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    TFPI tissue factor pathway inhibitor [ Homo sapiens (human) ]

    Gene ID: 7035, updated on 28-Oct-2024

    Summary

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    Official Symbol
    TFPIprovided by HGNC
    Official Full Name
    tissue factor pathway inhibitorprovided by HGNC
    Primary source
    HGNC:HGNC:11760
    See related
    Ensembl:ENSG00000003436 MIM:152310; AllianceGenome:HGNC:11760
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    EPI; TFI; LACI; TFPI1
    Summary
    This gene encodes a Kunitz-type serine protease inhibitor that regulates the tissue factor (TF)-dependent pathway of blood coagulation. The coagulation process initiates with the formation of a factor VIIa-TF complex, which proteolytically activates additional proteases (factors IX and X) and ultimately leads to the formation of a fibrin clot. The product of this gene inhibits the activated factor X and VIIa-TF proteases in an autoregulatory loop. Inhibition of the encoded protein restores hemostasis in animal models of hemophilia. This gene encodes multiple protein isoforms that differ in their inhibitory activity, specificity and cellular localization. [provided by RefSeq, Jul 2016]
    Expression
    Broad expression in liver (RPKM 42.6), placenta (RPKM 39.9) and 20 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See TFPI in Genome Data Viewer
    Location:
    2q32.1
    Exon count:
    13
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 2 NC_000002.12 (187464230..187554435, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 2 NC_060926.1 (187953180..188043364, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 2 NC_000002.11 (188328957..188419162, complement)

    Chromosome 2 - NC_000002.12Genomic Context describing neighboring genes Neighboring gene CALCRL and TFPI antisense RNA 1 Neighboring gene RNA, U6 small nuclear 989, pseudogene Neighboring gene Sharpr-MPRA regulatory region 15572 Neighboring gene MPRA-validated peak3978 silencer Neighboring gene MPRA-validated peak3980 silencer Neighboring gene MPRA-validated peak3982 silencer Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr2:188273472-188274250 Neighboring gene calcitonin receptor like receptor Neighboring gene Sharpr-MPRA regulatory region 13492 Neighboring gene MPRA-validated peak3983 silencer Neighboring gene glyceraldehyde-3-phosphate dehydrogenase pseudogene 59 Neighboring gene MPRA-validated peak3984 silencer Neighboring gene NANOG-H3K27ac hESC enhancer GRCh37_chr2:188384681-188385366 Neighboring gene Sharpr-MPRA regulatory region 10664 Neighboring gene P300/CBP strongly-dependent group 1 enhancer GRCh37_chr2:188411556-188412755 Neighboring gene NANOG hESC enhancer GRCh37_chr2:188422204-188422788 Neighboring gene NANOG hESC enhancer GRCh37_chr2:188422789-188423371 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr2:188430328-188430906 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr2:188430907-188431484 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr2:188480540-188481090 Neighboring gene NANOG hESC enhancer GRCh37_chr2:188483510-188484011 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr2:188535284-188535785 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr2:188540495-188541307 Neighboring gene MPRA-validated peak3986 silencer Neighboring gene NANOG hESC enhancer GRCh37_chr2:188565262-188565763 Neighboring gene uncharacterized LOC105373788 Neighboring gene ST13, Hsp70 interacting protein pseudogene 2

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

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    Related articles in PubMed

    1. Anti-tissue factor pathway inhibitor activity in subjects with antiphospholipid syndrome is associated with increased thrombin generation. Adams M, et al. Haematologica, 2004 Aug. PMID 15339683
    2. TFPI gene variation and ischemic stroke. Pedersen A, et al. Thromb Res, 2012 Sep. PMID 22749962
    3. The intron 7 -33T>C polymorphism in TFPI gene and cerebral venous thrombosis: evidence for a protective role. Prabhakar P, et al. Thromb Res, 2012 Oct. PMID 22836130
    4. Impaired tissue factor pathway inhibitor function is associated with recurrent venous thromboembolism in patients with first unprovoked deep venous thrombosis. Winckers K, et al. J Thromb Haemost, 2012 Oct. PMID 22900482
    5. Tissue factor pathway inhibitor production by human proximal tubular epithelial cells in culture. Sugawara T, et al. Thromb Res, 2003 May 1. PMID 12893029

    See all (267) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Elevated TFPI is a prognostic factor in hepatocellular carcinoma: Putative role of miR-7-5p and miR-1236-3p.
      Title: Elevated TFPI is a prognostic factor in hepatocellular carcinoma: Putative role of miR-7-5p and miR-1236-3p.
    2. The RNA-binding protein sorbin and SH3 domain-containing 2 are transcriptionally regulated by specificity protein 1 and function as tumor suppressors in bladder cancer by stabilizing tissue factor pathway inhibitor.
      Title: The RNA-binding protein sorbin and SH3 domain-containing 2 are transcriptionally regulated by specificity protein 1 and function as tumor suppressors in bladder cancer by stabilizing tissue factor pathway inhibitor.
    3. Activated protein C, protein S, and tissue factor pathway inhibitor cooperate to inhibit thrombin activation.
      Title: Activated protein C, protein S, and tissue factor pathway inhibitor cooperate to inhibit thrombin activation.
    4. Endothelial-dependent S-Sulfhydration of tissue factor pathway inhibitor regulates blood coagulation.
      Title: Endothelial-dependent S-Sulfhydration of tissue factor pathway inhibitor regulates blood coagulation.
    5. Mutations of TFPI-binding exosites on factor VII cause bleeding phenotypes in factor VII deficiency.
      Title: Mutations of TFPI-binding exosites on factor VII cause bleeding phenotypes in factor VII deficiency.
    6. Effects of human TFPI and CD47 expression and selectin and integrin inhibition during GalTKO.hCD46 pig lung perfusion with human blood.
      Title: Effects of human TFPI and CD47 expression and selectin and integrin inhibition during GalTKO.hCD46 pig lung perfusion with human blood.
    7. Single Nucleotide Polymorphisms from CSF2, FLT1, TFPI and TLR9 Genes Are Associated with Prelabor Rupture of Membranes.
      Title: Single Nucleotide Polymorphisms from CSF2, FLT1, TFPI and TLR9 Genes Are Associated with Prelabor Rupture of Membranes.
    8. Intersection of regulatory pathways controlling hemostasis and hemochorial placentation.
      Title: Intersection of regulatory pathways controlling hemostasis and hemochorial placentation.
    9. Circulating Tissue Factor Pathway Inhibitor (TFPI) is increased preceding preeclampsia diagnosis and in established preeclampsia.
      Title: Circulating Tissue Factor Pathway Inhibitor (TFPI) is increased preceding preeclampsia diagnosis and in established preeclampsia.
    10. Relation between Tissue Factor Pathway Inhibitor Activity and Cardiovascular Risk Factors and Diseases in a Large Population Sample.
      Title: Relation between Tissue Factor Pathway Inhibitor Activity and Cardiovascular Risk Factors and Diseases in a Large Population Sample.
    Submit: New GeneRIF Correction See all GeneRIFs (195)

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    EBI GWAS Catalog

    Description
    A genome-wide association study in Europeans and South Asians identifies five new loci for coronary artery disease.
    EBI GWAS Catalog
    Identification of heart rate-associated loci and their effects on cardiac conduction and rhythm disorders.
    EBI GWAS Catalog

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Genotypes

    HIV-1 interactions

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    Replication interactions

    Interaction Pubs
    HIV-1 infection (VSV-G pseudotyped) of CEMT4 T cells downregulates plasma membrane expression of TFPI PubMed

    Go to the HIV-1, Human Interaction Database

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables endopeptidase inhibitor activity TAS
    Traceable Author Statement
    more info
    		 PubMed 
    enables serine-type endopeptidase inhibitor activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    Process Evidence Code Pubs
    involved_in blood coagulation IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in cellular response to steroid hormone stimulus IEP
    Inferred from Expression Pattern
    more info
    		 PubMed 
    involved_in negative regulation of blood coagulation IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in negative regulation of peptidase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    located_in caveola IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in cell surface HDA PubMed 
    located_in cell surface IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in endoplasmic reticulum IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in extracellular region TAS
    Traceable Author Statement
    more info
    		  
    is_active_in extracellular space IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in extracellular space IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in plasma membrane TAS
    Traceable Author Statement
    more info
    		  
    located_in side of membrane IEA
    Inferred from Electronic Annotation
    more info
    		  

    General protein information

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    Preferred Names
    tissue factor pathway inhibitor
    Names
    anti-convertin
    extrinsic pathway inhibitor
    tissue factor pathway inhibitor (lipoprotein-associated coagulation inhibitor)

    NCBI Reference Sequences (RefSeq)

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    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_029714.2 RefSeqGene

      Range
      16326..106531
      Download
      GenBank, FASTA, Sequence Viewer (Graphics), LRG_604

    mRNA and Protein(s)

    1. NM_001032281.4 → NP_001027452.1  tissue factor pathway inhibitor isoform b precursor

      See identical proteins and their annotated locations for NP_001027452.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) uses an alternate in-frame exon in the 3' coding region compared to variant 1. The encoded isoform (b, also known as TFPIbeta) has a shorter and distinct C-terminus, which includes a glycosylphosphatidylinositol (GPI) anchor attachment site, compared to isoform a. Variants 2 and 3 both encode the same isoform (b).
      Source sequence(s)
      AF021834, BC015514, HY175080
      Consensus CDS
      CCDS33349.1
      UniProtKB/Swiss-Prot
      P10646
      Related
      ENSP00000342306.4, ENST00000339091.8
      Conserved Domains (2) summary
      cd00109
      Location:123 → 175
      KU; BPTI/Kunitz family of serine protease inhibitors; Structure is a disulfide rich alpha+beta fold. BPTI (bovine pancreatic trypsin inhibitor) is an extensively studied model structure.
      pfam00014
      Location:53 → 104
      Kunitz_BPTI; Kunitz/Bovine pancreatic trypsin inhibitor domain

    2. NM_001318941.3 → NP_001305870.1  tissue factor pathway inhibitor isoform b precursor

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) differs in the 5' UTR and uses an alternate in-frame exon in the 3' coding region compared to variant 1. The encoded isoform (b, also known as TFPIbeta) has a shorter and distinct C-terminus, which includes a glycosylphosphatidylinositol (GPI) anchor attachment site, compared to isoform a. Variants 2 and 3 both encode the same isoform (b).
      Source sequence(s)
      AF021834, BC015514, HY175080
      Consensus CDS
      CCDS33349.1
      UniProtKB/Swiss-Prot
      P10646
      Related
      ENSP00000386344.1, ENST00000409676.5
      Conserved Domains (2) summary
      cd00109
      Location:123 → 175
      KU; BPTI/Kunitz family of serine protease inhibitors; Structure is a disulfide rich alpha+beta fold. BPTI (bovine pancreatic trypsin inhibitor) is an extensively studied model structure.
      pfam00014
      Location:53 → 104
      Kunitz_BPTI; Kunitz/Bovine pancreatic trypsin inhibitor domain

    3. NM_001329239.2 → NP_001316168.1  tissue factor pathway inhibitor isoform a precursor

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) differs in the 5' UTR compared to variant 1 but encodes the same isoform (a, also known as TFPIalpha), which is secreted. Variants 1 and 4-6 encode the same isoform (a).
      Source sequence(s)
      AC007319, AC098485, CA418214
      Consensus CDS
      CCDS2294.1
      UniProtKB/Swiss-Prot
      O95103, P10646, Q53TS4
      UniProtKB/TrEMBL
      B2R8Y9
      Conserved Domains (2) summary
      cd00109
      Location:123 → 175
      KU; BPTI/Kunitz family of serine protease inhibitors; Structure is a disulfide rich alpha+beta fold. BPTI (bovine pancreatic trypsin inhibitor) is an extensively studied model structure.
      pfam00014
      Location:216 → 268
      Kunitz_BPTI; Kunitz/Bovine pancreatic trypsin inhibitor domain

    4. NM_001329240.2 → NP_001316169.1  tissue factor pathway inhibitor isoform a precursor

      Status: REVIEWED

      Description
      Transcript Variant: This variant (5) differs in the 5' UTR compared to variant 1 but encodes the same isoform (a, also known as TFPIalpha), which is secreted. Variants 1 and 4-6 encode the same isoform (a).
      Source sequence(s)
      AC007319, AC098485, CA418214
      Consensus CDS
      CCDS2294.1
      UniProtKB/Swiss-Prot
      O95103, P10646, Q53TS4
      UniProtKB/TrEMBL
      B2R8Y9
      Related
      ENSP00000376172.1, ENST00000392365.5
      Conserved Domains (2) summary
      cd00109
      Location:123 → 175
      KU; BPTI/Kunitz family of serine protease inhibitors; Structure is a disulfide rich alpha+beta fold. BPTI (bovine pancreatic trypsin inhibitor) is an extensively studied model structure.
      pfam00014
      Location:216 → 268
      Kunitz_BPTI; Kunitz/Bovine pancreatic trypsin inhibitor domain

    5. NM_001329241.2 → NP_001316170.1  tissue factor pathway inhibitor isoform a precursor

      Status: REVIEWED

      Description
      Transcript Variant: This variant (6) differs in the 5' UTR compared to variant 1 but encodes the same isoform (a, also known as TFPIalpha), which is secreted. Variants 1 and 4-6 encode the same isoform (a).
      Source sequence(s)
      AC007319, AC098485, CA418214
      Consensus CDS
      CCDS2294.1
      UniProtKB/Swiss-Prot
      O95103, P10646, Q53TS4
      UniProtKB/TrEMBL
      B2R8Y9
      Conserved Domains (2) summary
      cd00109
      Location:123 → 175
      KU; BPTI/Kunitz family of serine protease inhibitors; Structure is a disulfide rich alpha+beta fold. BPTI (bovine pancreatic trypsin inhibitor) is an extensively studied model structure.
      pfam00014
      Location:216 → 268
      Kunitz_BPTI; Kunitz/Bovine pancreatic trypsin inhibitor domain

    6. NM_006287.6 → NP_006278.1  tissue factor pathway inhibitor isoform a precursor

      See identical proteins and their annotated locations for NP_006278.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) encodes the longer isoform (a, also known as TFPIalpha), which is secreted. Variants 1 and 4-6 encode the same isoform (a).
      Source sequence(s)
      AC007319, CA418214, HY175080, J03225
      Consensus CDS
      CCDS2294.1
      UniProtKB/Swiss-Prot
      O95103, P10646, Q53TS4
      UniProtKB/TrEMBL
      B2R8Y9
      Related
      ENSP00000233156.3, ENST00000233156.9
      Conserved Domains (2) summary
      cd00109
      Location:123 → 175
      KU; BPTI/Kunitz family of serine protease inhibitors; Structure is a disulfide rich alpha+beta fold. BPTI (bovine pancreatic trypsin inhibitor) is an extensively studied model structure.
      pfam00014
      Location:216 → 268
      Kunitz_BPTI; Kunitz/Bovine pancreatic trypsin inhibitor domain

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000002.12 Reference GRCh38.p14 Primary Assembly

      Range
      187464230..187554435 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_047445619.1 → XP_047301575.1  tissue factor pathway inhibitor isoform X1

      UniProtKB/Swiss-Prot
      O95103, P10646, Q53TS4

    2. XM_047445620.1 → XP_047301576.1  tissue factor pathway inhibitor isoform X1

      UniProtKB/Swiss-Prot
      O95103, P10646, Q53TS4

    3. XM_047445621.1 → XP_047301577.1  tissue factor pathway inhibitor isoform X1

      UniProtKB/Swiss-Prot
      O95103, P10646, Q53TS4

    4. XM_047445618.1 → XP_047301574.1  tissue factor pathway inhibitor isoform X1

      UniProtKB/Swiss-Prot
      O95103, P10646, Q53TS4

    5. XM_047445617.1 → XP_047301573.1  tissue factor pathway inhibitor isoform X1

      UniProtKB/Swiss-Prot
      O95103, P10646, Q53TS4

    6. XM_047445622.1 → XP_047301578.1  tissue factor pathway inhibitor isoform X1

      UniProtKB/Swiss-Prot
      O95103, P10646, Q53TS4

    7. XM_047445623.1 → XP_047301579.1  tissue factor pathway inhibitor isoform X2

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060926.1 Alternate T2T-CHM13v2.0

      Range
      187953180..188043364 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054343583.1 → XP_054199558.1  tissue factor pathway inhibitor isoform X1

      UniProtKB/Swiss-Prot
      O95103, P10646, Q53TS4

    2. XM_054343584.1 → XP_054199559.1  tissue factor pathway inhibitor isoform X1

      UniProtKB/Swiss-Prot
      O95103, P10646, Q53TS4

    3. XM_054343585.1 → XP_054199560.1  tissue factor pathway inhibitor isoform X1

      UniProtKB/Swiss-Prot
      O95103, P10646, Q53TS4

    4. XM_054343582.1 → XP_054199557.1  tissue factor pathway inhibitor isoform X1

      UniProtKB/Swiss-Prot
      O95103, P10646, Q53TS4

    5. XM_054343581.1 → XP_054199556.1  tissue factor pathway inhibitor isoform X1

      UniProtKB/Swiss-Prot
      O95103, P10646, Q53TS4

    6. XM_054343586.1 → XP_054199561.1  tissue factor pathway inhibitor isoform X2

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    P10646.1 GenPept UniProtKB/Swiss-Prot:P10646

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