F3 (Coagulation Factor III, Tissue Factor)

Key Initiator of the Extrinsic Coagulation Cascade

Gene Information Card

Symbol F3
Full Name Coagulation Factor III, Tissue Factor
Gene Type protein-coding
Chromosomal Location 1p21.3
NCBI Gene ID 2152 ncbi.nlm.nih.gov/gene/2152
Ensembl ID ENSG00000117525
UniProt ID P13726
OMIM ID 134390
HGNC ID 3541
Aliases TF, TFA, CD142, thromboplastin, coagulation factor III

Description

The F3 gene encodes tissue factor (TF), a transmembrane glycoprotein that serves as the primary initiator of the extrinsic coagulation cascade. TF binds factor VII/VIIa, forming a complex that activates factor X to Xa, leading to thrombin generation and fibrin clot formation. Beyond hemostasis, TF plays roles in angiogenesis, inflammation, and tumor progression. Its expression is normally restricted to subendothelial tissues but is induced in endothelial cells and monocytes under pathological conditions.

Disease Associations

Disease category Pathophysiological mechanism Genomic evidence
Thrombosis (venous/arterial) Aberrant TF expression on activated endothelium or monocytes triggers uncontrolled coagulation ClinVar, OMIM
Disseminated intravascular coagulation (DIC) Systemic TF exposure from damaged tissues or cancer cells activates widespread clotting OMIM, NCBI
Cancer-associated thrombosis Tumor cells overexpress TF, promoting hypercoagulability and metastasis COSMIC, NCBI
Hemophilia A/B (bypass therapy) Recombinant TF pathway inhibitors (e.g., rFVIIa) used to restore hemostasis ClinVar, OMIM
Coronary artery disease Elevated TF levels in atherosclerotic plaques contribute to plaque thrombogenicity NCBI

Expression Profile

Tissue Expression
Tissue nTPM level
Lung 45.2 High
Placenta 38.1 High
Brain 12.5 Medium
Heart 8.3 Medium
Liver 2.1 Low
Skeletal Muscle 1.4 Low
Cell Line Expression
Cell Line nTPM Notes
A549 (lung carcinoma) 62.0 High TF expression
HUVEC (endothelial) 5.8 Inducible by cytokines
THP-1 (monocyte) 3.2 Low basal, upregulated by LPS
MCF7 (breast cancer) 1.5 Variable
K562 (leukemia) 0.9 Low
Data source:Human Protein Atlas(proteinatlas.org)

Mutations & Variants

Hotspot Mutations
Variant Type Frequency Functional Description
c.119G>A (p.Arg40Gln) Missense <0.01% Reduced TF activity; mild bleeding tendency
c.200C>T (p.Thr67Met) Missense <0.01% Altered factor VII binding
c.571G>A (p.Gly191Arg) Missense <0.01% Impaired procoagulant function
c.799C>T (p.Arg267Trp) Missense <0.01% Unknown clinical significance
Mutation functional classification

Loss of Function (LOF)

Missense variants (e.g., p.Arg40Gln) reduce TF activity, leading to mild bleeding disorders.

Gain of Function (GOF)

Not well-documented; overexpression in cancer is epigenetic rather than mutational.

Dominant Negative (DN)

No dominant-negative mutations reported.

Pathways

KEGG hsa04610 - Complement and coagulation cascades
Reactome R-HSA-140837 - Extrinsic pathway of fibrin clot formation
Reactome R-HSA-159740 - Formation of Fibrin Clot (Clotting Cascade)
WikiPathways WP558 - Coagulation cascades

Protein Summary

Tissue factor (TF) is a 263-amino acid transmembrane protein with an extracellular domain that binds factor VII/VIIa, a transmembrane domain anchoring it to the cell membrane, and a short cytoplasmic tail involved in signaling. The TF-VIIa complex initiates coagulation by proteolytically activating factor X. TF also mediates intracellular signaling via PAR2 (protease-activated receptor 2), influencing inflammation, angiogenesis, and tumor growth. Its expression is tightly regulated; ectopic expression in vascular cells is a hallmark of thrombotic diseases.

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Displaying Records 1 To 15 Of 650 Records
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