F7

Summary

F7 (coagulation factor VII, HGNC:3544) is a protein-coding gene on chromosome 13q34, encoding Coagulation factor VII (P08709). Initiates the extrinsic pathway of blood coagulation.

This gene encodes coagulation factor VII which is a vitamin K-dependent factor essential for hemostasis. This factor circulates in the blood in a zymogen form, and is converted to an active form by either factor IXa, factor Xa, factor XIIa, or thrombin by minor proteolysis. Upon activation of the factor VII, a heavy chain containing a catalytic domain and a light chain containing 2 EGF-like domains are generated, and two chains are held together by a disulfide bond. In the presence of factor III and calcium ions, the activated factor then further activates the coagulation cascade by converting factor IX to factor IXa and/or factor X to factor Xa. Defects in this gene can cause coagulopathy. Alternative splicing results in multiple transcript variants encoding different isoforms that may undergo similar proteolytic processing to generate mature polypeptides.

Source: NCBI Gene 2155 — RefSeq curated summary.

At a glance

• Gene–disease (curated): factor VII deficiency (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 14
• Clinical variants (ClinVar): 347 total — 28 pathogenic, 43 likely-pathogenic
• Phenotypes (HPO): 18
• Druggable target: yes — 8 molecules with ChEMBL bioactivity
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity unscored
• MANE Select transcript: NM_019616

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3544
Approved symbol	F7
Name	coagulation factor VII
Location	13q34
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000057593
Ensembl biotype	protein_coding
OMIM	613878
Entrez	2155

Gene structure

Transcript identifiers

Ensembl transcripts: 26 — 23 protein_coding, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000346342, ENST00000375581, ENST00000444337, ENST00000473085, ENST00000479674, ENST00000541084, ENST00000891239, ENST00000891240, ENST00000891241, ENST00000891242, ENST00000891243, ENST00000891244, ENST00000891245, ENST00000891246, ENST00000891247, ENST00000891248, ENST00000891249, ENST00000891250, ENST00000891251, ENST00000891252, ENST00000891253, ENST00000891254, ENST00000891255, ENST00000891256, ENST00000891257, ENST00000891258

RefSeq mRNA: 3 — MANE Select: NM_019616 NM_000131, NM_001267554, NM_019616

CCDS: CCDS73602, CCDS9528, CCDS9529

Canonical transcript exons

ENST00000346342 — 8 exons

Exon	Start	End
ENSE00000687189	113117473	113117596
ENSE00000862517	113105791	113105905
ENSE00001134999	113116766	113116875
ENSE00001135032	113110690	113110850
ENSE00001940886	113118413	113120685
ENSE00003582424	113115660	113115800
ENSE00003608396	113113847	113113960
ENSE00003655495	113113752	113113776

Expression profiles

Bgee: expression breadth ubiquitous, 156 present calls, max score 97.18.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.2490 / max 66.5832, expressed in 41 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
136197	0.2490	41

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	97.18	gold quality
liver	UBERON:0002107	95.37	gold quality
buccal mucosa cell	CL:0002336	94.87	silver quality
tendon of biceps brachii	UBERON:0008188	94.30	silver quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.21	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	79.05	gold quality
superficial temporal artery	UBERON:0001614	78.39	gold quality
mucosa of paranasal sinus	UBERON:0005030	77.43	gold quality
medial globus pallidus	UBERON:0002477	76.52	silver quality
gingival epithelium	UBERON:0001949	76.16	gold quality
globus pallidus	UBERON:0001875	75.29	silver quality
gingiva	UBERON:0001828	73.56	gold quality
cardia of stomach	UBERON:0001162	71.86	gold quality
ventral tegmental area	UBERON:0002691	71.42	silver quality
body of tongue	UBERON:0011876	71.15	gold quality
sperm	CL:0000019	71.14	gold quality
pericardium	UBERON:0002407	70.82	silver quality
secondary oocyte	CL:0000655	70.72	silver quality
vena cava	UBERON:0004087	70.44	gold quality
pons	UBERON:0000988	70.33	silver quality
visceral pleura	UBERON:0002401	70.15	silver quality
substantia nigra pars reticulata	UBERON:0001966	69.88	gold quality
lateral nuclear group of thalamus	UBERON:0002736	69.85	gold quality
pharyngeal mucosa	UBERON:0000355	69.68	gold quality
lateral globus pallidus	UBERON:0002476	69.67	gold quality
male germ cell	CL:0000015	69.48	gold quality
nasal cavity epithelium	UBERON:0005384	69.45	gold quality
superior vestibular nucleus	UBERON:0007227	69.28	gold quality
synovial joint	UBERON:0002217	68.93	silver quality
dorsal root ganglion	UBERON:0000044	68.80	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.79

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ATF4, CEBPB, DNMT1, EPAS1, FOS, HNF4A, PITX2, SP1

miRNA regulators (miRDB)

57 targeting F7, 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-6867-5P	100.00	82.21	3464
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-3120-5P	100.00	65.56	965
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-6888-3P	99.97	65.95	1170
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-6817-3P	99.79	68.35	2126
HSA-MIR-448	99.79	72.37	2103
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-3158-5P	99.65	67.51	1763
HSA-MIR-3177-5P	99.65	70.38	1174
HSA-MIR-298	99.63	67.56	1916
HSA-MIR-3682-3P	99.58	67.63	865
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-766-3P	99.47	65.24	1811
HSA-MIR-1275	99.47	67.90	2749
HSA-MIR-653-5P	99.46	67.35	1300
HSA-MIR-548B-3P	99.38	67.26	1000
HSA-MIR-6731-5P	99.28	67.42	2375
HSA-MIR-8085	99.28	67.56	2362
HSA-MIR-10522-5P	99.26	68.50	2087
HSA-MIR-4667-3P	99.26	65.45	1608
HSA-MIR-593-3P	99.22	67.28	1327

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity Not yet evaluated (unscored). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• 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)
• An analog of an F7 motif, Cys-Glu-Gln-Tyr-Cys exerts its antithrombotic effect by blocking the docking of Tyr101 into a hydrophobic pocket in the catalytic domain, disrupting an essential interaction between this domain & 2d EGF-like domain of F7. (PMID:11848442)
• Factor VII activity is an independent predictor of cardiovascular mortality in elderly women of a Sicilian population. (PMID:11858478)
• Finnish carriers of the Q allele of factor Vii r/Q353 have a decreased risk of fatal myocardial infarction. (PMID:11858502)
• significant activation of FVII occurs following infusion of APOA1 into healthy male fasting subjects (PMID:11916081)
• Four novel mutations have been identified: IVS 2+1G–>C Phe 24 deletion, Leu300Pro and Arg277His. Homozygosity for the IVS2+1G–>C mutation was lethal, whereas homozygosity for the Phe 24 deletion was accompanied by a severe bleeding tendency. (PMID:11920218)
• A frequent human coagulation Factor VII mutation (A294V, c152) in loop 140s affects the interaction with activators, tissue factor and substrates. (PMID:11931672)
• The R353Q polymorphism at codon 353 and the 10 base pair insertion polymorphism of the FVII gene were associated with FVIIc and FVIIAg levels. Heterozygous individuals had lower FVIIc and FVIIAg levels than those homozygous for the common alleles. (PMID:11943935)
• TF cytoplasmic domain-independent stimulation of protein synthesis via activation of S6 kinase contributes to FVIIa effects in pathophysiology. (PMID:12019261)
• Factor VIIa induces release of von Willebrand factor from human umbilical vein endothelial cells by a tyrosine kinase dependent pathway (PMID:12083486)
• Role of zymogenicity-determining residues in cofactor interaction and macromolecular substrate recognition (PMID:12135351)
• 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)
• A factor VIIa mutant with enhanced membrane affinity showed 10- to 13-fold higher activity in blood clotting in hemophiliacs. (PMID:12152685)
• FVII level is independently associated with inflammatory variables and suggest their pathophysiological link in hypercholesterolemic patients. (PMID:12208482)
• REVIEW: role of tissue factor-FVIIa complex in pathophysiological processes and effect of the inhibitors of the tissue factor:factor VII pathway (PMID:12356487)
• the inability of V154G FVIIa to accommodate an inhibitor in the active site, indicating an improperly shaped specificity pocket, would explain the low activity of the zymogen-like form of FVIIa, which is predominant in the absence of TF. (PMID:12358603)
• Two naturally occurring FVII mutations have no affinity change for TF; deficiency of coagulant activities is due to the loss of an efficient catalytic machinery in the FVII molecule. (PMID:12428089)
• factors II and X are essential for the hemostatic effects of rFVIIa, and that factors V and VIII promote these effects (PMID:12428092)
• mutagenesis of gamma-carboxyglutamic acid domain generates maximum enhancement of membrane contact site (PMID:12506121)
• The finding of FVII synthesis outside the liver–in normal and atherosclerotic vessels as well as smooth muscle cells, fibroblasts, and keratinocytes in vitro–may be indicative of other cellular functions for this coagulation protein. (PMID:12524237)
• 2 homozygous nucleotide substitutions were identified in the F7 gene: a IVS7+2T>G transversion involving the IVS7 donor splice site, followed by a mutation at nucleotide 10588 that would result in a missense variation (Arg224Gln). (PMID:12676783)
• FVIIa binding to tissue factor provided protection against apoptosis induced by growth factor deprivation, primarily through activation of PI3-kinase/Akt pathway, and to a lesser extent, p44/42 MAPK pathway (PMID:12738672)
• the factor VII R353 allele is associated with lower concentrations of plasma apolipoprotein B levels (PMID:12851844)
• the 4G/4G-PAI-1 genotype might be a protective factor against atherothrombotic cerebral infarction (ACI), whereas the factor V point mutation (1691G-A) and the factor VII Arg/Gln353 gene polymorphism have not proved to be risk factors for ACI (PMID:12859287)
• ARP1 interacted with two regions of the FVII 5’ flanking region, the hepatic nuclear factor 4 binding region and the nuclear hormone response region, indicating a role for ARP1 in transcriptional modulation of the FVII gene. (PMID:12871323)
• p21Ras activation is instrumental in FVIIa signal transduction and the FVIIa-dependent activation of p21Ras involves either PKC or Src-dependent mechanisms, depending on the cell type investigated. (PMID:12871370)
• Presence of the silent dimorphism H115H, the polymorphism R353Q and the mutation A294V. (PMID:12888866)
• Double heterozygous mutations coding the same amino acid of F VII were found in a pedigree with hereditary coagulation factor VII deficiency. (PMID:12903033)
• Factor Xa and thrombin, but not factor VIIa, induce expression of MCP-1, IL-8, IL-6 and VEGF, and expression of receptors implicated in signaling by these coagulation factors PAR-1, PAR-2 and PAR-3 in lung and dermal fibroblasts (PMID:12941034)
• plasma FVII with the promoter haplotype -670C/-630G/402A is related to increased coagulant activity, risk of an initial coronary event, and reporter gene expression (PMID:14521602)
• factor VIIa has a role in aggregation of alphaIIbbeta3-deficient platelets (PMID:14592825)
• the 60s loop of human coagulation factor VII has a role in interdomain crosstalk (PMID:14691565)
• model characterizes likely enzyme-binding exosites on FVIIa and Xa that may be involved in the ternary complex (sTF-VIIa-Xa) formation and the membrane binding region of the ternary complex. (PMID:14750502)
• The proteolytic domains of both VII and VIIa seem to interact with the same surface on thromboplastin (TF) with nearly identical residue energetics; therefore, zymogen VII can readily adopt a VIIa-like conformation required for binding to TF. (PMID:14756558)
• FVIIa induces cell survival through STAT5-dependent Bcl(XL) production and Jak2-dependent activation of PKB. TF/FVIIa-signal transduction is dependent on G12/G13 class G proteins. (PMID:15016732)
• an epidemiologic study revealed Plasma FVIIa concentrations were influenced by R353Q polymorphism, and the Q allele may be protective against premature myocardial infarction (PMID:15170085)
• Binding of FVIIa to TF on the surface of SMCs induces proliferation via a coagulation-independent mechanism and possibly indicates a new link between coagulation, inflammation, and atherosclerosis. (PMID:15173027)
• TF/FVIIa complex up-regulates the transcription of u-PAR in human ovarian cancer cells. (PMID:15182581)
• EGFR, PYK2, Yes, and SHP-2 are involved in transduction of the TF/FVIIa signal possibly via transactivation of the EGF receptor. (PMID:15213840)
• Factor VIIa has a role in mediating tenase function on activated platelets under flow (PMID:15304047)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	f7	ENSDARG00000034862
danio_rerio	f7i	ENSDARG00000075827
danio_rerio	f7l	ENSDARG00000100782
mus_musculus	F7	ENSMUSG00000031443
rattus_norvegicus	F7	ENSRNOG00000032737

Paralogs (16): F11 (ENSG00000088926), F9 (ENSG00000101981), HGFAC (ENSG00000109758), F10 (ENSG00000126218), KLK10 (ENSG00000129451), F12 (ENSG00000131187), C1RL (ENSG00000139178), C1R (ENSG00000159403), KLKB1 (ENSG00000164344), C1S (ENSG00000182326), PRSS55 (ENSG00000184647), CFD (ENSG00000197766), CFI (ENSG00000205403), PRSS51 (ENSG00000253649), HP (ENSG00000257017), HPR (ENSG00000261701)

Protein

Protein identifiers

Coagulation factor VII — P08709 (reviewed: P08709)

Alternative names: Proconvertin, Serum prothrombin conversion accelerator

All UniProt accessions (3): P08709, E9PH36, F5H8B0

UniProt curated annotations — full annotation on UniProt →

Function. Initiates the extrinsic pathway of blood coagulation. Serine protease that circulates in the blood in a zymogen form. Factor VII is converted to factor VIIa by factor Xa, factor XIIa, factor IXa, or thrombin by minor proteolysis. In the presence of tissue factor and calcium ions, factor VIIa then converts factor X to factor Xa by limited proteolysis. Factor VIIa also converts factor IX to factor IXa in the presence of tissue factor and calcium.

Subunit / interactions. Heterodimer of a light chain and a heavy chain linked by a disulfide bond. Interacts (activated) with iripin-8, a serine protease inhibitor from Ixodes ricinus saliva.

Subcellular location. Secreted.

Tissue specificity. Plasma.

Post-translational modifications. The vitamin K-dependent, enzymatic carboxylation of some glutamate residues allows the modified protein to bind calcium. The iron and 2-oxoglutarate dependent 3-hydroxylation of aspartate and asparagine is (R) stereospecific within EGF domains. O- and N-glycosylated. N-glycosylation at Asn-205 occurs cotranslationally and is mediated by STT3A-containing complexes, while glycosylation at Asn-382 is post-translational and is mediated STT3B-containing complexes before folding. O-fucosylated by POFUT1 on a conserved serine or threonine residue found in the consensus sequence C2-X(4,5)-[S/T]-C3 of EGF domains, where C2 and C3 are the second and third conserved cysteines. Can be either O-glucosylated or O-xylosylated at Ser-112 by POGLUT1 in vitro.

Disease relevance. Factor VII deficiency (FA7D) [MIM:227500] A hemorrhagic disease with variable presentation. The clinical picture can be very severe, with the early occurrence of intracerebral hemorrhages or repeated hemarthroses, or, in contrast, moderate with cutaneous-mucosal hemorrhages (epistaxis, menorrhagia) or hemorrhages provoked by a surgical intervention. Finally, numerous subjects are completely asymptomatic despite very low factor VII levels. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the peptidase S1 family.

Isoforms (2)

UniProt ID	Names	Canonical?
P08709-1	A	yes
P08709-2	B

RefSeq proteins (3): NP_000122, NP_001254483, NP_062562* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000152	EGF-type_Asp/Asn_hydroxyl_site	PTM
IPR000294	GLA_domain	Domain
IPR000742	EGF	Domain
IPR001254	Trypsin_dom	Domain
IPR001314	Peptidase_S1A	Family
IPR001881	EGF-like_Ca-bd_dom	Domain
IPR009003	Peptidase_S1_PA	Homologous_superfamily
IPR012224	Pept_S1A_FX	Family
IPR017857	Coagulation_fac-like_Gla_dom	Homologous_superfamily
IPR018097	EGF_Ca-bd_CS	Conserved_site
IPR018114	TRYPSIN_HIS	Active_site
IPR033116	TRYPSIN_SER	Active_site
IPR035972	GLA-like_dom_SF	Homologous_superfamily
IPR043504
IPR050442	Peptidase_S1_coag_factors	Family

Pfam: PF00008, PF00089, PF00594, PF14670

Enzyme classification (BRENDA):

• EC 3.4.21.21 — coagulation factor VIIa (BRENDA: 5 organisms, 78 substrates, 228 inhibitors, 104 Km, 93 kcat entries)

Substrate kinetics (BRENDA)

9 substrates with measured Km, best-characterized 9. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
FACTOR X	—	48
N-METHYLSULFONYL-D-PHE-GLY-ARG-P-NITROANILIDE	0.8–50	17
D-ILE-PRO-ARG-P-NITROANILIDE	0.85–10.4	14
D-ILE-PRO-ARG-4-NITROANILIDE	1.2–14	10
H-D-ISOLEUCYL-L-PROLYL-ARGININE-P-NITROANILIDE	1.5–9.8	8
BENZYLOXYCARBONYL-ARG-P-NITROBENZYL ESTER	0.19	1
METHANESULFONYL-D-CYCLOHEXYLALANYL-BUTYL-ARGININ	0.67	1
S-2288	11.8	1
SPECTROZYME FVIIA	0.67	1

UniProt features (219 total): sequence variant 122, strand 27, helix 17, disulfide bond 12, modified residue 11, turn 8, glycosylation site 5, domain 4, active site 3, site 2, mutagenesis site 2, chain 2, signal peptide 1, propeptide 1, binding site 1, splice variant 1

Structure

Experimental structures (PDB)

114 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
6R2W	X-RAY DIFFRACTION	1.25
5PAG	X-RAY DIFFRACTION	1.36
5PAX	X-RAY DIFFRACTION	1.36
4YLQ	X-RAY DIFFRACTION	1.4
5PAO	X-RAY DIFFRACTION	1.4
5PAV	X-RAY DIFFRACTION	1.4
5L0S	X-RAY DIFFRACTION	1.45
5PAE	X-RAY DIFFRACTION	1.45
5PB2	X-RAY DIFFRACTION	1.45
5PAS	X-RAY DIFFRACTION	1.48
5PAC	X-RAY DIFFRACTION	1.5
5PAF	X-RAY DIFFRACTION	1.5
4JZE	X-RAY DIFFRACTION	1.52
5PA9	X-RAY DIFFRACTION	1.55
5PAU	X-RAY DIFFRACTION	1.55
5PAK	X-RAY DIFFRACTION	1.56
8QOD	X-RAY DIFFRACTION	1.57
5PAQ	X-RAY DIFFRACTION	1.59
2BZ6	X-RAY DIFFRACTION	1.6
5PAM	X-RAY DIFFRACTION	1.6
5PAT	X-RAY DIFFRACTION	1.6
5PAN	X-RAY DIFFRACTION	1.62
5PAY	X-RAY DIFFRACTION	1.66
1KLI	X-RAY DIFFRACTION	1.69
5PAJ	X-RAY DIFFRACTION	1.7
2C4F	X-RAY DIFFRACTION	1.72
3TH2	X-RAY DIFFRACTION	1.72
5L30	X-RAY DIFFRACTION	1.73
5PAI	X-RAY DIFFRACTION	1.73
5L2Z	X-RAY DIFFRACTION	1.79

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P08709-F1	82.64	0.49

Antibody-complex structures (SAbDab): 2 — 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.

Catalytic / active sites (5): 404 (charge relay system); 113 (important for s-112 for o-xylosylation); 212–213 (cleavage; by factor xa, factor xiia, factor ixa, or thrombin); 253 (charge relay system); 302 (charge relay system)

Ligand- & substrate-binding residues (1): 398

Post-translational modifications (11): 66, 67, 74, 76, 79, 80, 85, 86, 89, 95, 123

Disulfide bonds (12): 77–82, 110–121, 115–130, 132–141, 151–162, 158–172, 174–187, 195–322, 219–224, 238–254, 370–389, 400–428

Glycosylation sites (5): 112, 112, 120, 205, 382

Mutagenesis-validated functional residues (2):

Position	Phenotype
112	complete loss of o-glycosylation and o-xylosylation by poglut1.
113	no effect on o-glycosylation by poglut1. drastic decrease in o-xylosylation.

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-1368108	BMAL1:CLOCK,NPAS2 activates circadian expression
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-9769735	Initiation of coagulation cascade
R-HSA-9769739	Regulation of clotting cascade
R-HSA-140834

MSigDB gene sets: 277 (showing top): GOBP_CIRCADIAN_RHYTHM, GOBP_PLATELET_DERIVED_GROWTH_FACTOR_RECEPTOR_SIGNALING_PATHWAY, MORF_RAGE, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_PROTEIN_ACTIVATION_CASCADE, MORF_FLT1, YAGI_AML_WITH_INV_16_TRANSLOCATION, GOBP_REGULATION_OF_WOUND_HEALING, GOBP_RESPONSE_TO_ESTRADIOL, GOBP_CELL_CHEMOTAXIS, GOBP_RESPONSE_TO_ACID_CHEMICAL, GOBP_INFLAMMATORY_RESPONSE, GOBP_REGULATION_OF_COAGULATION, STEARMAN_LUNG_CANCER_EARLY_VS_LATE_DN, GOBP_POSITIVE_REGULATION_OF_TOR_SIGNALING

GO Biological Process (30): response to hypoxia (GO:0001666), positive regulation of leukocyte chemotaxis (GO:0002690), blood coagulation (GO:0007596), circadian rhythm (GO:0007623), response to carbon dioxide (GO:0010037), positive regulation of platelet-derived growth factor receptor signaling pathway (GO:0010641), protein processing (GO:0016485), positive regulation of blood coagulation (GO:0030194), positive regulation of cell migration (GO:0030335), animal organ regeneration (GO:0031100), positive regulation of TOR signaling (GO:0032008), response to estradiol (GO:0032355), response to vitamin K (GO:0032571), response to genistein (GO:0033595), response to estrogen (GO:0043627), positive regulation of positive chemotaxis (GO:0050927), response to growth hormone (GO:0060416), response to cholesterol (GO:0070723), response to thyroxine (GO:0097068), response to Thyroid stimulating hormone (GO:1904400), response to 2,3,7,8-tetrachlorodibenzodioxine (GO:1904612), response to astaxanthin (GO:1905217), response to thyrotropin-releasing hormone (GO:1905225), proteolysis (GO:0006508), response to stress (GO:0006950), hemostasis (GO:0007599), response to hormone (GO:0009725), response to nutrient levels (GO:0031667), regulation of body fluid levels (GO:0050878), response to thyroid hormone (GO:0097066)

GO Molecular Function (8): serine-type endopeptidase activity (GO:0004252), signaling receptor binding (GO:0005102), calcium ion binding (GO:0005509), serine-type peptidase activity (GO:0008236), endopeptidase activity (GO:0004175), protein binding (GO:0005515), peptidase activity (GO:0008233), hydrolase activity (GO:0016787)

GO Cellular Component (8): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), endoplasmic reticulum lumen (GO:0005788), Golgi lumen (GO:0005796), plasma membrane (GO:0005886), extracellular matrix (GO:0031012), vesicle (GO:0031982), serine-type peptidase complex (GO:1905286)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Gamma-carboxylation, transport, and amino-terminal cleavage of proteins	3
Coagulation pathway	2
Circadian clock	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
response to oxygen-containing compound	3
positive regulation of chemotaxis	2
peptidase activity	2
intracellular organelle lumen	2
response to stress	1
response to decreased oxygen levels	1
positive regulation of leukocyte migration	1
regulation of leukocyte chemotaxis	1
leukocyte chemotaxis	1
hemostasis	1
wound healing	1
coagulation	1
rhythmic 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
blood coagulation	1
regulation of blood coagulation	1
positive regulation of coagulation	1
positive regulation of wound healing	1
positive regulation of hemostasis	1
cell migration	1
regulation of cell migration	1
positive regulation of cell motility	1
regeneration	1
animal organ development	1
TOR signaling	1
regulation of TOR signaling	1
positive regulation of intracellular signal transduction	1
response to lipid	1
response to vitamin	1
response to ketone	1
response to hydroxyisoflavone	1
response to hormone	1
positive chemotaxis	1
regulation of positive chemotaxis	1
response to peptide hormone	1
response to sterol	1

Protein interactions and networks

STRING

1186 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
F7	F3	P13726	999
F7	TFPI	P10646	949
F7	F8	P00451	935
F7	F9	P00740	931
F7	PROCR	Q9UNN8	915
F7	VWF	P04275	912
F7	ATP2C1	P98194	895
F7	SERPINC1	P01008	882
F7	THBD	P07204	873
F7	GGCX	P38435	832
F7	ATP2C2	O75185	817
F7	F2	P00734	794
F7	VKORC1	Q9BQB6	791
F7	GXYLT1	Q4G148	778
F7	SERPINE1	P05121	773

IntAct

19 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
F7	F7	psi-mi:“MI:0915”(physical association)	0.590
L3	F7	psi-mi:“MI:0407”(direct interaction)	0.440
F7	RCHY1	psi-mi:“MI:0915”(physical association)	0.370
ALB	SH3BP5	psi-mi:“MI:0914”(association)	0.350
F7	C1QL1	psi-mi:“MI:0914”(association)	0.350
SLX4	MYO1C	psi-mi:“MI:0914”(association)	0.350
USP49	ANKRD28	psi-mi:“MI:0914”(association)	0.350
UIMC1	PYCR3	psi-mi:“MI:0914”(association)	0.350
DMWD	P4HA2	psi-mi:“MI:0914”(association)	0.350
BECN1	F7	psi-mi:“MI:0914”(association)	0.350
GABARAPL1		psi-mi:“MI:0914”(association)	0.350
IKBKG	F7	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (19): F7 (Affinity Capture-MS), F7 (Affinity Capture-MS), C1QL1 (Affinity Capture-MS), NMU (Affinity Capture-MS), CRELD2 (Affinity Capture-MS), F7 (Affinity Capture-RNA), F7 (Reconstituted Complex), F3 (Co-crystal Structure), F7 (Biochemical Activity), F7 (Cross-Linking-MS (XL-MS)), F7 (Biochemical Activity), F7 (Affinity Capture-MS), F7 (Affinity Capture-MS), F7 (Affinity Capture-MS), F7 (Affinity Capture-MS)

ESM2 similar proteins: A0A1B0GVH4, A1L453, A4D1T9, A6H6T1, A8MTI9, A8QL53, A8QL57, B5U6Y3, E5RG02, O35453, O70169, P00745, P04070, P08709, P0CG03, P0DJE9, P22891, Q14BX2, Q28278, Q28661, Q2F9P2, Q2F9P4, Q2TV78, Q3V0Q7, Q402U7, Q4R7Y7, Q5FBW1, Q5M8S2, Q6AXZ6, Q6AY28, Q6IE62, Q6IE63, Q6PEW0, Q6UWB4, Q76HL1, Q7M756, Q7M761, Q7RTY5, Q7RTY7, Q7Z5A4

Diamond homologs: A0A1B0GVH4, A1L453, A2VE36, E5RG02, F2YMG0, O35205, O35453, O60235, O97370, P03952, P05981, P06868, P08001, P08709, P10323, P14272, P19236, P20231, P22457, P23578, P26262, P29293, P29786, P35035, P35036, P35038, P35039, P35040, P35041, P39675, P49275, P49864, P50342, P69526, P70375, P83748, P98139, Q05511, Q14B25, Q14BX2

SIGNOR signaling

10 interactions.

A	Effect	B	Mechanism
“Factor FVIIa:TF”	“up-regulates activity”	F7	cleavage
F9	“up-regulates activity”	F7	cleavage
F10	“up-regulates activity”	F7	cleavage
PROC	“down-regulates activity”	F7	cleavage
F2	“up-regulates activity”	F7
F7	“up-regulates activity”	F9	binding
F7	“up-regulates activity”	F10	binding
F7	“form complex”	“Factor FVIIa:TF”	binding
GGCX	“up-regulates activity”	F7	carboxylation
HPN	“up-regulates activity”	F7	cleavage

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	28
Likely pathogenic	43
Uncertain significance	166
Likely benign	34
Benign	19

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1071294	NM_019616.4(F7):c.724del (p.Asn241_Leu242insTer)	Pathogenic
1098445	NM_019616.4(F7):c.394G>T (p.Glu132Ter)	Pathogenic
1098448	NM_019616.4(F7):c.1272G>A (p.Trp424Ter)	Pathogenic
12069	NM_019616.4(F7):c.647G>A (p.Cys216Tyr)	Pathogenic
12071	NM_019616.4(F7):c.1190C>T (p.Thr397Met)	Pathogenic
12073	NM_019616.4(F7):c.283A>G (p.Asn95Asp)	Pathogenic
12074	NM_019616.4(F7):c.364+1G>C	Pathogenic
12075	NM_019616.4(F7):c.38T>C (p.Leu13Pro)	Pathogenic
12077	NM_019616.4(F7):c.783_799del (p.Arg262fs)	Pathogenic
12082	NC_000013.11:g.113105748C>G	Pathogenic
12084	NM_019616.4(F7):c.297C>A (p.Cys99Ter)	Pathogenic
12086	NM_019616.4(F7):c.562C>T (p.Gln188Ter)	Pathogenic
12087	NM_019616.4(F7):c.187G>A (p.Glu63Lys)	Pathogenic
12089	NM_019616.4(F7):c.1174G>T (p.Gly392Cys)	Pathogenic
12090	NM_019616.4(F7):c.917T>C (p.Phe306Ser)	Pathogenic
1322860	NM_019616.4(F7):c.568C>T (p.Arg190Ter)	Pathogenic
1322861	NM_019616.4(F7):c.1263C>G (p.Tyr421Ter)	Pathogenic
1691295	NM_019616.4(F7):c.225+1G>C	Pathogenic
1705959	NM_019616.4(F7):c.581del (p.Gly194fs)	Pathogenic
2634242	NM_019616.4(F7):c.1057C>T (p.Arg353Trp)	Pathogenic
3029413	NM_019616.4(F7):c.178T>C (p.Cys60Arg)	Pathogenic
3352537	NM_019616.4(F7):c.1008G>A (p.Met336Ile)	Pathogenic
3575772	NM_019616.4(F7):c.1157A>G (p.His386Arg)	Pathogenic
3765536	NM_019616.4(F7):c.225+1G>A	Pathogenic
3768242	NM_019616.4(F7):c.1249A>G (p.Arg417Gly)	Pathogenic
4530779	NM_019616.4(F7):c.279C>A (p.Cys93Ter)	Pathogenic
4541811	NM_019616.4(F7):c.1097T>C (p.Phe366Ser)	Pathogenic
4849355	NM_019616.4(F7):c.506-2A>G	Pathogenic
1098443	NM_019616.4(F7):c.220A>G (p.Arg74Gly)	Likely pathogenic
1098447	NM_019616.4(F7):c.737T>C (p.Leu246Pro)	Likely pathogenic

SpliceAI

1609 predictions. Top by Δscore:

Variant	Effect	Δscore
13:113113956:GACGC:G	donor_gain	1.0000
13:113113959:GC:G	donor_gain	1.0000
13:113115658:A:AG	acceptor_gain	1.0000
13:113115659:G:GG	acceptor_gain	1.0000
13:113117467:GCCCA:G	acceptor_loss	1.0000
13:113117468:CCCA:C	acceptor_loss	1.0000
13:113117469:CCAGG:C	acceptor_loss	1.0000
13:113117470:CA:C	acceptor_loss	1.0000
13:113117471:A:G	acceptor_loss	1.0000
13:113117472:G:GA	acceptor_loss	1.0000
13:113117596:GGTG:G	donor_loss	1.0000
13:113117597:GTG:G	donor_loss	1.0000
13:113117598:T:A	donor_loss	1.0000
13:113118409:CCA:C	acceptor_loss	1.0000
13:113118410:CA:C	acceptor_loss	1.0000
13:113118411:A:AG	acceptor_gain	1.0000
13:113118411:A:AT	acceptor_loss	1.0000
13:113118411:AG:A	acceptor_gain	1.0000
13:113118411:AGGC:A	acceptor_gain	1.0000
13:113118412:G:A	acceptor_loss	1.0000
13:113118412:G:GA	acceptor_gain	1.0000
13:113118412:GG:G	acceptor_gain	1.0000
13:113118412:GGC:G	acceptor_gain	1.0000
13:113118412:GGCG:G	acceptor_gain	1.0000
13:113118412:GGCGA:G	acceptor_gain	1.0000
13:113110846:GGACG:G	donor_gain	0.9900
13:113110847:G:GT	donor_gain	0.9900
13:113113961:G:GG	donor_gain	0.9900
13:113115655:CCCA:C	acceptor_loss	0.9900
13:113115656:CCA:C	acceptor_loss	0.9900

AlphaMissense

2883 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
13:113118639:G:C	W344C	0.997
13:113118639:G:T	W344C	0.997
13:113113951:T:A	C141S	0.995
13:113113952:G:C	C141S	0.995
13:113116872:G:C	W226C	0.995
13:113116872:G:T	W226C	0.995
13:113113873:T:A	C115S	0.994
13:113113874:G:C	C115S	0.994
13:113113891:T:A	C121S	0.994
13:113113892:G:C	C121S	0.994
13:113118805:T:A	C400S	0.994
13:113118806:G:C	C400S	0.994
13:113110788:T:A	C77S	0.993
13:113110789:G:C	C77S	0.993
13:113113920:C:G	C130W	0.993
13:113117503:T:A	C238S	0.993
13:113117504:G:C	C238S	0.993
13:113118631:A:C	S342R	0.993
13:113118633:C:A	S342R	0.993
13:113118633:C:G	S342R	0.993
13:113118806:G:A	C400Y	0.993
13:113110803:T:A	C82S	0.992
13:113110804:G:C	C82S	0.992
13:113113858:T:A	C110S	0.992
13:113113859:G:C	C110S	0.992
13:113118512:A:T	D302V	0.992
13:113118637:T:A	W344R	0.992
13:113118637:T:C	W344R	0.992
13:113113918:T:A	C130S	0.991
13:113113919:G:C	C130S	0.991

dbSNP variants (sampled 300 via entrez): RS1000315742 (13:113119549 C>T), RS1001159046 (13:113119512 C>T), RS1001484466 (13:113119409 C>T), RS1001711222 (13:113114720 G>A), RS1001718768 (13:113104686 A>G), RS1001749898 (13:113104425 G>A), RS1002017158 (13:113105146 A>G), RS1002105057 (13:113113423 G>A), RS1002191796 (13:113110990 G>A,C,T), RS1002248332 (13:113113546 GGTCACCCATA>G), RS1002254447 (13:113117685 C>G,T), RS1002439716 (13:113104624 G>A), RS1002590843 (13:113118049 G>A,C), RS1003236284 (13:113111153 C>G), RS1003321704 (13:113116231 C>T)

Disease associations

OMIM: gene MIM:613878 | disease phenotypes: MIM:227500, MIM:608446

GenCC curated gene-disease

Disease	Classification	Inheritance
congenital factor VII deficiency	Definitive	Autosomal recessive
factor VII deficiency	Definitive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
factor VII deficiency	Definitive	AR

Mondo (5): factor VII deficiency (MONDO:0002244), congenital factor VII deficiency (MONDO:0009211), myocardial infarction, susceptibility to (MONDO:0012039), hemophilia (MONDO:0018660), thrombocytopenia (MONDO:0002049)

Orphanet (2): Congenital factor VII deficiency (Orphanet:327), Hemophilia (Orphanet:448)

HPO phenotypes

18 total (18 of 18 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000132	Menorrhagia
HP:0000138	Ovarian cyst
HP:0000225	Gingival bleeding
HP:0000421	Epistaxis
HP:0000978	Bruising susceptibility
HP:0001892	Abnormal bleeding
HP:0002170	Intracranial hemorrhage
HP:0002239	Gastrointestinal hemorrhage
HP:0004846	Prolonged bleeding after surgery
HP:0005261	Joint hemorrhage
HP:0006298	Prolonged bleeding after dental extraction
HP:0008151	Prolonged prothrombin time
HP:0008169	Reduced factor VII activity
HP:0010881	Abnormality of the umbilical cord
HP:0011463	Childhood onset
HP:0011891	Post-partum hemorrhage
HP:0012233	Intramuscular hematoma

GWAS associations

14 associations (top):

Study	Trait	p-value
GCST000082_1	Factor VII	5.000000e-16
GCST000625_1	Factor VII levels	9.000000e-256
GCST001573_1	Prothrombin time	4.000000e-56
GCST006017_8	Prothrombin time	5.000000e-246
GCST006585_1057	Blood protein levels	2.000000e-191
GCST007401_27	Factor VII activity	4.000000e-22
GCST007401_28	Factor VII activity	2.000000e-19
GCST007401_29	Factor VII activity	6.000000e-38
GCST007401_30	Factor VII activity	0.000000e+00
GCST007401_31	Factor VII activity	0.000000e+00
GCST007401_32	Factor VII activity	2.000000e-58
GCST007401_8	Factor VII activity	0.000000e+00
GCST007402_1	Factor VII activity or levels	0.000000e+00
GCST008103_78	Bipolar disorder	1.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004619	factor VII measurement
EFO:0008390	prothrombin time measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D005168	Factor VII Deficiency	C15.378.100.100.310; C15.378.100.141.310; C15.378.463.310; C16.320.099.310
D013921	Thrombocytopenia	C15.378.140.855; C15.378.243.937

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (4): CHEMBL2095194 (PROTEIN COMPLEX), CHEMBL2111412 (SELECTIVITY GROUP), CHEMBL2111477 (SELECTIVITY GROUP), CHEMBL3991 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

8 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,363,030 (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
CHEMBL266349	MELAGATRAN	4	5,421
CHEMBL460026	ICOSAPENT	3	60,180
CHEMBL464982	GAMOLENIC ACID	3	26,552
CHEMBL4112929	MILVEXIAN	3	134
CHEMBL267476	LINOLEIC ACID	2	323,195
CHEMBL465183	DIHOMO-GAMMA-LINOLENIC ACID	2	2,022
CHEMBL8659	OLEIC ACID	2	713,838

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

PharmGKB variants

3 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs6046	F7		0.00	0
rs510317	F7		0.00	0
rs510335	F7		0.00	0

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — S1: Chymotrypsin

Most potent curated ligand interactions (2 total), top 2:

Ligand	Action	Affinity	Parameter
compound 1 [PMID: 16650987]	Inhibition	9.0	pKi
compound 11 [PMID: 16413183]	Inhibition	7.0	pKi

Binding affinities (BindingDB)

321 measured of 364 human assays (364 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
(15R)-2-[(1-aminoisoquinolin-6-yl)amino]-8-fluoro-4,15,17-trimethyl-7-[(3S)-oxolan-3-yl]oxy-13-oxa-4,11-diazatricyclo[14.2.2.16,10]henicosa-1(18),6,8,10(21),16,19-hexaene-3,12-dione	KI	0.02 nM	US-9174974: Macrocyclic factor VIIa inhibitors
(2R,15R)-2-[(1-aminoisoquinolin-6-yl)amino]-8-fluoro-4,15,17-trimethyl-7-[(3R)-oxolan-3-yl]oxy-13-oxa-4,11-diazatricyclo[14.2.2.16,10]henicosa-1(18),6,8,10(21),16,19-hexaene-3,12-dione	KI	0.05 nM	US-9174974: Macrocyclic factor VIIa inhibitors
(2R,15R)-2-[(1-aminoisoquinolin-6-yl)amino]-4,15,17-trimethyl-7-[1-(2H-tetrazol-5-yl)cyclopropyl]-13-oxa-4,11-diazatricyclo[14.2.2.16,10]henicosa-1(18),6,8,10(21),16,19-hexaene-3,12-dione	KI	0.12 nM	US-9174974: Macrocyclic factor VIIa inhibitors
(2R,15R)-2-[(1-aminoisoquinolin-6-yl)amino]-8-fluoro-7-[(2S)-1-hydroxypropan-2-yl]oxy-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	KI	0.14 nM	US-9174974: Macrocyclic factor VIIa inhibitors
(2R,15R)-2-[(1-amino-7-fluoroisoquinolin-6-yl)amino]-8-fluoro-4,15,17-trimethyl-7-propan-2-ylsulfonyl-13-oxa-4,11-diazatricyclo[14.2.2.16,10]henicosa-1(18),6,8,10(21),16,19-hexaene-3,12-dione	KI	0.14 nM	US-9174974: Macrocyclic factor VIIa inhibitors
(2R,15R)-2-[(1-aminoisoquinolin-6-yl)amino]-8-fluoro-4,15,17-trimethyl-7-[2-(2-oxopyrrolidin-1-yl)ethoxy]-13-oxa-4,11-diazatricyclo[14.2.2.16,10]henicosa-1(18),6,8,10(21),16,19-hexaene-3,12-dione	KI	0.14 nM	US-9174974: Macrocyclic factor VIIa inhibitors
(2R,15R)-2-[(1-aminoisoquinolin-6-yl)amino]-8-fluoro-7-[(2S)-1-methoxypropan-2-yl]oxy-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	KI	0.14 nM	US-9174974: Macrocyclic factor VIIa inhibitors
(2R,15R)-2-[(1-aminoisoquinolin-6-yl)amino]-7-(1,3-difluoropropan-2-yloxy)-8-fluoro-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	KI	0.15 nM	US-9174974: Macrocyclic factor VIIa inhibitors
(2R,15R)-2-[(1-amino-7-fluoroisoquinolin-6-yl)amino]-7-cyclopropylsulfonyl-8-fluoro-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	KI	0.17 nM	US-9174974: Macrocyclic factor VIIa inhibitors
(2R,15R)-2-[(1-aminoisoquinolin-6-yl)amino]-8-fluoro-7-[(2R)-1-hydroxypropan-2-yl]oxy-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	KI	0.17 nM	US-9174974: Macrocyclic factor VIIa inhibitors
(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	KI	0.17 nM	US-9174974: Macrocyclic factor VIIa inhibitors
(2R,15R)-2-[(1-aminoisoquinolin-6-yl)amino]-8-fluoro-7-(3-methoxypropoxy)-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	KI	0.2 nM	US-9174974: Macrocyclic factor VIIa inhibitors
(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	KI	0.23 nM	US-9174974: Macrocyclic factor VIIa inhibitors
(2R,15R)-2-[(1-aminoisoquinolin-6-yl)amino]-8-fluoro-7-[(3R,4S)-4-hydroxyoxolan-3-yl]oxy-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	KI	0.23 nM	US-9174974: Macrocyclic factor VIIa inhibitors
(2R,15R)-2-[(1-amino-7-fluoroisoquinolin-6-yl)amino]-7-cyclopropylsulfonyl-19-fluoro-17-methoxy-4,15-dimethyl-13-oxa-4,11-diazatricyclo[14.2.2.16,10]henicosa-1(18),6,8,10(21),16,19-hexaene-3,12-dione	KI	0.25 nM	US-9174974: Macrocyclic factor VIIa inhibitors
(2R,15R)-2-[(1-aminoisoquinolin-6-yl)amino]-7-cyclopropylsulfonyl-15-(fluoromethyl)-4,17-dimethyl-13-oxa-4,11-diazatricyclo[14.2.2.16,10]henicosa-1(18),6,8,10(21),16,19-hexaene-3,12-dione	KI	0.28 nM	US-9174974: Macrocyclic factor VIIa inhibitors
(2R,15R)-2-[(1-aminoisoquinolin-6-yl)amino]-N-ethyl-4,15,17-trimethyl-3,12-dioxo-N-(1,3-thiazol-2-ylmethyl)-13-oxa-4,11-diazatricyclo[14.2.2.16,10]henicosa-1(18),6,8,10(21),16,19-hexaene-7-carboxamide	KI	0.3 nM	US-9174974: Macrocyclic factor VIIa inhibitors
(2R,15R)-2-[(1-aminoisoquinolin-6-yl)amino]-7-tert-butylsulfonyl-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	KI	0.31 nM	US-9174974: Macrocyclic factor VIIa inhibitors
(2R,15R)-2-[(1-aminoisoquinolin-6-yl)amino]-7-[(2R)-2-cyclopropyl-2-hydroxyethoxy]-8-fluoro-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	KI	0.34 nM	US-9174974: Macrocyclic factor VIIa inhibitors
(2R)-N-[(3-aminobenzene)sulfonyl]-2-[(4-carbamimidoyl-3-hydroxyphenyl)amino]-2-(3,5-diethoxy-2-fluorophenyl)acetamide	KI	0.35 nM
(2R,15R)-2-[(1-amino-8-fluoroisoquinolin-6-yl)amino]-8-fluoro-4,15,17-trimethyl-7-propan-2-ylsulfonyl-13-oxa-4,11-diazatricyclo[14.2.2.16,10]henicosa-1(18),6,8,10(21),16,19-hexaene-3,12-dione	KI	0.36 nM	US-9174974: Macrocyclic factor VIIa inhibitors
(2R,15R)-2-[(1-amino-4-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	KI	0.43 nM	US-9174974: Macrocyclic factor VIIa inhibitors
(2R,15R)-2-[(1-aminoisoquinolin-6-yl)amino]-8-fluoro-7-[(1-isocyanocyclopropyl)methoxy]-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	KI	0.44 nM	US-9174974: Macrocyclic factor VIIa inhibitors
(2R,15R)-2-[(1-aminoisoquinolin-6-yl)amino]-8-fluoro-7-[(2S)-2-hydroxypropoxy]-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	KI	0.46 nM	US-9174974: Macrocyclic factor VIIa inhibitors
(2R,15R)-2-[(1-aminoisoquinolin-6-yl)amino]-7-cyclopropylsulfonyl-15-(difluoromethyl)-4,17-dimethyl-13-oxa-4,11-diazatricyclo[14.2.2.16,10]henicosa-1(18),6,8,10(21),16,19-hexaene-3,12-dione	KI	0.5 nM	US-9174974: Macrocyclic factor VIIa inhibitors
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]cyclopropane-1-carboxylic acid	KI	0.55 nM	US-9174974: Macrocyclic factor VIIa inhibitors
(2R,15R)-2-[(1-aminoisoquinolin-6-yl)amino]-N,N-diethyl-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-hexaene-7-carboxamide	KI	0.57 nM	US-9174974: Macrocyclic factor VIIa inhibitors
(2R)-2-[(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]butanoic acid	KI	0.61 nM	US-9174974: Macrocyclic factor VIIa inhibitors
(2R,15R)-2-[(1-aminoisoquinolin-6-yl)amino]-7-diethoxyphosphoryl-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	KI	0.62 nM	US-9174974: Macrocyclic factor VIIa inhibitors
(2R,15R)-2-[(1-amino-8-fluoroisoquinolin-6-yl)amino]-7-cyclopropylsulfonyl-8-fluoro-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	KI	0.66 nM	US-9174974: Macrocyclic factor VIIa inhibitors
(2R)-2-[(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]-4,4-difluorobutanoic acid	KI	0.9 nM	US-9174974: Macrocyclic factor VIIa inhibitors
(2R,15R)-2-[(1-amino-8-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	KI	1 nM	US-9174974: Macrocyclic factor VIIa inhibitors
(2R)-2-[(1-aminoisoquinolin-6-yl)amino]-7-ethylsulfonyl-17,20-dimethyl-13-oxa-4,11-diazatricyclo[14.2.2.16,10]henicosa-1(19),6,8,10(21),16(20),17-hexaene-3,12-dione	KI	1.1 nM	US-9174974: Macrocyclic factor VIIa inhibitors
(2R,15R)-2-[(1-aminoisoquinolin-6-yl)amino]-7-(azetidine-1-carbonyl)-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	KI	1.2 nM	US-9174974: Macrocyclic factor VIIa inhibitors
(2R,15R)-2-[(1-amino-4-fluoroisoquinolin-6-yl)amino]-4,15,17-trimethyl-7-propan-2-ylsulfonyl-13-oxa-4,11-diazatricyclo[14.2.2.16,10]henicosa-1(18),6,8,10(21),16,19-hexaene-3,12-dione	KI	1.2 nM	US-9174974: Macrocyclic factor VIIa inhibitors
(2R,15R)-2-[(1-amino-4-fluoroisoquinolin-6-yl)amino]-7-[(2S)-1-methoxypropan-2-yl]sulfonyl-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	KI	1.8 nM	US-9174974: Macrocyclic factor VIIa inhibitors
phenylglycine amide compound 10	KI	2 nM
(2R)-2-[(1-aminoisoquinolin-6-yl)amino]-7-cyclopropylsulfonyl-15,15-difluoro-4,17,20-trimethyl-13-oxa-4,11-diazatricyclo[14.2.2.16,10]henicosa-1(19),6,8,10(21),16(20),17-hexaene-3,12-dione	KI	2 nM	US-9174974: Macrocyclic factor VIIa inhibitors
(2R)-2-[(1-aminoisoquinolin-6-yl)amino]-N-ethyl-15,15-difluoro-4,17,20-trimethyl-3,12-dioxo-N-(1,3-thiazol-2-ylmethyl)-13-oxa-4,11-diazatricyclo[14.2.2.16,10]henicosa-1(19),6,8,10(21),16(20),17-hexaene-7-carboxamide	KI	2.2 nM	US-9174974: Macrocyclic factor VIIa inhibitors
(2R,15R)-2-[(1-amino-4-fluoroisoquinolin-6-yl)amino]-7-ethylsulfonyl-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	KI	2.3 nM	US-9174974: Macrocyclic factor VIIa inhibitors
(2R,15R)-2-[(1-aminoisoquinolin-6-yl)amino]-N,N,4,15,17-pentamethyl-3,12-dioxo-13-oxa-4,11-diazatricyclo[14.2.2.16,10]henicosa-1(18),6,8,10(21),16,19-hexaene-7-carboxamide	KI	2.5 nM	US-9174974: Macrocyclic factor VIIa inhibitors
(2S)-2-[(2R)-2-[4-(benzyloxy)-3-methoxyphenyl]-2-[(4-carbamimidoylphenyl)amino]acetamido]-2-phenylacetic acid	KI	4 nM
2-[3-(5-carbamimidoyl-1H-indol-2-yl)-4-hydroxy-5-(3-nitrophenyl)phenyl]acetic acid	KI	4 nM
2-[3-(5-carbamimidoyl-1H-1,3-benzodiazol-2-yl)-5-(5-fluoro-2-hydroxyphenyl)-4-hydroxyphenyl]butanedioic acid	KI	4 nM
2-[3-(5-carbamimidoyl-1H-1,3-benzodiazol-2-yl)-5-(5-chloro-2-hydroxyphenyl)-4-hydroxyphenyl]butanedioic acid	KI	5.4 nM
2-[3-(5-carbamimidoyl-1H-1,3-benzodiazol-2-yl)-4-hydroxy-5-(2-hydroxy-5-nitrophenyl)phenyl]butanedioic acid	KI	6 nM
(2S)-2-{2-[4-(benzyloxy)-5-methoxy-2-(2-phenylacetyl)phenyl]-2-[(4-carbamimidoylphenyl)amino]acetamido}-2-phenylacetic acid	KI	7 nM
substituted biphenyl derivative, 36ao	IC50	8 nM
2-[3-(3-bromo-5-chloro-2-hydroxyphenyl)-5-(5-carbamimidoyl-1H-1,3-benzodiazol-2-yl)-4-hydroxyphenyl]butanedioic acid	KI	9 nM
substituted biphenyl derivative, 36b	IC50	9 nM

ChEMBL bioactivities

936 potent at pChembl≥5 of 1030 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	Ki	0.02	nM	CHEMBL3930738
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
10.54	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
10.44	IC50	0.036	nM	CHEMBL499632
10.38	IC50	0.042	nM	CHEMBL487955
10.35	IC50	0.045	nM	CHEMBL505720
10.30	Ki	0.05	nM	CHEMBL3986081
10.28	IC50	0.052	nM	CHEMBL497067
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	Ki	0.078	nM	CHEMBL73737
10.04	IC50	0.092	nM	CHEMBL500948
10.01	IC50	0.097	nM	CHEMBL485705
10.01	IC50	0.098	nM	CHEMBL525274
9.98	IC50	0.104	nM	CHEMBL524548
9.92	Ki	0.12	nM	CHEMBL3902759
9.92	IC50	0.12	nM	CHEMBL224485
9.89	IC50	0.13	nM	CHEMBL526193
9.85	Ki	0.14	nM	CHEMBL3900166
9.85	Ki	0.14	nM	CHEMBL3977297
9.85	Ki	0.14	nM	CHEMBL3967595
9.85	Ki	0.14	nM	CHEMBL3903215
9.85	Ki	0.14	nM	CHEMBL3969432
9.82	Ki	0.15	nM	CHEMBL3906646
9.80	Ki	0.16	nM	CHEMBL3891120
9.77	Ki	0.17	nM	CHEMBL3961226
9.77	Ki	0.17	nM	CHEMBL3915633
9.77	Ki	0.17	nM	CHEMBL3891120
9.72	IC50	0.19	nM	CHEMBL499829
9.70	Ki	0.2	nM	CHEMBL3920165
9.66	Ki	0.22	nM	CHEMBL3984725
9.64	Ki	0.23	nM	CHEMBL3901391
9.64	Ki	0.23	nM	CHEMBL3892246
9.64	IC50	0.231	nM	CHEMBL504391

PubChem BioAssay actives

1119 with measured affinity, of 1897 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
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
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
(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
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
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
(5R,11R)-11-[(1-amino-4-fluoroisoquinolin-6-yl)amino]-16-cyclopropylsulfonyl-7-(2,2-difluoroethoxy)-5,13-dimethyl-2,13-diazatricyclo[13.3.1.16,10]icosa-1(19),6,8,10(20),15,17-hexaene-3,12-dione	1331371: Inhibition of recombinant human factor-7a/TF using S2288 as substrate measured after 60 mins at 37 degC	ki	0.0002	uM
[(2R,15R)-2-[(1-aminoisoquinolin-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]-ethoxyphosphinic acid	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	0.0003	uM
2-[2-[(4-carbamimidoylphenyl)carbamoyl]-4-[3-(hydroxymethyl)thiophen-2-yl]phenyl]-5-(2-methylpropylcarbamoyl)benzoic acid	397857: Inhibition of tissue factor/factor 7a	ic50	0.0003	uM
2-[2-[(4-carbamimidoylphenyl)carbamoyl]-4-(3-hydroxyprop-1-ynyl)phenyl]-5-(2-methylpropylcarbamoyl)benzoic acid	397857: Inhibition of tissue factor/factor 7a	ic50	0.0003	uM
(2R)-N-(3-aminophenyl)sulfonyl-2-(4-carbamimidoyl-3-hydroxyanilino)-2-(3,5-diethoxy-2-fluorophenyl)acetamide	1195253: Inhibition of human factor 7a	ki	0.0003	uM
(2R,15R)-2-[(1-amino-4-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	0.0004	uM
2-[2-[(4-carbamimidoylphenyl)carbamoyl]-4-(4-hydroxybut-1-ynyl)phenyl]-5-(2-methylpropylcarbamoyl)benzoic acid	397857: Inhibition of tissue factor/factor 7a	ic50	0.0005	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Ethinyl Estradiol	affects binding, increases expression, affects cotreatment, decreases expression, affects reaction	6
Benzo(a)pyrene	affects methylation, decreases expression, decreases methylation	4
Gestodene	affects cotreatment, increases expression, affects reaction	3
Warfarin	affects response to substance, decreases expression, increases reaction	3
Aflatoxin B1	affects methylation, decreases expression, decreases methylation	3
ethinyl estradiol-desogestrel combination	increases expression, affects reaction	2
Contraceptives, Oral	increases expression, increases activity	2
Valproic Acid	decreases expression, affects expression	2
Cyclosporine	decreases expression, increases expression	2
Levonorgestrel	affects cotreatment, decreases expression, increases expression	2
methyleugenol	decreases expression	1
propionaldehyde	decreases expression	1
bisphenol A	increases expression	1
antibiotic G 418	increases activity, increases expression	1
ethyl-p-hydroxybenzoate	decreases expression	1
norgestimate	affects cotreatment, increases expression	1
sodium arsenite	decreases expression	1
butyraldehyde	decreases expression	1
perfluorooctanoic acid	decreases expression	1
dienogest	affects cotreatment, increases expression	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	increases methylation	1
CycloProvera	decreases expression	1
CMF protocol	decreases expression	1
pentanal	decreases expression	1
norgestimate, ethinyl estradiol drug combination	increases expression	1
estradiol, norethindrone drug combination	decreases expression	1
estradiol valerate-dienogest	affects cotreatment, increases expression	1
abrine	decreases expression	1
NuvaRing	increases expression	1

ChEMBL screening assays

255 unique, capped per target: 237 binding, 17 functional, 1 admet

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
CHEMBL4621401	ADMET	Inhibition of human F7a using fluorescent peptide as substrate by florescence assay	Structure-Based Design and Preclinical Characterization of Selective and Orally Bioavailable Factor XIa Inhibitors: Demonstrating the Power of an Integrated S1 Protease Family Approach. — J Med Chem

Cellosaurus cell lines

5 cell lines: 2 transformed cell line, 1 induced pluripotent stem cell, 1 cancer cell line, 1 telomerase immortalized cell line

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

Cellosaurus	Name	Category	Sex
CVCL_A1ND	YCMi002-A	Induced pluripotent stem cell	Female
CVCL_E3FM	HEK293T-FVII	Transformed cell line	Female
CVCL_E3FN	HepG2-FVII	Cancer cell line	Male
CVCL_WG88	HEK293-Nrf2 clone 2-FVII	Transformed cell line	Female
CVCL_XY59	imHC-FVII	Telomerase immortalized cell line	Sex unspecified

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00707772	PHASE4	COMPLETED	Pegasys® Plus Ribavirin in Hemophilic Patients With Hepatitis C Virus Infection
NCT04108260	PHASE4	UNKNOWN	The Effectiveness of Recombinant Coagulation Factor IX With Recombinant Albumin (rIX-FP) in Severe Hemophilia B Patients
NCT05728528	PHASE4	COMPLETED	Impact of Moderate Intensity Physical Activities on PK-guided EHL FVIII Concentrates Prophylaxis Severe HA Patients
NCT06752850	PHASE4	ACTIVE_NOT_RECRUITING	A Study to Investigate the Course of Synovial Hypertrophy in Patients With Haemophilia A on Efanesoctocog Alfa Prophylaxis
NCT07406139	PHASE4	RECRUITING	PCC Treatment for Hemophilia Patients With Inhibitor（2022PCC-A）
NCT00039858	PHASE4	COMPLETED	Evaluation of Argatroban Injection in Pediatric Patients Requiring Anticoagulant Alternatives to Heparin
NCT00239733	PHASE4	TERMINATED	Anti-D for Treating Thrombocytopenia in Adults Infected With Hepatitis C Virus With or Without HIV Co-Infection
NCT00907478	PHASE4	COMPLETED	Study on Bone Marrow Morphology in Adults Receiving Romiplostim for Treatment of Thrombocytopenia Associated With Immune Thrombocytopenia Purpura (ITP)
NCT01727401	PHASE4	TERMINATED	Thromboprophylaxis of Venous Thromboembolism in Acutely-ill Medical Inpatients With Thrombocytopenia
NCT02032134	PHASE4	TERMINATED	Protocol for the Infusion of Buffy Coat-derived Cryopreserved Platelets in Patients With Severe Thrombocytopenia
NCT02267993	PHASE4	COMPLETED	Efficacy and Safety of rhTPO for the Treatment of Thrombocytopenia After Chemotherapy in AML Patients
NCT03633019	PHASE4	UNKNOWN	High-dose Use of rhTPO in CIT Patients
NCT03688191	PHASE4	UNKNOWN	Study of Sirolimus in CTD-TP in China
NCT04906083	PHASE4	UNKNOWN	Avatrombopag in Patients With End-stage Liver Disease and Thrombocytopenia
NCT05217719	PHASE4	UNKNOWN	Effects of Recombinant Human Thrombopoietin on Platelet Levels in ICU Patients
NCT05255003	PHASE4	RECRUITING	STrategies for Anticoagulation in Patients With thRombocytopenia and Cancer-associated Thrombosis
NCT05382013	PHASE4	UNKNOWN	Efficacy and Safety of Avatrombopag for Treating TCP in HBV-ACLF Patients Receiving ALSS Treatment
NCT05944458	PHASE4	COMPLETED	Efficacy of Intravenous N-Acetylcysteine in Preventing Linezolid-Induced Thrombocytopenia in Critically Ill Patients
NCT06562738	PHASE4	RECRUITING	Clinical Study on Efficacy and Safety of Hetrombopag in the Preoperative Patients of Thrombocytopenia
NCT03079063	PHASE3	COMPLETED	Study Comparing the Pharmacokinetic of Biosimilar Eptacog Alfa With Novoseven®, in Patients With Congenital Factor VII Deficiency
NCT00606060	PHASE3	COMPLETED	BAY14-2222 Continuous Infusion in Surgeries
NCT02306694	PHASE3	COMPLETED	Prospective Biomarkers of Bone Metabolism in Hemophilia A
NCT02548143	PHASE3	COMPLETED	LR769 in Congenital Hemophilia Patients With Inhibitors Undergoing Elective Surgery or Invasive Procedures
NCT03549871	PHASE3	COMPLETED	A Study of Fitusiran in Severe Hemophilia A and B Patients Previously Receiving Factor or Bypassing Agent Prophylaxis
NCT03754790	PHASE3	ACTIVE_NOT_RECRUITING	Long-term Safety and Efficacy Study of Fitusiran in Patients With Hemophilia A or B, With or Without Inhibitory Antibodies to Factor VIII or IX
NCT03974113	PHASE3	ACTIVE_NOT_RECRUITING	Fitusiran Prophylaxis in Male Pediatric Subjects Aged 1 to Less Than 12 Years With Hemophilia A or B
NCT05662319	PHASE3	ACTIVE_NOT_RECRUITING	A Study to Test a Medicine (Fitusiran) Injected Under the Skin for Preventing Bleeding Episodes in Male Adolescent or Adult Participants With Severe Hemophilia
NCT05695391	PHASE3	TERMINATED	A Phase 3 Study of the Safety and Efficacy of Coagulation Factor VIIa (Recombinant) for the Prevention of Excessive Bleeding in Patients With Congenital Hemophilia A or B With Inhibitors to Factor VIII or IX Undergoing Elective Major Surgical Procedures SCOPE HIM
NCT06922045	PHASE3	RECRUITING	Phase III Clinical Trial of STSP-0601 for Injection in Hemophilia Patients
NCT07285460	PHASE3	RECRUITING	A Study to Investigate the Efficacy and Safety of Fitusiran Prophylaxis in Male Participants Aged 1 to Less Than 12 Years With Hemophilia A or B
NCT00037791	PHASE3	COMPLETED	Safety and Efficacy of (PN-152,243)/PN-196,444 in the Prevention of Thrombocytopenia
NCT00039910	PHASE3	COMPLETED	Safety and Efficacy of (PN-152,243)/PN-196,444 in the Prevention of Thrombocytopenia
NCT00073580	PHASE3	COMPLETED	Angiomax in Patients With HIT/HITTS Type II Undergoing Off-Pump Coronary Artery Bypass Grafting (CABG) (CHOOSE)
NCT00102323	PHASE3	COMPLETED	AMG 531 Treatment of Thrombocytopenic Subjects With Immune (Idiopathic) Thrombocytopenic Purpura (ITP) Refractory to Splenectomy
NCT00102336	PHASE3	COMPLETED	AMG 531 Treatment of Thrombocytopenic Subjects With Immune (Idiopathic) Thrombocytopenic Purpura (ITP) Prior to Splenectomy
NCT00116688	PHASE3	COMPLETED	Open Label Extension Study of Romiplostim (AMG 531) in Thrombocytopenic Patients With Immune (Idiopathic) Thrombocytopenic Purpura (ITP)
NCT00128713	PHASE3	COMPLETED	Optimal Platelet Dose Strategy for Management of Thrombocytopenia
NCT00151866	PHASE3	COMPLETED	Efficacy of Transfusions With Platelets Stored in Platelet Additive Solution II Versus Plasma
NCT00261924	PHASE3	COMPLETED	Efficacy and Safety Study of Platelets Treated for Pathogen Inactivation and Stored for Up to Seven Days
NCT00415532	PHASE3	COMPLETED	Romiplostim (AMG 531) Versus Medical Standard of Care for Immune (Idiopathic) Thrombocytopenic Purpura