TFPI
protein-codingtissue factor pathway inhibitor
Gene 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]
- LACI
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~101.5 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 TFPI variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_006287.6. 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 | 17 | 1 | 18 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 3 | 3 | ||||
| Total | 0 | 0 | 21 | 0 | 1 | 22 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_006278.1 | 7 | MANE Select | |
| Ensembl | ENSP00000233156.3 | 7 | MANE Select | |
| RefSeq | NP_001027452.1 | 6 | Standard | |
| RefSeq | NP_001305870.1 | 6 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Complement and coagulation cascades - Homo sapiens (human)
- Integrated Breast Cancer Pathway
- Dengue-2 Interactions with Complement and Coagulation Cascades
- Complement and Coagulation Cascades
- Extrinsic Pathway of Fibrin Clot Formation
Biological Process
- blood coagulation
- blood coagulation, extrinsic pathway
- negative regulation of endopeptidase activity
- negative regulation of blood coagulation
- response to estradiol
Molecular Function
- endopeptidase inhibitor activity
- serine-type endopeptidase inhibitor activity
Cellular Component
- extracellular region
- extracellular space
- endoplasmic reticulum
- plasma membrane
- caveola
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000233156
- Coding exons
- 7
- Length
- 101531
- Individuals with no LoFs
- 125502
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 7
- Defined
- 125509
- p
- 0.0000279
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.31 | 113 | 159 | 0.709 | 0.00000798 | 2021 |
| Missense (PolyPhen) | 27 | 56.2 | 0.48043 | 741 | ||
| Synonymous | 0.593 | 48 | 53.5 | 0.897 | 0.00000265 | 523 |
| Loss of Function | 2.81 | 4 | 16.2 | 0.247 | 9.92e-7 | 187 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.000048 | 0.000044 | rare |
| South Asian | 0.000043 | 0.000033 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Inhibits factor X (X(a)) directly and, in a Xa-dependent way, inhibits VIIa/tissue factor activity, presumably by forming a quaternary Xa/LACI/VIIa/TF complex. It possesses an antithrombotic action and also the ability to associate with lipoproteins in plasma.;
Recessive Scores
- pRec
- 0.321
Intolerance Scores
- LoFtool
- 0.754
- RVIS EVS
- 0.33
- RVIS percentile EVS
- 73.27
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.930
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |