TFPI2
protein-codingtissue factor pathway inhibitor 2
Gene summary
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]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~5.4 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to TFPI2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_006528.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 1 | ||||
| missense | 32 | 5 | 1 | 38 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 3 | 3 | ||||
| Total | 0 | 0 | 35 | 5 | 2 | 42 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_006519.1 | 5 | MANE Select | |
| Ensembl | ENSP00000222543.5 | 5 | MANE Select | |
| RefSeq | NP_001257932.1 | 5 | Standard | |
| RefSeq | NP_001257933.1 | 5 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| tfpi2 | Danio rerio | Structure: cardiac muscle cell Quality: decreased amount abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- blood coagulation
- negative regulation of endopeptidase activity
- cellular response to fluid shear stress
Molecular Function
- serine-type endopeptidase inhibitor activity
- extracellular matrix structural constituent
Cellular Component
- extracellular space
- extracellular matrix
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000222543
- Coding exons
- 5
- Length
- 5595
- Individuals with no LoFs
- 125655
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 93
- Defined
- 125748
- p
- 0.000370
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.145 | 140 | 135 | 1.04 | 0.00000720 | 1539 |
| Missense (PolyPhen) | 41 | 45.556 | 0.9 | 452 | ||
| Synonymous | 0.240 | 49 | 51.2 | 0.957 | 0.00000256 | 435 |
| Loss of Function | 1.09 | 6 | 9.67 | 0.620 | 4.07e-7 | 124 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.0015 | 0.0015 | notable |
| Latino/Admixed American | 0.00012 | 0.00012 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.0019 | 0.0019 | notable |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00022 | 0.00022 | rare |
| South Asian | 0.00017 | 0.00016 | rare |
| Other | 0.00017 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- 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. {ECO:0000269|PubMed:7872799}.;
Recessive Scores
- pRec
- 0.177
Intolerance Scores
- LoFtool
- 0.663
- RVIS EVS
- 0.55
- RVIS percentile EVS
- 81.38
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.378
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |