267777	RITANSERIN	2	4,811

PharmGKB: 1 entry (CPIC guideline: no)

GtoPdb / IUPHAR curated pharmacology

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

Target class: gpcr — Formylpeptide receptors

Most potent curated ligand interactions (9 total), top 9:

Ligand	Action	Affinity	Parameter
humanin	Full agonist	8.95	pEC50
LXA4	Full agonist	8.82	pKd
WKYMVm	Full agonist	8.52	pEC50
F2L	Full agonist	8.2	pEC50
F2L-[125I]Tyr	Full agonist	8.0	pKd
annexin I-(2-26)	Full agonist	7.0	pEC50
fMet-Met-Tyr-Ala-Leu-Phe	Full agonist	6.0	pEC50
WRWWWW	Antagonist	6.0	pIC50
Hp(2-20)	Full agonist	5.0	pEC50

Binding affinities (BindingDB)

5 measured of 51 human assays (52 total across all organisms); most potent 5 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
(S)-6-amino-2-((S)-2-amino-3-(1H-indol-3-yl)propanamido)-N-((5R,8S,11S,14S)-5-carbamoyl-15-(4-hydroxyphenyl)-8-isopropyl-11-(2-(methylthio)ethyl)-7,10,13-trioxo-2-thia-6,9,12-triazapentadecan-14-yl)hexanamide	EC50	1 nM
N-(4-Iodophenyl)-2-[5-(3-methoxybenzyl)-3-methyl-6-oxo-6H-pyridazin-1-yl]-acetamide	EC50	1800 nM
CHEMBL2391437	EC50	10200 nM
CHEMBL2391254	EC50	14600 nM
CHEMBL2391256	EC50	17400 nM

ChEMBL bioactivities

415 potent at pChembl≥5 of 428 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.42	EC50	3.8	nM	CHEMBL3728341
8.18	EC50	6.6	nM	CHEMBL3733191
8.13	EC50	7.4	nM	CHEMBL3730664
8.00	EC50	10	nM	CHEMBL552527
7.92	EC50	12	nM	CHEMBL3731635
7.89	EC50	13	nM	CHEMBL3730156
7.82	EC50	15	nM	CHEMBL3731671
7.82	EC50	15	nM	CHEMBL3731035
7.82	EC50	15	nM	CHEMBL3728830
7.80	EC50	16	nM	CHEMBL3728649
7.80	EC50	16	nM	CHEMBL3731316
7.75	EC50	18	nM	CHEMBL3730919
7.70	EC50	20	nM	CHEMBL3731064
7.58	EC50	26	nM	CHEMBL3733261
7.57	EC50	27	nM	CHEMBL3732345
7.57	EC50	27	nM	CHEMBL3731822
7.55	EC50	28	nM	CHEMBL3732539
7.54	EC50	29	nM	CHEMBL3729493
7.52	EC50	30	nM	CHEMBL3728150
7.50	EC50	32	nM	CHEMBL3729722
7.48	EC50	33	nM	CHEMBL3732902
7.39	EC50	41	nM	CHEMBL3729460
7.36	EC50	44	nM	CHEMBL3729342
7.34	EC50	46	nM	CHEMBL3728769
7.33	EC50	47	nM	CHEMBL3728352
7.28	EC50	52	nM	CHEMBL3732978
7.24	EC50	57	nM	CHEMBL3727697
7.24	EC50	58	nM	CHEMBL3730217
7.22	EC50	60	nM	CHEMBL3730955
7.21	EC50	61	nM	CHEMBL3729805
7.21	EC50	62	nM	CHEMBL3730330
7.19	EC50	65	nM	CHEMBL3728125
7.19	EC50	64	nM	CHEMBL3731680
7.18	EC50	66	nM	CHEMBL3729273
7.17	EC50	68	nM	CHEMBL3731599
7.17	EC50	67	nM	CHEMBL3728119
7.17	EC50	67	nM	CHEMBL3728646
7.15	EC50	71	nM	CHEMBL3732566
7.14	EC50	72	nM	CHEMBL3728781
7.13	EC50	74	nM	CHEMBL3730257
7.12	EC50	75	nM	CHEMBL3733287
7.10	EC50	79	nM	CHEMBL3732885
7.05	EC50	89	nM	CHEMBL3733253
7.04	EC50	91	nM	CHEMBL3732281
7.04	EC50	91	nM	CHEMBL3727450
7.03	EC50	94	nM	CHEMBL3729633
7.03	EC50	94	nM	CHEMBL3732163
7.02	EC50	95	nM	CHEMBL3730159
7.00	EC50	100	nM	CHEMBL3728511
7.00	EC50	99	nM	CHEMBL3730922

PubChem BioAssay actives

2 with measured affinity, of 99 total; 2 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
(2S)-6-amino-2-[[(2S)-2-amino-3-(1H-indol-3-yl)propanoyl]amino]-N-[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2R)-1-amino-4-methylsulfanyl-1-oxobutan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-4-methylsulfanyl-1-oxobutan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]hexanamide	428659: Agonist activity at FPRL2 expressed in human HL60 cells assessed as induction of intracellular calcium flux by FLIPR3 calcium assay	ec50	0.0100	uM
(2S)-2-[[(2S)-2-[[(2S)-2-formamido-4-methylsulfanylbutanoyl]amino]-4-methylpentanoyl]amino]-3-phenylpropanoic acid	428659: Agonist activity at FPRL2 expressed in human HL60 cells assessed as induction of intracellular calcium flux by FLIPR3 calcium assay	ec50	1.9000	uM

CTD chemical–gene interactions

15 total (human), top 15 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	increases expression, increases abundance	2
aflatoxin B2	increases methylation	1
nickel sulfate	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
CGP 52608	affects binding, increases reaction	1
beta-hydroxy simvastatin acid	increases expression	1
Acetaminophen	decreases expression	1
Calcitriol	decreases expression	1
Doxorubicin	decreases expression	1
Lipopolysaccharides	affects response to substance, increases expression, decreases expression	1
Nickel	increases expression	1
Ozone	increases abundance, increases expression	1
Aflatoxin B1	decreases methylation	1
Antirheumatic Agents	decreases expression	1
Particulate Matter	increases abundance, increases expression	1

ChEMBL screening assays

8 unique, capped per target: 4 functional, 4 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1051691	Functional	Agonist activity at FPRL2 expressed in human HL60 cells assessed as induction of intracellular calcium flux by FLIPR3 calcium assay	6-methyl-2,4-disubstituted pyridazin-3(2H)-ones: a novel class of small-molecule agonists for formyl peptide receptors. — *J Med Chem*
CHEMBL2393753	Binding	Agonist activity at FPR3 (unknown origin) transfected in human HL60 cells assessed as induction of Ca2+ mobilization relative to WKYMVm	Further studies on 2-arylacetamide pyridazin-3(2H)-ones: design, synthesis and evaluation of 4,6-disubstituted analogs as formyl peptide receptors (FPRs) agonists. — *Eur J Med Chem*

Cellosaurus cell lines

1 cell lines: 1 spontaneously immortalized cell line

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

Cellosaurus	Name	Category	Sex
CVCL_KV16	cAMP Hunter CHO-K1 FPR3 Gi	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 FPR3 across ~30M SureChEMBL compounds — explore on Sugi Predict.