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27 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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TFPI
tissue factor pathway inhibitor
Chromosome 2 · 2q32.1
NCBI Gene: 7035Ensembl: ENSG00000003436.17HGNC: HGNC:11760UniProt: P10646
270PubMed Papers
20Diseases
4Drugs
0Pathogenic Variants
CLINICAL
FDA Approved Target
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
caveolacell surfacenegative regulation of blood coagulationcellular response to steroid hormone stimulushemophilia Ahemophilia Bhemorrhagehemophilia
✦AI Summary

TFPI (tissue factor pathway inhibitor) is a crucial anticoagulant protein that regulates blood coagulation through multiple mechanisms. Its primary function is to inhibit factor Xa directly and, in a factor Xa-dependent manner, inhibit the tissue factor/factor VIIa complex by forming a quaternary complex (TF-FVIIa-FXa-TFPI), effectively preventing further coagulation cascade activation 1. TFPI works synergistically with protein S to enhance factor Xa inhibition and is particularly important when activated protein C is present 2. The protein is predominantly expressed by megakaryocytes and microvascular endothelium under normal conditions, with endothelial cells providing anticoagulant activity through both surface-expressed heparin-like proteoglycans and TFPI 34. Beyond its classical anticoagulant role, TFPI has emerged as a regulator of erythropoiesis, where erythroblast-derived TFPI promotes heme biosynthesis in central macrophages through ERK1/2-GATA1 signaling 5. Clinically, TFPI deficiency presents therapeutic opportunities for hemophilia treatment, as TFPI inhibition can restore hemostasis through the extrinsic pathway without requiring factors VIII or IX 6. Additionally, TFPI demonstrates protective effects against atherosclerosis by inhibiting endothelial activation and vascular smooth muscle cell proliferation 7.

Sources cited
1
TFPI inhibits factor Xa directly and forms quaternary complex with TF-FVIIa-FXa to prevent coagulation
PMID: 10856975
2
TFPI works synergistically with protein S to enhance factor Xa inhibition
PMID: 22425215
3
TFPI is normally expressed by megakaryocytes and microvascular endothelium
PMID: 7482419
4
Endothelial cells provide anticoagulant activity through surface heparin-like proteoglycans and TFPI
PMID: 39522336
5
TFPI regulates erythropoiesis by promoting heme biosynthesis in central macrophages through ERK1/2-GATA1 signaling
PMID: 38729948
6
TFPI inhibition can restore hemostasis in hemophilia through extrinsic pathway
PMID: 27207418
7
TFPI has protective effects against atherosclerosis by inhibiting endothelial activation and VSMC proliferation
PMID: 30695687
Disease Associationsⓘ20
hemophilia AOpen Targets
0.56Moderate
hemophilia BOpen Targets
0.55Moderate
hemorrhageOpen Targets
0.53Moderate
hemophiliaOpen Targets
0.51Moderate
drug toxicityOpen Targets
0.37Weak
neurodegenerative diseaseOpen Targets
0.37Weak
hemorrhagic diseaseOpen Targets
0.36Weak
myocardial infarctionOpen Targets
0.36Weak
Alzheimer diseaseOpen Targets
0.32Weak
HypercholesterolemiaOpen Targets
0.32Weak
multiple sclerosisOpen Targets
0.32Weak
lysosomal storage diseaseOpen Targets
0.32Weak
Parkinson diseaseOpen Targets
0.32Weak
Respiratory insufficiencyOpen Targets
0.31Weak
endometriosisOpen Targets
0.31Weak
contact dermatitisOpen Targets
0.30Weak
Meniere diseaseOpen Targets
0.30Weak
idiopathic pulmonary fibrosisOpen Targets
0.26Weak
COVID-19Open Targets
0.22Weak
basal cell carcinomaOpen Targets
0.21Weak
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Drug Targets4
ANDEXANET ALFAApproved
Tissue factor pathway inhibitor inhibitor
BAY-1093884Phase II
Tissue factor pathway inhibitor inhibitor
hemophilia B
CONCIZUMABApproved
Tissue factor pathway inhibitor inhibitor
hemorrhage
MARSTACIMABApproved
Tissue factor pathway inhibitor inhibitor
Related Genes
SERPINE1Protein interaction100%PLGProtein interaction95%VWFProtein interaction92%SERPINC1Protein interaction88%F2Protein interaction88%F3Protein interaction88%
Tissue Expression6 tissues
Liver
100%
Lung
83%
Heart
20%
Ovary
13%
Brain
4%
Bone Marrow
2%
Gene Interaction Network
Click a node to explore
TFPISERPINE1PLGVWFSERPINC1F2F3
PROTEIN STRUCTURE
Preparing viewer…
PDB5NMV · 1.65 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.56Moderately Constrained
pLIⓘ
0.90Intolerant
Observed/Expected LoF0.33 [0.20–0.56]
RankingsWhere TFPI stands among ~20K protein-coding genes
  • #1,368of 20,598
    Most Researched270 · top 10%
  • #458of 1,025
    FDA-Approved Drug Targets3
  • #3,614of 17,882
    Most Constrained (LOEUF)0.56 · top quartile
Genes detectedTFPI
Sources retrieved27 papers
Response time—
📄 Sources
27▼
1
Targeting TFPI for hemophilia treatment.
PMID: 27207418
Thromb Res · 2016
1.00
2
TFPI-dependent activities of protein S.
PMID: 22425215
Thromb Res · 2012
0.90
3
Functionally distinct anticoagulant mechanisms of endothelial cells.
PMID: 39522336
Thromb Res · 2024
0.80
4
Steroids and Malignancy Increase Local Heparanase and Decrease Markers of Osteoblast Activity in Bone Tissue Microcirculation.
PMID: 39766213
Biomolecules · 2024
0.80
5
Post-transcriptional, post-translational and pharmacological regulation of tissue factor pathway inhibitor.
PMID: 30439766
Blood Coagul Fibrinolysis · 2018
0.72