F3

Summary

F3 (coagulation factor III, tissue factor, HGNC:3541) is a protein-coding gene on chromosome 1p21.3, encoding Tissue factor (P13726). Initiates blood coagulation by forming a complex with circulating factor VII or VIIa.

This gene encodes coagulation factor III which is a cell surface glycoprotein. This factor enables cells to initiate the blood coagulation cascades, and it functions as the high-affinity receptor for the coagulation factor VII. The resulting complex provides a catalytic event that is responsible for initiation of the coagulation protease cascades by specific limited proteolysis. Unlike the other cofactors of these protease cascades, which circulate as nonfunctional precursors, this factor is a potent initiator that is fully functional when expressed on cell surfaces, for example, on monocytes. There are 3 distinct domains of this factor: extracellular, transmembrane, and cytoplasmic. Platelets and monocytes have been shown to express this coagulation factor under procoagulatory and proinflammatory stimuli, and a major role in HIV-associated coagulopathy has been described. Platelet-dependent monocyte expression of coagulation factor III has been described to be associated with Coronavirus Disease 2019 (COVID-19) severity and mortality. This protein is the only one in the coagulation pathway for which a congenital deficiency has not been described. Alternate splicing results in multiple transcript variants.

Source: NCBI Gene 2152 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 53 total
• Druggable target: yes — 10 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001993

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3541
Approved symbol	F3
Name	coagulation factor III, tissue factor
Location	1p21.3
Locus type	gene with protein product
Status	Approved
Aliases	CD142, TF
Ensembl gene	ENSG00000117525
Ensembl biotype	protein_coding
OMIM	134390
Entrez	2152

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 4 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000334047, ENST00000370207, ENST00000478217, ENST00000480356, ENST00000949532, ENST00000949533

RefSeq mRNA: 2 — MANE Select: NM_001993 NM_001178096, NM_001993

CCDS: CCDS53345, CCDS750

Canonical transcript exons

ENST00000334047 — 6 exons

Exon	Start	End
ENSE00000777351	94533090	94533268
ENSE00000777352	94532321	94532480
ENSE00001452073	94541537	94541759
ENSE00001906129	94529173	94530596
ENSE00003564765	94540257	94540368
ENSE00003626552	94535965	94536164

Expression profiles

Bgee: expression breadth ubiquitous, 285 present calls, max score 99.69.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 73.3829 / max 3360.5072, expressed in 1464 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
13403	72.2898	1448
201586	0.3085	162
201585	0.1953	103
201583	0.1825	89
13401	0.1569	79
13402	0.1137	48
201584	0.0740	22
201582	0.0621	23

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mucosa of paranasal sinus	UBERON:0005030	99.69	gold quality
palpebral conjunctiva	UBERON:0001812	99.67	gold quality
nasal cavity epithelium	UBERON:0005384	99.63	gold quality
nasal cavity mucosa	UBERON:0001826	99.25	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	99.16	gold quality
peritoneum	UBERON:0002358	97.92	gold quality
omental fat pad	UBERON:0010414	97.92	gold quality
amniotic fluid	UBERON:0000173	97.90	gold quality
stromal cell of endometrium	CL:0002255	97.77	gold quality
left uterine tube	UBERON:0001303	97.72	gold quality
lower lobe of lung	UBERON:0008949	97.45	gold quality
adipose tissue of abdominal region	UBERON:0007808	97.43	gold quality
gall bladder	UBERON:0002110	97.40	gold quality
left ovary	UBERON:0002119	97.39	gold quality
decidua	UBERON:0002450	97.23	gold quality
trachea	UBERON:0003126	97.19	gold quality
buccal mucosa cell	CL:0002336	97.17	gold quality
epithelium of nasopharynx	UBERON:0001951	97.17	gold quality
right ovary	UBERON:0002118	97.13	gold quality
minor salivary gland	UBERON:0001830	97.12	gold quality
adenohypophysis	UBERON:0002196	97.11	gold quality
mouth mucosa	UBERON:0003729	96.85	gold quality
seminal vesicle	UBERON:0000998	96.61	gold quality
left lobe of thyroid gland	UBERON:0001120	96.59	gold quality
rectum	UBERON:0001052	96.44	gold quality
right lobe of thyroid gland	UBERON:0001119	96.23	gold quality
mucosa of stomach	UBERON:0001199	96.21	gold quality
caudate nucleus	UBERON:0001873	96.17	gold quality
pituitary gland	UBERON:0000007	96.12	gold quality
olfactory bulb	UBERON:0002264	96.08	gold quality

Single-cell (SCXA)

Detected in 17 experiment(s), a significant marker in 15.

Experiment	Marker?	Max mean expression
E-GEOD-98556	yes	2302.53
E-HCAD-11	yes	1981.94
E-MTAB-8410	yes	1971.83
E-MTAB-9906	yes	1001.62
E-MTAB-9154	yes	445.05
E-GEOD-84465	yes	380.89
E-MTAB-3929	yes	345.64
E-MTAB-6701	yes	61.84
E-GEOD-135922	yes	47.70
E-GEOD-134144	yes	43.02
E-MTAB-7316	yes	35.22
E-GEOD-137537	yes	31.42
E-CURD-46	yes	9.42
E-GEOD-130148	yes	8.58
E-ENAD-21	no	2809.79

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

89 targeting F3, 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-5011-5P	100.00	83.46	5820
HSA-MIR-5692A	100.00	74.40	6850
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-223-3P	99.99	70.14	1140
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-8075	99.97	67.20	962
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-17-5P	99.89	73.83	2665
HSA-MIR-106B-5P	99.88	74.72	2795
HSA-MIR-20A-5P	99.88	74.76	2769

Literature-anchored findings (GeneRIF, showing 40)

• The complex between tissue factor and factor VIIa initiates coagulation and intracellular signaling, alters gene expression, and promotes metastasis. (PMID:11583305)
• selective activation of NF-kappaB (p50/p65) during intensive physical exercise does not result in the expression (PMID:11744662)
• TF-FVIIa interaction elicits intracellular signalling events implicated in sepsis, inflammation, angiogenesis, metastasis and atherosclerosis. These include the sequential activation of Src-like kinases, MAP kinases, small GTPases and calcium signalling. (PMID:11776298)
• tissue factor/tissue factor pathway inhibitor imbalance is associated with myocardial infarction at young age in Japanese men. (PMID:11816707)
• TF promotes metastasis by a pathway that does not involve high expression of known PARs by tumor cells. PAR1 enhances the metastatic potential of cells with high TF expression. (PMID:11816709)
• Resveratrol does not inhibit the activation or translocation of NF-kappaB/Rel proteins but inhibits NF-kappaB/Rel-dependent transcription of the gene for TF by impairing the transactivation potential of p65. (PMID:11858183)
• Endothelin-1 enhances TF expression in monocytes from health individuals. No additional stimulation was seen in monocytes from heart failure subjects, who nonetheless have 2.5 times as much TF as controls. (PMID:11858185)
• In children with sepsis-induced multiple organ failure, a cytokine-associated increase in circulating TF and systemic activity was predicted. Increased TF was associated with the development of coagulopathy and tended to be associated with mortality. (PMID:11858480)
• pH dependence of fVIIa amidolytic activity in complex with soluble tissue factor (PMID:11876644)
• differentiation of human monocytes into macrophages in culture enhances their tissue factor expression. (PMID:11882315)
• results suggest involvement of tissue factor in the process of metastasis and progression of colorectal cancer may depend on increased angiogenesis (PMID:11921018)
• Coronary no-reflow is caused by shedding of active tissue factor from dissected atherosclerotic plaque. (PMID:11929768)
• TF-apoprotein selectively binds Hb, most probably via the carbohydrate moieties (alpha-d-glucosyl; alpha-d-mannosyl and N-acetyl-beta-d-glucosaminyl residues) of TF, and enhances its procoagulant activity. (PMID:11943929)
• signaling increased transcription as well as mRNA stabilization leading to up-regulation of interleukin-8 synthesis (PMID:11973337)
• Enhanced monocyte tissue factor expression is implicated in the hemostatic diathesis characterizing hepatosplenic schistosomiasis. (PMID:11994566)
• Fluvastatin upregulated IkappaB alpha in unstimulated as well as in TNFalpha-stimulated HUVEC cells and also impaired the TNFalpha-induced Cdc42 prenylation, indicating that fluvastatin interferes with transcriptional activation of tissue factor gene. (PMID:12008961)
• TF cytoplasmic domain-independent stimulation of protein synthesis via activation of S6 kinase contributes to FVIIa effects in pathophysiology. (PMID:12019261)
• expression of TF and TFPI in human melanoma (PMID:12028585)
• Tissue factor is the receptor for plasminogen type 1 on 1-LN human prostate cancer cells; Plasminogen type 2, containing only one O-linked oligosaccharide chain, did not bind to tissue factor on 1-LN human prostate cancer cells (PMID:12036889)
• Thrombin functions studied during tissue factor-induced blood coagulation (PMID:12070020)
• Tissue factor activity is upregulated in human endothelial cells exposed to oscillatory shear stress. (PMID:12083487)
• expression on monocyte subpopulations during normal pregnancy (PMID:12083501)
• monocyte adhesion and transmigration induce tissue factor expression (PMID:12095134)
• data indicate that endothelial cell surface expression of TF and extrinsic clotting factors are critical in augmenting capillary leak following intravascular tumor necrosis factor administration (PMID:12149215)
• tissue factor expression by LPS-stimulated human monocytes is inhibited by adenosine and involves the adenosine A3 receptor, specifically (PMID:12152652)
• a three-dimensional model of the ternary complex between FVIIa:TF:FIX was built using a full-space search algorithm in combination with computational graphics (PMID:12152682)
• REVIEW:clotting-dependent and -independent mechanisms of TF-induced angiogenesis in cancer (PMID:12172458)
• non-activated and activated platelets contain an inactive form of TF that may develop functional activity following its release (PMID:12189027)
• effect of platelet-derived CD40L on the tissue factor activity of human CD40-positive melanoma cells and monocytes (PMID:12192302)
• levels of tissue factor in placenta and myometrium, over tissue factor in blood plasma may be clinically significant in obstetrics, for instance, in the etiology of DIC in placental abruption (PMID:12270558)
• 15d-PGJ2 down-regulates LPS- and TNFalpha-induced TF activity through inhibition of TF gene transcription. (PMID:12353085)
• REVIEW: role of tissue factor-FVIIa complex in pathophysiological processes and effect of the inhibitors of the tissue factor:factor VII pathway (PMID:12356487)
• correlation between tissue factor (TF) expression and hepatic metastasis and prognosis in rectal cancer (PMID:12408769)
• Mice expressing low levels of human TF in an mTF(-/-) background had significantly shorter lifespans than wild-type mice, in part, because of spontaneous fatal hemorrhages. Low-TF mice had a selective heart defect with hemosiderin deposition & fibrosis. (PMID:12426405)
• Tissue factor initiates blood coagulation via circulating microvesicles and platelets. (PMID:12514112)
• the Gla and first epidermal growth factor-like domains of factor X play a role in the prothrombinase and tissue factor-factor VIIa complexes. (PMID:12529356)
• REVIEW: model of the intravascular TF pathway in which adhesive interactions of the TF bearing platelets and microvesicles to neutrophils and monocytes enable blood coagulation (PMID:12540946)
• The influence of several eicosanoids of the lipoxygenase pathway on regulation of LPS-induced tissue factor was examined in whole blood. (PMID:12544727)
• These data support a transcriptional role for both nuclear factor-kappaB and p38 mitogen-activated protein kinase, but not MEK1, in tissue factor gene expression in human dermal microvascular endothelial cells. (PMID:12603864)
• M type 1 and 3 strains of group A streptococci are potent inducers of TF synthesis; findings suggest that a novel interaction between group A streptococci and host cells contributes to the observed coagulopathy in Strep toxic shock syndrome (PMID:12654807)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	f3a	ENSDARG00000099124
mus_musculus	F3	ENSMUSG00000028128
rattus_norvegicus	F3	ENSRNOG00000011800

Paralogs (11): IL20RA (ENSG00000016402), IFNGR1 (ENSG00000027697), IL10RA (ENSG00000110324), IFNAR1 (ENSG00000142166), IL22RA1 (ENSG00000142677), IFNAR2 (ENSG00000159110), IFNGR2 (ENSG00000159128), IL22RA2 (ENSG00000164485), IL20RB (ENSG00000174564), IFNLR1 (ENSG00000185436), IL10RB (ENSG00000243646)

Protein

Protein identifiers

Tissue factor — P13726 (reviewed: P13726)

Alternative names: Coagulation factor III, Thromboplastin

All UniProt accessions (1): P13726

UniProt curated annotations — full annotation on UniProt →

Function. Initiates blood coagulation by forming a complex with circulating factor VII or VIIa. The [TF:VIIa] complex activates factors IX or X by specific limited proteolysis. TF plays a role in normal hemostasis by initiating the cell-surface assembly and propagation of the coagulation protease cascade.

Subunit / interactions. Interacts with HSPE; the interaction, inhibited by heparin, promotes the generation of activated factor X and activates coagulation in the presence of activated factor VII.

Subcellular location. Membrane Secreted.

Tissue specificity. Lung, placenta and pancreas.

Induction. TF expression is highly dependent upon cell type. TF can also be induced by the inflammatory mediators interleukin 1 and TNF, as well as by endotoxin, to appear on monocytes and vascular endothelial cells as a component of cellular immune response.

Similarity. Belongs to the tissue factor family.

Isoforms (2)

UniProt ID	Names	Canonical?
P13726-1	1, flTF	yes
P13726-2	2, asHTF

RefSeq proteins (2): NP_001171567, NP_001984* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001187	Tissue_factor	Family
IPR003961	FN3_dom	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR015373	Interferon/interleukin_rcp_dom	Domain
IPR030472	Tissue_Factor_CS	Conserved_site
IPR036116	FN3_sf	Homologous_superfamily
IPR050650

Pfam: PF01108, PF09294

UniProt features (49 total): strand 22, helix 6, sequence variant 4, short sequence motif 3, glycosylation site 2, disulfide bond 2, splice variant 2, topological domain 2, signal peptide 1, chain 1, sequence conflict 1, transmembrane region 1, turn 1, lipid moiety-binding region 1

Structure

Experimental structures (PDB)

54 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
6R2W	X-RAY DIFFRACTION	1.25
4YLQ	X-RAY DIFFRACTION	1.4
8QOD	X-RAY DIFFRACTION	1.57
2HFT	X-RAY DIFFRACTION	1.69
2C4F	X-RAY DIFFRACTION	1.72
3TH2	X-RAY DIFFRACTION	1.72
2A2Q	X-RAY DIFFRACTION	1.8
3TH4	X-RAY DIFFRACTION	1.8
4IBL	X-RAY DIFFRACTION	1.8
1JPS	X-RAY DIFFRACTION	1.85
2AER	X-RAY DIFFRACTION	1.87
8QQ6	X-RAY DIFFRACTION	1.87
2FLB	X-RAY DIFFRACTION	1.95
1DAN	X-RAY DIFFRACTION	2
1Z6J	X-RAY DIFFRACTION	2
2EC9	X-RAY DIFFRACTION	2
2FIR	X-RAY DIFFRACTION	2
1O5D	X-RAY DIFFRACTION	2.05
2PUQ	X-RAY DIFFRACTION	2.05
1FAK	X-RAY DIFFRACTION	2.1
1UJ3	X-RAY DIFFRACTION	2.1
1BOY	X-RAY DIFFRACTION	2.2
1WTG	X-RAY DIFFRACTION	2.2
2ZWL	X-RAY DIFFRACTION	2.2
3ELA	X-RAY DIFFRACTION	2.2
2B7D	X-RAY DIFFRACTION	2.24
4Z6A	X-RAY DIFFRACTION	2.25
4ZMA	X-RAY DIFFRACTION	2.3
2FLR	X-RAY DIFFRACTION	2.35
1TFH	X-RAY DIFFRACTION	2.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P13726-F1	85.40	0.70

Antibody-complex structures (SAbDab): 7 — 1AHW, 1JPS, 1UJ3, 4M7L, 5W06, 8CN9, 9P0X

Functional residue map

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

Post-translational modifications (1): 277

Disulfide bonds (2): 81–89, 218–241

Glycosylation sites (2): 169, 156

Function

Pathways and Gene Ontology

Reactome pathways

11 pathways

ID	Pathway
R-HSA-9031628	NGF-stimulated transcription
R-HSA-9769735	Initiation of coagulation cascade
R-HSA-9769739	Regulation of clotting cascade
R-HSA-140834
R-HSA-109582	Hemostasis
R-HSA-140877
R-HSA-162582	Signal Transduction
R-HSA-166520	Signaling by NTRKs
R-HSA-187037	Signaling by NTRK1 (TRKA)
R-HSA-198725	Nuclear Events (kinase and transcription factor activation)
R-HSA-9006934	Signaling by Receptor Tyrosine Kinases

MSigDB gene sets: 721 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_MCMV_INFECTION_DN, GOBP_MYELOID_CELL_DIFFERENTIATION, GOBP_PLATELET_DERIVED_GROWTH_FACTOR_RECEPTOR_SIGNALING_PATHWAY, BERENJENO_ROCK_SIGNALING_NOT_VIA_RHOA_DN, LEE_NEURAL_CREST_STEM_CELL_DN, GOBP_PROTEIN_ACTIVATION_CASCADE, GOBP_REGULATION_OF_PROTEASOMAL_UBIQUITIN_DEPENDENT_PROTEIN_CATABOLIC_PROCESS, GOBP_ANTIMICROBIAL_HUMORAL_RESPONSE, GOBP_POSITIVE_REGULATION_OF_ENDOCYTOSIS, GOBP_REGULATION_OF_WOUND_HEALING, HARRIS_HYPOXIA, GOBP_INFLAMMATORY_RESPONSE, GOBP_POSITIVE_REGULATION_OF_INTERLEUKIN_8_PRODUCTION, GOBP_RESPONSE_TO_PEPTIDE, GOBP_REGULATION_OF_COAGULATION

GO Biological Process (16): positive regulation of endothelial cell proliferation (GO:0001938), activation of plasma proteins involved in acute inflammatory response (GO:0002541), activation of blood coagulation via clotting cascade (GO:0002543), blood coagulation (GO:0007596), positive regulation of gene expression (GO:0010628), positive regulation of platelet-derived growth factor receptor signaling pathway (GO:0010641), protein processing (GO:0016485), cytokine-mediated signaling pathway (GO:0019221), positive regulation of cell migration (GO:0030335), positive regulation of TOR signaling (GO:0032008), positive regulation of interleukin-8 production (GO:0032757), positive regulation of angiogenesis (GO:0045766), positive regulation of positive chemotaxis (GO:0050927), positive regulation of endothelial cell apoptotic process (GO:2000353), response to stress (GO:0006950), hemostasis (GO:0007599)

GO Molecular Function (5): protease binding (GO:0002020), cytokine receptor activity (GO:0004896), phospholipid binding (GO:0005543), serine-type endopeptidase activity (GO:0004252), protein binding (GO:0005515)

GO Cellular Component (8): obsolete extracellular space (GO:0005615), plasma membrane (GO:0005886), external side of plasma membrane (GO:0009897), cell surface (GO:0009986), membrane (GO:0016020), extracellular matrix (GO:0031012), serine-type peptidase complex (GO:1905286), extracellular region (GO:0005576)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
Coagulation pathway	2
Nuclear Events (kinase and transcription factor activation)	1
Signaling by Receptor Tyrosine Kinases	1
Signaling by NTRKs	1
Signaling by NTRK1 (TRKA)	1
Signal Transduction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
acute inflammatory response	2
endothelial cell proliferation	1
regulation of endothelial cell proliferation	1
positive regulation of epithelial cell proliferation	1
protein processing	1
positive regulation of blood coagulation	1
hemostasis	1
wound healing	1
coagulation	1
gene expression	1
regulation of gene expression	1
positive regulation of macromolecule biosynthetic process	1
positive regulation of signal transduction	1
regulation of platelet-derived growth factor receptor signaling pathway	1
platelet-derived growth factor receptor signaling pathway	1
proteolysis	1
protein maturation	1
cell surface receptor signaling pathway	1
cellular response to cytokine stimulus	1
cell migration	1
regulation of cell migration	1
positive regulation of cell motility	1
TOR signaling	1
regulation of TOR signaling	1
positive regulation of intracellular signal transduction	1
positive regulation of cytokine production	1
interleukin-8 production	1
regulation of interleukin-8 production	1
angiogenesis	1
regulation of angiogenesis	1
positive regulation of vasculature development	1
positive chemotaxis	1
positive regulation of chemotaxis	1
regulation of positive chemotaxis	1
positive regulation of apoptotic process	1
endothelial cell apoptotic process	1
regulation of endothelial cell apoptotic process	1
response to stimulus	1
regulation of body fluid levels	1

Protein interactions and networks

STRING

1948 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
F3	TFPI	P10646	999
F3	F7	P08709	999
F3	F10	P00742	998
F3	F2	P00734	993
F3	VWF	P04275	980
F3	F9	P00740	978
F3	THBD	P07204	963
F3	SERPINC1	P01008	958
F3	PLAT	P00750	922
F3	SELPLG	Q14242	919
F3	PLG	P00747	918
F3	SELP	P16109	905
F3	TFPI2	P48307	898
F3	SERPINE1	P05121	887
F3	CRP	P02741	881
F3	F8	P00451	881

IntAct

30 interactions, top by confidence:

A	B	Type	Score
F7	F3	psi-mi:“MI:0407”(direct interaction)	0.880
F3	F7	psi-mi:“MI:2364”(proximity)	0.880
F7	F3	psi-mi:“MI:0915”(physical association)	0.880
F3	F7	psi-mi:“MI:0407”(direct interaction)	0.880
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
F7	F7	psi-mi:“MI:0915”(physical association)	0.590
F3	HPCAL4	psi-mi:“MI:0915”(physical association)	0.560
F3	TM9SF4	psi-mi:“MI:0915”(physical association)	0.560
TNFSF8	LGALS8	psi-mi:“MI:0914”(association)	0.530
CFTR	PLEKHG3	psi-mi:“MI:0914”(association)	0.480
F3	F2RL1	psi-mi:“MI:0915”(physical association)	0.400
F3	P4HB	psi-mi:“MI:0915”(physical association)	0.400
F3	DAD1	psi-mi:“MI:0914”(association)	0.350
HLA-C	TMEM131L	psi-mi:“MI:0914”(association)	0.350
P2RX2	TMEM131L	psi-mi:“MI:0914”(association)	0.350
SCN3B	A2ML1	psi-mi:“MI:0914”(association)	0.350
CLEC4A		psi-mi:“MI:0914”(association)	0.350
MICA	TNFRSF10B	psi-mi:“MI:0914”(association)	0.350
VSIG4	TNFRSF10B	psi-mi:“MI:0914”(association)	0.350
A4GNT	CLGN	psi-mi:“MI:0914”(association)	0.350
NCR1	ORC4	psi-mi:“MI:0914”(association)	0.350
FCRL2	HBD	psi-mi:“MI:0914”(association)	0.350
F3	HPCAL4	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (31): DAD1 (Affinity Capture-MS), TM9SF4 (Affinity Capture-MS), RAB13 (Affinity Capture-MS), STX12 (Affinity Capture-MS), TM9SF4 (Affinity Capture-MS), DAD1 (Affinity Capture-MS), F3 (Biochemical Activity), F3 (Biochemical Activity), F3 (Reconstituted Complex), F3 (Affinity Capture-Western), STUB1 (Affinity Capture-Western), F7 (Reconstituted Complex), F3 (Two-hybrid), F3 (Reconstituted Complex), F3 (Co-crystal Structure)

ESM2 similar proteins: D5K8A9, K7NA32, K7NAJ3, O09030, O70458, O70535, O95256, O95727, P13726, P14719, P17181, P20352, P21183, P24055, P27931, P30931, P33005, P34902, P38484, P40189, P40190, P42533, P42702, P42703, P43303, P78552, Q00560, Q01344, Q01638, Q04790, Q5XNR9, Q65Z14, Q6UXL0, Q764M8, Q7T2L7, Q8JZL1, Q8K5B1, Q8NFM7, Q8NI17, Q90369

Diamond homologs: P13726, P20352, P24055, P30931, P42533, Q9JLU8

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
MAPK14	down-regulates	F3	phosphorylation
PRKCA	up-regulates	F3	phosphorylation
NfKb-p65/p50	“up-regulates quantity by expression”	F3	“transcriptional regulation”
“Blood vessel damage”	up-regulates	F3
F3	“form complex”	“Factor FVIIa:TF”	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	37
Likely benign	7
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

1911 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:94540298:C:A	W57C	0.999
1:94540298:C:G	W57C	0.999
1:94540300:A:G	W57R	0.997
1:94540300:A:T	W57R	0.997
1:94536111:C:G	C89S	0.996
1:94536112:A:T	C89S	0.996
1:94540331:C:A	W46C	0.996
1:94540331:C:G	W46C	0.996
1:94540333:A:G	W46R	0.994
1:94540333:A:T	W46R	0.994
1:94536112:A:G	C89R	0.992
1:94540266:A:T	V68D	0.992
1:94540305:A:G	L55S	0.992
1:94535982:A:C	F132C	0.991
1:94536060:C:G	R106P	0.991
1:94536135:C:G	C81S	0.991
1:94536136:A:T	C81S	0.991
1:94536146:C:A	W77C	0.991
1:94536146:C:G	W77C	0.991
1:94536136:A:G	C81R	0.990
1:94540299:C:G	W57S	0.990
1:94540316:G:C	F51L	0.990
1:94540316:G:T	F51L	0.990
1:94540318:A:G	F51L	0.990
1:94535982:A:G	F132S	0.989
1:94540327:A:G	S48P	0.988
1:94535981:G:C	F132L	0.987
1:94535981:G:T	F132L	0.987
1:94535983:A:G	F132L	0.987
1:94536102:G:A	T92I	0.987

dbSNP variants (sampled 300 via entrez): RS1000017502 (1:94528689 C>T), RS1000327297 (1:94541444 C>G,T), RS1000402405 (1:94541739 G>A,C,T), RS1000446004 (1:94540524 A>G), RS1000665954 (1:94541646 T>A,C), RS1000835089 (1:94535667 C>T), RS1000885182 (1:94534865 G>C), RS1001111121 (1:94540091 A>G), RS1001177887 (1:94541819 C>T), RS1001213260 (1:94541128 T>C), RS1001380350 (1:94534762 T>C), RS1001559343 (1:94540991 T>C), RS1001792935 (1:94534962 G>A), RS1002012412 (1:94542515 G>A), RS1002296158 (1:94530089 A>T)

Disease associations

OMIM: gene MIM:134390 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST001049_2	D-dimer levels	6.000000e-52
GCST001369_1	Type 2 diabetes	6.000000e-06
GCST001798_2	End-stage coagulation	4.000000e-08
GCST008667_11	Smoking status (heavy vs never)	4.000000e-07
GCST009731_37	Blood protein levels in cardiovascular risk	6.000000e-10
GCST012139_1	D-dimer levels in HIV infection	2.000000e-13

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004507	D dimer measurement
EFO:0006527	smoking status measurement
EFO:0010623	tissue factor measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL2095194 (PROTEIN COMPLEX), CHEMBL4081 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

10 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,482,932 (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
CHEMBL1140	NIACINAMIDE	4	231,688
CHEMBL460026	ICOSAPENT	3	60,180
CHEMBL464982	GAMOLENIC ACID	3	26,552
CHEMBL140	CURCUMIN	3	93,882
CHEMBL27759	ENTINOSTAT	3	6,584
CHEMBL267476	LINOLEIC ACID	2	323,195
CHEMBL465183	DIHOMO-GAMMA-LINOLENIC ACID	2	2,022
CHEMBL8659	OLEIC ACID	2	713,838
CHEMBL487182	TETRAHYDROPALMATINE	2	2,677
CHEMBL99	TRICHOSTATIN	1	22,314

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

PharmGKB clinical annotations

2 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs1799852	Efficacy	3	adalimumab	Crohn Disease
rs3917643	Efficacy	3	simvastatin	Myocardial Ischemia

PharmGKB variants

3 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs841698	F3		0.00	0
rs3917643	F3	3	1.75	1	simvastatin
rs1799852	TF	3	0.00	1	adalimumab

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Blood coagulation components

ChEMBL bioactivities

558 potent at pChembl≥5 of 607 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
11.00	IC50	0.01	nM	CHEMBL505189
11.00	IC50	0.01	nM	CHEMBL505190
10.96	IC50	0.011	nM	CHEMBL484616
10.96	IC50	0.011	nM	CHEMBL506771
10.96	IC50	0.011	nM	CHEMBL526504
10.92	IC50	0.012	nM	CHEMBL523251
10.89	IC50	0.013	nM	CHEMBL520364
10.85	IC50	0.014	nM	CHEMBL506772
10.70	IC50	0.02	nM	CHEMBL524370
10.68	IC50	0.021	nM	CHEMBL524732
10.62	IC50	0.024	nM	CHEMBL503584
10.60	IC50	0.025	nM	CHEMBL487956
10.55	IC50	0.028	nM	CHEMBL4066780
10.54	IC50	0.029	nM	CHEMBL507281
10.52	IC50	0.03	nM	CHEMBL488778
10.48	IC50	0.033	nM	CHEMBL507020
10.47	IC50	0.034	nM	CHEMBL484615
10.46	IC50	0.035	nM	CHEMBL510111
10.44	IC50	0.036	nM	CHEMBL499632
10.38	IC50	0.042	nM	CHEMBL487955
10.35	IC50	0.045	nM	CHEMBL505720
10.28	IC50	0.053	nM	CHEMBL17201
10.28	IC50	0.052	nM	CHEMBL497067
10.27	IC50	0.054	nM	CHEMBL230128
10.22	Ki	0.06	nM	CHEMBL3956096
10.22	IC50	0.06	nM	CHEMBL498047
10.17	IC50	0.067	nM	CHEMBL519886
10.12	IC50	0.076	nM	CHEMBL527118
10.11	IC50	0.078	nM	CHEMBL4070749
10.11	Ki	0.078	nM	CHEMBL73737
10.04	IC50	0.092	nM	CHEMBL500948
10.02	IC50	0.095	nM	VITALBOSIDE A
10.01	IC50	0.097	nM	CHEMBL485705
10.01	IC50	0.098	nM	CHEMBL525274
9.98	IC50	0.104	nM	CHEMBL524548
9.92	IC50	0.12	nM	4’-HYDROXYCHALCONE
9.92	IC50	0.12	nM	CHEMBL224485
9.89	IC50	0.13	nM	CHEMBL526193
9.85	Ki	0.14	nM	CHEMBL3900166
9.80	Ki	0.16	nM	CHEMBL3891120
9.72	IC50	0.19	nM	CHEMBL499829
9.66	Ki	0.22	nM	CHEMBL3984725
9.66	IC50	0.221	nM	CHEMBL4092579
9.66	IC50	0.221	nM	OLEANONIC ACID
9.66	IC50	0.221	nM	HEDERAGENIN
9.64	Ki	0.23	nM	CHEMBL3901391
9.64	IC50	0.231	nM	CHEMBL504391
9.62	Ki	0.24	nM	CHEMBL3898956
9.59	IC50	0.26	nM	2,6-DIBENZYLIDENECYCLOHEXANONE
9.55	Ki	0.28	nM	CHEMBL3978562

PubChem BioAssay actives

555 with measured affinity, of 949 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
135986123	397857: Inhibition of tissue factor/factor 7a	ic50	<0.0001	uM
[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl] (1R,3aS,5aR,5bR,7aR,8R,9S,11aR,11bR,13bS)-9-hydroxy-8-(hydroxymethyl)-5a,5b,8,11a-tetramethyl-1-prop-1-en-2-yl-1,2,3,4,5,6,7,7a,9,10,11,11b,12,13,13a,13b-hexadecahydrocyclopenta[a]chrysene-3a-carboxylate	1436859: Inhibition of LPS-induced tissue factor procoagulant activity in human THP1 cells preincubated for 1 hr followed by LPS addition measured after 5 hrs using factor 10a chromogenic substrate in presence of prothrombin complex	ic50	<0.0001	uM
[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl] (4aS,6aR,6aS,6bR,8aR,10S,12aR,14bS)-10-hydroxy-2,2,6a,6b,9,9,12a-heptamethyl-1,3,4,5,6,6a,7,8,8a,10,11,12,13,14b-tetradecahydropicene-4a-carboxylate	1436859: Inhibition of LPS-induced tissue factor procoagulant activity in human THP1 cells preincubated for 1 hr followed by LPS addition measured after 5 hrs using factor 10a chromogenic substrate in presence of prothrombin complex	ic50	<0.0001	uM
2-[2-[(4-carbamimidoylphenyl)carbamoyl]-4-methoxyphenyl]-5-(2-methylpropylcarbamoyl)benzoic acid	397857: Inhibition of tissue factor/factor 7a	ic50	<0.0001	uM
2-[4-[4-(aminomethyl)thiophen-3-yl]-2-[(4-carbamimidoylphenyl)carbamoyl]phenyl]-5-(2-methylpropylcarbamoyl)benzoic acid	397857: Inhibition of tissue factor/factor 7a	ic50	<0.0001	uM
2-[2-[(4-carbamimidoylphenyl)carbamoyl]-4-prop-1-ynylphenyl]-5-(2-methylpropylcarbamoyl)benzoic acid	397857: Inhibition of tissue factor/factor 7a	ic50	<0.0001	uM
2-[2-[(4-carbamimidoylphenyl)carbamoyl]-4-(thiophen-2-ylmethyl)phenyl]-5-(2-methylpropylcarbamoyl)benzoic acid	397857: Inhibition of tissue factor/factor 7a	ic50	<0.0001	uM
2-[2-[(4-carbamimidoylphenyl)carbamoyl]-4-(furan-3-yl)phenyl]-5-(2-methylpropylcarbamoyl)benzoic acid	397857: Inhibition of tissue factor/factor 7a	ic50	<0.0001	uM
2-[2-[(4-carbamimidoylphenyl)carbamoyl]-4-[3-(hydroxymethyl)furan-2-yl]phenyl]-5-(2-methylpropylcarbamoyl)benzoic acid	397857: Inhibition of tissue factor/factor 7a	ic50	<0.0001	uM
2-[2-[(4-carbamimidoylphenyl)carbamoyl]-4-thiophen-2-ylphenyl]-5-(2-methylpropylcarbamoyl)benzoic acid	397857: Inhibition of tissue factor/factor 7a	ic50	<0.0001	uM
2-[2-[(4-carbamimidoylphenyl)carbamoyl]-4-thiophen-3-ylphenyl]-5-(2-methylpropylcarbamoyl)benzoic acid	397857: Inhibition of tissue factor/factor 7a	ic50	<0.0001	uM
2-[2-[(4-carbamimidoylphenyl)carbamoyl]-4-ethenylphenyl]-5-(2-methylpropylcarbamoyl)benzoic acid	397857: Inhibition of tissue factor/factor 7a	ic50	<0.0001	uM
2-[2-[(4-carbamimidoylphenyl)carbamoyl]-4-[2-(hydroxymethyl)thiophen-3-yl]phenyl]-5-(2-methylpropylcarbamoyl)benzoic acid	397857: Inhibition of tissue factor/factor 7a	ic50	<0.0001	uM
2-[2-[(4-carbamimidoylphenyl)carbamoyl]-4-prop-2-enylphenyl]-5-(2-methylpropylcarbamoyl)benzoic acid	397857: Inhibition of tissue factor/factor 7a	ic50	<0.0001	uM
2-[2-[(4-carbamimidoylphenyl)carbamoyl]-4-(1H-pyrrol-2-yl)phenyl]-5-(2-methylpropylcarbamoyl)benzoic acid	397857: Inhibition of tissue factor/factor 7a	ic50	<0.0001	uM
2-[2-[(4-carbamimidoylphenyl)carbamoyl]-4-(3-hydroxyprop-1-en-2-yl)phenyl]-5-(2-methylpropylcarbamoyl)benzoic acid	397857: Inhibition of tissue factor/factor 7a	ic50	<0.0001	uM
2-[2-[(4-carbamimidoylphenyl)carbamoyl]-4-(3-methylbut-2-enyl)phenyl]-5-(2-methylpropylcarbamoyl)benzoic acid	397857: Inhibition of tissue factor/factor 7a	ic50	<0.0001	uM
2-[2-[(4-carbamimidoylphenyl)carbamoyl]-4-(4-hydroxybut-1-en-2-yl)phenyl]-5-(2-methylpropylcarbamoyl)benzoic acid	397857: Inhibition of tissue factor/factor 7a	ic50	<0.0001	uM
2-[2-[(4-carbamimidoylphenyl)carbamoyl]-4-(furan-2-yl)phenyl]-5-(2-methylpropylcarbamoyl)benzoic acid	397857: Inhibition of tissue factor/factor 7a	ic50	<0.0001	uM
2-[2-[(4-carbamimidoylphenyl)carbamoyl]-4-[4-(hydroxymethyl)thiophen-3-yl]phenyl]-5-(2-methylpropylcarbamoyl)benzoic acid	397857: Inhibition of tissue factor/factor 7a	ic50	<0.0001	uM
2-[4-[4-(azidomethyl)thiophen-3-yl]-2-[(4-carbamimidoylphenyl)carbamoyl]phenyl]-5-(2-methylpropylcarbamoyl)benzoic acid	397857: Inhibition of tissue factor/factor 7a	ic50	<0.0001	uM
2-[2-[(4-carbamimidoylphenyl)carbamoyl]-4-[2-(hydroxymethyl)furan-3-yl]phenyl]-5-(2-methylpropylcarbamoyl)benzoic acid	397857: Inhibition of tissue factor/factor 7a	ic50	<0.0001	uM
2-[2-[(4-carbamimidoylphenyl)carbamoyl]-4-[4-(hydroxymethyl)furan-3-yl]phenyl]-5-(2-methylpropylcarbamoyl)benzoic acid	397857: Inhibition of tissue factor/factor 7a	ic50	<0.0001	uM
2-[4-benzyl-2-[(4-carbamimidoylphenyl)carbamoyl]phenyl]-5-(2-methylpropylcarbamoyl)benzoic acid	397857: Inhibition of tissue factor/factor 7a	ic50	<0.0001	uM
2-[2-[(4-carbamimidoylphenyl)carbamoyl]-4-ethynylphenyl]-5-(2-methylpropylcarbamoyl)benzoic acid	397857: Inhibition of tissue factor/factor 7a	ic50	<0.0001	uM
2-[2-[(4-carbamimidoylphenyl)carbamoyl]-4-prop-1-en-2-ylphenyl]-5-(2-methylpropylcarbamoyl)benzoic acid	397857: Inhibition of tissue factor/factor 7a	ic50	<0.0001	uM
2-[4-[(Z)-but-2-enyl]-2-[(4-carbamimidoylphenyl)carbamoyl]phenyl]-5-(2-methylpropylcarbamoyl)benzoic acid	397857: Inhibition of tissue factor/factor 7a	ic50	<0.0001	uM
1-[(2R,15R)-2-[(1-amino-4-fluoroisoquinolin-6-yl)amino]-4,15,17-trimethyl-3,12-dioxo-13-oxa-4,11-diazatricyclo[14.2.2.16,10]henicosa-1(18),6,8,10(21),16,19-hexaen-7-yl]cyclobutane-1-carboxylic acid	1316610: Inhibition of recombinant human TF-factor 7a using factor 10 as substrate at 37 degC	ki	0.0001	uM
1-[(2R,15R)-2-[(1-amino-4-fluoroisoquinolin-6-yl)amino]-4,15,17-trimethyl-3,12-dioxo-13-oxa-4,11-diazatricyclo[14.2.2.16,10]henicosa-1(18),6,8,10(21),16,19-hexaen-7-yl]cyclohexane-1-carboxylic acid	1316610: Inhibition of recombinant human TF-factor 7a using factor 10 as substrate at 37 degC	ki	0.0001	uM
2-[3-(3-aminophenyl)-5-chloro-2-hydroxyphenyl]-3H-benzimidazole-5-carboximidamide	72364: Binding affinity for factor VIIa/TF	ki	0.0001	uM
[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl] (1R,3aS,5aR,5bR,7aR,9S,11aR,11bR,13bS)-9-hydroxy-5a,5b,8,8,11a-pentamethyl-1-prop-1-en-2-yl-1,2,3,4,5,6,7,7a,9,10,11,11b,12,13,13a,13b-hexadecahydrocyclopenta[a]chrysene-3a-carboxylate	1436859: Inhibition of LPS-induced tissue factor procoagulant activity in human THP1 cells preincubated for 1 hr followed by LPS addition measured after 5 hrs using factor 10a chromogenic substrate in presence of prothrombin complex	ic50	0.0001	uM
2-[2-[(4-carbamimidoylphenyl)carbamoyl]phenyl]-5-(2-methylpropylcarbamoyl)benzoic acid	397857: Inhibition of tissue factor/factor 7a	ic50	0.0001	uM
2-[2-[(4-carbamimidoylphenyl)carbamoyl]-4-phenylphenyl]-5-(2-methylpropylcarbamoyl)benzoic acid	397857: Inhibition of tissue factor/factor 7a	ic50	0.0001	uM
2-[2-[(4-carbamimidoylphenyl)carbamoyl]-4-(1,3-thiazol-2-yl)phenyl]-5-(2-methylpropylcarbamoyl)benzoic acid	397857: Inhibition of tissue factor/factor 7a	ic50	0.0001	uM
2-[2-[(4-carbamimidoylphenyl)carbamoyl]-4-[(1Z)-3-methylbuta-1,3-dienyl]phenyl]-5-(2-methylpropylcarbamoyl)benzoic acid	397857: Inhibition of tissue factor/factor 7a	ic50	0.0001	uM
2-[2-[(4-carbamimidoylphenyl)carbamoyl]-4-[(E)-3-hydroxyprop-1-enyl]phenyl]-5-(2-methylpropylcarbamoyl)benzoic acid	397857: Inhibition of tissue factor/factor 7a	ic50	0.0001	uM
2-[2-[(4-carbamimidoylphenyl)carbamoyl]-4-propylphenyl]-5-(2-methylpropylcarbamoyl)benzoic acid	397857: Inhibition of tissue factor/factor 7a	ic50	0.0001	uM
2-[4-(azidomethyl)-2-[(4-carbamimidoylphenyl)carbamoyl]phenyl]-5-(2-methylpropylcarbamoyl)benzoic acid	397857: Inhibition of tissue factor/factor 7a	ic50	0.0001	uM
2-[2-[(4-carbamimidoylphenyl)carbamoyl]-4-(1-methylpyrrol-2-yl)phenyl]-5-(2-methylpropylcarbamoyl)benzoic acid	397857: Inhibition of tissue factor/factor 7a	ic50	0.0001	uM
2-[2-[(4-carbamimidoylphenyl)carbamoyl]-4-hydroxyphenyl]-5-(2-methylpropylcarbamoyl)benzoic acid	397857: Inhibition of tissue factor/factor 7a	ic50	0.0001	uM
2-[2-[(4-carbamimidoylphenyl)carbamoyl]-4-ethylphenyl]-5-(2-methylpropylcarbamoyl)benzoic acid	397857: Inhibition of tissue factor/factor 7a	ic50	0.0001	uM
(4aR,5R,6aR,6aS,6bR,8aR,10S,12aR,14bS)-5,10-dihydroxy-2,2,6a,6b,9,9,12a-heptamethyl-1,3,4,5,6,6a,7,8,8a,10,11,12,13,14b-tetradecahydropicene-4a-carboxylic acid	1436859: Inhibition of LPS-induced tissue factor procoagulant activity in human THP1 cells preincubated for 1 hr followed by LPS addition measured after 5 hrs using factor 10a chromogenic substrate in presence of prothrombin complex	ic50	0.0001	uM
(4aS,6aR,6aS,6bR,8aR,10S,12aR,14bS)-2,2,6a,6b,9,9,12a-heptamethyl-10-[(2R,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-1,3,4,5,6,6a,7,8,8a,10,11,12,13,14b-tetradecahydropicene-4a-carboxylic acid	1436859: Inhibition of LPS-induced tissue factor procoagulant activity in human THP1 cells preincubated for 1 hr followed by LPS addition measured after 5 hrs using factor 10a chromogenic substrate in presence of prothrombin complex	ic50	0.0001	uM
(2R,15R)-2-[(1-aminoisoquinolin-6-yl)amino]-7-cyclopropylsulfonyl-4,15,17-trimethyl-13-oxa-4,11-diazatricyclo[14.2.2.16,10]henicosa-1(18),6,8,10(21),16,19-hexaene-3,12-dione	1315769: Inhibition of full-length human TF/recombinant human factor 7a assessed as decrease in conversion of factor 10 to factor 10a by measuring S2765 hydrolysis after 15 mins	ki	0.0002	uM
(2R,15R)-2-[(1-amino-7-fluoroisoquinolin-6-yl)amino]-7-cyclopropylsulfonyl-4,15,17-trimethyl-13-oxa-4,11-diazatricyclo[14.2.2.16,10]henicosa-1(18),6,8,10(21),16,19-hexaene-3,12-dione	1315769: Inhibition of full-length human TF/recombinant human factor 7a assessed as decrease in conversion of factor 10 to factor 10a by measuring S2765 hydrolysis after 15 mins	ki	0.0002	uM
(4aS,6aR,6aS,6bR,8aR,12aR,14bS)-2,2,6a,6b,9,9,12a-heptamethyl-10-oxo-3,4,5,6,6a,7,8,8a,11,12,13,14b-dodecahydro-1H-picene-4a-carboxylic acid	1436859: Inhibition of LPS-induced tissue factor procoagulant activity in human THP1 cells preincubated for 1 hr followed by LPS addition measured after 5 hrs using factor 10a chromogenic substrate in presence of prothrombin complex	ic50	0.0002	uM
1-[(2R,15R)-2-[(1-amino-4-fluoroisoquinolin-6-yl)amino]-4,15,17-trimethyl-3,12-dioxo-13-oxa-4,11-diazatricyclo[14.2.2.16,10]henicosa-1(18),6,8,10(21),16,19-hexaen-7-yl]cyclopentane-1-carboxylic acid	1316610: Inhibition of recombinant human TF-factor 7a using factor 10 as substrate at 37 degC	ki	0.0002	uM
(1R,3aS,5aR,5bR,7aR,8R,9S,11aR,11bR,13bS)-9-hydroxy-8-(hydroxymethyl)-5a,5b,8,11a-tetramethyl-1-prop-1-en-2-yl-1,2,3,4,5,6,7,7a,9,10,11,11b,12,13,13a,13b-hexadecahydrocyclopenta[a]chrysene-3a-carboxylic acid	1436859: Inhibition of LPS-induced tissue factor procoagulant activity in human THP1 cells preincubated for 1 hr followed by LPS addition measured after 5 hrs using factor 10a chromogenic substrate in presence of prothrombin complex	ic50	0.0002	uM
2-[2-[(4-carbamimidoylphenyl)carbamoyl]-4-pyridin-4-ylphenyl]-5-(2-methylpropylcarbamoyl)benzoic acid	397857: Inhibition of tissue factor/factor 7a	ic50	0.0002	uM
3-[3-[(4-carbamimidoylphenyl)carbamoyl]-4-[2-carboxy-4-(2-methylpropylcarbamoyl)phenyl]phenyl]thiophene-2-carboxylic acid	397857: Inhibition of tissue factor/factor 7a	ic50	0.0002	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Arsenic Trioxide	decreases activity, affects expression, decreases expression, decreases reaction	13
Tretinoin	increases expression, decreases expression, decreases reaction, affects expression, decreases activity	12
Lipopolysaccharides	decreases reaction, increases activity, increases expression, affects binding, increases reaction (+2 more)	8
Simvastatin	affects response to substance, decreases expression, decreases reaction, increases expression, decreases activity	8
Particulate Matter	decreases reaction, affects reaction, increases reaction, decreases methylation, increases abundance (+3 more)	8
SB 203580	decreases reaction, increases expression, decreases expression	5
Benzo(a)pyrene	affects methylation, decreases expression, increases expression	5
Valproic Acid	increases expression	5
2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one	decreases reaction, increases expression, decreases expression	4
pyrazolanthrone	decreases reaction, increases expression, affects cotreatment	4
Resveratrol	increases activity, increases expression, decreases expression, decreases reaction	4
Doxorubicin	decreases expression, affects expression, affects response to substance, affects activity, affects cleavage (+6 more)	4
Tetrachlorodibenzodioxin	affects expression, increases expression	4
sodium arsenite	increases expression, increases reaction, decreases expression	3
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one	decreases reaction, increases expression, decreases expression, increases reaction	3
U 0126	decreases reaction, increases expression, decreases expression	3
Dexamethasone	increases reaction, affects cotreatment, increases expression	3
Estradiol	increases expression, affects cotreatment	3
Histamine	increases reaction, affects cotreatment, increases activity, decreases reaction, increases expression	3
Progesterone	affects cotreatment, increases expression, decreases reaction	3
Tetradecanoylphorbol Acetate	decreases reaction, increases expression, increases activity	3
Vitamin E	decreases activity, decreases expression, decreases reaction, increases activity, increases expression	3
Aflatoxin B1	affects expression, increases expression, increases methylation	3
sulforaphane	increases expression	2
geranylgeraniol	decreases expression, decreases reaction	2
mercuric bromide	increases expression, affects cotreatment	2
perfluorooctane sulfonic acid	decreases expression	2
chloropicrin	decreases expression	2
lipopolysaccharide, Escherichia coli O111 B4	decreases reaction, increases activity, increases expression	2
Air Pollutants	decreases reaction, increases reaction, decreases methylation, increases abundance, increases expression	2

ChEMBL screening assays

87 unique, capped per target: 68 binding, 19 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1005944	Binding	Inhibition of human tissue factor/factor 7a	Novel 3-carboxamide-coumarins as potent and selective FXIIa inhibitors. — J Med Chem
CHEMBL855827	Functional	Anticoagulant activity in human plasma measured as prothrombin time	Preparation of 1-(3-aminobenzo[d]isoxazol-5-yl)-1H-pyrazolo[4,3-d]pyrimidin-7(6H)-ones as potent, selective, and efficacious inhibitors of coagulation factor Xa. — Bioorg Med Chem Lett

Cellosaurus cell lines

3 cell lines: 2 cancer cell line, 1 spontaneously immortalized cell line

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

Cellosaurus	Name	Category	Sex
CVCL_E6QB	Genomeditech CHO-K1 H_F3	Spontaneously immortalized cell line	Female
CVCL_SM72	HAP1 F3 (-) 1	Cancer cell line	Male
CVCL_SM73	HAP1 F3 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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