TFPI

Summary

TFPI (tissue factor pathway inhibitor, HGNC:11760) is a protein-coding gene on chromosome 2q32.1, encoding Tissue factor pathway inhibitor (P10646). 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.

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.

Source: NCBI Gene 7035 — RefSeq curated summary.

At a glance

• GWAS associations: 26 (top 5% of genes corpus-wide)
• Clinical variants (ClinVar): 3 total
• GTEx eGene: eQTL in 28 tissues, sQTL in 12 (q < 0.05)
• Drug target: yes — 4 curated mechanism-of-action drugs
• Approved drugs (ChEMBL mechanism of action): 3 — Andexanet Alfa, Concizumab, Marstacimab
• Constraint (gnomAD): pLI 0.90 (loss-of-function intolerant), LOEUF 0.56 (moderately constrained)
• MANE Select transcript: NM_006287

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11760
Approved symbol	TFPI
Name	tissue factor pathway inhibitor
Location	2q32.1
Locus type	gene with protein product
Status	Approved
Aliases	EPI, TFI, TFPI1
Ensembl gene	ENSG00000003436
Ensembl biotype	protein_coding
OMIM	152310
Entrez	7035

Gene structure

Transcript identifiers

Ensembl transcripts: 71 — 64 protein_coding, 5 nonsense_mediated_decay, 2 retained_intron

MANE Select: ENST00000233156

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 3, TSL 2: 3, TSL 3: 2, TSL 4: 1, TSL 5: 3

ENST00000233156, ENST00000339091, ENST00000392365, ENST00000409676, ENST00000417013, ENST00000420747, ENST00000421427, ENST00000435414, ENST00000437725, ENST00000453013, ENST00000481132, ENST00000481389, ENST00000897898, ENST00000897899, ENST00000897900, ENST00000897901, ENST00000897902, ENST00000897903, ENST00000897904, ENST00000897905, ENST00000897906, ENST00000897907, ENST00000897908, ENST00000897909, ENST00000897910, ENST00000897911, ENST00000897912, ENST00000897913, ENST00000897914, ENST00000897915, ENST00000897916, ENST00000897917, ENST00000897918, ENST00000897919, ENST00000897920, ENST00000897921, ENST00000897922, ENST00000897923, ENST00000897924, ENST00000897925, ENST00000897926, ENST00000938019, ENST00000938021, ENST00000938022, ENST00000938023, ENST00000971368, ENST00000971369, ENST00000971370, ENST00000971371, ENST00000971372, ENST00001004052, ENST00001004053, ENST00001004054, ENST00001004055, ENST00001004056, ENST00001004057, ENST00001004058, ENST00001004059, ENST00001004060, ENST00001004061, ENST00001004062, ENST00001029416, ENST00001029417, ENST00001093550, ENST00001093551, ENST00001109456, ENST00001109457, ENST00001109458, ENST00001109459, ENST00001120178, ENST00001142717

RefSeq mRNA: 6 — MANE Select: NM_006287 NM_001032281, NM_001318941, NM_001329239, NM_001329240, NM_001329241, NM_006287

CCDS: CCDS2294, CCDS33349

Canonical transcript exons

ENST00000233156 — 8 exons

Exon	Start	End
ENSE00000783643	187484124	187484216
ENSE00001447089	187464230	187467042
ENSE00003474693	187467753	187467932
ENSE00003507057	187503648	187503770
ENSE00003508654	187488337	187488375
ENSE00003665068	187484811	187484987
ENSE00003784034	187496881	187497078
ENSE00003846247	187554200	187554435

Expression profiles

Bgee: expression breadth ubiquitous, 262 present calls, max score 98.94.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 83.6761 / max 2043.0902, expressed in 1665 samples.

Highest expression (Bgee): lung, lower lobe of lung, visceral pleura, placenta, upper lobe of lung.

Genetic regulation across tissues (GTEx eQTL / sQTL)

TFPI is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 28 tissues and its splicing (sQTL) in 12 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 40 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Muscle Skeletal	eqtl	7.3e-48	-0.47	2:187547635:A:C
Heart Left Ventricle	eqtl	2.3e-28	-0.44	2:187547517:T:A
Esophagus Muscularis	eqtl	9.0e-25	-0.35	2:187547517:T:A
Esophagus Mucosa	eqtl	5.3e-24	-0.30	2:187547635:A:C
Esophagus Gastroesophageal Junction	eqtl	4.4e-22	-0.38	2:187547517:T:A
Cells Cultured fibroblasts	sqtl	1.0e-18	-0.47	2:187475669:T:C
Heart Atrial Appendage	eqtl	2.6e-14	-0.40	2:187546821:CCTGT:C
Cells Cultured fibroblasts	eqtl	2.1e-13	+0.23	2:187443020:G:A
Colon Sigmoid	eqtl	1.3e-08	-0.25	2:187547517:T:A
Artery Tibial	eqtl	7.0e-08	-0.18	2:187333719:G:A
Thyroid	eqtl	1.2e-07	-0.28	2:187569017:A:G
Nerve Tibial	eqtl	3.7e-07	+0.15	2:187487335:G:GTACA
Skin Sun Exposed Lower leg	eqtl	4.5e-07	-0.19	2:187491383:A:G
Lung	eqtl	1.3e-06	+0.17	2:187556372:T:C
Adipose Subcutaneous	sqtl	3.0e-06	+0.59	2:187465704:GTCATGAAGCTAT:G
Lung	sqtl	8.5e-06	-0.23	2:187302130:T:C
Testis	eqtl	3.0e-05	-0.18	2:187212666:T:TAAAG
Artery Aorta	eqtl	5.3e-05	-0.28	2:187611904:C:T
Thyroid	sqtl	1.9e-04	+0.66	2:187513565:C:T
Artery Tibial	sqtl	2.5e-04	+0.26	2:187441502:G:A

FANTOM5 promoters

showing 10 of 15 alternative TSS:

Promoter ID	TPM avg	Samples expressed
32815	68.0943	1634
32816	7.7339	1421
32809	3.7566	373
32804	1.0636	545
32799	0.8750	445
32801	0.5342	261
32806	0.4967	281
32800	0.2803	131
32808	0.1812	81
32805	0.1810	91

Top tissues by expression

showing 100 of 293 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
right lung	UBERON:0002167	98.94	gold quality
lower lobe of lung	UBERON:0008949	98.30	gold quality
visceral pleura	UBERON:0002401	98.26	gold quality
placenta	UBERON:0001987	98.04	gold quality
upper lobe of lung	UBERON:0008948	98.04	gold quality
upper lobe of left lung	UBERON:0008952	98.00	gold quality
stromal cell of endometrium	CL:0002255	97.76	gold quality
lung	UBERON:0002048	97.72	gold quality
liver	UBERON:0002107	97.66	gold quality
pericardium	UBERON:0002407	97.38	gold quality
right lobe of liver	UBERON:0001114	97.22	gold quality
superficial temporal artery	UBERON:0001614	96.97	gold quality
jejunal mucosa	UBERON:0000399	96.67	gold quality
gall bladder	UBERON:0002110	96.63	gold quality
adrenal tissue	UBERON:0018303	96.22	gold quality
islet of Langerhans	UBERON:0000006	96.20	gold quality
nephron tubule	UBERON:0001231	96.12	gold quality
duodenum	UBERON:0002114	95.74	gold quality
calcaneal tendon	UBERON:0003701	95.64	gold quality
renal glomerulus	UBERON:0000074	95.58	gold quality
metanephric glomerulus	UBERON:0004736	95.55	gold quality
left coronary artery	UBERON:0001626	95.11	gold quality
mucosa of stomach	UBERON:0001199	95.01	gold quality
subcutaneous adipose tissue	UBERON:0002190	95.00	gold quality
coronary artery	UBERON:0001621	94.91	gold quality
kidney epithelium	UBERON:0004819	94.78	gold quality
right coronary artery	UBERON:0001625	94.75	gold quality
omental fat pad	UBERON:0010414	94.70	gold quality
peritoneum	UBERON:0002358	94.68	gold quality
metanephros	UBERON:0000081	94.51	gold quality
adipose tissue of abdominal region	UBERON:0007808	94.49	gold quality
pleura	UBERON:0000977	94.41	gold quality
synovial joint	UBERON:0002217	94.21	gold quality
adipose tissue	UBERON:0001013	94.00	gold quality
connective tissue	UBERON:0002384	93.86	gold quality
layer of synovial tissue	UBERON:0007616	93.79	gold quality
skin of hip	UBERON:0001554	93.78	gold quality
metanephros cortex	UBERON:0010533	93.69	gold quality
smooth muscle tissue	UBERON:0001135	93.54	gold quality
tibial artery	UBERON:0007610	93.50	gold quality
popliteal artery	UBERON:0002250	93.49	gold quality
endocervix	UBERON:0000458	93.48	gold quality
thoracic mammary gland	UBERON:0005200	93.46	gold quality
mammary gland	UBERON:0001911	93.17	gold quality
mucosa of urinary bladder	UBERON:0001259	93.12	gold quality
mammary duct	UBERON:0001765	92.99	gold quality
left uterine tube	UBERON:0001303	92.96	gold quality
colonic epithelium	UBERON:0000397	92.72	gold quality
tendon	UBERON:0000043	92.71	gold quality
aorta	UBERON:0000947	92.70	gold quality
right lobe of thyroid gland	UBERON:0001119	92.67	gold quality
urinary bladder	UBERON:0001255	92.61	gold quality
cauda epididymis	UBERON:0004360	92.57	gold quality
urethra	UBERON:0000057	92.50	gold quality
parietal pleura	UBERON:0002400	92.44	gold quality
heart right ventricle	UBERON:0002080	92.43	gold quality
jejunum	UBERON:0002115	92.18	gold quality
lymph node	UBERON:0000029	92.07	gold quality
left lobe of thyroid gland	UBERON:0001120	92.07	gold quality
kidney	UBERON:0002113	92.07	gold quality
right atrium auricular region	UBERON:0006631	92.06	gold quality
adult mammalian kidney	UBERON:0000082	91.93	gold quality
tibial nerve	UBERON:0001323	91.92	gold quality
ascending aorta	UBERON:0001496	91.83	gold quality
trabecular bone tissue	UBERON:0002483	91.83	gold quality
cardiac atrium	UBERON:0002081	91.81	gold quality
small intestine	UBERON:0002108	91.77	gold quality
thoracic aorta	UBERON:0001515	91.69	gold quality
thyroid gland	UBERON:0002046	91.61	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	91.54	gold quality
adult organism	UBERON:0007023	91.49	gold quality
small intestine Peyer’s patch	UBERON:0003454	91.48	gold quality
cortex of kidney	UBERON:0001225	91.47	gold quality
epithelium of mammary gland	UBERON:0003244	91.43	gold quality
ectocervix	UBERON:0012249	90.95	gold quality
descending thoracic aorta	UBERON:0002345	90.84	gold quality
lower esophagus muscularis layer	UBERON:0035833	90.78	gold quality
lower esophagus	UBERON:0013473	90.74	gold quality
rectum	UBERON:0001052	90.64	gold quality
heart	UBERON:0000948	90.18	gold quality
pancreas	UBERON:0001264	90.05	gold quality
caput epididymis	UBERON:0004358	89.97	gold quality
mammalian vulva	UBERON:0000997	89.90	gold quality
body of uterus	UBERON:0009853	89.76	gold quality
sural nerve	UBERON:0015488	89.15	gold quality
vena cava	UBERON:0004087	89.05	gold quality
fundus of stomach	UBERON:0001160	88.99	gold quality
myocardium	UBERON:0002349	88.98	gold quality
myometrium	UBERON:0001296	88.92	gold quality
gastrocnemius	UBERON:0001388	88.63	gold quality
cardiac muscle of right atrium	UBERON:0003379	88.49	gold quality
vagina	UBERON:0000996	88.31	gold quality
muscle layer of sigmoid colon	UBERON:0035805	88.29	gold quality
heart left ventricle	UBERON:0002084	88.23	gold quality
cardiac ventricle	UBERON:0002082	88.21	gold quality
muscle of leg	UBERON:0001383	88.05	gold quality
esophagus	UBERON:0001043	88.00	gold quality
germinal epithelium of ovary	UBERON:0001304	87.89	gold quality
hindlimb stylopod muscle	UBERON:0004252	87.76	gold quality
epithelial cell of pancreas	CL:0000083	87.74	gold quality

Single-cell (SCXA)

Detected in 37 experiment(s), a significant marker in 33.

Experiment	Marker?	Max mean expression
E-CURD-88	yes	4072.34
E-MTAB-8205	yes	3279.06
E-HCAD-23	yes	2986.67
E-GEOD-124263	yes	2925.46
E-MTAB-6701	yes	2732.54
E-MTAB-8142	yes	2612.27
E-ANND-2	yes	2599.85
E-HCAD-24	yes	2214.21
E-HCAD-1	yes	2183.34
E-MTAB-8410	yes	2061.35
E-MTAB-8271	yes	2045.39
E-CURD-46	yes	1823.49
E-MTAB-6308	yes	1821.73
E-MTAB-9388	yes	1632.01
E-CURD-112	yes	1591.17

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 64 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Liver	tissue	254.3	medium
Placenta	tissue	179.5	high
Lung	tissue	95.1	medium
Gallbladder	tissue	54.0	high
Kidney	tissue	52.6	high
Adipose tissue	tissue	52.1	not detected
Duodenum	tissue	49.6	low
Urinary bladder	tissue	49.4	medium
Tongue	tissue	39.9
Breast	tissue	39.8	medium
Small intestine	tissue	39.4	medium
Cervix	tissue	39.1
Lymph node	tissue	31.4	medium
Esophagus	tissue	31.4	medium
Fallopian tube	tissue	30.4	low
Smooth muscle	tissue	28.6	low
Vagina	tissue	27.2	low
Rectum	tissue	26.4	high
Ovary	tissue	26.3	medium
Heart muscle	tissue	24.8	medium
Endometrium 1	tissue	24.1	medium
Pancreas	tissue	23.5	medium
Choroid plexus	tissue	21.6
Colon	tissue	20.4	high
Spleen	tissue	19.6	low
Appendix	tissue	19.6	high
Epididymis	tissue	17.6	medium
Tonsil	tissue	16.6	medium
Thyroid gland	tissue	14.6	medium
Hippocampus	tissue	12.9	medium
Prostate	tissue	12.9	medium
Stomach 1	tissue	12.4	high
Seminal vesicle	tissue	12.1	medium
Adrenal gland	tissue	11.7	medium
Postcentral gyrus	tissue	11.5
Nucleus accumbens	tissue	11.2
Thymus	tissue	10.4
Skin 1	tissue	10.1	low
Skeletal muscle	tissue	10.1	medium
Locus coeruleus	tissue	9.7
Bone marrow	tissue	7.8	medium
Testis	tissue	6.6	medium
Parathyroid gland	tissue	6.6	medium
Salivary gland	tissue	5.6	not detected
Pituitary gland	tissue	5.5
Retina	tissue	4.9
Frontal cortex	tissue	4.7
Caudate putamen	tissue	3.0
Substantia nigra	tissue	0.6
Spinal cord	tissue	0.4
Superior colliculi	tissue	0.3
Putamen	tissue	0.2
Medulla oblongata	tissue	0.2
Pons	tissue	0.1
Hypothalamus	tissue	0.1
Hippocampal formation	tissue	0.1
Olfactory bulb	tissue	0.1
Cerebral cortex	tissue	0.0	medium
Basal ganglia	tissue	0.0	medium
Cerebellum	tissue	0.0	medium

Brain sub-regions (HPA Brain Atlas): detected in 188; highest nTPM — Blood vessel (50.7), Area postrema (20.7), Dorsal motor vagal complex (17.7), Flocculonodular lobe (15.9), Vermis (15.7).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ADTRP

miRNA regulators (miRDB)

Targeting TFPI by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 113 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-3682-5P	99.93	67.97	1163
HSA-MIR-9902	99.89	69.15	2250

Functional genomics

gnomAD constraint: pLI 0.901, LOEUF 0.558, missense Z 1.5 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000233156 — one region, missense o/e 0.83.

Literature-anchored findings (GeneRIF, showing 40)

• The purpose of this review is to outline recent developments in the field related to the structural specificity and biology of TFPI. (PMID:11686353)
• protease inhibitor of extrinsic coagulation (PMID:11693665)
• circadian variations in healthy adults and in subjects with type II diabetes; possible role in increased vascular wall uptake of lipoproteins in diabetic subjects (PMID:11697721)
• Bemiparin and fluid flow modulate the expression, activity and release of tissue factor pathway inhibitor in human endothelial cells in vitro. Bemiparin enhanced TFPI mRNA in EC under the arterial flow. (PMID:11776326)
• Recombinant tissue factor pathway inhibitor prevents lipopolysaccharide-induced systemic hypotension in rats by inhibiting excessive production of nitric oxide. (PMID:11776329)
• The presence of TFPI in human cardiomyocytes is confirmed in ventricle from cardiac soidosis, myocarditis, and AMI patients. (PMID:11816723)
• The C-terminal domain of TFPI molecule plays a predominant role in the binding to ox-LDL and the binding through the C-terminal part is essential for the ox-LDL-dependent reduction of the anticoagulant activity of TFPI. (PMID:11848461)
• Plasma levels of the Factor Xa (FXa)-TFPI complex were significantly higher in patients with solid tumours, compared to patients with haematological malignancy and healthy controls. (PMID:11864704)
• expression of TF and TFPI in human melanoma (PMID:12028585)
• The tissue factor pathway inhibitor C536T mutation is not associated with the risk of stroke in young adults. (PMID:12038800)
• MMP-8 cleaves TFPI following Ser(174) in the connecting region between the second and third Kunitz domains 75 M(-1).s(-1)) as well as following Lys(20) within the NH(2)-terminal region. MMP-8 cleavage of TFPI decreases the anticoagulant activity of TFPI (PMID:12117418)
• biochemistry, molecular biology, physiology and physiopathology (review) (PMID:12193974)
• The CC genotype of the TFPI intron 7 33T–>C polymorphism is an independent protective factor for venous thromboembolism, an effect probably mediated by increased TFPI levels. (PMID:12195688)
• levels in placenta and myometrium; the concentration seems to be too low to prevent initiation of coagulation (PMID:12270558)
• exploration of active components in oxidized low-density lipoprotein that reduce activity of TFPI (PMID:12408975)
• The intact C-terminus in GPI-anchored TFPI indicates it is not directly attached to a GPI anchor; rather, it most likely associates with placental endothelium by binding to a GPI-anchored protein. (PMID:12482841)
• Transfectants expressing equal levels of GPI-linked TFPI or transmembrane TFPI displayed equal anticoagulant potency as assessed by tissue factor-mediated conversion of factor X to factor Xa. (PMID:12540955)
• High TFPI levels in ovarian follicular fluid underline its physiological importance for maintaining the hypocoagulable state. TFPI in seminal plasma samples of infertile men was reduced, suggesting a correlation between seminal coagulation & fertility. (PMID:12818258)
• Most aPL recognized full-length TFPI, but not a truncated form of TFPI lacking the C-terminus of the molecule; aPL with high titer anti-TFPI limit TFPI action and are associated with the APS. (PMID:12871406)
• TFPI of proximal tubular epithelial cells may act against generation of thrombin and tubular fibrin formation induced by tissue factor activation. (PMID:12893029)
• The TF and TFPI levels depend significantly on the renal function; elevated TF and TFPI levels may be related to thrombosis and atherosclerosis in chronic renal failure patients on peritoneal dialysis (PMID:14610342)
• TFPI is involved in the process of thrombus formation in vivo in patients with ACS, which suggests a potential role for TFPI in modulating coronary thrombosis. (PMID:14656922)
• Immobilized rTFPI slows fibrin deposition on vascular graft material by inhibiting contact pathway and blood borne tissue factor procoagulant arising from either alternatively spliced form of tissue factor or from tissue factor containing microparticles. (PMID:15307537)
• Immunoglobulin G fractions from subjects with antiphospholipid syndrome have inhibitory activity against tissue factor pathway inhibitor (TFPI). (PMID:15339683)
• results suggest that the inhibitory effect of the LMWH tinzaparin on endothelial tube formation is associated with stimulation of the release of TFPI, but not to anti-Factor Xa activity (PMID:15351861)
• TF and TFPI mRNA expression, protein levels and activity in trophoblast cells were determined and compared to human umbilical vein endothelial cells (PMID:15467908)
• both in humans and mice, there are temporal variations in TFPI activity (PMID:15604416)
• caveolin regulates the inhibition by cell-bound TFPI of the active protease production by the extrinsic pathway of coagulation (PMID:15817451)
• polymorphisms in and around the TFPI structural gene may be the major genetic determinants of variation in TFPI levels (PMID:15845911)
• TFPI may regulate the activity of abundant Tissue Factor in human semen (PMID:15886798)
• a rapid and economic alternative to the determination of total TFPI antigen by ELISA in plasma samples after heparin application (PMID:16113753)
• glycosylation and gene expression induced by stimulation of cells with inflammatory stimuli were compared for the 2 isoforms; Although TFPIalpha comprises 80% of the surface-TFPI, TFPIbeta was responsible for the bulk of the FVIIa/TF inhibitory activity (PMID:16246254)
• thrombosis patients with low levels of free TFPI are at an increased risk of recurrent venous thromboembolism (PMID:16270631)
• changes in circulating tissue factor procoagulant activity (PCA) and other procoagulation proteins in healthy volunteers exposed to 24 h of selective hyperinsulinemia, selective hyperglycemia, or combined hyperinsulinemia and hyperglycemia (PMID:16380494)
• Versican G3 domain promotes blood coagulation through suppressing the activity of tissue factor pathway inhibitor-1 (PMID:16431924)
• data suggest that protein S deficiency not only increases the risk of thrombosis by impairing the protein C system but also by reducing the ability of TFPI to down-regulate the extrinsic coagulation pathway (PMID:16488980)
• TF induction in conjunction with TFPI suppression may be relevant for the increased frequency of myocardial infarction observed in cocaine consumers (PMID:16516912)
• circadian rhythms affect expression of melatonin and tissue factor pathway inhibitor type (PMID:16879232)
• platelets TFPI is also released in microvesicles or as a soluble protein (PMID:17082321)
• TFPI-1 is expressed by breast cancer and other cancer cell lines maintained in cell culture. (PMID:17180732)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	tfpia	ENSDARG00000034718
mus_musculus	Tfpi	ENSMUSG00000027082
rattus_norvegicus	Tfpi	ENSRNOG00000005039
drosophila_melanogaster	CG7565	FBGN0035833
caenorhabditis_elegans		WBGENE00008449
caenorhabditis_elegans		WBGENE00010792
caenorhabditis_elegans		WBGENE00015355
caenorhabditis_elegans		WBGENE00021939

Paralogs (13): EPPIN (ENSG00000101448), TFPI2 (ENSG00000105825), AMBP (ENSG00000106927), LRP11 (ENSG00000120256), WFIKKN1 (ENSG00000127578), KIAA0319 (ENSG00000137261), KIAA0319L (ENSG00000142687), SPINT4 (ENSG00000149651), WFDC8 (ENSG00000158901), SPINT1 (ENSG00000166145), SPINT2 (ENSG00000167642), WFIKKN2 (ENSG00000173714), WFDC6 (ENSG00000243543)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1095418) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 21 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal fontanelle morphology	1
kinked tail	1
short tail	1
poor circulation	1
abnormal visceral yolk sac morphology	1
absent visceral yolk sac blood islands	1
hemorrhage	1
intracranial hemorrhage	1
abnormal blood coagulation	1
pallor	1
embryonic growth retardation	1
abnormal thrombosis	1
pericardial effusion	1
abnormal circulating protein level	1
spinal hemorrhage	1
abnormal acute phase protein level	1
perinatal lethality, complete penetrance	1
prenatal lethality, complete penetrance	1
embryonic lethality during organogenesis, incomplete penetrance	1
lethality throughout fetal growth and development, incomplete penetrance	1
increased susceptibility to induced thrombosis	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Actinia tenebrosa	A0A6P8HC43	100.0%	Diamond
Anemonia viridis	P0DN06	100.0%	Diamond
Macaca mulatta	P29216	100.0%	Diamond
Macaca fascicularis	P53601	100.0%	Diamond
Capra hircus	P62756	100.0%	Diamond
Ovis aries	P62757	100.0%	Diamond
Sus scrofa	P79307	100.0%	Diamond
Pan troglodytes	Q5IS80	100.0%	Diamond
Anemonia sulcata	Q9TWG0	100.0%	Diamond
Californiconus californicus	D2Y488	98.3%	Diamond
Lychas mucronatus	P0DJ45	97.5%	Diamond
Bombyx mori	P10831	96.8%	Diamond
Eristicophis macmahoni	P24541	96.7%	Diamond
Rhipicephalus microplus	Q8WPI2	95.8%	Diamond
Pinctada margaritifera	H2A0N5	94.9%	Diamond
Pinctada maxima	P86964	94.9%	Diamond
Anthopleura fuscoviridis	P0DMJ3	94.5%	Diamond
Dendroaspis polylepis polylepis	P00979	93.1%	Diamond
Dendroaspis angusticeps	P00980	93.1%	Diamond
Bos taurus	Q08E66	92.0%	Diamond
Haemaphysalis longicornis	B6ZIW0	90.1%	Diamond
Haemaphysalis doenitzi	C0HMC7	90.1%	Diamond
Mesocricetus auratus	Q60559	86.8%	Diamond
Meriones unguiculatus	Q62577	86.8%	Diamond
Equus caballus	P04365	86.6%	Diamond
Dichotomyctere fluviatilis	O73683	83.9%	Diamond
Takifugu rubripes	O93279	80.4%	Diamond
Anthopleura elegantissima	P86862	80.0%	Diamond
Notamacropus eugenii	O62845	76.8%	Diamond
Trichosurus vulpecula	Q29143	76.8%	Diamond
Bitis gabonica	Q6T269	75.5%	Diamond
Ixodes ricinus	Q9GP15	74.5%	Diamond
Anthopleura aff. xanthogrammica	P0DMX0	74.3%	Diamond
Oryctolagus cuniculus	P19761	72.1%	Diamond
Stichodactyla haddoni	B1B5I8	71.7%	Diamond
Sabellastarte magnifica	P84875	68.6%	Diamond
Vespa bicolor	C0LNR2	66.2%	Diamond
Conus striatus	P0C1X2	65.9%	Diamond
Conus bullatus	P0CY85	65.9%	Diamond
Gallus gallus	P15989	65.3%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
CALCRL-AS1	ncRNA	105373786
CALCRL	protein-coding	10203
ZSWIM2	protein-coding	151112
FAM171B	protein-coding	165215
LINC01090	ncRNA	104355152

Protein

Protein identifiers

Tissue factor pathway inhibitor — P10646 (reviewed: P10646)

Alternative names: Extrinsic pathway inhibitor, Lipoprotein-associated coagulation inhibitor

All UniProt accessions (6): P10646, C9J103, C9JKV3, C9JP39, C9JQ14, C9JT76

UniProt curated annotations — full annotation on UniProt →

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.

Subcellular location. Secreted Microsome membrane.

Tissue specificity. Mostly in endothelial cells.

Post-translational modifications. O-glycosylated.

Domain organisation. This inhibitor contains three inhibitory domains. The first domain interacts with VIIa and TF, the second one with Xa.

Miscellaneous. GPI-anchored.

Isoforms (2)

UniProt ID	Names	Canonical?
P10646-1	Alpha, TFPIalpha	yes
P10646-2	Beta, TFPIbeta

RefSeq proteins (6): NP_001027452, NP_001305870, NP_001316168, NP_001316169, NP_001316170, NP_006278* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002223	Kunitz_BPTI	Domain
IPR008296	TFPI-like	Family
IPR020901	Prtase_inh_Kunz-CS	Conserved_site
IPR036880	Kunitz_BPTI_sf	Homologous_superfamily
IPR050098	TFPI/VKTCI-like	Family

Pfam: PF00014

UniProt features (59 total): strand 17, disulfide bond 9, helix 7, mutagenesis site 6, glycosylation site 5, site 4, domain 3, turn 3, splice variant 2, signal peptide 1, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

9 structures by resolution:

PDB	Title	Method	Resolution (Å)
5NMV	Crystal structure of 2F22 Fab fragment against TFPI1	X-RAY DIFFRACTION	1.65
4DTG	Hemostatic effect of a monoclonal antibody mAb 2021 blocking the interaction between FXa …	X-RAY DIFFRACTION	1.8
6BX8	Human Mesotrypsin (PRSS3) Complexed with Tissue Factor Pathway Inhibitor Variant …	X-RAY DIFFRACTION	1.98
4BQD	KD1 of human TFPI in complex with a synthetic peptide	X-RAY DIFFRACTION	2.48
1TFX	COMPLEX OF THE SECOND KUNITZ DOMAIN OF TISSUE FACTOR PATHWAY INHIBITOR WITH PORCINE …	X-RAY DIFFRACTION	2.6
7V1N	Structure of the Clade 2 C. difficile TcdB in complex with its receptor TFPI	ELECTRON MICROSCOPY	3.2
9P0X	Nanodisc-embedded human TF/FVIIa/XK1 in complex with 10H10 Fab (nanodisc-subtracted)	ELECTRON MICROSCOPY	3.7
1ADZ	THE SOLUTION STRUCTURE OF THE SECOND KUNITZ DOMAIN OF TISSUE FACTOR PATHWAY INHIBITOR …	SOLUTION NMR
1IRH	The Solution Structure of The Third Kunitz Domain of Tissue Factor Pathway Inhibitor	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P10646-F1	74.04	0.48

Antibody-complex structures (SAbDab)

4 antibodies co-crystallized with this protein: 4DTG, 5NMV, 9P0X, CONCIZUMAB

Human Protein Atlas

Protein class: Predicted secreted proteins, Plasma proteins, Candidate cardiovascular disease genes, FDA approved drug targets, Biotech drugs, Small molecule drugs

Protein evidence: Evidence at protein level

Antibody reliability (HPA): IH supported

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (4)

Position	Role
64–65	reactive bond
135–136	reactive bond
227–228	reactive bond
256	not glycosylated

Disulfide bonds (9)

Type	Positions
Disulfide bond	54–104, 63–87, 79–100, 125–175, 134–158, 150–171, 217–267, 226–250, 242–263

Glycosylation sites (5)

Type	Positions
N-linked (glcnac…) asparagine	145, 195
O-linked (galnac…) serine	202
O-linked (galnac…) threonine	203, 42

Mutagenesis-validated functional residues (6)

Position	Phenotype
49	results in resistance to mmp9-mediated cleavage.
64	abolishes inhibition of vii(a)/tf.
115	results in resistant to elane-mediated cleavage. results in resistant to elane- and ctsg-mediated cleavage; when associated with a-117.
117	results in resistant to elane- and ctsg-mediated cleavage; when associated with a-115.
135	abolishes inhibition of x(a).
227	abolishes inhibition of vii(a)/tf.

Function

Pathways and Gene Ontology

Reactome pathways

2 curated (TAS) of 5; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

5 pathways:

ID	Pathway	Evidence
R-HSA-9769735	Initiation of coagulation cascade	curated
R-HSA-9769739	Regulation of clotting cascade	curated
R-HSA-109582	Hemostasis	—
R-HSA-140834		—
R-HSA-140877		—

MSigDB gene sets: 320 (showing top): VERHAAK_AML_WITH_NPM1_MUTATED_DN, TONKS_TARGETS_OF_RUNX1_RUNX1T1_FUSION_MONOCYTE_UP, GOBP_REGULATION_OF_WOUND_HEALING, GOBP_CELLULAR_RESPONSE_TO_LIPID, GOBP_REGULATION_OF_COAGULATION, GOZGIT_ESR1_TARGETS_DN, GOCC_CELL_SURFACE, SARRIO_EPITHELIAL_MESENCHYMAL_TRANSITION_DN, KORKOLA_CHORIOCARCINOMA, SENESE_HDAC1_AND_HDAC2_TARGETS_DN, GOBP_NEGATIVE_REGULATION_OF_COAGULATION, GOBP_WOUND_HEALING, GOBP_NEGATIVE_REGULATION_OF_MULTICELLULAR_ORGANISMAL_PROCESS, GOBP_CELLULAR_RESPONSE_TO_HORMONE_STIMULUS, LI_WILMS_TUMOR_VS_FETAL_KIDNEY_1_UP

GO Biological Process (6): blood coagulation (GO:0007596), negative regulation of blood coagulation (GO:0030195), cellular response to steroid hormone stimulus (GO:0071383), hemostasis (GO:0007599), negative regulation of peptidase activity (GO:0010466), cellular response to lipid (GO:0071396)

GO Molecular Function (3): endopeptidase inhibitor activity (GO:0004866), serine-type endopeptidase inhibitor activity (GO:0004867), peptidase inhibitor activity (GO:0030414)

GO Cellular Component (5): extracellular region (GO:0005576), plasma membrane (GO:0005886), caveola (GO:0005901), cell surface (GO:0009986), side of membrane (GO:0098552)

Reactome top-level categories

1 top-level categories:

Category	Pathways
Coagulation pathway	2

GO top-level categories

30 GO namespaces:

Category	Terms
cellular anatomical structure	3
peptidase activity	2
membrane	2
hemostasis	1
wound healing	1
coagulation	1
blood coagulation	1
regulation of blood coagulation	1
negative regulation of coagulation	1
negative regulation of wound healing	1
negative regulation of hemostasis	1
cellular response to hormone stimulus	1
response to steroid hormone	1
cellular response to lipid	1
regulation of body fluid levels	1
negative regulation of proteolysis	1
negative regulation of hydrolase activity	1
regulation of peptidase activity	1
response to lipid	1
cellular response to chemical stimulus	1
endopeptidase activity	1
peptidase inhibitor activity	1
endopeptidase regulator activity	1
serine-type endopeptidase activity	1
endopeptidase inhibitor activity	1
enzyme inhibitor activity	1
peptidase regulator activity	1
cell periphery	1
plasma membrane raft	1
leaflet of membrane bilayer	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 4 of 15 annotations. The rest are phylogenetic / computational / electronic (IEA).

4 experimentally-supported GO terms:

GO term	NS	Evidence
cellular response to steroid hormone stimulus	BP	expression pattern
negative regulation of blood coagulation	BP	direct assay
caveola	CC	direct assay
cell surface	CC	direct assay

Protein interactions and networks

STRING

showing 15 of 1,160 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TFPI	F3	P13726	970
TFPI	F7	P08709	942
TFPI	THBD	P07204	934
TFPI	F2	P00734	908
TFPI	SERPINC1	P01008	897
TFPI	F10	P00742	858
TFPI	PROCR	Q9UNN8	850
TFPI	SERPIND1	P05546	814
TFPI	CLMP	Q9H6B4	765
TFPI	PLG	P00747	757
TFPI	ELANE	P08246	742
TFPI	VWF	P04275	736
TFPI	F2R	P25116	730
TFPI	PLAT	P00750	721
TFPI	F8	P00451	717

IntAct

Human interaction partners of TFPI in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

2 partners by confidence:

Partner	Interaction type	MIscore	Records
MASP2	cleavage reaction	0.440	1
KCNIP4	physical association	0.400	2

BioGRID (28 interactions; top human partners by supporting records): APP (Reconstituted Complex; 2 records), F10 (Affinity Capture-Western; 2 records), KCNIP4 (Affinity Capture-MS; 2 records), APOA1 (Cross-Linking-MS (XL-MS)), ATG14 (Affinity Capture-MS), BCAS2 (Co-fractionation), BSG (Proximity Label-MS), ELAVL1 (Affinity Capture-RNA), ERBB2 (Proximity Label-MS), FLNA (Cross-Linking-MS (XL-MS)), HIAT1 (Affinity Capture-MS), MYC (Affinity Capture-MS), NUPR1 (Affinity Capture-MS), PRSS3 (Co-crystal Structure), RAF1 (Affinity Capture-MS)

SIGNOR signaling

1 signaling interactions:

A	Effect	B	Mechanism
TFPI	up-regulates	VLDLR	binding

Protein complexes (CORUM) (2)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

2 complexes by size:

Complex	Subunits	Members
★ F3-F7-F10-TFPI complex	4	TFPI, F10, F3, F7
★ F10-TFPI complex	2	TFPI, F10

Disease & clinical

Genetic variants

Variant evidence for TFPI: 3 ClinVar records (0 pathogenic / likely pathogenic); 26 GWAS associations.

ClinVar

3 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	1
Likely benign	0
Benign	0

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 40 predictions of 1,027):

Position(s)	Effect	Δscore	Sites
2:187467827	donor_gain	1.0000
2:187484122–187484123	donor_loss	1.0000	6
2:187484217–187484218	acceptor_loss	1.0000	6
2:187484227	acceptor_gain	1.0000
2:187484988–187484989	acceptor_loss	1.0000	2
2:187554198–187554199	donor_loss	1.0000	5
2:187467043–187467044	acceptor_loss	0.9900	6
2:187484809–187484810	donor_loss	0.9900	5
2:187484988–187484989	acceptor_loss	0.9900	3
2:187488335–187488336	donor_loss	0.9900	5

AlphaMissense

487 missense substitutions predicted likely pathogenic (of 2,035 scored), across 105 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
N163	8	0.983	0.996
N92	8	0.981	0.994
N255	8	0.981	0.995
F153	8	0.932	0.990
F245	8	0.930	0.986
F82	8	0.919	0.992
N161	8	0.884	0.986
C134	7	0.990	0.996
C54	7	0.989	0.995
C158	7	0.988	0.996
C171	7	0.988	0.997
C79	7	0.987	0.996
C150	7	0.987	0.996
C125	7	0.986	0.992
C100	7	0.983	0.995
C217	7	0.983	0.995
C175	7	0.982	0.992
C267	7	0.981	0.991
C242	7	0.980	0.994
F257	7	0.980	0.994

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Disease associations

OMIM: gene MIM:152310 | disease phenotypes:

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (1 panels, 0 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

1 panels:

Panel	Rating
Thrombophilia with a likely monogenic cause	amber

GWAS associations

26 associations:

Study	Trait	p-value
GCST010699_91	Brain morphology (min-P)	9e-27
GCST010703_145	Brain morphology (MOSTest)	5e-22
GCST007487_34	Waist-to-hip ratio adjusted for BMI (additive genetic model)	2e-14
GCST010701_33	Cortical surface area (MOSTest)	3e-14
GCST010700_8	Cortical thickness (MOSTest)	5e-14
GCST007483_21	Waist-to-hip ratio adjusted for BMI (additive genetic model)	3e-12
GCST010702_108	Subcortical volume (MOSTest)	4e-12
GCST90020025_333	Waist-to-hip ratio adjusted for BMI	4e-12
GCST90020027_1949	Waist-hip index	1e-11
GCST90020029_901	Waist circumference adjusted for body mass index	2e-11
GCST90020024_317	A body shape index	1e-10
GCST010698_79	Subcortical volume (min-P)	3e-10
GCST010146_8	Serum immune biomarker levels	9e-10
GCST012227_1361	Hip circumference adjusted for BMI	3e-9
GCST90020024_316	A body shape index	3e-9
GCST007502_16	Waist-to-hip ratio adjusted for BMI (additive genetic model)	4e-9
GCST012229_66	Hip index	1e-8
GCST90020029_900	Waist circumference adjusted for body mass index	1e-8
GCST010241_244	Apolipoprotein A1 levels	2e-8
GCST012227_1362	Hip circumference adjusted for BMI	4e-8
GCST001969_1	Heart rate	5e-8
GCST007500_46	Waist-to-hip ratio adjusted for BMI (additive genetic model)	5e-8
GCST007494_9	Waist-to-hip ratio adjusted for BMI (additive genetic model)	2e-7
GCST007492_7	Waist-to-hip ratio adjusted for BMI (additive genetic model)	3e-6
GCST004744_65	Lung adenocarcinoma	6e-6
GCST007637_7	Diffusing capacity of carbon monoxide	7e-6

EFO canonical traits (from GWAS)

9 canonical traits:

EFO ID	Trait name
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0009369	diffusing capacity of the lung for carbon monoxide
EFO:0004869	YKL40 measurement
EFO:0004872	inflammatory biomarker measurement
EFO:0004614	apolipoprotein A 1 measurement
EFO:0004346	neuroimaging measurement
EFO:0004840	cortical thickness
EFO:0008039	BMI-adjusted hip circumference
EFO:0007789	BMI-adjusted waist circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3713062 (SINGLE PROTEIN)

Drugs by curated mechanism of action (ChEMBL)

Drugs whose curated ChEMBL mechanism of action targets the TFPI protein itself — single-protein targets only (drugs acting on a protein family or complex that merely includes it are excluded). Includes antibodies and oligonucleotides that bioactivity screening does not capture.

4 curated-mechanism drugs:

Drug	Modality	Max phase
ANDEXANET ALFA	Protein	4
CONCIZUMAB	Antibody	4
MARSTACIMAB	Antibody	4
BAY-1093884	Unknown	2

PharmGKB: 1 entry (CPIC guideline: no)

ChEMBL bioactivities

3466 potent at pChembl≥5 of 3573 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.27	Kd	0.054	nM	CHEMBL4545581
10.22	EC50	0.06	nM	CHEMBL4543933
9.52	Kd	0.3	nM	CHEMBL3894172
9.47	IC50	0.337	nM	CHEMBL4473203
9.28	IC50	0.52	nM	CHEMBL4473203
9.25	IC50	0.56	nM	CHEMBL4447126
9.24	IC50	0.57	nM	CHEMBL4467258
9.24	IC50	0.58	nM	CHEMBL4515587
9.24	IC50	0.57	nM	CHEMBL4544981
9.22	IC50	0.6	nM	CHEMBL4570697
9.21	IC50	0.61	nM	CHEMBL4450425
9.21	IC50	0.61	nM	CHEMBL4517882
9.19	IC50	0.65	nM	CHEMBL4476135
9.19	IC50	0.64	nM	CHEMBL4470799
9.18	IC50	0.66	nM	CHEMBL4555480
9.18	IC50	0.66	nM	CHEMBL4449476
9.15	IC50	0.71	nM	CHEMBL4443775
9.14	IC50	0.72	nM	CHEMBL4556108
9.14	IC50	0.72	nM	CHEMBL4463366
9.13	IC50	0.74	nM	CHEMBL4574858
9.11	IC50	0.78	nM	CHEMBL4439410
9.06	IC50	0.87	nM	CHEMBL4527541
9.06	IC50	0.88	nM	CHEMBL4515393
9.04	IC50	0.92	nM	CHEMBL4448457
9.03	IC50	0.94	nM	CHEMBL4475900
9.02	IC50	0.96	nM	CHEMBL4581025
9.00	IC50	1.01	nM	CHEMBL4476540
8.98	IC50	1.04	nM	CHEMBL4563370
8.97	IC50	1.06	nM	CHEMBL4513672
8.96	Kd	1.1	nM	CHEMBL3958046
8.94	IC50	1.14	nM	CHEMBL4451907
8.92	EC50	1.2	nM	CHEMBL4445250
8.91	IC50	1.22	nM	CHEMBL4593874
8.88	IC50	1.32	nM	CHEMBL4436906
8.87	IC50	1.34	nM	CHEMBL4529807
8.82	EC50	1.5	nM	CHEMBL4589534
8.80	Kd	1.6	nM	CHEMBL4451698
8.79	IC50	1.63	nM	CHEMBL4588428
8.79	IC50	1.63	nM	CHEMBL4440879
8.76	IC50	1.75	nM	CHEMBL4472115
8.73	IC50	1.86	nM	CHEMBL4520832
8.71	IC50	1.94	nM	CHEMBL4442890
8.71	IC50	1.94	nM	CHEMBL4462279
8.70	IC50	1.99	nM	CHEMBL4434734
8.70	EC50	2	nM	CHEMBL4548806
8.69	IC50	2.03	nM	CHEMBL4454494
8.69	IC50	2.05	nM	CHEMBL4576960
8.69	IC50	2.06	nM	CHEMBL4448017
8.69	IC50	2.04	nM	CHEMBL4564338
8.68	EC50	2.1	nM	CHEMBL4447812

CTD chemical–gene interactions

124 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Estradiol	decreases expression, decreases reaction, affects expression, affects cotreatment, increases expression (+1 more)	10
Valproic Acid	increases expression, affects cotreatment, decreases expression	6
Tetrachlorodibenzodioxin	affects cotreatment, increases expression, decreases expression	4
methylmercuric chloride	decreases expression, increases expression	3
trichostatin A	increases expression, affects cotreatment	3
(+)-JQ1 compound	affects cotreatment, decreases expression	3
Acetaminophen	decreases expression, affects cotreatment	3
Cyclosporine	increases expression, decreases expression, affects cotreatment	3
Particulate Matter	decreases expression, increases abundance, affects cotreatment, increases expression	3
graphene oxide	increases expression	2
bisphenol A	affects expression, decreases expression	2
sodium arsenite	decreases expression, increases abundance, increases expression	2
mercuric bromide	increases expression, affects cotreatment	2
chromium hexavalent ion	increases expression, increases abundance	2
belinostat	increases expression, affects cotreatment	2
Fulvestrant	affects cotreatment, increases secretion, decreases expression, decreases reaction, decreases secretion (+1 more)	2
Vorinostat	affects cotreatment, increases expression	2
Panobinostat	affects cotreatment, increases expression	2
Air Pollutants	affects cotreatment, decreases expression, increases abundance, increases oxidation	2
Ethanol	decreases expression, affects cotreatment, increases abundance	2
Arsenic	increases abundance, increases expression	2
Benzo(a)pyrene	decreases expression, increases methylation, affects methylation	2
Copper	affects binding, affects cotreatment, increases expression	2
Doxorubicin	decreases expression, affects response to substance	2
Phenylmercuric Acetate	increases expression, affects cotreatment	2
Smoke	decreases expression, increases expression	2
Tobacco Smoke Pollution	affects expression, decreases expression	2
Genistein	decreases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, increases expression	2
Raloxifene Hydrochloride	affects cotreatment, increases secretion, decreases expression, decreases reaction, decreases secretion (+1 more)	2

ChEMBL screening assays

116 unique, capped per target: 116 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4419588	Binding	Binding affinity to TFPI (unknown origin) incubated for 1.5 hrs using tracer peptide JBT0131 by competition ELISA	TFPI inhibitors and methods of use

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for TFPI across ~30M SureChEMBL compounds — explore on Sugi Predict.