This gene encodes a member of the Kunitz-type serine proteinase inhibitor family. The protein can inhibit a variety of serine proteases including factor VIIa/tissue factor, factor Xa, plasmin, trypsin, chymotryspin and plasma kallikrein. This gene has been identified as a tumor suppressor gene in several types of cancer. Alternative splicing results in multiple transcript varia... See more...

Aliases for TFPI2 Gene

Aliases for TFPI2 Gene

  • Tissue Factor Pathway Inhibitor 2 2 3 4 5
  • TFPI-2 2 3 4
  • PP5 2 3 4
  • Placental Protein 5 3 4
  • REF1 2 3
  • Retinal Pigment Epithelium Cell Factor 1 3
  • TFPI2 5

External Ids for TFPI2 Gene

Previous GeneCards Identifiers for TFPI2 Gene

  • GC07M092051
  • GC07M093113
  • GC07M093127
  • GC07M093159
  • GC07M093352
  • GC07M093514
  • GC07M088123

Summaries for TFPI2 Gene

Entrez Gene Summary for TFPI2 Gene

  • This gene encodes a member of the Kunitz-type serine proteinase inhibitor family. The protein can inhibit a variety of serine proteases including factor VIIa/tissue factor, factor Xa, plasmin, trypsin, chymotryspin and plasma kallikrein. This gene has been identified as a tumor suppressor gene in several types of cancer. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2012]

GeneCards Summary for TFPI2 Gene

TFPI2 (Tissue Factor Pathway Inhibitor 2) is a Protein Coding gene. Diseases associated with TFPI2 include Fibrosarcoma and Choriocarcinoma. Among its related pathways are Matrix Metalloproteinases and Formation of Fibrin Clot (Clotting Cascade). Gene Ontology (GO) annotations related to this gene include serine-type endopeptidase inhibitor activity and peptidase inhibitor activity. An important paralog of this gene is TFPI.

UniProtKB/Swiss-Prot Summary for TFPI2 Gene

  • May play a role in the regulation of plasmin-mediated matrix remodeling. Inhibits trypsin, plasmin, factor VIIa/tissue factor and weakly factor Xa. Has no effect on thrombin.

Gene Wiki entry for TFPI2 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for TFPI2 Gene

Genomics for TFPI2 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for TFPI2 Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around TFPI2 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for TFPI2

Top Transcription factor binding sites by QIAGEN in the TFPI2 gene promoter:
  • ER-alpha
  • FOXD3
  • FOXO4
  • Nkx3-1
  • Nkx3-1 v1
  • Nkx3-1 v2
  • Nkx3-1 v3
  • Nkx3-1 v4
  • POU3F2
  • STAT5B

Genomic Locations for TFPI2 Gene

Latest Assembly
chr7:93,885,396-93,890,753
(GRCh38/hg38)
Size:
5,358 bases
Orientation:
Minus strand

Previous Assembly
chr7:93,514,708-93,520,065
(GRCh37/hg19 by Entrez Gene)
Size:
5,358 bases
Orientation:
Minus strand

chr7:93,514,709-93,520,303
(GRCh37/hg19 by Ensembl)
Size:
5,595 bases
Orientation:
Minus strand

Genomic View for TFPI2 Gene

Genes around TFPI2 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
TFPI2 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for TFPI2 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for TFPI2 Gene

Proteins for TFPI2 Gene

  • Protein details for TFPI2 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P48307-TFPI2_HUMAN
    Recommended name:
    Tissue factor pathway inhibitor 2
    Protein Accession:
    P48307
    Secondary Accessions:
    • Q66ME8
    • Q8NAK6
    • Q9UC86

    Protein attributes for TFPI2 Gene

    Size:
    235 amino acids
    Molecular mass:
    26934 Da
    Quaternary structure:
    • Finds in a complex with ABCB1, TFPI2 and PPP2R3C; leading to the dephosphorylation of ABCB1.

    Three dimensional structures from OCA and Proteopedia for TFPI2 Gene

    Alternative splice isoforms for TFPI2 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for TFPI2 Gene

Post-translational modifications for TFPI2 Gene

  • Glycosylation at Asn116 and Asn170
  • Modification sites at PhosphoSitePlus

Other Protein References for TFPI2 Gene

No data available for DME Specific Peptides for TFPI2 Gene

Domains & Families for TFPI2 Gene

Gene Families for TFPI2 Gene

Human Protein Atlas (HPA):
  • Predicted intracellular proteins
  • Predicted secreted proteins

Protein Domains for TFPI2 Gene

InterPro:
Blocks:
  • Pancreatic trypsin inhibitor (Kunitz)
ProtoNet:

Suggested Antigen Peptide Sequences for TFPI2 Gene

GenScript: Design optimal peptide antigens:
  • TFPI2 variant (A4ZVU7_HUMAN)
  • cDNA FLJ35180 fis, clone PLACE6014882, highly similar to TISSUE FACTOR PATHWAY INHIBITOR 2 (Q8NAK6_HUMAN)
  • Placental protein 5 (TFPI2_HUMAN)

Graphical View of Domain Structure for InterPro Entry

P48307

UniProtKB/Swiss-Prot:

TFPI2_HUMAN :
  • This inhibitor contains three inhibitory domains.
Domain:
  • This inhibitor contains three inhibitory domains.
genes like me logo Genes that share domains with TFPI2: view

Function for TFPI2 Gene

Molecular function for TFPI2 Gene

UniProtKB/Swiss-Prot Function:
May play a role in the regulation of plasmin-mediated matrix remodeling. Inhibits trypsin, plasmin, factor VIIa/tissue factor and weakly factor Xa. Has no effect on thrombin.
GENATLAS Biochemistry:
tissue factor pathway inhibitor 2,serine proteinase inhibitor (see TSG7B)

Phenotypes From GWAS Catalog for TFPI2 Gene

Gene Ontology (GO) - Molecular Function for TFPI2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004867 serine-type endopeptidase inhibitor activity IEA,IBA 21873635
GO:0005201 extracellular matrix structural constituent TAS 8914837
GO:0030414 peptidase inhibitor activity IEA --
genes like me logo Genes that share ontologies with TFPI2: view
genes like me logo Genes that share phenotypes with TFPI2: view

Animal Models for research

  • Taconic Biosciences Mouse Models for TFPI2

miRNA for TFPI2 Gene

miRTarBase miRNAs that target TFPI2

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for TFPI2

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Animal Models , Transcription Factor Targets and HOMER Transcription for TFPI2 Gene

Localization for TFPI2 Gene

Subcellular locations from UniProtKB/Swiss-Prot for TFPI2 Gene

Secreted.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for TFPI2 gene
Compartment Confidence
extracellular 5
plasma membrane 2
cytoskeleton 2
nucleus 2
mitochondrion 1
endoplasmic reticulum 1
cytosol 1
lysosome 1

Gene Ontology (GO) - Cellular Components for TFPI2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005576 extracellular region IEA --
GO:0005615 extracellular space IBA 21873635
GO:0031012 extracellular matrix TAS 8914837
genes like me logo Genes that share ontologies with TFPI2: view

No data available for Subcellular locations from the Human Protein Atlas (HPA) for TFPI2 Gene

Pathways & Interactions for TFPI2 Gene

PathCards logo

SuperPathways for TFPI2 Gene

SuperPathway Contained pathways
1 Formation of Fibrin Clot (Clotting Cascade)
2 Matrix Metalloproteinases
.69
3 Cell adhesion_Plasmin signaling
-
genes like me logo Genes that share pathways with TFPI2: view

Pathways by source for TFPI2 Gene

1 GeneGo (Thomson Reuters) pathway for TFPI2 Gene
  • Cell adhesion_Plasmin signaling
1 R&D Systems pathway for TFPI2 Gene
1 Qiagen pathway for TFPI2 Gene
  • Inhibition of Matrix Metalloproteinases

Gene Ontology (GO) - Biological Process for TFPI2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0007596 blood coagulation IEA --
GO:0007599 hemostasis IEA --
GO:0010466 negative regulation of peptidase activity IEA --
GO:0010951 negative regulation of endopeptidase activity IEA --
GO:0071498 cellular response to fluid shear stress IEA --
genes like me logo Genes that share ontologies with TFPI2: view

No data available for SIGNOR curated interactions for TFPI2 Gene

Drugs & Compounds for TFPI2 Gene

(3) Drugs for TFPI2 Gene - From: Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials

(5) Additional Compounds for TFPI2 Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with TFPI2: view

Transcripts for TFPI2 Gene

mRNA/cDNA for TFPI2 Gene

3 REFSEQ mRNAs :
14 NCBI additional mRNA sequence :
6 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for TFPI2

Alternative Splicing Database (ASD) splice patterns (SP) for TFPI2 Gene

ExUns: 1a · 1b · 1c ^ 2a · 2b · 2c ^ 3a · 3b ^ 4 ^ 5 ^ 6a · 6b · 6c · 6d
SP1: - -
SP2: - - -
SP3: -
SP4: - - -
SP5: - -
SP6:

Relevant External Links for TFPI2 Gene

GeneLoc Exon Structure for
TFPI2

Expression for TFPI2 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for TFPI2 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for TFPI2 Gene

This gene is overexpressed in Adipose - Visceral (Omentum) (x4.0).

Protein differential expression in normal tissues from HIPED for TFPI2 Gene

This gene is overexpressed in Amniocyte (45.2) and Placenta (22.7).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for TFPI2 Gene



Protein tissue co-expression partners for TFPI2 Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for TFPI2

SOURCE GeneReport for Unigene cluster for TFPI2 Gene:

Hs.438231

mRNA Expression by UniProt/SwissProt for TFPI2 Gene:

P48307-TFPI2_HUMAN
Tissue specificity: Umbilical vein endothelial cells, liver, placenta, heart, pancreas, and maternal serum at advanced pregnancy.

Evidence on tissue expression from TISSUES for TFPI2 Gene

  • Nervous system(4.4)
  • Lung(4)
  • Heart(3)
  • Intestine(2.6)
  • Pancreas(2.3)
  • Eye(2.2)
  • Kidney(2.2)
  • Liver(2.1)
genes like me logo Genes that share expression patterns with TFPI2: view

No data available for Phenotype-based relationships between genes and organs from Gene ORGANizer for TFPI2 Gene

Orthologs for TFPI2 Gene

This gene was present in the common ancestor of animals.

Orthologs for TFPI2 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia TFPI2 30 31
  • 99.43 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia TFPI2 30 31
  • 80.52 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia TFPI2 30 31
  • 80.46 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Tfpi2 30
  • 68.33 (n)
Mouse
(Mus musculus)
Mammalia Tfpi2 30 17 31
  • 67.99 (n)
OneToOne
Platypus
(Ornithorhynchus anatinus)
Mammalia TFPI2 31
  • 42 (a)
OneToOne
Oppossum
(Monodelphis domestica)
Mammalia ELP 31
  • 21 (a)
ManyToMany
Chicken
(Gallus gallus)
Aves TFPI2 30 31
  • 63.72 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia TFPI2 31
  • 48 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia tfpi2 30
  • 62.07 (n)
Zebrafish
(Danio rerio)
Actinopterygii tfpi2 30 31
  • 52.89 (n)
OneToOne
Worm
(Caenorhabditis elegans)
Secernentea mec-9 31
  • 8 (a)
ManyToMany
F22E12.1 31
  • 6 (a)
ManyToMany
ZK287.4 31
  • 5 (a)
ManyToMany
mec-1 31
  • 3 (a)
ManyToMany
Species where no ortholog for TFPI2 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Fruit Fly (Drosophila melanogaster)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Squirt (Ciona savignyi)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Wheat (Triticum aestivum)

Evolution for TFPI2 Gene

ENSEMBL:
Gene Tree for TFPI2 (if available)
TreeFam:
Gene Tree for TFPI2 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for TFPI2: view image

Paralogs for TFPI2 Gene

(13) SIMAP similar genes for TFPI2 Gene using alignment to 5 proteins:

  • TFPI2_HUMAN
  • A4ZVU7_HUMAN
  • F5H3J8_HUMAN
  • H7C4A3_HUMAN
  • Q8NAK6_HUMAN
genes like me logo Genes that share paralogs with TFPI2: view

Variants for TFPI2 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for TFPI2 Gene

SNP ID Clinical significance and condition Chr 07 pos Variation AA Info Type
rs111975101 Benign: not provided 93,890,146(-) T/G
NM_006528.4(TFPI2):c.262A>C (p.Arg88=)
SYNONYMOUS
rs113538343 Likely Benign: not provided 93,889,100(-) C/T
NM_006528.4(TFPI2):c.395G>A (p.Arg132Gln)
MISSENSE
rs113676641 Benign: not provided 93,890,129(-) G/A
NM_006528.4(TFPI2):c.271+8C>T
INTRON
rs143367024 Benign: not provided 93,886,846(-) G/A
NM_006528.4(TFPI2):c.682C>T (p.Arg228Trp)
MISSENSE_VARIANT,THREE_PRIME_UTR
rs12669450 - p.Arg231Gln

dbSNP identifiers (rs#s) for variants without ClinVar clinical significance for TFPI2 Gene

All consequence types are included: molecular consequences (e.g. missense, synonymous), and location-based (e.g. intron, upstream).

Structural Variations from Database of Genomic Variants (DGV) for TFPI2 Gene

Variant ID Type Subtype PubMed ID
nsv1023193 CNV gain 25217958
nsv607849 CNV gain 21841781

Variation tolerance for TFPI2 Gene

Residual Variation Intolerance Score: 84.1% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 1.23; 24.67% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for TFPI2 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
TFPI2

SNP Genotyping and Copy Number Assays for research

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for TFPI2 Gene

Disorders for TFPI2 Gene

MalaCards: The human disease database

(7) MalaCards diseases for TFPI2 Gene - From: COP and GCD

Disorder Aliases PubMed IDs
fibrosarcoma
  • fibrocytic tumor
choriocarcinoma
  • chorioepithelioma
amelanotic melanoma
  • melanoma amelanotic
ovarian clear cell carcinoma
  • clear-cell ovarian carcinoma
hellp syndrome
  • hemolysis, elevated liver enzymes, lowered platelets
- elite association - COSMIC cancer census association via MalaCards
Search TFPI2 in MalaCards View complete list of genes associated with diseases

Additional Disease Information for TFPI2

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
Atlas
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
Open Targets Platform
genes like me logo Genes that share disorders with TFPI2: view

No data available for UniProtKB/Swiss-Prot and Genatlas for TFPI2 Gene

Publications for TFPI2 Gene

  1. cDNA cloning and mRNA expression of a serine proteinase inhibitor secreted by cancer cells: identification as placental protein 5 and tissue factor pathway inhibitor-2. (PMID: 7896752) Miyagi Y … Miyazaki K (Journal of biochemistry 1994) 2 3 4 23
  2. Influence of MMP-2 and MMP-9 promoter polymorphisms on gene expression and clinical outcome of non-small cell lung cancer. (PMID: 17208328) Rollin J … Gruel Y (Lung cancer (Amsterdam, Netherlands) 2007) 3 23 41
  3. Analysis of sequence variations in the promoter region of the human tissue factor pathway inhibitor 2 gene in apoplectic patients and blood donors. (PMID: 16247609) Siegling S … Götting C (Annals of hematology 2006) 3 23 41
  4. Genomic structure and promoter activity of the human tissue factor pathway inhibitor-2 gene. (PMID: 11342222) Kamei S … Kisiel W (Biochimica et biophysica acta 2001) 3 4 23
  5. Cloning of the cDNA encoding mouse PP5/TFPI-2 and mapping of the gene to chromosome 6. (PMID: 8945635) Miyagi Y … Miyazaki K (DNA and cell biology 1996) 2 3 23

Products for TFPI2 Gene

Sources for TFPI2 Gene