Selected-GenAtlas references SOURCE GeneCards NCBI Gene Swiss-Prot Ensembl
HGNC UniGene Nucleotide OMIM UCSC
Home Page
FLASH GENE
Symbol TFPI contributors: mct/ - updated : 22-10-2017
HGNC name tissue factor pathway inhibitor (lipoprotein-associated coagulation inhibitor)
HGNC id 11760
Location 2q32.1      Physical location : 188.328.959 - 188.419.219
Synonym name
  • extrinsic pathway inhibitor
  • lipoprotein-associated coagulation inhibitor
  • tissue factor pathway inhibitor
  • Synonym symbol(s) LACI, EPI, TFI, TFPI1
    DNA
    TYPE functioning gene
    STRUCTURE 101.57 kb     8 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked Y status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    9 - 3927 35 304 - 2010 20519147
    7 - 1166 - 251 - 1993 8104873
    EXPRESSION
    Type
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularvessel    
    Skin/Tegumentskin     Homo sapiens
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / hematopoieticbone marrow   
    Blood / hematopoieticplasma   
    Epithelialbarrier liningepidermisstratum basale  Homo sapiens
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Blood/Hematopoieticmonocyte
    Blood/Hematopoieticplatelet
    Cardiovascularendothelial cell
    Lymphoid/Immunemacrophage
    cell lineage
    cell lines expressed by breast cancer and other cancer cell lines
    fluid/secretion plasma
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • acidic N-terminal region,
  • three tandem Kunitz-type (58AA motif containing three intrachain disulfide bonds) domains
  • a basic C-terminus
  • conjugated GlycoP
    HOMOLOGY
    Homologene
    FAMILY
    CATEGORY regulatory
    SUBCELLULAR LOCALIZATION extracellular
        plasma membrane
    basic FUNCTION
  • tissue factor pathway inhibitor
  • lipoprotein associated coagulation inhibitor (Xa, VIIa-TF inhibitor)
  • serine proteinase inhibitor
  • regulates factor X activation
  • primary physiologic inhibitor of tissue factor and is present within platelets
  • influences the angiogenic process via a non-haemostatic pathway, by downregulating the migratory mechanisms of endothelial cells
  • endogenous inhibitor regulating Tissue factor-induced blood coagulation
  • its presence in association with breast cancer cells localised in regional lymph nodes may indicate its role in lymphatic spread
  • with PROS1, act together in down-regulating coagulation
  • TFPI and PROS1 are major regulators of thrombin generation both in the absence and presence of activated protein C (APC)
  • primary physiological inhibitor of tissue factor (TF) induced coagulation
  • may, via its C terminus, modulate cell surface, heparin, and lipopolysaccharide interactions as well as participate in growth inhibition
  • role for TFPI in cutaneous defense against infections
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS coagulation/hemostasis
    PATHWAY
    metabolism
    signaling
    a component
  • formation of a complex with FIII, FVIIa, Fxa
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • FIII
  • binds to protein S (PROS1) in plasma
  • procoagulant role of PROC pathway may have important implications for the regulation of F3- and TFPI-dependent biologic responses and for fine tuning of the hemostatic balance in the vascular system
  • ADTRP-dependent up-regulation of TFPI expression and activity by androgen represents a novel mechanism of increasing the anticoagulant protection of the endothelium
  • regulation of TFPI expression is likely one potential mechanism by which ADTRP regulates primitive myelopoiesis and definitive hematopoiesis
  • POU1F1 is a transcription factor that regulates TFPI transcription in response to ADTRP
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --other  
    weaker expression in cancer cells localised in lymph node metastatic foci of breast cancer
    constitutional     --low  
    in genetic and acquired protein S deficiency and concomitant TFPI deficiency substantially contributes to the hypercoagulable state associated with protein S deficiency
    constitutional     --over  
    in pregnant patients at 20 weeks gestation who subsequently develop preeclampsia
    constitutional       gain of function
    in acute skin wounds as well as wound edges of chronic leg ulcers
    Susceptibility
  • putative susceptibility gene for venous thrombosis (536GC->T)
  • risk of restenosis after coronary angioplasty
  • to venous thromboembolism
  • Variant & Polymorphism other
  • low levels of free TFPI are at an increased risk of recurrent venous thromboembolism
  • minus 33C allele has been reported to be associated with elevated total TFPI plasma levels compared to the minus 33T and has thus been suggested to be associated with a lowered risk of venous thrombosis
  • Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    bloodcoagulation 
    inhibition of TFPI might be a promising novel treatment approach, especially in haemophilia patients with FVIII inhibitors
    ANIMAL & CELL MODELS