F2

Summary

F2 (coagulation factor II, thrombin, HGNC:3535) is a protein-coding gene on chromosome 11p11.2, encoding Prothrombin (P00734). Thrombin, which cleaves bonds after Arg and Lys, converts fibrinogen to fibrin and activates factors V, VII, VIII, XIII, and, in complex with thrombomodulin, protein C.

This gene encodes the prothrombin protein (also known as coagulation factor II). This protein is proteolytically cleaved in multiple steps to form the activated serine protease thrombin. The activated thrombin enzyme plays an important role in thrombosis and hemostasis by converting fibrinogen to fibrin during blood clot formation, by stimulating platelet aggregation, and by activating additional coagulation factors. Thrombin also plays a role in cell proliferation, tissue repair, and angiogenesis as well as maintaining vascular integrity during development and postnatal life. Peptides derived from the C-terminus of this protein have antimicrobial activity against E. coli and P. aeruginosa. Mutations in this gene lead to various forms of thrombosis and dysprothrombinemia. Rapid increases in cytokine levels following coronavirus infections can dysregulate the coagulation cascade and produce thrombosis, compromised blood supply, and organ failure.

Source: NCBI Gene 2147 — RefSeq curated summary.

At a glance

• Gene–disease (curated): thrombophilia due to thrombin defect (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 18
• Clinical variants (ClinVar): 473 total — 21 pathogenic, 17 likely-pathogenic
• Phenotypes (HPO): 41
• Druggable target: yes — 48 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_000506

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3535
Approved symbol	F2
Name	coagulation factor II, thrombin
Location	11p11.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000180210
Ensembl biotype	protein_coding
OMIM	176930
Entrez	2147

Gene structure

Transcript identifiers

Ensembl transcripts: 36 — 34 protein_coding, 2 retained_intron

ENST00000311907, ENST00000442468, ENST00000469189, ENST00000490274, ENST00000530231, ENST00000862093, ENST00000862094, ENST00000862095, ENST00000862096, ENST00000862097, ENST00000862098, ENST00000862099, ENST00000862100, ENST00000862101, ENST00000862102, ENST00000862103, ENST00000862104, ENST00000862105, ENST00000862106, ENST00000862107, ENST00000862108, ENST00000862109, ENST00000862110, ENST00000862111, ENST00000862112, ENST00000862113, ENST00000862114, ENST00000862115, ENST00000862116, ENST00000862117, ENST00000862118, ENST00000862119, ENST00000862120, ENST00000862121, ENST00000862122, ENST00000862123

RefSeq mRNA: 1 — MANE Select: NM_000506 NM_000506

CCDS: CCDS31476

Canonical transcript exons

ENST00000311907 — 14 exons

Exon	Start	End
ENSE00001181524	46723382	46723518
ENSE00001181527	46723180	46723285
ENSE00001181532	46720790	46720840
ENSE00001181538	46720523	46720547
ENSE00001181543	46719702	46719862
ENSE00001227030	46739265	46739506
ENSE00001646362	46729380	46729561
ENSE00001650441	46727996	46728163
ENSE00001657931	46728664	46728837
ENSE00001680217	46739048	46739118
ENSE00001688723	46725859	46726173
ENSE00001770269	46726711	46726837
ENSE00001931088	46719213	46719314
ENSE00003785308	46726498	46726626

Expression profiles

Bgee: expression breadth ubiquitous, 117 present calls, max score 99.46.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 8.1630 / max 3039.8244, expressed in 139 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
114155	8.1508	139
114156	0.0122	7

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	99.46	gold quality
liver	UBERON:0002107	99.36	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.70	gold quality
oocyte	CL:0000023	77.83	silver quality
secondary oocyte	CL:0000655	72.79	silver quality
tongue squamous epithelium	UBERON:0006919	65.49	gold quality
Brodmann (1909) area 10	UBERON:0013541	65.32	gold quality
frontal pole	UBERON:0002795	64.95	gold quality
middle frontal gyrus	UBERON:0002702	64.67	gold quality
paraflocculus	UBERON:0005351	64.44	gold quality
hair follicle	UBERON:0002073	63.40	gold quality
triceps brachii	UBERON:0001509	61.22	gold quality
lateral nuclear group of thalamus	UBERON:0002736	61.06	gold quality
myocardium	UBERON:0002349	60.50	gold quality
heart right ventricle	UBERON:0002080	60.46	gold quality
vastus lateralis	UBERON:0001379	60.23	gold quality
biceps brachii	UBERON:0001507	60.10	gold quality
quadriceps femoris	UBERON:0001377	59.44	gold quality
vena cava	UBERON:0004087	59.10	gold quality
cerebellar vermis	UBERON:0004720	59.06	gold quality
esophagus squamous epithelium	UBERON:0006920	58.36	gold quality
gluteal muscle	UBERON:0002000	57.70	gold quality
epithelium of esophagus	UBERON:0001976	57.61	gold quality
nasal cavity epithelium	UBERON:0005384	57.37	gold quality
cerebellar hemisphere	UBERON:0002245	56.91	gold quality
cartilage tissue	UBERON:0002418	56.83	gold quality
cerebellar cortex	UBERON:0002129	56.81	gold quality
cerebellum	UBERON:0002037	56.62	gold quality
right hemisphere of cerebellum	UBERON:0014890	56.56	gold quality
postcentral gyrus	UBERON:0002581	56.09	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-MTAB-9388	yes	10.96
E-ANND-3	no	2.61

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): DEAF1, ELK1, FOXA2, HIF1A, HNF4A, NFATC1, NFKB, NR4A3, RELA, SP1, SP3, TCF3, YBX1

miRNA regulators (miRDB)

5 targeting F2, 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-450A-1-3P	100.00	69.33	1837
HSA-MIR-218-1-3P	98.63	67.97	832
HSA-MIR-1292-5P	96.74	62.14	238
HSA-MIR-8059	95.11	66.30	646
HSA-MIR-4471	95.11	66.84	755

Literature-anchored findings (GeneRIF, showing 40)

• The abundant local thrombin demonstrated in human thrombi has implications for thrombus lysis and extension: incomplete lysis and exposure of active thrombin may lead to re-occlusion of vessels. (PMID:11686320)
• Thrombin induces increased expression and secretion of VEGF from human FS4 fibroblasts, DU145 prostate cells and CHRF megakaryocytes. (PMID:11686329)
• When recombinant provWF was incubated with increasing amounts of purified thrombin, provWF processing was dose-dependent. The specific cleavage of vWFpp was confirmed by immunoblots using an anti-vWFpp antibody and by NH2-terminal amino-acid analysis. (PMID:11776313)
• Comparison of fibrinogen clotting activity with fibrin binding activity identified twenty residues involved in fibrinogen recognition with 4 of these residues important in fibrin binding (Lys65, His66, Tyr71, Arg73). (PMID:11776315)
• Association of prothrombin gene mutation with Behcet’s disease. (PMID:11820731)
• Mothers with prothrombin A20210 mutation have a higher risk of having low birth-weight infants or fetal loss, possibly due to underperfusion of the placenta. (PMID:11836168)
• In prothrombin Perija, mutation of Gly-548 to Ala near the substrate binding pocket cavity wall blocks thrombin proteolytic activity. The methyl group blocks entry of the substrate Arg guanidino group into the cavity & catalytic Ser-525. (PMID:11858488)
• Proexosite I blockage decreases recognition of prothrombin as substrate by factor Xa-factor Va complex & prothrombinase complex. Data obtained with human platelets suggest that proexosite I may play an important role in prothrombin activation. (PMID:11858489)
• No association was found between factor II g20210A promoter variant and fatal myocardial infarction in Finland. (PMID:11858502)
• Thrombin induces increased expression and secretion of angiopoietin-2 from human umbilical vein endothelial cells. (PMID:11861279)
• In the Spanish population, the prothrombin 20210A (PT20210A) allele is the most prevalent genetic risk factor for venous thromboembolism in hemophilia A. (PMID:11869940)
• Delayed, reduced or inhibited thrombin production reduces platelet contractile force and results in weaker clot formation. (PMID:11943932)
• role of thrombin in the neo-vascularization of malignant gliomas (PMID:11956584)
• Data suggesting a physical association between factor Xa and prothrombin, and that factor Xa has an increased affinity for prothrombin in the presence of factor Va. (PMID:11983337)
• Mechanism of thrombin-induced angiogenesis. Review. (PMID:12023846)
• Role of thrombin and its major cellular receptor, protease-activated receptor-1, in pulmonary fibrosis. Review. (PMID:12023853)
• G20210A is a bifunctional polymorphism, as it not only alters the efficiency of mRNA processing, but also the decay rate of prothrombin mRNA. (PMID:12038788)
• prevalence of FVL, FII G20210A and MTHFR C677T in women with three or more pregnancy losses (PMID:12042290)
• G20210A mutation contributes to the process of arterial wall thickening and is associated with the occurrence of ischemic events in a cohort of elderly persons with established atherosclerosis. (PMID:12048131)
• TRAP causes more intense changes in signaling through tyrosine phosphorylation of proteins associated with the cytoskeletal fraction than thrombin. (PMID:12057926)
• effect of factor VIII deficiency on generation (PMID:12058364)
• This study confirms the presence of G20210A mutation in the Romanian population, and demonstrates a link between venous leg ulcers and this polymorphism in the prothrombin gene. (PMID:12067473)
• functional epitope of thrombin recognizing thrombomodulin was mapped using Ala-scanning mutagenesis of 54 residues located around the active site, the Na(+) binding loop, the 186-loop, the autolysis loop, exosite I, and exosite II (PMID:12068020)
• Thrombin functions studied during tissue factor-induced blood coagulation (PMID:12070020)
• The G20210A mutation does not affect the stability of prothrombin mRNA but, rather, effects a change in the location of the 3’-cleavage/polyadenylation reaction (PMID:12070052)
• Data show that factor V activation is associated with the stepwise release of the B-domain after incubation with thrombin, which results in a gradual exposure of the factor Xa-binding site. (PMID:12163491)
• the inhibitory sequence for prothrombinase was delineated using a synthetic peptide library representing human prothrombin fragment 2 (F2) sequence (PMID:12165293)
• The presence of the G20210A factor II gene mutation is associated with the occurrence of a previous systemic embolism. (PMID:12208422)
• prospective study of the G20210A polymorphism in the gene, plasma concentration and incidence of venous thromboembolism (PMID:12447958)
• prevalence of mutation and factor V G1691A (factor V-Leiden) mutation in a recurrent miscarriage population (PMID:12447960)
• Interaction between the FII 20210A and FXIII-A Leu34 alleles forms a synergistic coeffect that strongly predisposes for MI, placing combined carriers at high risk for MI. (PMID:12480694)
• Thrombin upregulates COX-2-derived prostaglandin E2 synthesis by both catalytic cleavage of proteinase-activated receptor 1 and bFGF-dependent noncatalytic activity. (PMID:12505789)
• Interactions within thrombin that involve autolytic loop-2 and the Na(+)-binding site primarily enhance thrombin action on fibrinogen, but impair thrombin action on protein C. (PMID:12588872)
• Prothrombin binds selectively to the surface of apoptotic, but not viable, Jurkat cells and supports the binding of systemic lupus erythematosus-derived prothrombin-dependent lupus anticoagulant antibody to apoptotic cells. (PMID:12626602)
• Data present the 1.8 A crystallographic structure of S195A thrombin in two conformational states: active site occupied and active site free. (PMID:12679024)
• relationship between serum levels and the expression of Des-gamma-carboxy prothrombin (DCP)in cancer and surrounding non-cancer liver tissues of hepatocellular carcinoma patients (PMID:12684661)
• factor V Leiden or prothrombin G20210A associated with cryptogenic stroke whereas other coagulation abnormalities did not, supporting the possibility of paradoxical embolism behind strokes in patients with patent foramen ovale (PMID:12695749)
• Results show that VR1 is a subsite of exosite 1 on thrombin’s surface, which regulates exclusive binding of either plasminogen activator inhibitor 1 or thrombomodulin. (PMID:12709053)
• investigated the distribution of the prothrombin variant G20210A (PT20210A) in patients with thrombophilic conditions living in the French Basque Country (PMID:12734676)
• prothrombin has a factor Va-dependent recognition site for the prothrombinase complex (PMID:12750382)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	F2	ENSMUSG00000027249
rattus_norvegicus	F2	ENSRNOG00000016325

Paralogs (1): PAMR1 (ENSG00000149090)

Protein

Protein identifiers

Prothrombin — P00734 (reviewed: P00734)

Alternative names: Coagulation factor II

All UniProt accessions (3): P00734, C9JV37, E9PIT3

UniProt curated annotations — full annotation on UniProt →

Function. Thrombin, which cleaves bonds after Arg and Lys, converts fibrinogen to fibrin and activates factors V, VII, VIII, XIII, and, in complex with thrombomodulin, protein C. Functions in blood homeostasis, inflammation and wound healing. Activates coagulation factor XI (F11); activation is promoted by the contact with negatively charged surfaces. Triggers the production of pro-inflammatory cytokines, such as MCP-1/CCL2 and IL8/CXCL8, in endothelial cells.

Subunit / interactions. Heterodimer (named alpha-thrombin) of a light and a heavy chain; disulfide-linked. Forms a heterodimer with SERPINA5. In plasma, interacts (via N-terminus) with alpha-1-microglobulin with molar ratio 1:2 and 1:1; this interaction does not prevent the activation of prothrombin to thrombin. Interacts (thrombin) with iripin-8, a serine protease inhibitor from Ixodes ricinus saliva. Interacts (thrombin) with iripin-3, a serine protease inhibitor from Ixodes ricinus saliva. Interacts (thrombin) with Anopheles albimanus salivary thrombin inhibitor anophelin; the interaction results in thrombin inhibition. Interacts (thrombin) with Anopheles gambiae salivary thrombin inhibitor anophelin; the interaction results in thrombin inhibition. Interacts (thrombin) with Amblyomma variegatum variegin; the interaction results in thrombin inhibition. Interacts (thrombin) with Xenopsylla cheopis salivary thrombin inhibitor XC-42. Interacts (thrombin) with Xenopsylla cheopis salivary thrombin inhibitor XC-43.

Subcellular location. Secreted. Extracellular space.

Tissue specificity. Expressed by the liver and secreted in plasma.

Post-translational modifications. The gamma-carboxyglutamyl residues, which bind calcium ions, result from the carboxylation of glutamyl residues by a microsomal enzyme, the vitamin K-dependent carboxylase. The modified residues are necessary for the calcium-dependent interaction with a negatively charged phospholipid surface, which is essential for the conversion of prothrombin to thrombin. N-glycosylated. N-glycan heterogeneity at Asn-121: Hex3HexNAc3 (minor), Hex4HexNAc3 (minor) and Hex5HexNAc4 (major). At Asn-143: Hex4HexNAc3 (minor) and Hex5HexNAc4 (major). In the penultimate step of the coagulation cascade, prothrombin is converted to thrombin by the prothrombinase complex composed of factor Xa (F10), cofactor Va (F5), and phospholipids. This activation requires factor Xa-catalyzed sequential cleavage at 2 sites, Arg-314 and Arg-363, along 2 possible pathways. In the first pathway, the first cleavage occurs at Arg-314, leading to the formation of the inactive intermediate prethrombin-2. This pathway preferentially occurs on platelets and in the absence of cofactor Va. In the second pathway, the first cleavage occurs at Arg-363, which separates protease domain into 2 chains that remain connected through a disulfide bond and generates the active intermediate meizothrombin. The presence of cofactor Va directs activation along the meizothrombin pathway and greatly accelerates the rate of cleavage at Arg-363, but has a smaller effect on the cleavage of meizothrombin at Arg-314. Meizothrombin accumulates as an intermediate when prothrombinase is assembled on the membrane of red blood cells.

Disease relevance. Factor II deficiency (FA2D) [MIM:613679] A very rare blood coagulation disorder characterized by mucocutaneous bleeding symptoms. The severity of the bleeding manifestations correlates with blood factor II levels. The disease is caused by variants affecting the gene represented in this entry. Ischemic stroke (ISCHSTR) [MIM:601367] A stroke is an acute neurologic event leading to death of neural tissue of the brain and resulting in loss of motor, sensory and/or cognitive function. Ischemic strokes, resulting from vascular occlusion, is considered to be a highly complex disease consisting of a group of heterogeneous disorders with multiple genetic and environmental risk factors. Disease susceptibility is associated with variants affecting the gene represented in this entry. Thrombophilia due to thrombin defect (THPH1) [MIM:188050] A multifactorial disorder of hemostasis characterized by abnormal platelet aggregation in response to various agents and recurrent thrombi formation. The disease is caused by variants affecting the gene represented in this entry. A common genetic variation in the 3-prime untranslated region of the prothrombin gene is associated with elevated plasma prothrombin levels and an increased risk of venous thrombosis. Pregnancy loss, recurrent, 2 (RPRGL2) [MIM:614390] A common complication of pregnancy, resulting in spontaneous abortion before the fetus has reached viability. The term includes all miscarriages from the time of conception until 24 weeks of gestation. Recurrent pregnancy loss is defined as 3 or more consecutive spontaneous abortions. Disease susceptibility is associated with variants affecting the gene represented in this entry.

Activity regulation. Activity is promoted in the presence of negatively charged surfaces, such as polyphosphate and dextran sulfate. Inhibited by SERPINA5.

Miscellaneous. It is not known whether 1 or 2 smaller activation peptides, with additional cleavage after Arg-314, are released in natural blood clotting. Thrombin can itself cleave the N-terminal fragment (fragment 1) of the prothrombin, prior to its activation by factor Xa. The cleavage after Arg-198, observed in vitro, does not occur in plasma.

Similarity. Belongs to the peptidase S1 family.

RefSeq proteins (1): NP_000497* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000001	Kringle	Domain
IPR000294	GLA_domain	Domain
IPR001254	Trypsin_dom	Domain
IPR001314	Peptidase_S1A	Family
IPR003966	Prothrombin/thrombin	Family
IPR009003	Peptidase_S1_PA	Homologous_superfamily
IPR013806	Kringle-like	Homologous_superfamily
IPR018056	Kringle_CS	Conserved_site
IPR018114	TRYPSIN_HIS	Active_site
IPR018992	Thrombin_light_chain	Domain
IPR033116	TRYPSIN_SER	Active_site
IPR035972	GLA-like_dom_SF	Homologous_superfamily
IPR037111	Thrombin_light_chain_sf	Homologous_superfamily
IPR038178	Kringle_sf	Homologous_superfamily
IPR043504
IPR051659	Serine_Protease_S1-Domain	Family

Pfam: PF00051, PF00089, PF00594, PF09396

Enzyme classification (BRENDA):

• EC 3.4.21.5 — thrombin (BRENDA: 10 organisms, 199 substrates, 440 inhibitors, 100 Km, 96 kcat entries)

Substrate kinetics (BRENDA)

38 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
D-PHENYLALANYL-PIPECOLYL-L-ARGININE-4-NITROANILI	0.0026–0.298	14
TOSYL-ARG METHYL ESTER	0.0063–0.3	8
D-PHE-L-PIPECOLYL-L-ARG-4-NITROANILIDE	0.0015–0.0632	7
BENZOYL-ARG ETHYL ESTER	0.0052–0.0079	5
PROTEIN C	0.002–0.0032	5
D-PHE-PRO-ARG-4-NITROANILIDE	0.0003–0.013	4
D-PHE-PRO-LYS-4-NITROANILIDE	0.004–0.072	4
D-PHE-PRO-PHE-4-NITROANILIDE	0.017–0.11	4
DI-L-GLU-L-PRO-L-ARG-4-NITROANILIDE	0.1471–0.2829	4
FIBRINOGEN	0.0032–0.0528	4
TOSYL-GLY-PRO-ARG-4-NITROANILIDE	0.0085–0.0164	4
BENZOYL-ARG METHYL ESTER	0.0075–0.0088	2
BENZOYL-L-ARG-P-NITROANILIDE	0.143–0.84	2
FIBRINOGEN AALPHA CHAIN	0.0036–0.0113	2
FIBRINOPEPTIDE A	0.0051–0.013	2

UniProt features (156 total): strand 41, sequence conflict 24, helix 18, turn 14, sequence variant 13, disulfide bond 12, modified residue 10, domain 4, active site 3, site 3, chain 3, glycosylation site 3, mutagenesis site 3, peptide 2, signal peptide 1, propeptide 1, region of interest 1

Structure

Experimental structures (PDB)

475 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
5AFY	X-RAY DIFFRACTION	1.12
4UD9	X-RAY DIFFRACTION	1.12
4UE7	X-RAY DIFFRACTION	1.13
4UDW	X-RAY DIFFRACTION	1.16
4UEH	X-RAY DIFFRACTION	1.16
5AF9	X-RAY DIFFRACTION	1.18
3RM2	X-RAY DIFFRACTION	1.23
5AHG	X-RAY DIFFRACTION	1.24
2BVR	X-RAY DIFFRACTION	1.25
3VXE	X-RAY DIFFRACTION	1.25
2UUF	X-RAY DIFFRACTION	1.26
3SI4	X-RAY DIFFRACTION	1.27
5JZY	X-RAY DIFFRACTION	1.27
6FJT	X-RAY DIFFRACTION	1.27
3U8O	X-RAY DIFFRACTION	1.28
5MM6	X-RAY DIFFRACTION	1.29
2CF8	X-RAY DIFFRACTION	1.3
2CN0	X-RAY DIFFRACTION	1.3
3SV2	X-RAY DIFFRACTION	1.3
6TKL	X-RAY DIFFRACTION	1.3
6T4A	X-RAY DIFFRACTION	1.31
6T56	X-RAY DIFFRACTION	1.31
2UUJ	X-RAY DIFFRACTION	1.32
6T3Q	X-RAY DIFFRACTION	1.33
6YB6	X-RAY DIFFRACTION	1.33
6YHG	X-RAY DIFFRACTION	1.33
6ROT	X-RAY DIFFRACTION	1.34
3RM0	X-RAY DIFFRACTION	1.34
3QX5	X-RAY DIFFRACTION	1.35
6T53	X-RAY DIFFRACTION	1.35

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P00734-F1	84.37	0.56

Antibody-complex structures (SAbDab): 2 — 5E8E, 8UF7

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 (6): 406 (charge relay system); 462 (charge relay system); 568 (charge relay system); 198–199 (cleavage; by thrombin); 314–315 (cleavage; by factor xa); 363–364 (cleavage; by factor xa)

Post-translational modifications (10): 49, 50, 57, 59, 62, 63, 68, 69, 72, 75

Disulfide bonds (12): 60–65, 90–103, 108–186, 129–169, 157–181, 213–291, 234–274, 262–286, 336–482, 391–407, 536–550, 564–594

Glycosylation sites (3): 121, 143, 416

Mutagenesis-validated functional residues (3):

Position	Phenotype
314	loss of cleavage by factor xa.
363	loss of cleavage by factor xa.
568	loss of catalytic activity; no effect on cleavage at r-198 by factor xa.

Function

Pathways and Gene Ontology

Reactome pathways

38 pathways

ID	Pathway
R-HSA-159740	Gamma-carboxylation of protein precursors
R-HSA-159763	Transport of gamma-carboxylated protein precursors from the endoplasmic reticulum to the Golgi apparatus
R-HSA-159782	Removal of aminoterminal propeptides from gamma-carboxylated proteins
R-HSA-202733	Cell surface interactions at the vascular wall
R-HSA-375276	Peptide ligand-binding receptors
R-HSA-381426	Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)
R-HSA-416476	G alpha (q) signalling events
R-HSA-456926	Thrombin signalling through proteinase activated receptors (PARs)
R-HSA-76009	Platelet Aggregation (Plug Formation)
R-HSA-9657688	Defective factor XII causes hereditary angioedema
R-HSA-9672391	Defective F8 cleavage by thrombin
R-HSA-9769733	Fibrin formation
R-HSA-9769735	Initiation of coagulation cascade
R-HSA-9769739	Regulation of clotting cascade
R-HSA-9769743	Amplification and propagation of coagulation cascade
R-HSA-977606	Regulation of Complement cascade
R-HSA-9918481	Dengue Virus-Host Interactions
R-HSA-140837
R-HSA-140875
R-HSA-109582	Hemostasis
R-HSA-140877
R-HSA-159854	Gamma-carboxylation, transport, and amino-terminal cleavage of proteins
R-HSA-162582	Signal Transduction
R-HSA-163841	Gamma carboxylation, hypusinylation, hydroxylation, and arylsulfatase activation
R-HSA-1643685	Disease
R-HSA-166658	Complement cascade
R-HSA-168249	Innate Immune System
R-HSA-168256	Immune System
R-HSA-372790	Signaling by GPCR
R-HSA-373076	Class A/1 (Rhodopsin-like receptors)

MSigDB gene sets: 421 (showing top): MODULE_172, GOBP_POSITIVE_REGULATION_OF_CALCIUM_ION_TRANSPORT, GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_NEGATIVE_REGULATION_OF_CELL_DEVELOPMENT, GOBP_PROTEIN_ACTIVATION_CASCADE, GOBP_NEGATIVE_REGULATION_OF_PROTEOLYSIS, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_ANTIMICROBIAL_HUMORAL_RESPONSE, YAGI_AML_WITH_INV_16_TRANSLOCATION, GOBP_REGULATION_OF_CELL_MORPHOGENESIS, GOBP_REGULATION_OF_WOUND_HEALING, PID_HNF3B_PATHWAY, GOBP_INFLAMMATORY_RESPONSE, GOBP_REGULATION_OF_COAGULATION, GNF2_GSTM1

GO Biological Process (37): proteolysis (GO:0006508), acute-phase response (GO:0006953), cell surface receptor signaling pathway (GO:0007166), blood coagulation (GO:0007596), positive regulation of cell population proliferation (GO:0008284), regulation of cell shape (GO:0008360), response to wounding (GO:0009611), negative regulation of platelet activation (GO:0010544), platelet activation (GO:0030168), regulation of blood coagulation (GO:0030193), positive regulation of blood coagulation (GO:0030194), negative regulation of blood coagulation (GO:0030195), positive regulation of cell growth (GO:0030307), positive regulation of insulin secretion (GO:0032024), positive regulation of collagen biosynthetic process (GO:0032967), fibrinolysis (GO:0042730), negative regulation of proteolysis (GO:0045861), positive regulation of receptor signaling pathway via JAK-STAT (GO:0046427), negative regulation of astrocyte differentiation (GO:0048712), positive regulation of release of sequestered calcium ion into cytosol (GO:0051281), regulation of cytosolic calcium ion concentration (GO:0051480), obsolete cytolysis by host of symbiont cells (GO:0051838), positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0051897), negative regulation of fibrinolysis (GO:0051918), antimicrobial humoral immune response mediated by antimicrobial peptide (GO:0061844), thrombin-activated receptor signaling pathway (GO:0070493), neutrophil-mediated killing of gram-negative bacterium (GO:0070945), blood coagulation, fibrin clot formation (GO:0072378), negative regulation of cytokine production involved in inflammatory response (GO:1900016), positive regulation of protein localization to nucleus (GO:1900182), positive regulation of phospholipase C-activating G protein-coupled receptor signaling pathway (GO:1900738), ligand-gated ion channel signaling pathway (GO:1990806), positive regulation of reactive oxygen species metabolic process (GO:2000379), G protein-coupled receptor signaling pathway (GO:0007186), hemostasis (GO:0007599), regulation of gene expression (GO:0010468), regulation of body fluid levels (GO:0050878)

GO Molecular Function (13): lipopolysaccharide binding (GO:0001530), serine-type endopeptidase activity (GO:0004252), signaling receptor binding (GO:0005102), calcium ion binding (GO:0005509), growth factor activity (GO:0008083), heparin binding (GO:0008201), receptor ligand activity (GO:0048018), thrombospondin receptor activity (GO:0070053), endopeptidase activity (GO:0004175), protein binding (GO:0005515), peptidase activity (GO:0008233), serine-type peptidase activity (GO:0008236), hydrolase activity (GO:0016787)

GO Cellular Component (9): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), endoplasmic reticulum lumen (GO:0005788), Golgi lumen (GO:0005796), plasma membrane (GO:0005886), extracellular exosome (GO:0070062), blood microparticle (GO:0072562), external side of plasma membrane (GO:0009897), extracellular matrix (GO:0031012)

Reactome top-level categories

Rollup of top-11 pathways:

Category	Pathways
Coagulation pathway	4
Gamma-carboxylation, transport, and amino-terminal cleavage of proteins	3
Platelet activation, signaling and aggregation	2
Hemostasis	1
Class A/1 (Rhodopsin-like receptors)	1
Metabolism of proteins	1
GPCR downstream signalling	1
Defects of contact activation system and kallikrein-kinin system	1
Defective factor VIII causes hemophilia A	1
Complement cascade	1
Dengue Virus Infection	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
blood coagulation	4
signal transduction	2
positive regulation of cellular process	2
negative regulation of blood coagulation	2
regulation of blood coagulation	2
peptidase activity	2
cellular anatomical structure	2
intracellular organelle lumen	2
protein metabolic process	1
acute inflammatory response	1
hemostasis	1
wound healing	1
coagulation	1
cell population proliferation	1
regulation of cell population proliferation	1
regulation of cell morphogenesis	1
regulation of biological quality	1
response to stress	1
regulation of platelet activation	1
platelet activation	1
negative regulation of cell activation	1
cell activation	1
regulation of response to external stimulus	1
regulation of coagulation	1
regulation of wound healing	1
regulation of hemostasis	1
positive regulation of coagulation	1
positive regulation of wound healing	1
positive regulation of hemostasis	1
negative regulation of coagulation	1
negative regulation of wound healing	1
negative regulation of hemostasis	1
regulation of cell growth	1
cell growth	1
positive regulation of growth	1
insulin secretion	1
positive regulation of protein secretion	1
regulation of insulin secretion	1
positive regulation of peptide hormone secretion	1
positive regulation of biosynthetic process	1

Protein interactions and networks

STRING

2598 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
F2	F3	P13726	993
F2	SERPINC1	P01008	980
F2	ALB	P02768	974
F2	F10	P00742	972
F2	MTHFR	P42898	935
F2	AFP	P02771	929
F2	THBD	P07204	928
F2	F8	P00451	923
F2	TFPI	P10646	919
F2	GPT	P24298	918
F2	APOH	P02749	913
F2	VWF	P04275	894
F2	CRP	P02741	887
F2	FGA	P02671	887
F2	F5	P12259	887

IntAct

60 interactions, top by confidence:

A	B	Type	Score
F2		psi-mi:“MI:0915”(physical association)	0.730
F2		psi-mi:“MI:0407”(direct interaction)	0.730
	F2	psi-mi:“MI:0915”(physical association)	0.730
	F2	psi-mi:“MI:0194”(cleavage reaction)	0.730
F2	APP	psi-mi:“MI:0915”(physical association)	0.560
F2		psi-mi:“MI:0407”(direct interaction)	0.560
	F2	psi-mi:“MI:0407”(direct interaction)	0.560
YWHAQ	IGLC7	psi-mi:“MI:0914”(association)	0.530
C1QBP	F2	psi-mi:“MI:0914”(association)	0.460
F2R	F2	psi-mi:“MI:0407”(direct interaction)	0.440
SERPINA5	F2	psi-mi:“MI:0407”(direct interaction)	0.440
F2	F8	psi-mi:“MI:0407”(direct interaction)	0.440
F2		psi-mi:“MI:0570”(protein cleavage)	0.440

BioGRID (51): F2 (Co-localization), F2 (Co-localization), F2 (Affinity Capture-MS), SERPINE1 (Reconstituted Complex), MAPT (Biochemical Activity), F2 (Affinity Capture-MS), FGA (Co-crystal Structure), SERPIND1 (Co-crystal Structure), F2 (Reconstituted Complex), F2 (Co-crystal Structure), CPB2 (Reconstituted Complex), THBD (Reconstituted Complex), F2 (Affinity Capture-MS), S (Biochemical Activity), APOC3 (Affinity Capture-MS)

ESM2 similar proteins: A0A1S4GMJ4, A0A1S4H5M5, A0A1S4H5S2, A0A1S4HE51, A6MFK7, A6MFK8, A8JUP7, O01887, O35086, O62589, P00734, P00735, P05049, P05156, P15638, P18292, P19007, P19221, P28175, P29598, P98119, Q05589, Q17800, Q19AZ8, Q1L659, Q24568, Q26422, Q27081, Q28801, Q3UQ41, Q4QXT9, Q5E9P5, Q5R5A4, Q5RDI1, Q60574, Q61129, Q61646, Q62558, Q66TN7, Q6DIV5

Diamond homologs: A0A7J6K144, O18783, P00734, P06868, P08519, P12545, P14210, P14417, P17945, P20918, P26927, P26928, P80010, Q01177, Q01973, Q08048, Q16609, Q24K22, Q29485, Q2TV78, Q5R537, Q5R8X6, Q76BS1, Q7M323, Q867B7, Q9BH09, Q9V6K3, Q9Z139, A6MFK7, A6MFK8, B5G6G5, O00187, O15393, O19045, O88947, O97399, P00735, P00740, P00741, P00742

SIGNOR signaling

38 interactions.

A	Effect	B	Mechanism
F2	up-regulates	F2RL1	binding
F2	up-regulates	F2RL2	binding
dabigatran	down-regulates	F2	“chemical inhibition”
F2	up-regulates	F2RL3	binding
F2	up-regulates	F2R	cleavage
F2	up-regulates	F2R	binding
F2	“up-regulates activity”	“GPIb-IX-V complex”	binding
SERPINA1	“down-regulates activity”	F2	binding
F2	“up-regulates activity”	Fibrinogen	cleavage
F2	“up-regulates activity”	F7
F2	“up-regulates activity”	F5
F2	“form complex”	Thrombin-Thrombomodulin	binding
GGCX	“up-regulates activity”	F2	carboxylation
F2	up-regulates	LRP1	binding
F10	“up-regulates activity”	F2	cleavage
bivalirudin	“down-regulates activity”	F2	“chemical inhibition”
“Factor Va-Xa”	“up-regulates activity”	F2	cleavage
F2	“up-regulates activity”	F2R	cleavage
F2	“down-regulates activity”	F2R	cleavage
F2	“up-regulates activity”	F5	cleavage
F2	“up-regulates activity”	F8	cleavage

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 32 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
Regulation of clotting cascade	8	71.7×	2e-11
Post-translational protein phosphorylation	5	19.3×	2e-04
Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)	5	16.6×	4e-04
Hemostasis	6	8.3×	1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	21
Likely pathogenic	17
Uncertain significance	120
Likely benign	250
Benign	24

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
13303	NM_000506.3(F2):c.940C>T (p.Arg314Cys)	Pathogenic
13306	NM_000506.3(F2):c.1802G>T (p.Gly601Val)	Pathogenic
13307	NM_000506.3(F2):c.1139T>C (p.Met380Thr)	Pathogenic
13308	NM_000506.3(F2):c.1292G>A (p.Arg431His)	Pathogenic
13309	NM_000506.5(F2):c.462_463insT (p.Asn155Ter)	Pathogenic
13311	NM_000506.3(F2):c.1027G>A (p.Glu343Lys)	Pathogenic
13312	NM_000506.3(F2):c.1054G>A (p.Glu352Lys)	Pathogenic
13313	NM_000506.5(F2):c.1274G>A (p.Arg425His)	Pathogenic
13314	NM_000506.3(F2):c.1785C>G (p.Asp595Glu)	Pathogenic
2706763	NM_000506.5(F2):c.1499G>A (p.Arg500Gln)	Pathogenic
2735585	NM_000506.5(F2):c.1015C>T (p.Arg339Ter)	Pathogenic
2735586	NM_000506.5(F2):c.1786C>T (p.Arg596Trp)	Pathogenic
2806215	NM_000506.5(F2):c.13C>T (p.Arg5Ter)	Pathogenic
2872207	NM_000506.5(F2):c.923_926del (p.Asp308fs)	Pathogenic
2884504	NM_000506.5(F2):c.392dup (p.Trp132fs)	Pathogenic
2957927	NM_000506.5(F2):c.349C>T (p.Arg117Ter)	Pathogenic
2966946	NM_000506.5(F2):c.954dup (p.Glu319Ter)	Pathogenic
3015914	NM_000506.5(F2):c.1678C>T (p.Arg560Ter)	Pathogenic
31922	NM_000506.5(F2):c.1787G>T (p.Arg596Leu)	Pathogenic
4686696	NM_000506.5(F2):c.552del (p.Val185fs)	Pathogenic
692073	NM_000506.5(F2):c.1787G>A (p.Arg596Gln)	Pathogenic
1098519	NM_000506.5(F2):c.995G>C (p.Gly332Ala)	Likely pathogenic
1098520	NM_000506.5(F2):c.1070A>G (p.Glu357Gly)	Likely pathogenic
1098522	NM_000506.5(F2):c.1270G>A (p.Val424Met)	Likely pathogenic
1098523	NM_000506.5(F2):c.1496G>A (p.Gly499Glu)	Likely pathogenic
13305	NM_000506.3(F2):c.1273C>T (p.Arg425Cys)	Likely pathogenic
1684489	NM_000506.5(F2):c.1094T>A (p.Val365Glu)	Likely pathogenic
2631315	NM_000506.5(F2):c.454_457del (p.Leu152fs)	Likely pathogenic
2735584	NM_000506.5(F2):c.422+1G>A	Likely pathogenic
2885128	NM_000506.5(F2):c.1745G>A (p.Trp582Ter)	Likely pathogenic

SpliceAI

2040 predictions. Top by Δscore:

Variant	Effect	Δscore
11:46719863:G:GG	donor_gain	1.0000
11:46719863:GT:G	donor_loss	1.0000
11:46719864:T:G	donor_loss	1.0000
11:46723516:GTG:G	donor_gain	1.0000
11:46723519:G:GG	donor_gain	1.0000
11:46723520:T:A	donor_loss	1.0000
11:46726709:A:AG	acceptor_gain	1.0000
11:46726710:G:GG	acceptor_gain	1.0000
11:46726710:GACT:G	acceptor_gain	1.0000
11:46726945:C:G	donor_gain	1.0000
11:46727994:A:AG	acceptor_gain	1.0000
11:46727995:G:GG	acceptor_gain	1.0000
11:46727995:G:GT	acceptor_loss	1.0000
11:46727995:GGC:G	acceptor_gain	1.0000
11:46727995:GGCA:G	acceptor_gain	1.0000
11:46728146:C:T	donor_gain	1.0000
11:46728163:GG:G	donor_loss	1.0000
11:46728650:T:TA	acceptor_gain	1.0000
11:46728651:G:A	acceptor_gain	1.0000
11:46728659:TGCA:T	acceptor_loss	1.0000
11:46728660:GCAG:G	acceptor_loss	1.0000
11:46728661:CA:C	acceptor_loss	1.0000
11:46728663:GGT:G	acceptor_gain	1.0000
11:46728663:GGTAC:G	acceptor_gain	1.0000
11:46728788:A:AG	donor_gain	1.0000
11:46728789:G:GG	donor_gain	1.0000
11:46728793:C:G	donor_gain	1.0000
11:46739045:A:AG	acceptor_gain	1.0000
11:46739046:A:G	acceptor_gain	1.0000
11:46739116:AAGG:A	donor_loss	1.0000

AlphaMissense

4069 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:46739309:G:C	W590C	1.000
11:46739309:G:T	W590C	1.000
11:46723248:T:A	C129S	0.999
11:46723249:G:C	C129S	0.999
11:46723259:G:C	W132C	0.999
11:46723259:G:T	W132C	0.999
11:46723428:T:A	C157S	0.999
11:46723429:G:C	C157S	0.999
11:46726010:G:C	W237C	0.999
11:46726010:G:T	W237C	0.999
11:46726836:T:A	W377R	0.999
11:46726836:T:C	W377R	0.999
11:46728036:T:A	C391S	0.999
11:46728037:G:A	C391Y	0.999
11:46728037:G:C	C391S	0.999
11:46728045:A:C	S394R	0.999
11:46728047:C:A	S394R	0.999
11:46728047:C:G	S394R	0.999
11:46728086:C:G	C407W	0.999
11:46728749:G:C	D462H	0.999
11:46728750:A:C	D462A	0.999
11:46728750:A:T	D462V	0.999
11:46729417:T:A	W504R	0.999
11:46729417:T:C	W504R	0.999
11:46729419:G:C	W504C	0.999
11:46729419:G:T	W504C	0.999
11:46729513:T:A	C536S	0.999
11:46729514:G:C	C536S	0.999
11:46729555:T:A	C550S	0.999
11:46729555:T:C	C550R	0.999

dbSNP variants (sampled 300 via entrez): RS1000082186 (11:46734630 G>A), RS1000134791 (11:46734257 T>G), RS1000196604 (11:46729112 C>G,T), RS1000434996 (11:46727240 T>G), RS1000646970 (11:46728006 C>A,G), RS1000814110 (11:46721138 G>A), RS1000969940 (11:46727667 A>G), RS1001089599 (11:46734298 GT>G), RS1001098112 (11:46721406 G>A), RS1001640532 (11:46730621 G>C), RS1001724739 (11:46718041 C>T), RS1001765544 (11:46724227 A>G), RS1001819450 (11:46722458 C>T), RS1002102467 (11:46722608 A>G), RS1002157797 (11:46719797 G>C,T)

Disease associations

OMIM: gene MIM:176930 | disease phenotypes: MIM:188050, MIM:613679, MIM:614390

GenCC curated gene-disease

Disease	Classification	Inheritance
thrombophilia due to thrombin defect	Definitive	Autosomal dominant
congenital prothrombin deficiency	Strong	Autosomal recessive

ClinGen Gene-Disease Validity (2)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
thrombophilia due to thrombin defect	Definitive	AD
congenital prothrombin deficiency	Definitive	AR

Mondo (7): thrombophilia due to thrombin defect (MONDO:0008559), congenital prothrombin deficiency (MONDO:0013361), cerebral palsy (MONDO:0006497), pregnancy loss, recurrent, susceptibility to, 2 (MONDO:0013728), ischemic stroke (MONDO:1060198), venous thromboembolism (MONDO:0005399), prostate cancer (MONDO:0008315)

Orphanet (2): Congenital factor II deficiency (Orphanet:325), Familial prostate cancer (Orphanet:1331)

HPO phenotypes

41 total (30 of 41 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000132	Menorrhagia
HP:0000225	Gingival bleeding
HP:0000421	Epistaxis
HP:0000978	Bruising susceptibility
HP:0001297	Stroke
HP:0001426	Non-Mendelian inheritance
HP:0001892	Abnormal bleeding
HP:0001903	Anemia
HP:0001907	Thromboembolism
HP:0002170	Intracranial hemorrhage
HP:0002204	Pulmonary embolism
HP:0002239	Gastrointestinal hemorrhage
HP:0002625	Deep venous thrombosis
HP:0002907	Microscopic hematuria
HP:0003010	Prolonged bleeding time
HP:0003577	Congenital onset
HP:0003581	Adult onset
HP:0003645	Prolonged partial thromboplastin time
HP:0003828	Variable expressivity
HP:0004419	Recurrent thrombophlebitis
HP:0004420	Arterial thrombosis
HP:0004936	Venous thrombosis
HP:0005261	Joint hemorrhage
HP:0005305	Cerebral venous thrombosis
HP:0006298	Prolonged bleeding after dental extraction
HP:0008151	Prolonged prothrombin time
HP:0011462	Young adult onset
HP:0011463	Childhood onset

GWAS associations

18 associations (top):

Study	Trait	p-value
GCST000763_2	Immunoglobulin A	2.000000e-06
GCST002808_9	Venous thromboembolism	2.000000e-09
GCST003390_2	Thrombosis	1.000000e-24
GCST004256_6	Venous thromboembolism	5.000000e-13
GCST004256_8	Venous thromboembolism	8.000000e-09
GCST004521_122	Autism spectrum disorder or schizophrenia	3.000000e-13
GCST004521_165	Autism spectrum disorder or schizophrenia	3.000000e-08
GCST005580_99	Intraocular pressure	7.000000e-11
GCST006017_6	Prothrombin time	1.000000e-09
GCST006803_20	Schizophrenia	3.000000e-13
GCST007511_23	Alzheimer’s disease (late onset)	6.000000e-06
GCST007825_4	Alzheimer’s disease or fasting glucose levels (pleiotropy)	3.000000e-16
GCST009030_16	Venous thromboembolism	1.000000e-31
GCST009030_17	Venous thromboembolism	1.000000e-15
GCST009097_7	Venous thromboembolism	1.000000e-59
GCST90002388_535	Lymphocyte count	6.000000e-11
GCST90002393_226	Monocyte count	1.000000e-12
GCST90010718_2	Thumb osteoarthritis severity (hand Klsum)	5.000000e-08

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0004747	protein measurement
EFO:0003907	deep vein thrombosis
EFO:0004695	intraocular pressure measurement
EFO:0008390	prothrombin time measurement
EFO:1001870	late-onset Alzheimers disease
EFO:0004587	lymphocyte count
EFO:0005091	monocyte count

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D002547	Cerebral Palsy	C10.228.140.140.254
D007020	Hypoprothrombinemias	C15.378.100.100.550; C15.378.100.141.550; C15.378.463.550; C16.320.099.550
D011471	Prostatic Neoplasms	C04.588.945.440.770; C12.100.500.260.750; C12.100.500.565.625; C12.200.294.260.750; C12.200.294.565.625; C12.200.758.409.750; C12.900.619.750
D054556	Venous Thromboembolism	C14.907.355.590.700

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (5): CHEMBL204 (SINGLE PROTEIN), CHEMBL2096988 (SELECTIVITY GROUP), CHEMBL2111379 (SELECTIVITY GROUP), CHEMBL2111401 (SELECTIVITY GROUP), CHEMBL2111477 (SELECTIVITY GROUP)

Molecules with ChEMBL bioactivity

48 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 591,861 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1091250	INDIGOTINDISULFONATE	4	340
CHEMBL1166	ARGATROBAN	4	231
CHEMBL1200370	BENZOYL PEROXIDE	4	354,767
CHEMBL1201073	SUCCIMER	4	10,987
CHEMBL1269025	EDOXABAN	4	2,356
CHEMBL1364144	METHYLPREDNISOLONE ACETATE	4	13,435
CHEMBL1544	LIOTHYRONINE	4	23,700
CHEMBL1560	CAPTOPRIL	4	66,415
CHEMBL198362	RIVAROXABAN	4	11,497
CHEMBL2103855	TELOTRISTAT	4	310
CHEMBL2107831	LUSUTROMBOPAG	4	122
CHEMBL231779	APIXABAN	4	9,262
CHEMBL25105	HEXAMIDINE	4	5,666
CHEMBL266349	MELAGATRAN	4	5,421
CHEMBL311498	CIANIDANOL	4	59,647
CHEMBL325041	BORTEZOMIB	4	13,120
CHEMBL333826	DEQUALINIUM	4	1,116
CHEMBL338802	SULFAGUANIDINE	4	4,956
CHEMBL512351	BETRIXABAN	4	1,084
CHEMBL522038	XIMELAGATRAN	4	7,429
CHEMBL5314348	BIVALIRUDIN	4
CHEMBL539697	DABIGATRAN ETEXILATE	4
CHEMBL55	PENTAMIDINE	4
CHEMBL64894	GENTIAN VIOLET	4
CHEMBL273264	NAFAMOSTAT	3
CHEMBL4112929	MILVEXIAN	3
CHEMBL48361	DABIGATRAN	3
CHEMBL50	QUERCETIN	3
CHEMBL590799	CAMOSTAT	3
CHEMBL85164	CAMOSTAT MESILATE	3

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs1799963	Toxicity	2B	hormonal contraceptives for systemic use	Stroke;Venous Thrombosis

PharmGKB variants

3 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs5896	F2		0.00	0
rs1799963	F2	2B	3.00	1	hormonal contraceptives for systemic use
rs3136516	F2		0.00	0

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Blood coagulation components

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

Ligand	Action	Affinity	Parameter
lepirudin	Inhibition	13.0	pKi
desirudin	Inhibition	12.7	pKi
Dup-714	Inhibition	10.39	pKi
AZ12971554	Inhibition	9.52	pKi
melagatran	Inhibition	8.7	pKi
bivalirudin	Inhibition	8.6	pKi
AR-H067637	Inhibition	8.4	pIC50
dabigatran	Inhibition	8.3	pKi
BAY 3389934	Inhibition	8.28	pIC50
argatroban	Inhibition	7.7	pKi
WX-UK1	Inhibition	6.3	pKi

Binding affinities (BindingDB)

1114 measured of 1725 human assays (1769 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
(2S)-N-[(2S)-1-(1,3-benzothiazol-2-yl)-5-carbamimidamido-1-oxopentan-2-yl]-1-[(2R)-2-(methylamino)-3,3-diphenylpropanoyl]pyrrolidine-2-carboxamide	KI	0.00065 nM
3-chloro-N-{4-chloro-2-[(5-chloropyridin-2-yl)carbamoyl]-6-methoxyphenyl}-4-{[3,4-dihydro-2H-pyrrol-5-yl(methyl)amino]methyl}thiophene-2-carboxamide	KI	0.004 nM
3-chloro-N-{4-chloro-2-[(5-chloropyridin-2-yl)carbamoyl]-6-methoxyphenyl}-4-{[2-(methylsulfanyl)-4,5-dihydro-1H-imidazol-1-yl]methyl}thiophene-2-carboxamide	KI	0.004 nM
3-chloro-N-{4-chloro-2-[(5-chloropyridin-2-yl)carbamoyl]-6-methoxyphenyl}-4-(4,5-dihydro-1H-imidazol-1-ylmethyl)thiophene-2-carboxamide	KI	0.004 nM
3-chloro-N-{4-chloro-2-[(5-chloropyridin-2-yl)carbamoyl]-6-methoxyphenyl}-4-{[2-(ethylamino)-1H-imidazol-1-yl]methyl}thiophene-2-carboxamide	KI	0.005 nM
(2S)-1-[(2R)-2-amino-3-phenylpropanoyl]-N-[1-(1,3-benzothiazol-2-yl)-5-carbamimidamido-1-oxopentan-2-yl]pyrrolidine-2-carboxamide	KI	0.0055 nM
4-[(2-amino-1H-imidazol-1-yl)methyl]-3-chloro-N-{4-chloro-2-[(5-chloropyridin-2-yl)carbamoyl]-6-methoxyphenyl}thiophene-2-carboxamide	KI	0.006 nM
2-(5-carbamimidamido-2-{[(2S)-1-[(2R)-2-(methylamino)-3-phenylpropanoyl]pyrrolidin-2-yl]formamido}pentanoyl)-1,3-benzothiazole-6-carboxamide	KI	0.007 nM
3-chloro-N-{4-chloro-2-[(5-chloropyridin-2-yl)carbamoyl]-6-methoxyphenyl}-4-{[2-(propan-2-ylamino)-1H-imidazol-1-yl]methyl}thiophene-2-carboxamide	KI	0.008 nM
3-chloro-N-{4-chloro-2-[(5-chloropyridin-2-yl)carbamoyl]-6-methoxyphenyl}-4-[(2-imino-1,3-oxazolidin-3-yl)methyl]thiophene-2-carboxamide	KI	0.01 nM
3-chloro-N-{4-chloro-2-[(5-chloropyridin-2-yl)carbamoyl]-6-methoxyphenyl}-4-[(2-imino-1,3-thiazolidin-3-yl)methyl]thiophene-2-carboxamide	KI	0.01 nM
3-chloro-N-{4-chloro-2-[(5-chloropyridin-2-yl)carbamoyl]-6-methoxyphenyl}-4-[(2-iminoimidazolidin-1-yl)methyl]thiophene-2-carboxamide	KI	0.01 nM
3-chloro-N-{4-chloro-2-[(5-chloropyridin-2-yl)carbamoyl]-6-methoxyphenyl}-4-[(2-methyl-4,5-dihydro-1H-imidazol-1-yl)methyl]thiophene-2-carboxamide	KI	0.01 nM
3-chloro-N-{4-chloro-2-[(5-chloropyridin-2-yl)carbamoyl]-6-methoxyphenyl}-4-[(N-methylethanimidamido)methyl]thiophene-2-carboxamide	KI	0.01 nM
3-chloro-N-{4-chloro-2-[(5-chloropyridin-2-yl)carbamoyl]-6-methoxyphenyl}-4-(3-methylcarbamimidamidomethyl)thiophene-2-carboxamide	KI	0.01 nM
3-chloro-N-{4-chloro-2-[(5-chloropyridin-2-yl)carbamoyl]-6-methoxyphenyl}-4-[(2-methyl-1H-imidazol-1-yl)methyl]thiophene-2-carboxamide	KI	0.01 nM
[2-[[(1R)-1-(3-chlorophenyl)-2-fluoroethyl]amino]-7-methoxy-1,3-benzoxazol-5-yl]-[(5R)-2-(2-hydroxyethyl)-2,5-dimethylmorpholin-4-yl]methanone	IC50	0.01 nM	US-9493472: Substituted benzoxazoles
3-chloro-N-{4-chloro-2-[(5-chloropyridin-2-yl)carbamoyl]-6-methoxyphenyl}-4-{[4,5-dihydro-1,3-oxazol-2-yl(ethyl)amino]methyl}thiophene-2-carboxamide	KI	0.012 nM
3-chloro-N-{4-chloro-2-[(5-chloropyridin-2-yl)carbamoyl]-6-methoxyphenyl}-4-{[5,6-dihydro-4H-1,3-oxazin-2-yl(methyl)amino]methyl}thiophene-2-carboxamide	KI	0.012 nM
(2S)-N-[(2S)-1-(1,3-benzothiazol-2-yl)-5-carbamimidamido-1-oxopentan-2-yl]-1-[(2R)-2-cyclohexyl-2-(methylamino)acetyl]pyrrolidine-2-carboxamide	KI	0.018 nM
3-chloro-N-{4-chloro-2-[(5-chloropyridin-2-yl)carbamoyl]-6-methoxyphenyl}-4-({methyl[2-(pyrrolidin-1-yl)ethyl]amino}methyl)thiophene-2-carboxamide	KI	0.019 nM
3-chloro-N-{4-chloro-2-[(5-chloropyridin-2-yl)carbamoyl]-6-methoxyphenyl}-4-{[(ethylcarbamoyl)(methyl)amino]methyl}thiophene-2-carboxamide	KI	0.02 nM
3-chloro-N-{4-chloro-2-[(5-chloropyridin-2-yl)carbamoyl]-6-methoxyphenyl}-4-{[1H-imidazol-2-yl(methyl)amino]methyl}thiophene-2-carboxamide	KI	0.02 nM
3-[({[4-chloro-5-({4-chloro-2-[(5-chloropyridin-2-yl)carbamoyl]-6-methoxyphenyl}carbamoyl)thiophen-3-yl]methyl}(methyl)carbamoyl)amino]propanoic acid	KI	0.022 nM
3-chloro-N-{4-chloro-2-[(5-chloropyridin-2-yl)carbamoyl]-6-methoxyphenyl}-4-(1H-imidazol-1-ylmethyl)thiophene-2-carboxamide	KI	0.022 nM
3-chloro-N-{4-chloro-2-[(5-chloropyridin-2-yl)carbamoyl]-6-methoxyphenyl}-4-({3-(dimethylamino)propylamino}methyl)thiophene-2-carboxamide	KI	0.024 nM
3-chloro-N-{4-chloro-2-[(5-chloropyridin-2-yl)carbamoyl]-6-methoxyphenyl}-4-{[4,5-dihydro-1,3-thiazol-2-yl(methyl)amino]methyl}thiophene-2-carboxamide	KI	0.024 nM
4-{[carbamoyl(methyl)amino]methyl}-3-chloro-N-{4-chloro-2-[(5-chloropyridin-2-yl)carbamoyl]-6-methoxyphenyl}thiophene-2-carboxamide	KI	0.026 nM
3-chloro-N-{4-chloro-2-[(5-chloropyridin-2-yl)carbamoyl]-6-methoxyphenyl}-4-{[methyl(4-oxo-4,5-dihydro-1,3-oxazol-2-yl)amino]methyl}thiophene-2-carboxamide	KI	0.026 nM
3-chloro-N-{4-chloro-2-[(5-chloropyridin-2-yl)carbamoyl]-6-methoxyphenyl}-4-{[ethyl(4-methyl-4,5-dihydro-1,3-oxazol-2-yl)amino]methyl}thiophene-2-carboxamide	KI	0.031 nM
3-chloro-N-{4-chloro-2-[(5-chloropyridin-2-yl)carbamoyl]-6-methoxyphenyl}-4-[(2-imino-4-oxoimidazolidin-1-yl)methyl]thiophene-2-carboxamide	KI	0.034 nM
3-chloro-N-{4-chloro-2-[(5-chloropyridin-2-yl)carbamoyl]-6-methoxyphenyl}-4-{[methyl({[2-(pyrrolidin-1-yl)ethyl]carbamoyl})amino]methyl}thiophene-2-carboxamide	KI	0.036 nM
3-chloro-N-{4-chloro-2-[(5-chloropyridin-2-yl)carbamoyl]-6-methoxyphenyl}-4-{[methane(methyl)sulfonamido]methyl}thiophene-2-carboxamide	KI	0.045 nM
3-chloro-N-{4-chloro-2-[(5-chloropyridin-2-yl)carbamoyl]-6-methoxyphenyl}-4-({(2-hydroxyethyl)carbamoylamino}methyl)thiophene-2-carboxamide	KI	0.05 nM
3-chloro-N-{4-chloro-2-[(5-chloropyridin-2-yl)carbamoyl]-6-methoxyphenyl}-4-{[methyl(1,3-oxazol-2-yl)amino]methyl}thiophene-2-carboxamide	KI	0.059 nM
6-[4-(2-{[(3R)-3-hydroxypyrrolidin-1-yl]methyl}phenyl)phenyl]-1-(4-methoxyphenyl)-7-oxo-1H,4H,5H,6H,7H-pyrazolo[3,4-c]pyridine-3-carboxamide	KI	0.07 nM
1-(4-methoxyphenyl)-7-oxo-6-[4-(2-oxopiperidin-1-yl)phenyl]-1H,4H,5H,6H,7H-pyrazolo[3,4-c]pyridine-3-carboxamide	KI	0.075 nM
Razaxaban Analogue	KI	0.1 nM
[2-[[1-(3-chlorophenyl)-2-fluoroethyl]amino]-7-methoxy-1,3-benzoxazol-5-yl]-[(5R)-2-(2-hydroxypropyl)-2,5-dimethylmorpholin-4-yl]methanone	IC50	0.1 nM	US-9493472: Substituted benzoxazoles
benzamidine- based compound, 6	KI	0.1 nM
(2S)-N-[1-(1,3-benzothiazol-2-yl)-5-carbamimidamido-1-oxopentan-2-yl]-1-[(2R)-3-(4-fluorophenyl)-2-(methylamino)propanoyl]pyrrolidine-2-carboxamide	KI	0.12 nM
4-{[tert-butyl(4,5-dihydro-1,3-oxazol-2-yl)amino]methyl}-3-chloro-N-{4-chloro-2-[(5-chloropyridin-2-yl)carbamoyl]-6-methoxyphenyl}thiophene-2-carboxamide	KI	0.12 nM
3-chloro-N-{4-chloro-2-[(5-chloropyridin-2-yl)carbamoyl]-6-methoxyphenyl}-4-{[methyl(5-methyl-4,5-dihydro-1,3-oxazol-2-yl)amino]methyl}thiophene-2-carboxamide	KI	0.12 nM
(2S)-N-[5-carbamimidamido-1-(6-methoxy-1,3-benzothiazol-2-yl)-1-oxopentan-2-yl]-1-[(2R)-2-(methylamino)-3-phenylpropanoyl]pyrrolidine-2-carboxamide	KI	0.14 nM
(2S)-N-[5-carbamimidamido-1-(6-fluoro-1,3-benzothiazol-2-yl)-1-oxopentan-2-yl]-1-[(2R)-2-(methylamino)-3-phenylpropanoyl]pyrrolidine-2-carboxamide	KI	0.15 nM
1-(3-amino-1,2-benzoxazol-5-yl)-N-[2-fluoro-4-(2-sulfamoylphenyl)phenyl]-3-(trifluoromethyl)-1H-pyrazole-5-carboxamide; 2,2,2-trifluoroacetic acid	KI	0.16 nM
3-chloro-N-{4-chloro-2-[(5-chloropyridin-2-yl)carbamoyl]-6-methoxyphenyl}-4-[(4-methylpiperazin-1-yl)methyl]thiophene-2-carboxamide	KI	0.16 nM
[2-[[(1S)-1-(3-chlorophenyl)-2-fluoroethyl]amino]-7-methoxy-1,3-benzoxazol-5-yl]-[(4R)-4-ethoxy-2-(hydroxymethyl)pyrrolidin-1-yl]methanone	IC50	0.16 nM	US-9493472: Substituted benzoxazoles
Razaxaban Analogue	KI	0.17 nM
6-[4-(2-{[(3R)-3-hydroxypyrrolidin-1-yl]methyl}phenyl)phenyl]-1-(4-methoxyphenyl)-3-(trifluoromethyl)-1H,4H,5H,6H,7H-pyrazolo[3,4-c]pyridin-7-one	KI	0.18 nM

ChEMBL bioactivities

5614 potent at pChembl≥5 of 6100 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
11.00	IC50	0.01	nM	CHEMBL4108739
11.00	Ki	0.01	nM	CHEMBL121212
11.00	Ki	0.01	nM	CHEMBL120079
10.96	Ki	0.011	nM	CHEMBL285285
10.89	Ki	0.013	nM	CHEMBL323583
10.89	Ki	0.013	nM	CHEMBL330949
10.82	Ki	0.015	nM	CHEMBL1159688
10.82	Ki	0.015	nM	CHEMBL1682691
10.82	Ki	0.015	nM	CHEMBL124300
10.82	Ki	0.015	nM	CHEMBL119877
10.82	Ki	0.015	nM	CHEMBL420540
10.77	Ki	0.017	nM	CHEMBL331571
10.74	Ki	0.018	nM	CHEMBL103874
10.74	Ki	0.018	nM	CHEMBL353760
10.74	Ki	0.018	nM	CHEMBL285285
10.72	Ki	0.019	nM	CHEMBL291026
10.70	Ki	0.02	nM	CHEMBL7860
10.70	Ki	0.02	nM	CHEMBL2419745
10.70	Ki	0.02	nM	CHEMBL92615
10.70	Ki	0.02	nM	CHEMBL120308
10.70	Ki	0.02	nM	CHEMBL122410
10.64	Ki	0.023	nM	CHEMBL36012
10.62	Ki	0.024	nM	CHEMBL290577
10.57	Ki	0.027	nM	CHEMBL287918
10.55	Ki	0.028	nM	CHEMBL3349045
10.55	Ki	0.028	nM	CHEMBL291261
10.52	IC50	0.03	nM	EFEGATRAN
10.52	Ki	0.03	nM	CHEMBL120187
10.48	Ki	0.033	nM	CHEMBL103342
10.47	Ki	0.034	nM	CHEMBL291261
10.46	Ki	0.035	nM	CHEMBL415375
10.46	Ki	0.035	nM	CHEMBL306797
10.44	Ki	0.036	nM	CHEMBL1159692
10.44	Ki	0.036	nM	CHEMBL1159694
10.40	Ki	0.04	nM	CHEMBL607008
10.40	Ki	0.04	nM	CHEMBL195366
10.40	Ki	0.04	nM	CHEMBL426101
10.40	Ki	0.04	nM	CHEMBL198820
10.40	Ki	0.04	nM	CHEMBL296737
10.40	Ki	0.04	nM	CHEMBL290376
10.39	Ki	0.041	nM	CHEMBL290376
10.39	Kd	0.041	nM	CHEMBL290376
10.38	Ki	0.042	nM	CHEMBL290376
10.38	IC50	0.042	nM	CHEMBL143418
10.38	Ki	0.042	nM	CHEMBL191441
10.38	Ki	0.042	nM	CHEMBL143418
10.38	Ki	0.042	nM	CHEMBL287918
10.36	Ki	0.044	nM	CHEMBL1159690
10.35	Ki	0.045	nM	CHEMBL9582
10.35	Ki	0.045	nM	CHEMBL1159689

PubChem BioAssay actives

2677 with measured affinity, of 6100 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-(aminomethyl)-5-chlorophenyl]methyl]-2-[6-(2,2-difluoro-2-pyridin-2-ylethyl)imino-1-hydroxy-2-pyridinyl]acetamide	238307: Binding affinity against thrombin in human plasma	ki	<0.0001	uM
N-[[5-chloro-2-(tetrazol-1-yl)phenyl]methyl]-2-[3-cyano-6-(2,2-difluoro-2-pyridin-2-ylethyl)imino-1-hydroxy-2-pyridinyl]acetamide	238307: Binding affinity against thrombin in human plasma	ki	<0.0001	uM
N-[[2-(aminomethyl)-5-chlorophenyl]methyl]-2-[3-cyano-6-(2,2-difluoro-2-pyridin-2-ylethyl)imino-1-hydroxy-2-pyridinyl]acetamide	238307: Binding affinity against thrombin in human plasma	ki	<0.0001	uM
N-[[2-(aminomethyl)-5-chlorophenyl]methyl]-2-[3-(benzylsulfonylamino)-6-methyl-2-oxo-1-pyridinyl]acetamide	211602: Inhibitory constant evaluated against thrombin (Factor IIa)	ki	<0.0001	uM
methyl N-[(2R)-1-[(2S)-2-[(6-carbamimidoyl-3-pyridinyl)methylcarbamoyl]pyrrolidin-1-yl]-1-oxo-3,3-diphenylpropan-2-yl]carbamate	211044: In vitro inhibition constant (Ki) against human thrombin	ki	<0.0001	uM
2-[6-chloro-3-[(2,2-difluoro-2-pyridin-2-ylethyl)amino]-2-oxopyrazin-1-yl]-N-[[5-chloro-2-(tetrazol-1-yl)phenyl]methyl]acetamide	1381627: Binding affinity to thrombin (unknown origin)	ki	<0.0001	uM
(2S)-N-[(4-carbamimidoylphenyl)methyl]-1-[(2R)-2-(methanesulfonamido)-3,3-diphenylpropanoyl]pyrrolidine-2-carboxamide	211022: Binding affinity against human thrombin	ki	<0.0001	uM
methyl N-[(2R)-1-[(2S)-2-[(4-carbamimidoylphenyl)methylcarbamoyl]pyrrolidin-1-yl]-1-oxo-3,3-diphenylpropan-2-yl]carbamate	211044: In vitro inhibition constant (Ki) against human thrombin	ki	<0.0001	uM
2-[3-(benzylsulfonylamino)-6-methyl-2-oxo-1-pyridinyl]-N-[[5-chloro-2-(tetrazol-1-yl)phenyl]methyl]acetamide	211217: Inhibitory potency against human thrombin	ki	<0.0001	uM
2-[6-chloro-3-[(2,2-difluoro-2-pyridin-2-ylethyl)amino]-2-oxopyrazin-1-yl]-N-[[5-chloro-2-(1,2,4-triazol-1-yl)phenyl]methyl]acetamide	1381627: Binding affinity to thrombin (unknown origin)	ki	<0.0001	uM
(2S)-N-[(4-carbamimidoyl-3-fluorophenyl)methyl]-1-[(2R)-3,3-diphenyl-2-(sulfamoylamino)propanoyl]pyrrolidine-2-carboxamide	211044: In vitro inhibition constant (Ki) against human thrombin	ki	<0.0001	uM
N-[[5-chloro-2-(tetrazol-1-yl)phenyl]methyl]-2-[3-[[2,2-difluoro-2-(1-oxidopyridin-1-ium-2-yl)ethyl]amino]-2-oxopyrazin-1-yl]acetamide	211217: Inhibitory potency against human thrombin	ki	<0.0001	uM
2-[[(2R)-1-[(2S)-2-[(4-carbamimidoylphenyl)methylcarbamoyl]pyrrolidin-1-yl]-1-oxo-3,3-diphenylpropan-2-yl]amino]acetic acid	211044: In vitro inhibition constant (Ki) against human thrombin	ki	<0.0001	uM
N-[[5-chloro-2-(tetrazol-1-yl)phenyl]methyl]-2-[3-[(2,2-difluoro-2-pyridin-2-ylethyl)amino]-2-oxopyrazin-1-yl]acetamide	211217: Inhibitory potency against human thrombin	ki	<0.0001	uM
N-[[2-(aminomethyl)-5-chlorophenyl]methyl]-2-[6-chloro-3-[[2,2-difluoro-2-(1-oxidopyridin-1-ium-2-yl)ethyl]amino]-2-oxopyrazin-1-yl]acetamide	211602: Inhibitory constant evaluated against thrombin (Factor IIa)	ki	<0.0001	uM
(2S)-N-[(6-carbamimidoyl-3-pyridinyl)methyl]-1-[(2R)-3,3-diphenyl-2-(sulfamoylamino)propanoyl]pyrrolidine-2-carboxamide	211044: In vitro inhibition constant (Ki) against human thrombin	ki	<0.0001	uM
(2S)-N-[(4-carbamimidoyl-2-fluorophenyl)methyl]-1-[(2R)-3,3-diphenyl-2-(sulfamoylamino)propanoyl]pyrrolidine-2-carboxamide	211044: In vitro inhibition constant (Ki) against human thrombin	ki	<0.0001	uM
2-[[5-chloro-2-(1,2,4-triazol-1-yl)phenyl]methyl]-N-(2,2-difluoro-2-pyridin-2-ylethyl)-6-methyl-[1,3]oxazolo[4,5-c]pyridin-4-amine	254280: Inhibitory constant against thrombin	ki	<0.0001	uM
methyl N-[(2R)-1-[(2S)-2-[(5-carbamimidoylthiophen-2-yl)methylcarbamoyl]pyrrolidin-1-yl]-1-oxo-3,3-diphenylpropan-2-yl]carbamate	211044: In vitro inhibition constant (Ki) against human thrombin	ki	<0.0001	uM
(2S)-N-[(4-carbamimidoylthiophen-2-yl)methyl]-1-[(2R)-3,3-diphenyl-2-(sulfamoylamino)propanoyl]pyrrolidine-2-carboxamide	211044: In vitro inhibition constant (Ki) against human thrombin	ki	<0.0001	uM
(2S)-N-[(5-carbamimidoylthiophen-2-yl)methyl]-1-[(2R)-2-(methanesulfonamido)-3,3-diphenylpropanoyl]pyrrolidine-2-carboxamide	211022: Binding affinity against human thrombin	ki	<0.0001	uM
(2S)-N-[(5-carbamimidoylfuran-3-yl)methyl]-1-[(2R)-3,3-diphenyl-2-(sulfamoylamino)propanoyl]pyrrolidine-2-carboxamide	211044: In vitro inhibition constant (Ki) against human thrombin	ki	<0.0001	uM
3-[[(2R)-1-[(2S)-2-[(5-carbamimidoylthiophen-2-yl)methylcarbamoyl]pyrrolidin-1-yl]-1-oxo-3,3-diphenylpropan-2-yl]amino]propanoic acid	211044: In vitro inhibition constant (Ki) against human thrombin	ki	<0.0001	uM
2-[6-chloro-3-[[2,2-difluoro-2-(1-oxidopyridin-1-ium-2-yl)ethyl]amino]-2-oxopyrazin-1-yl]-N-[[5-chloro-2-(1,2,4-triazol-1-yl)phenyl]methyl]acetamide	1381627: Binding affinity to thrombin (unknown origin)	ki	<0.0001	uM
(2S)-N-[(2S)-1-(1,3-benzothiazol-2-yl)-5-(diaminomethylideneamino)-1-oxopentan-2-yl]-1-[(2R)-3-cyclohexyl-2-(methylamino)propanoyl]pyrrolidine-2-carboxamide	210994: Binding affinity to human thrombin	ki	<0.0001	uM
(2S)-N-[[2-(aminomethyl)-5-chlorophenyl]methyl]-1-(7-chloro-5-hydroxyindeno[1,2-b]pyridine-5-carbonyl)pyrrolidine-2-carboxamide	238219: Inhibition of coagulation factor II (thrombin) of human	ki	<0.0001	uM
(2S)-N-[(2S)-1-(1,3-benzothiazol-2-yl)-5-(diaminomethylideneamino)-1-oxopentan-2-yl]-1-[(2R)-2-cyclohexyl-2-(methylamino)acetyl]pyrrolidine-2-carboxamide	1797150: Enzyme Inhibition Assay from Article 10.1021/jm0303857: “In-depth study of tripeptide-based alpha-ketoheterocycles as inhibitors of thrombin. Effective utilization of the S1’ subsite and its implications to structure-based drug design.”	ki	<0.0001	uM
(2S)-N-[(2S)-1-(1,3-benzothiazol-2-yl)-5-(diaminomethylideneamino)-1-oxopentan-2-yl]-1-[(2R)-2-(methylamino)-3,3-diphenylpropanoyl]pyrrolidine-2-carboxamide	1797150: Enzyme Inhibition Assay from Article 10.1021/jm0303857: “In-depth study of tripeptide-based alpha-ketoheterocycles as inhibitors of thrombin. Effective utilization of the S1’ subsite and its implications to structure-based drug design.”	ki	<0.0001	uM
N-[[2-(aminomethyl)-5-chlorophenyl]methyl]-2-[3-chloro-6-(2,2-difluoro-2-pyridin-2-ylethyl)imino-1-hydroxy-2-pyridinyl]acetamide	238307: Binding affinity against thrombin in human plasma	ki	<0.0001	uM
N-[(6-amino-2-methyl-3-pyridinyl)methyl]-2-[3-[(2,2-difluoro-2-pyridin-2-ylethyl)amino]-6-methyl-2-oxopyrazin-1-yl]acetamide	1254752: Inhibition of Thrombin (unknown origin)	ki	<0.0001	uM
benzyl N-[(2R)-1-[(2S)-2-[[(1S)-4-methoxy-1-[(2S,6R)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.02,6]decan-4-yl]butyl]carbamoyl]pyrrolidin-1-yl]-1-oxo-3-phenylpropan-2-yl]carbamate	210857: Binding affinity against alpha thrombin	ki	<0.0001	uM
(2S)-N-[(2S)-5-(diaminomethylideneamino)-1-oxopentan-2-yl]-1-[(2R)-2-(methylamino)-3-phenylpropanoyl]pyrrolidine-2-carboxamide	210656: Concentration required to inhibit thrombin was determined	ic50	<0.0001	uM
[(1R)-1-[[(2S)-1-[(2R)-2-acetamido-3-phenylpropanoyl]pyrrolidine-2-carbonyl]amino]-4-(diaminomethylideneamino)butyl]boronic acid	211182: Inhibition constant for binding with thrombin was determined	ki	<0.0001	uM
(20S)-20-benzyl-8,25-dichloro-18-methyl-12-oxa-1,4,18,21,23-pentazatricyclo[20.3.1.06,11]hexacosa-6(11),7,9,22,24-pentaene-3,26-dione	211202: Inhibitory activity against thrombin IIa	ki	<0.0001	uM
2-[2-[[2-(aminomethyl)phenyl]methylamino]-2-hydroxyethyl]-6-[(2,2-difluoro-2-pyridin-2-ylethyl)amino]-1-oxidopyridin-1-ium-3-carbonitrile	238307: Binding affinity against thrombin in human plasma	ki	<0.0001	uM
2-[5-(diaminomethylideneamino)-2-[[(2S)-1-[(2R)-2-(methylamino)-3-phenylpropanoyl]pyrrolidine-2-carbonyl]amino]pentanoyl]-1,3-benzothiazole-6-carboxamide	1797150: Enzyme Inhibition Assay from Article 10.1021/jm0303857: “In-depth study of tripeptide-based alpha-ketoheterocycles as inhibitors of thrombin. Effective utilization of the S1’ subsite and its implications to structure-based drug design.”	ki	<0.0001	uM
(2S)-N-[(4-carbamimidoylphenyl)methyl]-1-[(2R)-3-cyclohexyl-2-(methanesulfonamido)propanoyl]pyrrolidine-2-carboxamide	211022: Binding affinity against human thrombin	ki	<0.0001	uM
ethyl 2-[2-[2-[[2-[[5-chloro-2-(1,2,4-triazol-1-yl)phenyl]methyl]-[1,3]oxazolo[4,5-c]pyridin-4-yl]amino]ethyl]piperidin-1-yl]acetate	254280: Inhibitory constant against thrombin	ki	0.0001	uM
2-[3-chloro-6-(2,2-difluoro-2-pyridin-2-ylethyl)imino-1-hydroxy-2-pyridinyl]-N-[[5-chloro-2-(1,2,4-triazol-1-yl)phenyl]methyl]acetamide	238307: Binding affinity against thrombin in human plasma	ki	0.0001	uM
N-[(5-carbamimidoylthiophen-2-yl)methyl]-2-[6-methyl-2-oxo-3-(2-phenylethylamino)pyrazin-1-yl]acetamide	211179: In vitro inhibitory constant against human thrombin (FIIa).	ki	0.0001	uM
2-[6-chloro-3-[(2,2-difluoro-2-pyridin-2-ylethyl)amino]-2-oxopyrazin-1-yl]-N-[[2-(tetrazol-1-yl)phenyl]methyl]acetamide	211217: Inhibitory potency against human thrombin	ki	0.0001	uM
2-[3-(benzylsulfonylamino)-6-methyl-2-oxo-1-pyridinyl]-N-[(5-carbamimidoylthiophen-2-yl)methyl]acetamide	211179: In vitro inhibitory constant against human thrombin (FIIa).	ki	0.0001	uM
N-[[5-chloro-2-(1,2,4-triazol-1-yl)phenyl]methyl]-2-[3-[[2,2-difluoro-2-(1-oxidopyridin-1-ium-2-yl)ethyl]amino]-2-oxopyrazin-1-yl]acetamide	211217: Inhibitory potency against human thrombin	ki	0.0001	uM
2-[6-chloro-3-[(2,2-difluoro-2-pyridin-2-ylethyl)amino]-2-oxopyrazin-1-yl]-N-[[3-(tetrazol-1-yl)-2-pyridinyl]methyl]acetamide	211217: Inhibitory potency against human thrombin	ki	0.0001	uM
N-[[5-chloro-2-(tetrazol-1-yl)phenyl]methyl]-2-[6-(2,2-difluoro-2-pyridin-2-ylethyl)imino-1-hydroxy-2-pyridinyl]acetamide	238307: Binding affinity against thrombin in human plasma	ki	0.0001	uM
(2S)-N-[(1S)-1-(4-aminocyclohexyl)-3-(methylamino)-2,3-dioxopropyl]-1-[(2R)-2-(methylamino)-3-phenylpropanoyl]pyrrolidine-2-carboxamide	211572: Binding affinity towards thrombin	ki	0.0001	uM
N-[2-(1-benzylpiperidin-2-yl)ethyl]-2-[[5-chloro-2-(1,2,4-triazol-1-yl)phenyl]methyl]-[1,3]oxazolo[4,5-c]pyridin-4-amine	254280: Inhibitory constant against thrombin	ki	0.0001	uM
(2S)-N-[(4-aminocyclohexyl)methyl]-1-[(2R)-2-amino-3,3-dicyclohexylpropanoyl]pyrrolidine-2-carboxamide	211186: Inhibitory activity against human thrombin	ki	0.0001	uM
2-[[5-chloro-2-(1,2,4-triazol-1-yl)phenyl]methyl]-N-(2,2-difluoro-2-piperidin-2-ylethyl)-[1,3]oxazolo[4,5-c]pyridin-4-amine	254280: Inhibitory constant against thrombin	ki	0.0001	uM
N-[[2-(2-aminoethyl)-5-chlorophenyl]methyl]-2-[3-(benzylsulfonylamino)-6-methyl-2-oxo-1-pyridinyl]acetamide	211602: Inhibitory constant evaluated against thrombin (Factor IIa)	ki	0.0001	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bivalirudin	affects binding, decreases activity, decreases reaction, increases expression, increases cleavage	10
Heparin	increases cleavage, affects binding, affects localization, increases abundance, increases reaction (+5 more)	7
ximelagatran	decreases cleavage, affects binding, decreases activity	4
Ethinyl Estradiol	increases expression, decreases activity, decreases expression, affects cotreatment	4
argatroban	affects binding, decreases activity	3
Gestodene	affects cotreatment, decreases activity, decreases expression, increases expression	3
ML 7	decreases reaction, increases phosphorylation, decreases activity, affects activity	3
Adenosine Triphosphate	decreases reaction, increases secretion, affects reaction, increases abundance, affects cotreatment	3
Calcium	decreases reaction, increases localization, increases abundance, increases uptake	3
Quercetin	increases expression, increases localization, decreases reaction, increases abundance	3
Cyclosporine	decreases expression	3
bisphenol A	affects expression, affects cotreatment, decreases methylation	2
N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide	decreases reaction, increases abundance, decreases activity	2
lepirudin	affects binding, decreases activity	2
Y 27632	decreases reaction, increases phosphorylation, decreases activity	2
Resveratrol	decreases reaction, increases abundance, increases expression, increases phosphorylation	2
Benzo(a)pyrene	decreases expression, increases methylation	2
Contraceptives, Oral	increases activity, increases expression	2
Dexamethasone	affects expression, increases expression, increases reaction	2
Diethylhexyl Phthalate	affects cotreatment, increases expression, decreases expression, decreases reaction	2
Doxorubicin	increases cleavage, affects reaction, affects expression	2
Nickel	affects binding, decreases reaction, increases uptake	2
Nitric Oxide	increases abundance, increases reaction, decreases reaction	2
Thromboxane B2	increases abundance, increases chemical synthesis, decreases reaction	2
Warfarin	affects response to substance, decreases expression, increases reaction	2
Medroxyprogesterone Acetate	increases expression, increases reaction	2
Simvastatin	decreases reaction, affects localization, affects reaction, decreases expression, decreases activity	2
aristolochic acid I	increases expression	1
Asian ginseng	affects cotreatment, increases expression, decreases expression, decreases reaction	1
ginger extract	decreases expression, increases abundance	1

ChEMBL screening assays

1269 unique, capped per target: 1216 binding, 38 functional, 13 admet, 2 toxicity

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1000101	Binding	Inhibition of thrombin by spectrophotometric assay	Dysinosins B-D, inhibitors of factor VIIa and thrombin from the Australian sponge Lamellodysidea chlorea. — J Nat Prod
CHEMBL1614423	Functional	PUBCHEM_BIOASSAY: Thrombin 1536 HTS Dose Response Confirmation. (Class of assay: confirmatory) [Related pubchem assays: 1046 (Thrombin 1536 HTS; hits were confirmed in this assay)]	PubChem BioAssay data set
CHEMBL4016670	ADMET	Drug metabolism in human serum assessed as thrombin-mediated 2-thienylacetyl-Trp1-(alpha-Me)Trp2-Arg3-Pro4-Arg5-OH metabolite formation at 1 mM after 120 mins by RP-HPLC analysis	Discovery of a Human Neuromedin U Receptor 1-Selective Hexapeptide Agonist with Enhanced Serum Stability. — J Med Chem

Cellosaurus cell lines

2 cell lines: 2 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_4W10	GM16028	Transformed cell line	Female
CVCL_W239	GM16000	Transformed cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00077753	PHASE4	COMPLETED	EXCLAIM:Extended Prophylaxis for Venous ThromboEmbolism (VTE) in Acutely Ill Medical Patients With Prolonged Immobilization
NCT00196118	PHASE4	COMPLETED	Study of IVC Filter Retrieval With the Günther Tulip Vena Cava Filter
NCT00437697	PHASE4	TERMINATED	Thromboprophylaxis in Critically Ill Patients
NCT00445328	PHASE4	TERMINATED	Dalteparin vs Unfractionated Heparin For The Prevention Of Venous Thromboembolism (VTE) In Hospitalized Acutely Ill Medical Patients
NCT00689520	PHASE4	COMPLETED	Long-Term Low-Molecular-Weight Heparin Versus Oral Anticoagulants in Deep Venous Thrombosis
NCT00851864	PHASE4	COMPLETED	Safety and Efficacy of Therapeutic Anticoagulation With Tinzaparin During Pregnancy Via Weight-based Dosing
NCT00966277	PHASE4	COMPLETED	Dalteparin for Primary Venous Thromboembolism (VTE) Prophylaxis in Pancreatic Cancer Patients
NCT00967304	PHASE4	COMPLETED	Clinical Decision Rule Validation Study to Predict Low Recurrent Risk in Patients With Unprovoked Venous Thromboembolism
NCT01119261	PHASE4	COMPLETED	EUropean Pharmacogenetics of AntiCoagulant Therapy - Acenocoumarol
NCT01119274	PHASE4	COMPLETED	EUropean Pharmacogenetics of AntiCoagulant Therapy - Phenprocoumon
NCT01119300	PHASE4	COMPLETED	EUropean Pharmacogenetics of AntiCoagulant Therapy - Warfarin
NCT01210755	PHASE4	COMPLETED	Study in Healthy Volunteers of the Reversion by Haemostatic Drugs of the Anticoagulant Effect of New Anti-thrombotics
NCT01304108	PHASE4	COMPLETED	Improving Venous Thromboembolism Prophylaxis
NCT01467583	PHASE4	COMPLETED	Fondaparinux in Critically Ill Patients With Renal Failure
NCT01916707	PHASE4	UNKNOWN	Weight Based Enoxaparin in Trauma Patients
NCT02095509	PHASE4	COMPLETED	Pharmacokinetics of Enoxaparin in Intensive Care Patients
NCT02396732	PHASE4	TERMINATED	Aspirin and Enoxaparin for VTE in Trauma
NCT02412982	PHASE4	COMPLETED	Evaluation of Venous Thromboembolism Prevention in High-Risk Trauma Patients
NCT02464969	PHASE4	COMPLETED	Apixaban for the Acute Treatment of Venous Thromboembolism in Children
NCT02474212	PHASE4	COMPLETED	: Pharmacokinetics of Enoxaparin After Coronary Artery Bypass Graft Surgery
NCT02559856	PHASE4	COMPLETED	Comparison of Bleeding Risk Between Rivaroxaban and Apixaban: The Pilot Study
NCT02856295	PHASE4	COMPLETED	anti10a Levels in Women Treated With LMWH in the Postpartum Period
NCT02945280	PHASE4	TERMINATED	Apixaban for Routine Management of Upper Extremity Deep Venous Thrombosis
NCT02958969	PHASE4	COMPLETED	Apixaban for Primary Prevention of Venous Thromboembolism in Patients With Multiple Myeloma
NCT03006562	PHASE4	TERMINATED	PREvention of VENous ThromboEmbolism Following Radical Prostatectomy
NCT03158792	PHASE4	COMPLETED	Enoxaparin 20mg Versus 30mg Subcutaneously Once Daily in Elderly Patients With Impaired Renal Function
NCT03196349	PHASE4	TERMINATED	Comparison of Oral Anticoagulants for Extended VEnous Thromboembolism
NCT03244020	PHASE4	ENROLLING_BY_INVITATION	LMWH vs Aspirin for VTE Prophylaxis in Orthopaedic Oncology
NCT03266783	PHASE4	COMPLETED	Comparison of Bleeding Risk Between Rivaroxaban and Apixaban for the Treatment of Acute Venous Thromboembolism
NCT03426982	PHASE4	UNKNOWN	Comparision Between Activated Partial Thromboplastin Time Versus Anti-Xa Activity in Heparin Monitoring
NCT03678506	PHASE4	TERMINATED	Apixaban for Extended Anticoagulation (APIDULCIS)
NCT03988101	PHASE4	COMPLETED	Role of Statin in Venous Dysfunction in Patients With Venous Thromboembolism Event
NCT03988231	PHASE4	WITHDRAWN	Enoxaparin Versus Placebo for Venous Thromboembolism Prevention in Low Risk Cancer Patients After Surgical Procedures: a Randomized, Double Blind, Placebo Controlled Clinical Trial Pilot Study
NCT04128254	PHASE4	UNKNOWN	A Prospective Study in Chinese Patients With Lower Extremity Ankle Fracture of Oral Anticoagulants to Prevent Venous Thromboembolism (VTE)
NCT04157881	PHASE4	COMPLETED	A Study on the Impact of Rabeprazole-induced Elevated Stomach pH on APO-Dabigatran Exposure in Healthy Volunteers
NCT04168203	PHASE4	COMPLETED	Extended-Duration Low-Intensity Apixaban to Prevent Recurrence in High-Risk Patients With Provoked Venous Thromboembolism
NCT04169269	PHASE4	UNKNOWN	Deep Vein Thrombosis Prophylaxis Adherence: Enoxaparin vs Rivaroxaban
NCT04263038	PHASE4	RECRUITING	Clinical Surveillance vs. Anticoagulation for Low-risk Patients With Isolated Subsegmental Pulmonary Embolism
NCT04352439	PHASE4	COMPLETED	Aspirin for Prevention of Venous Thromboembolism Among Ovarian Cancer Patients Receiving Neoadjuvant Chemotherapy
NCT04409834	PHASE4	COMPLETED	Prevention of Arteriovenous Thrombotic Events in Critically-Ill COVID-19 Patients Trial