F2RL2

Summary

F2RL2 (coagulation factor II thrombin receptor like 2, HGNC:3539) is a protein-coding gene on chromosome 5q13.3, encoding Proteinase-activated receptor 3 (O00254). Receptor for activated thrombin coupled to G proteins that stimulate phosphoinositide hydrolysis.

This gene encodes a member of the protease-activated receptor (PAR) family which is a subfamily of the seven transmembrane G protein-coupled cell surface receptor family. The encoded protein acts as a cofactor in the thrombin-mediated cleavage and activation of the protease-activated receptor family member PAR4. The encoded protein plays an essential role in hemostasis and thrombosis. Alternate splicing results in multiple transcript variants that encode different isoforms.

Source: NCBI Gene 2151 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 61 total
• Druggable target: yes
• MANE Select transcript: NM_004101

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3539
Approved symbol	F2RL2
Name	coagulation factor II thrombin receptor like 2
Location	5q13.3
Locus type	gene with protein product
Status	Approved
Aliases	PAR3
Ensembl gene	ENSG00000164220
Ensembl biotype	protein_coding
OMIM	601919
Entrez	2151

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000296641, ENST00000504899

RefSeq mRNA: 2 — MANE Select: NM_004101 NM_001256566, NM_004101

CCDS: CCDS4031, CCDS58959

Canonical transcript exons

ENST00000296641 — 2 exons

Exon	Start	End
ENSE00001082567	76615482	76618642
ENSE00001082569	76623167	76623403

Expression profiles

Bgee: expression breadth ubiquitous, 154 present calls, max score 89.34.

FANTOM5 (CAGE): breadth broad, TPM avg 7.9308 / max 645.9191, expressed in 832 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
62166	3.1886	662
62167	2.7309	635
62165	1.4621	493
62168	0.3648	174
62164	0.1843	88

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
stromal cell of endometrium	CL:0002255	89.34	gold quality
pigmented layer of retina	UBERON:0001782	84.31	gold quality
upper leg skin	UBERON:0004262	78.59	gold quality
gall bladder	UBERON:0002110	76.91	gold quality
islet of Langerhans	UBERON:0000006	75.01	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	73.07	silver quality
lower esophagus muscularis layer	UBERON:0035833	72.06	gold quality
lower esophagus	UBERON:0013473	72.01	gold quality
buccal mucosa cell	CL:0002336	71.84	silver quality
skin of hip	UBERON:0001554	71.72	gold quality
mucosa of stomach	UBERON:0001199	71.64	gold quality
smooth muscle tissue	UBERON:0001135	70.94	gold quality
nipple	UBERON:0002030	69.95	silver quality
calcaneal tendon	UBERON:0003701	69.84	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	69.47	gold quality
muscle layer of sigmoid colon	UBERON:0035805	69.15	gold quality
minor salivary gland	UBERON:0001830	68.86	gold quality
skin of abdomen	UBERON:0001416	65.83	gold quality
mouth mucosa	UBERON:0003729	65.66	gold quality
rectum	UBERON:0001052	64.90	gold quality
saliva-secreting gland	UBERON:0001044	64.52	gold quality
sigmoid colon	UBERON:0001159	64.50	gold quality
colonic epithelium	UBERON:0000397	64.42	silver quality
dorsal root ganglion	UBERON:0000044	64.30	silver quality
zone of skin	UBERON:0000014	64.21	gold quality
skin of leg	UBERON:0001511	64.18	gold quality
tendon	UBERON:0000043	64.03	gold quality
bone marrow cell	CL:0002092	64.02	silver quality
descending thoracic aorta	UBERON:0002345	63.55	gold quality
thoracic mammary gland	UBERON:0005200	63.22	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-MTAB-8271	no	288.71
E-ANND-3	no	4.47

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

125 targeting F2RL2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-17-5P	99.89	73.83	2665
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-605-3P	99.88	69.22	1833
HSA-MIR-3140-3P	99.88	68.47	2069
HSA-MIR-106B-5P	99.88	74.72	2795
HSA-MIR-20A-5P	99.88	74.76	2769
HSA-MIR-20B-5P	99.88	74.01	2621

Literature-anchored findings (GeneRIF, showing 39)

• mitochondrial and cytoplasmic variants are both essential for viability (PMID:11796729)
• analysis of the mechanism of high Mr thioredoxin reductase from Drosophila melanogaster (PMID:12816954)
• changing of His106 to asparagine, glutamine, and phenylalanine in various C-terminal mutants of Drosophila melanogaster thioredoxin reductase drops catalytic activity without change in pH profile (PMID:15670839)
• X-ray crystal structure of thioredoxin reductase at 2.4 A resolution; demonstrated that tetrapeptides equivalent to the oxidized C-terminal active sites of both mouse mitochondrial TR (mTR3) and DmTR are substrates for the truncated forms of both enzymes (PMID:17385893)
• redox potentials provide direct evidence for proposed catalytic mechanism of DmTrxR, & cast new light on essential role of DmTrx system in cycling GSSG/GSH & maintaining intracellular redox homeostasis in D. melanogaster without glutathione reductase. (PMID:17550271)
• rates of steps in both the reductive and the oxidative half-reactions are markedly diminished in H464’Q thioredoxin reductase as compared to those of wild-type enzyme, indicating that His-464’ is involved in both half-reactions (PMID:18211101)
• the role of Glu-469’ in catalysis by DmTrxR (PMID:18991392)
• Molecular orbital calculations suggested that the C-terminal hexapeptide Pro-Ala-Ser-Cys-Cys-Ser-OH functions as a redox center that alleviates the necessity for selenium in Dm-TrxR. (PMID:21389620)
• Overexpression of mitochondrial TXNRD2 in Drosophila melanogaster extended median lifespan in female flies with a small lifespan extension in males; in contrast, overexpression of the cytosolic form, TXNRD1, did not produce a lifespan extension. (PMID:28474396)
• differentiation of human monocytes is associated with differential expression of functionally active PARs that mediate distinct regulatory functions in inflammation and atherogenesis. (PMID:12805069)
• findings support a role for PAR1, and potentially PAR2 and PAR3 in the invasive phase of human placentation (PMID:14507634)
• PAR-3 is expressed in human SMC and triggers intracellular calcium signaling. (PMID:14515192)
• expression of PAR3 mRNA and protein in cells undergoing megakaryocytic maturation suggests a developmental role for PAR3; regulation of PAR3 expression appears to be specifically coupled to the protein kinase C system. (PMID:15504554)
• PAR3 receptors and analogues can mediate cell signaling by interaction with PAR1-type thrombin receptors (PMID:15582715)
• a Na-independent Cl-/HCO3- exchange mechanism mediates the recovery of pHi from alkalosis in platelets and that thrombin activates this exchanger by a direct regulatory pathway (PMID:15850610)
• The changes in levels of blood coagulation factor ii in folic acid deficient rats are reversed by treatment with folic acid. (PMID:16046705)
• F2R genetic variants may influence the natural history of CHD in patients at high risk of cardiovascular events. (PMID:17347481)
• PAR3 has a role in allosterically regulating PAR1 signaling governing increased endothelial permeability (PMID:17376866)
• PAR-3 is able to signal autonomously to induce IL-8 release mediated by ERK1/2 phosphorylation, which contributes actively to inflammatory responses (PMID:18264801)
• Thrombin-mediated increases in cytosolic [Ca2+] involve different mechanisms in human pulmonary artery smooth muscle and endothelial cells. (PMID:18836030)
• This study demonstrates that the anticoagulant profile of thrombin often caused by a mutation of the thrombin scaffold finds its likely molecular origin in the stabilization of the inactive E* form. (PMID:19473969)
• Down-regulation of connexin and par-3 signals early anaplasia and malignant change in rectal cancer. (PMID:19513616)
• Mechanism of the anticoagulant activity of thrombin mutant W215A/E217A. (PMID:19586901)
• upregulated thrombin generation and inhibition of fibrinolysis, occurred in one-third of the Stem cell transplant patients associating with the development of Graft versus host disease (PMID:19718071)
• Lower plasma levels of thrombin-antithrombin complex correlate to higher recanalisation rates after ischaemic stroke (PMID:19806263)
• Human cytomegalovirus induces PARs expression through transcriptional activation in endothelial cells, increasing sensitivity to thrombin. (PMID:20155436)
• genetic polymorphism is associated with peripheral arterial disease severity (PMID:20390230)
• A novel role is identified for PAR3 in thrombin signaling. (PMID:20442298)
• FXa bound in a punctate manner to thrombi under shear, while thrombin and fibrin(ogen) distributed ubiquitously over platelet-fibrin thrombi (PMID:20454680)
• Low concentrations of alpha-thrombin accelerate tissue factor-induced thrombin generation on the surface of vascular smooth muscle cells, and this effect is mediated by PAR-3 and PAR-4. (PMID:20930172)
• Human PAR-3 is regulated post-transcriptionally via the mRNA-stabilizing factor HuR, whereas transcriptional control involves nuclear factor of activated T cells (NFAT). (PMID:21596928)
• PAR-3 receptors interact with thrombin and increase heme oxygenase-1 expression in synovial fibroblasts. (PMID:22541814)
• Elevated expression of PAR-3, but not PAR-4, was detected in the lungs of idiopathic pulmonary fibrosis patients. (PMID:23739922)
• A unique contributory role for PAR3 in the complex mechanisms underlying Activated protein C cytoprotective effects. (PMID:23788139)
• Data indicate that knockdowns of all three PARs PAR-1, PAR-2, and PAR-3 exhibited changes in the expression of CDC42, which correlated with the changes in their invasion. (PMID:23921961)
• In pancreatic adenocarcinoma cells, PAR3 knockdown enhances cell adhesion. We propose this is due to increased expression of E-cadherin, leading to a greater adhesion of free-floating cells to cells bound to the surface via integrins, particularly ITGalphav. (PMID:24699825)
• These data provide intriguing novel insights into the diversification of functional selectivity of protease signaling achievable by canonical and noncanonical PAR activation, such as the activation of vascular-protective Tie2 by noncanonical PAR3 activation. (PMID:25320242)
• TFRGAP, a PAR-3 mimicking peptide significantly induced the phosphorylation of eNOS-Thr-495 with minimal phosphorylation of eNOS-Ser-1177 with no change in nitric oxide production. (PMID:26729042)
• PAR3 is essential in thrombin stimulated insulin secretion. (PMID:26742564)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	F2RL2	ENSDARG00000079472
danio_rerio	f2rl2	ENSDARG00000090524
mus_musculus	F2rl2	ENSMUSG00000021675
rattus_norvegicus	F2rl2	ENSRNOG00000018054

Paralogs (16): P2RY10 (ENSG00000078589), GPR18 (ENSG00000125245), F2RL3 (ENSG00000127533), GPR55 (ENSG00000135898), LPAR6 (ENSG00000139679), GPR65 (ENSG00000140030), GPR17 (ENSG00000144230), LPAR4 (ENSG00000147145), CYSLTR2 (ENSG00000152207), F2RL1 (ENSG00000164251), CYSLTR1 (ENSG00000173198), GPR4 (ENSG00000177464), GPR35 (ENSG00000178623), F2R (ENSG00000181104), P2RY8 (ENSG00000182162), GPR20 (ENSG00000204882)

Protein

Protein identifiers

Proteinase-activated receptor 3 — O00254 (reviewed: O00254)

Alternative names: Coagulation factor II receptor-like 2, Thrombin receptor-like 2

All UniProt accessions (1): O00254

UniProt curated annotations — full annotation on UniProt →

Function. Receptor for activated thrombin coupled to G proteins that stimulate phosphoinositide hydrolysis.

Subunit / interactions. Interacts with INSC/inscuteable and probably GPSM2.

Subcellular location. Cell membrane.

Tissue specificity. Highest expression in the megakaryocytes of the bone marrow, lower in mature megakaryocytes, in platelets and in a variety of other tissues such as heart and gut.

Post-translational modifications. A proteolytic cleavage generates a new N-terminus that functions as a tethered ligand.

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

Isoforms (2)

UniProt ID	Names	Canonical?
O00254-1	1	yes
O00254-2	2

RefSeq proteins (2): NP_001243495, NP_004092* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000276	GPCR_Rhodpsn	Family
IPR003912	Protea_act_rcpt	Family
IPR003943	Prot_act_rcpt_3	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain

Pfam: PF00001

UniProt features (29 total): topological domain 8, transmembrane region 7, glycosylation site 3, sequence variant 3, mutagenesis site 2, signal peptide 1, propeptide 1, site 1, chain 1, disulfide bond 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O00254-F1	76.60	0.33

Functional residue map

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

Catalytic / active sites (1): 38–39 (cleavage; by thrombin)

Disulfide bonds (1): 166–245

Glycosylation sites (3): 25, 82, 331

Mutagenesis-validated functional residues (2):

Position	Phenotype
39	no proteolytic cleavage by thrombin.
40	altered signal upon thrombin cleavage.

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-375276	Peptide ligand-binding receptors
R-HSA-416476	G alpha (q) signalling events
R-HSA-456926	Thrombin signalling through proteinase activated receptors (PARs)

MSigDB gene sets: 203 (showing top): RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, REACTOME_PLATELET_ACTIVATION_SIGNALING_AND_AGGREGATION, GOBP_PLATELET_ACTIVATION, PID_RHOA_PATHWAY, GOBP_WOUND_HEALING, REACTOME_PEPTIDE_LIGAND_BINDING_RECEPTORS, FINAK_BREAST_CANCER_SDPP_SIGNATURE, BACH2_01, KEGG_NEUROACTIVE_LIGAND_RECEPTOR_INTERACTION, PID_THROMBIN_PAR4_PATHWAY, TGANTCA_AP1_C, NRF2_Q4, ATF4_Q2, GOCC_APICAL_PLASMA_MEMBRANE, GOMF_PEPTIDE_RECEPTOR_ACTIVITY

GO Biological Process (10): G protein-coupled receptor signaling pathway (GO:0007186), blood coagulation (GO:0007596), response to wounding (GO:0009611), platelet activation (GO:0030168), positive regulation of insulin secretion (GO:0032024), ligand-gated ion channel signaling pathway (GO:1990806), signal transduction (GO:0007165), hemostasis (GO:0007599), regulation of biological quality (GO:0065008), thrombin-activated receptor signaling pathway (GO:0070493)

GO Molecular Function (6): phosphatidylinositol-4,5-bisphosphate phospholipase C activity (GO:0004435), G protein-coupled receptor activity (GO:0004930), thrombin-activated receptor activity (GO:0015057), receptor ligand activity (GO:0048018), proteinase-activated receptor activity (GO:0001648), protein binding (GO:0005515)

GO Cellular Component (5): extracellular region (GO:0005576), plasma membrane (GO:0005886), apical plasma membrane (GO:0016324), protein-containing complex (GO:0032991), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Class A/1 (Rhodopsin-like receptors)	1
GPCR downstream signalling	1
Platelet activation, signaling and aggregation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
signal transduction	3
G protein-coupled receptor signaling pathway	2
cellular anatomical structure	2
G protein-coupled receptor activity	1
hemostasis	1
wound healing	1
coagulation	1
response to stress	1
cell activation	1
blood coagulation	1
insulin secretion	1
positive regulation of protein secretion	1
regulation of insulin secretion	1
positive regulation of peptide hormone secretion	1
ligand-gated monoatomic ion channel activity	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
regulation of body fluid levels	1
biological regulation	1
C-type glycerophospholipase activity	1
transmembrane signaling receptor activity	1
proteinase-activated receptor activity	1
thrombin-activated receptor signaling pathway	1
signaling receptor binding	1
signaling receptor activator activity	1
G protein-coupled peptide receptor activity	1
binding	1
membrane	1
cell periphery	1
apical part of cell	1
plasma membrane region	1
cellular_component	1

Protein interactions and networks

STRING

828 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
F2RL2	EPRS1	P07814	832
F2RL2	PYDC1	Q8WXC3	827
F2RL2	SDR42E2	A6NKP2	442
F2RL2	FAM162B	Q5T6X4	403
F2RL2	COL6A5	A8TX70	402
F2RL2	PIGR	P01833	399
F2RL2	CXCL8	P10145	398
F2RL2	CASP8	Q14790	393
F2RL2	CCL2	P13500	387
F2RL2	RAB19	A4D1S5	387
F2RL2	CXCL10	P02778	386
F2RL2	CASP3	P42574	353
F2RL2	GRIP2	Q9C0E4	350
F2RL2	SMCO4	Q9NRQ5	343
F2RL2	IQGAP2	Q13576	308

IntAct

20 interactions, top by confidence:

A	B	Type	Score
PATJ	F2RL2	psi-mi:“MI:0915”(physical association)	0.460
PATJ	F2RL2	psi-mi:“MI:0403”(colocalization)	0.460
F2RL2	ABL1	psi-mi:“MI:0915”(physical association)	0.400
CRK	F2RL2	psi-mi:“MI:0915”(physical association)	0.400
F2RL2	SRC	psi-mi:“MI:0915”(physical association)	0.400
F2RL2	FYN	psi-mi:“MI:0915”(physical association)	0.400
GRB2	F2RL2	psi-mi:“MI:0915”(physical association)	0.400
F2RL2	NCK1	psi-mi:“MI:0915”(physical association)	0.400
F2RL2	PLCG1	psi-mi:“MI:0915”(physical association)	0.400
F2RL2	Pard6a	psi-mi:“MI:0915”(physical association)	0.400
F2RL2	RAMP1	psi-mi:“MI:0915”(physical association)	0.400
RAMP1	F2RL2	psi-mi:“MI:0915”(physical association)	0.400
F2RL2	RAMP2	psi-mi:“MI:0915”(physical association)	0.400
RAMP2	F2RL2	psi-mi:“MI:0915”(physical association)	0.400
RAMP3	F2RL2	psi-mi:“MI:0915”(physical association)	0.400
F2RL2	F2RL2	psi-mi:“MI:2364”(proximity)	0.270
F2R	F2RL2	psi-mi:“MI:2364”(proximity)	0.270

ESM2 similar proteins: A7YY44, B0UXR0, B5X337, E7FEL0, O00254, O08675, O14843, O15529, O15552, O46685, P25116, P26824, P30558, P34996, P46093, P47749, P47900, P48042, P49650, P49651, P49652, P50132, P55085, P55086, P56488, P59902, Q00991, Q09QM4, Q13304, Q15743, Q1JQB3, Q2HJA4, Q3UFD7, Q4KLH9, Q58D85, Q63645, Q76EI6, Q86VZ1, Q8BFQ3, Q8BLG2

Diamond homologs: A0A4W3GG95, A0A6I8PUB9, A6QLE7, D4A7K7, E7FEL0, E9QJ73, O00254, O08675, O46685, P0C0W8, P0C5J4, P32246, P32249, P32250, P34996, P35366, P35383, P41231, P41232, P46093, P47900, P48042, P49650, P49651, P49652, P50132, P56482, P58826, P59902, P79928, P97266, Q149R9, Q15743, Q1JQB3, Q2Y2P0, Q3U6B2, Q3ZC80, Q4G072, Q4KLH9, Q5E9H8

SIGNOR signaling

11 interactions.

A	Effect	B	Mechanism
F2	up-regulates	F2RL2	binding
F2RL2	“up-regulates activity”	GNAS	binding
F2RL2	“up-regulates activity”	GNAL	binding
F2RL2	“up-regulates activity”	GNAI1	binding
F2RL2	“up-regulates activity”	GNAI3	binding
F2RL2	“up-regulates activity”	GNAO1	binding
F2RL2	“up-regulates activity”	GNA14	binding
F2RL2	“up-regulates activity”	GNA15	binding
F2RL2	“up-regulates activity”	GNA12	binding
Thrombin	“up-regulates activity”	F2RL2	“chemical activation”
GRK1	“down-regulates activity”	F2RL2	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 13 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Downstream signal transduction	5	158.6×	1e-08
FCGR3A-mediated phagocytosis	6	93.6×	5e-09

GO biological processes:

GO term	Partners	Fold	FDR
ephrin receptor signaling pathway	5	143.3×	5e-08

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	52
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

226 predictions. Top by Δscore:

Variant	Effect	Δscore
5:76618640:TGC:T	acceptor_gain	1.0000
5:76618641:GCCT:G	acceptor_loss	1.0000
5:76618643:C:CA	acceptor_loss	1.0000
5:76618643:C:CC	acceptor_gain	1.0000
5:76618649:T:TC	acceptor_gain	1.0000
5:76623166:CCACT:C	donor_gain	1.0000
5:76618638:CATGC:C	acceptor_gain	0.9900
5:76618641:GC:G	acceptor_gain	0.9900
5:76618642:CC:C	acceptor_gain	0.9900
5:76618644:T:C	acceptor_loss	0.9900
5:76618649:T:C	acceptor_gain	0.9900
5:76623166:CCA:C	donor_gain	0.9900
5:76618639:ATGC:A	acceptor_gain	0.9800
5:76618648:A:AC	acceptor_gain	0.9800
5:76623355:T:A	donor_gain	0.9700
5:76623161:GCTT:G	donor_loss	0.9500
5:76623162:CTT:C	donor_loss	0.9500
5:76623164:TAC:T	donor_loss	0.9500
5:76623165:A:C	donor_loss	0.9500
5:76623166:C:CG	donor_loss	0.9500
5:76623166:C:CT	donor_gain	0.9500
5:76618648:A:C	acceptor_gain	0.9100
5:76618645:G:GC	acceptor_gain	0.8900
5:76623381:G:A	donor_gain	0.8700
5:76623165:A:AC	donor_gain	0.8600
5:76623166:C:CC	donor_gain	0.8600
5:76623300:AGTT:A	donor_gain	0.8500
5:76623164:TACC:T	donor_gain	0.8300
5:76623165:ACCA:A	donor_gain	0.8300
5:76618645:G:C	acceptor_gain	0.8100

AlphaMissense

2453 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:76618230:C:A	W159C	0.986
5:76618230:C:G	W159C	0.986
5:76617663:A:C	S348R	0.981
5:76617663:A:T	S348R	0.981
5:76617665:T:G	S348R	0.981
5:76618232:A:G	W159R	0.980
5:76618232:A:T	W159R	0.980
5:76618143:G:C	S188R	0.976
5:76618143:G:T	S188R	0.976
5:76618145:T:G	S188R	0.976
5:76618210:C:G	C166S	0.976
5:76618211:A:T	C166S	0.976
5:76617973:C:G	C245S	0.975
5:76617974:A:T	C245S	0.975
5:76617654:A:C	S351R	0.974
5:76617654:A:T	S351R	0.974
5:76617656:T:G	S351R	0.974
5:76617974:A:G	C245R	0.968
5:76618055:A:G	W218R	0.968
5:76618055:A:T	W218R	0.968
5:76617973:C:T	C245Y	0.964
5:76618211:A:G	C166R	0.962
5:76617756:G:C	S317R	0.960
5:76617756:G:T	S317R	0.960
5:76617758:T:G	S317R	0.960
5:76618209:G:C	C166W	0.960
5:76617765:A:C	F314L	0.958
5:76617765:A:T	F314L	0.958
5:76617767:A:G	F314L	0.958
5:76617972:G:C	C245W	0.958

dbSNP variants (sampled 300 via entrez): RS1001085233 (5:76624945 G>A), RS1001203235 (5:76616463 T>C), RS1001477786 (5:76620969 A>G), RS1001755422 (5:76622156 G>C), RS1001866844 (5:76623765 A>C), RS1001897956 (5:76624017 C>G), RS1002234443 (5:76617513 T>C), RS1002606691 (5:76617911 A>G), RS1002964583 (5:76615071 T>C), RS1003124059 (5:76618639 A>T), RS1003296999 (5:76620491 A>G), RS1003419356 (5:76618369 G>C), RS1003432917 (5:76620771 A>G), RS1003572376 (5:76622840 C>T), RS1003843424 (5:76623646 A>G)

Disease associations

OMIM: gene MIM:601919 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST008755_1	Phenylephrine infusion rate during anesthesia	2.000000e-07
GCST010231_6	Mean platelet volume	3.000000e-08

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5477 (SINGLE PROTEIN)

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: gpcr — Proteinase-activated receptors

CTD chemical–gene interactions

58 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, affects cotreatment, decreases expression, affects expression, decreases methylation	7
sodium arsenite	increases reaction, decreases expression, affects cotreatment, increases abundance, increases expression	4
trichostatin A	affects cotreatment, decreases expression	3
Benzo(a)pyrene	increases expression, increases methylation	3
lead acetate	decreases reaction, increases expression, increases reaction	2
mercuric bromide	increases expression, affects cotreatment	2
entinostat	decreases expression, affects cotreatment	2
Vorinostat	affects cotreatment, decreases expression	2
Panobinostat	affects cotreatment, decreases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Aflatoxin B1	increases expression, increases methylation	2
p-Chloromercuribenzoic Acid	increases expression, affects cotreatment	2
perfluorotetradecanoic acid	increases expression	1
methylmercuric chloride	decreases expression, increases expression	1
methyleugenol	increases expression	1
bisphenol A	increases expression	1
2-methyl-4-isothiazolin-3-one	decreases expression	1
quercitrin	decreases expression	1
zinc chloride	decreases expression	1
perfluorooctanoic acid	increases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
nickel sulfate	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, increases expression	1
phenethyl isothiocyanate	increases expression	1
perfluorooctane sulfonic acid	increases expression	1
CGP 52608	increases reaction, affects binding	1
2-palmitoylglycerol	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression, increases expression	1
nutlin 3	affects cotreatment, increases expression	1
abrine	decreases expression	1

ChEMBL screening assays

4 unique, capped per target: 3 binding, 1 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4883370	Binding	PRESTO-Tango GPCRome screening (F2RL2)	Data for DCP probe UCSF924
CHEMBL996098	Functional	Agonist activity at PAR3	Discovery of potent and selective small-molecule PAR-2 agonists. — J Med Chem

Clinical trials (associated diseases)

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