F5

Summary

F5 (coagulation factor V, HGNC:3542) is a protein-coding gene on chromosome 1q24.2, encoding Coagulation factor V (P12259). Central regulator of hemostasis.

This gene encodes an essential cofactor of the blood coagulation cascade. This factor circulates in plasma, and is converted to the active form by the release of the activation peptide by thrombin during coagulation. This generates a heavy chain and a light chain which are held together by calcium ions. The activated protein is a cofactor that participates with activated coagulation factor X to activate prothrombin to thrombin. Defects in this gene result in either an autosomal recessive hemorrhagic diathesis or an autosomal dominant form of thrombophilia, which is known as activated protein C resistance.

Source: NCBI Gene 2153 — RefSeq curated summary.

At a glance

• Gene–disease (curated): thrombophilia due to activated protein C resistance (Definitive, ClinGen) — +2 more curated relationships
• GWAS associations: 40
• Clinical variants (ClinVar): 1,463 total — 60 pathogenic, 38 likely-pathogenic
• Phenotypes (HPO): 60
• Druggable target: yes — 2 molecules with ChEMBL bioactivity
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_000130

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3542
Approved symbol	F5
Name	coagulation factor V
Location	1q24.2
Locus type	gene with protein product
Status	Approved
Aliases	fV
Ensembl gene	ENSG00000198734
Ensembl biotype	protein_coding
OMIM	612309
Entrez	2153

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 4 protein_coding, 1 retained_intron

ENST00000367796, ENST00000367797, ENST00000495481, ENST00000904427, ENST00000904428

RefSeq mRNA: 1 — MANE Select: NM_000130 NM_000130

CCDS: CCDS1281

Canonical transcript exons

ENST00000367797 — 25 exons

Exon	Start	End
ENSE00000789603	169544296	169544508
ENSE00000789604	169546442	169546592
ENSE00000789605	169549801	169550015
ENSE00000789606	169550640	169550739
ENSE00000789607	169552557	169552734
ENSE00000789610	169559153	169559296
ENSE00000789613	169582431	169582522
ENSE00000814494	169540294	169543114
ENSE00000814495	169536506	169536680
ENSE00000814496	169530786	169531022
ENSE00000814502	169523197	169523352
ENSE00000814503	169520520	169520664
ENSE00000814505	169515444	169515626
ENSE00001168273	169518412	169518563
ENSE00001168281	169523801	169523904
ENSE00001168291	169524837	169524908
ENSE00001367181	169525901	169526017
ENSE00001376235	169529608	169529818
ENSE00001388919	169527915	169528094
ENSE00001435673	169555182	169555347
ENSE00001435704	169556646	169556867
ENSE00003609709	169560554	169560766
ENSE00003638555	169572221	169572343
ENSE00003855085	169511951	169514459
ENSE00003897926	169586229	169586481

Expression profiles

Bgee: expression breadth ubiquitous, 206 present calls, max score 98.57.

FANTOM5 (CAGE): breadth broad, TPM avg 4.5581 / max 300.2296, expressed in 363 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
15849	2.9074	327
15848	1.3850	263
15850	0.1264	30
15846	0.0779	39
15847	0.0614	32

Top tissues by expression

280 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	98.57	gold quality
liver	UBERON:0002107	98.15	gold quality
choroid plexus epithelium	UBERON:0003911	97.27	gold quality
pancreatic ductal cell	CL:0002079	92.73	gold quality
placenta	UBERON:0001987	91.98	gold quality
cranial nerve II	UBERON:0000941	89.63	gold quality
monocyte	CL:0000576	89.23	gold quality
leukocyte	CL:0000738	88.99	gold quality
mononuclear cell	CL:0000842	88.93	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	88.86	gold quality
blood	UBERON:0000178	88.16	gold quality
gall bladder	UBERON:0002110	88.14	gold quality
epithelial cell of pancreas	CL:0000083	88.06	silver quality
granulocyte	CL:0000094	87.43	gold quality
renal glomerulus	UBERON:0000074	86.43	gold quality
metanephric glomerulus	UBERON:0004736	85.81	gold quality
trabecular bone tissue	UBERON:0002483	83.92	gold quality
tendon of biceps brachii	UBERON:0008188	83.11	gold quality
heart right ventricle	UBERON:0002080	80.44	gold quality
bone marrow	UBERON:0002371	79.75	gold quality
parietal pleura	UBERON:0002400	78.57	gold quality
olfactory bulb	UBERON:0002264	77.89	gold quality
nasal cavity mucosa	UBERON:0001826	77.77	gold quality
caput epididymis	UBERON:0004358	77.75	gold quality
heart left ventricle	UBERON:0002084	77.63	gold quality
cardiac ventricle	UBERON:0002082	77.57	gold quality
minor salivary gland	UBERON:0001830	77.32	gold quality
spleen	UBERON:0002106	77.06	gold quality
tibia	UBERON:0000979	76.86	gold quality
apex of heart	UBERON:0002098	76.41	gold quality

Single-cell (SCXA)

Detected in 8 experiment(s), a significant marker in 7.

Experiment	Marker?	Max mean expression
E-GEOD-100618	yes	1402.47
E-HCAD-29	yes	298.07
E-MTAB-5061	yes	9.39
E-ANND-3	yes	6.67
E-GEOD-81608	yes	5.97
E-ENAD-27	yes	5.09
E-GEOD-81547	yes	4.83
E-GEOD-83139	no	3.84

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ESR1

miRNA regulators (miRDB)

122 targeting F5, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AU-5P	99.94	71.24	3488
HSA-MIR-548AY-5P	99.94	71.23	3502
HSA-MIR-548B-5P	99.94	71.23	3502
HSA-MIR-548BB-5P	99.94	71.27	3509
HSA-MIR-548C-5P	99.94	71.24	3488
HSA-MIR-548D-5P	99.94	71.23	3502
HSA-MIR-548H-5P	99.94	71.24	3488

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 34)

• The combined effect of aprotinin and extracorporeal circulation resulted in lowered APC ratios for Factor V Leiden blood. Increased risk of perioperative thrombosis in cardiac surgical patients heterozygous for the F5L mutation is predicted. (PMID:11761087)
• Screening 35 polymorphisms in 27 candidate genes showed that the R485K polymorphism in the coagulation factor V gene is associated with severe preeclampsia. (PMID:11776341)
• This review of hemostatic variables identifying those at risk of in-patient hospital death from pulmonary embolism (PE)notes that the prevalence of factor V Leiden may be a ‘milder’ genetic risk factor for PE than for deep venous thrombosis (PMID:11806843)
• N-linked carbohydrate moieties play a substantial role in the activated protein C-catalyzed cleavage and inactivation of pro-cofactor V (but not the derived cofactor factor Va) at position Arg306, the initial cleavage site. (PMID:11814362)
• no interaction of venous thromboembolism with the R2 allele of Factor V or with FV Leiden was observed. (PMID:11816705)
• Association of factor V Leiden gene mutation with Behcet’s disease. (FAactor V LEeiden) (PMID:11820731)
• Mothers with factor V Leiden have a higher risk of having low birth-weight infants or fetal loss, possibly due to underperfusion of the placenta. (PMID:11836168)
• Factor V Leiden mutation is associated with delayed graft function, acute rejection & chronic graft dysfunction after kidney transplantation. Continuous subclinical renal microthrombosis due to Facor V Leiden may contribute to chronic graft dysfunction. (PMID:11858477)
• A homozygous nucleotide change (G6395A) was found in 2 pts with Factor V deficiency. This results in the replacement of an Arg by a His in position 2074, located in the Factor V C2-domain. Mutations in this domain have not previously been described. (PMID:11858490)
• No association was found between factor V Leiden and fatal myocardial infarction in Finland. (PMID:11858502)
• A decrease of factor V may contribute to the thrombotic effects of oral contraceptives. Effects of combined oral contraceptives vs. progestagens only on factors VII, IX and XI were different in women with and without FV Leiden. (PMID:11859850)
• The effect of factor V mutations at R306G, R306T, R506Q, R679A on activated protein C resistance were studied. Arg306 mutations cause mildly reduced APC No effect was seen for the Ala679 mutation. (PMID:11943934)
• mutation associated with preeclampsia in pregnant Japanese women. (PMID:11950065)
• Factor Va increases the affinity of factor Xa for prothrombin. (PMID:11983337)
• Factor V Arg2074Cys: a novel missense mutation in the C2 domain of factor V is associated with hemorrhagic diathesis. (PMID:12038802)
• prevalence of FVL, FII G20210A and MTHFR C677T in women with three or more pregnancy losses (PMID:12042290)
• identifies FVa binding site in the positive exosite of APC that is primarily involved in binding and cleaving at Arg(506) on FVa (PMID:12063259)
• These results suggest that that there is no association between the factor V Leiden mutation and recurrent spontaneous abortion in the Malay population. (PMID:12069143)
• evaluation of Factor V Leiden as a risk factor for myocardial infarction, ischemic stroke, or non-MI ischemic heart disease (PMID:12070000)
• The 2 FV variants FV Hong Kong and FV Cambridge yielded identical APC resistance patterns, with APC responses being intermediate to those of wild-type FV and FV Leiden (Arg506Gln) (PMID:12091344)
• Activated protein C cleaves factor Va more efficiently on endothelium than on platelet surfaces. (PMID:12091346)
• Data show that factor V activation is associated with the stepwise release of the B-domain after incubation with thrombin, which results in a gradual exposure of the factor Xa-binding site. (PMID:12163491)
• inactivation of plasma FVa by APC is not impaired in human volunteers with acute hyperhomocysteinemia. (PMID:12200374)
• The factor V Leiden mutation is associated with the occurrence of a previous systemic embolism. (PMID:12208422)
• Prevalence of the FV Leiden mutation in polycythemia vera and essential thrombocythemia is comparable with that in the general population. It is a risk factor for venous thromboembolism (VTE) before and at time of diagnosis and for VTE recurrence. (PMID:12221665)
• molecular basis of quantitative factor V deficiency associated with haplotype (PMID:12239164)
• The effect of FV concentration and FV isoform composition on the APC-response was determined by reconstituting FV-deficient plasma with purified FV1 and FV2 in different molar ratios and varying FV concentrations and determining APC sensitivity ratios. (PMID:12353074)
• A binding site for activated factor X (Xa) is located on the heavy chain of factor Va between Glu323-Val331, a sequence which competes with factor Va for high affinity binding to factor Xa on the membrane surface. (PMID:12379114)
• characterization of Factor Va binding sites for Factor Xa (PMID:12384508)
• The effect of the Arg2074Cys mutation on FV secretion, stability, and activity (PMID:12393490)
• apart from the FVL, the F5 locus itself plays a relatively minor role in normal variation in activated protein C resistance, including the HR2 haplotype polymorphisms (PMID:12393556)
• REVIEW: genetics and roles in normal hemostasis and dysfunction in blood coagulation disorders (PMID:12393635)
• prevalence of mutation and prothrombin G20210A gene mutations in a recurrent miscarriage population (PMID:12447960)
• There are increased frequencies of Factor V Leiden mutations/polymorphisms potentially causing thrombophilia in patients with no flow-limiting stenoses after myocardial infarction. (PMID:12514663)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	f5	ENSDARG00000055705
mus_musculus	F5	ENSMUSG00000026579
rattus_norvegicus	F5	ENSRNOG00000057855

Paralogs (35): NRXN3 (ENSG00000021645), TLL1 (ENSG00000038295), CP (ENSG00000047457), DCBLD2 (ENSG00000057019), HEPH (ENSG00000089472), TLL2 (ENSG00000095587), NRP1 (ENSG00000099250), PCOLCE (ENSG00000106333), CNTNAP3 (ENSG00000106714), CUBN (ENSG00000107611), CNTNAP1 (ENSG00000108797), NRXN2 (ENSG00000110076), MEP1A (ENSG00000112818), NRP2 (ENSG00000118257), CUZD1 (ENSG00000138161), MFGE8 (ENSG00000140545), MEP1B (ENSG00000141434), PDGFC (ENSG00000145431), CNTNAP4 (ENSG00000152910), CNTNAP3B (ENSG00000154529), CNTNAP5 (ENSG00000155052), CDCP2 (ENSG00000157211), PCOLCE2 (ENSG00000163710), EDIL3 (ENSG00000164176), NETO1 (ENSG00000166342), BMP1 (ENSG00000168487), PDGFD (ENSG00000170962), NETO2 (ENSG00000171208), CNTNAP2 (ENSG00000174469), NRXN1 (ENSG00000179915), HEPHL1 (ENSG00000181333), F8 (ENSG00000185010), ASTL (ENSG00000188886), MFRP (ENSG00000235718), CNTNAP3C (ENSG00000283378)

Protein

Protein identifiers

Coagulation factor V — P12259 (reviewed: P12259)

Alternative names: Activated protein C cofactor, Proaccelerin, labile factor

All UniProt accessions (2): A0A0A0MRJ7, P12259

UniProt curated annotations — full annotation on UniProt →

Function. Central regulator of hemostasis. It serves as a critical cofactor for the prothrombinase activity of factor Xa that results in the activation of prothrombin to thrombin.

Subunit / interactions. Factor Va, the activated form of factor V, is composed of a heavy chain and a light chain, non-covalently bound. The interaction between the two chains is calcium-dependent. Forms heterodimer with SERPINA5.

Subcellular location. Secreted.

Tissue specificity. Plasma.

Post-translational modifications. Thrombin activates factor V proteolytically to the active cofactor, factor Va (formation of a heavy chain at the N-terminus and a light chain at the C-terminus). Sulfation is required for efficient thrombin cleavage and activation and for full procoagulant activity. Activated protein C inactivates factor V and factor Va by proteolytic degradation. Phosphorylated by FAM20C in the extracellular medium.

Disease relevance. Factor V deficiency (FA5D) [MIM:227400] A blood coagulation disorder leading to a hemorrhagic diathesis known as parahemophilia. The disease is caused by variants affecting the gene represented in this entry. Thrombophilia due to activated protein C resistance (THPH2) [MIM:188055] A hemostatic disorder due to defective degradation of factor V by activated protein C. It is characterized by a poor anticoagulant response to activated protein C resulting in tendency to thrombosis. The disease is caused by variants affecting the gene represented in this entry. Budd-Chiari syndrome (BDCHS) [MIM:600880] A syndrome caused by obstruction of hepatic venous outflow involving either the hepatic veins or the terminal segment of the inferior vena cava. Obstructions are generally caused by thrombosis and lead to hepatic congestion and ischemic necrosis. Clinical manifestations observed in the majority of patients include hepatomegaly, right upper quadrant pain and abdominal ascites. Budd-Chiari syndrome is associated with a combination of disease states including primary myeloproliferative syndromes and thrombophilia due to factor V Leiden, protein C deficiency and antithrombin III deficiency. Budd-Chiari syndrome is a rare but typical complication in patients with polycythemia vera. Disease susceptibility is associated with variants affecting the gene represented in this entry. Ischemic stroke (ISCHSTR) [MIM:601367] A stroke is an acute neurologic event leading to death of neural tissue of the brain and resulting in loss of motor, sensory and/or cognitive function. Ischemic strokes, resulting from vascular occlusion, is considered to be a highly complex disease consisting of a group of heterogeneous disorders with multiple genetic and environmental risk factors. Disease susceptibility is associated with variants affecting the gene represented in this entry. Pregnancy loss, recurrent, 1 (RPRGL1) [MIM:614389] A common complication of pregnancy, resulting in spontaneous abortion before the fetus has reached viability. The term includes all miscarriages from the time of conception until 24 weeks of gestation. Recurrent pregnancy loss is defined as 3 or more consecutive spontaneous abortions. Disease susceptibility is associated with variants affecting the gene represented in this entry.

Activity regulation. Inhibited by SERPINA5.

Domain organisation. Domain B contains 35 x 9 AA tandem repeats, and 2 x 17 AA repeats.

Similarity. Belongs to the multicopper oxidase family.

RefSeq proteins (1): NP_000121* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000421	FA58C	Domain
IPR008972	Cupredoxin	Homologous_superfamily
IPR008979	Galactose-bd-like_sf	Homologous_superfamily
IPR011707	Cu-oxidase-like_N	Domain
IPR024715	Factor_5/8-like	Family
IPR033138	Cu_oxidase_CS	Conserved_site
IPR050633	Neuropilin_MCO_CoagFactor	Family

Pfam: PF00754, PF07732

UniProt features (325 total): strand 124, repeat 37, sequence variant 35, glycosylation site 27, helix 23, turn 19, domain 11, region of interest 9, modified residue 9, disulfide bond 7, site 7, sequence conflict 4, compositionally biased region 4, binding site 4, chain 3, signal peptide 1, propeptide 1

Structure

Experimental structures (PDB)

18 structures.

PDB	Method	Resolution (Å)
9I24	X-RAY DIFFRACTION	1.2
3P6Z	X-RAY DIFFRACTION	1.7
3S9C	X-RAY DIFFRACTION	1.8
1CZT	X-RAY DIFFRACTION	1.87
1CZS	X-RAY DIFFRACTION	1.9
1CZV	X-RAY DIFFRACTION	2.4
3P70	X-RAY DIFFRACTION	2.55
9MOV	ELECTRON MICROSCOPY	3
8TN9	ELECTRON MICROSCOPY	3.05
9MOT	ELECTRON MICROSCOPY	3.15
8FDG	ELECTRON MICROSCOPY	3.2
9I2H	ELECTRON MICROSCOPY	3.28
7KVE	ELECTRON MICROSCOPY	3.3
7KVF	ELECTRON MICROSCOPY	3.6
9YQ8	ELECTRON MICROSCOPY	3.84
7TPP	ELECTRON MICROSCOPY	4.1
7KXY	ELECTRON MICROSCOPY	4.4
9CTH	ELECTRON MICROSCOPY	6.47

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P12259-F1	62.57	0.22

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 (7): 334–335 (cleavage; by activated protein c); 534–535 (cleavage; by activated protein c); 707–708 (cleavage; by activated protein c); 737–738 (cleavage; by thrombin); 1022–1023 (cleavage; by activated protein c); 1046–1047 (cleavage; by thrombin); 1573–1574 (cleavage; by thrombin)

Ligand- & substrate-binding residues (4): 139; 140; 1843; 1845

Post-translational modifications (9): 640, 693, 724, 726, 859, 1522, 1538, 1543, 1593

Disulfide bonds (7): 167–193, 248–329, 500–526, 603–684, 1725–1751, 1907–2061, 2066–2221

Glycosylation sites (27): 821, 938, 977, 1074, 1083, 1103, 1106, 1479, 1499, 1559, 1703, 2010, 2209, 51, 55, 239, 297, 382, 460, 468 …

Function

Pathways and Gene Ontology

Reactome pathways

11 pathways

ID	Pathway
R-HSA-114608	Platelet degranulation
R-HSA-204005	COPII-mediated vesicle transport
R-HSA-381426	Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)
R-HSA-5694530	Cargo concentration in the ER
R-HSA-8957275	Post-translational protein phosphorylation
R-HSA-9769735	Initiation of coagulation cascade
R-HSA-9769739	Regulation of clotting cascade
R-HSA-9769743	Amplification and propagation of coagulation cascade
R-HSA-9930449	Defective cleavage of FV variant at a.a.534
R-HSA-9930479	Defective cleavage of FV variant at R334
R-HSA-140875

MSigDB gene sets: 323 (showing top): GOBP_PROTEIN_ACTIVATION_CASCADE, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOCC_SECRETORY_GRANULE, REACTOME_PLATELET_ACTIVATION_SIGNALING_AND_AGGREGATION, REACTOME_MEMBRANE_TRAFFICKING, GOBP_WOUND_HEALING, GOBP_PROTEIN_MATURATION, GOBP_RESPONSE_TO_KETONE, HOSHIDA_LIVER_CANCER_SUBCLASS_S3, TGCTGAY_UNKNOWN, GOCC_COATED_VESICLE, HSIAO_LIVER_SPECIFIC_GENES, MODULE_99, GOBP_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, FONTAINE_PAPILLARY_THYROID_CARCINOMA_DN

GO Biological Process (4): blood coagulation (GO:0007596), blood circulation (GO:0008015), response to vitamin K (GO:0032571), hemostasis (GO:0007599)

GO Molecular Function (3): copper ion binding (GO:0005507), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (10): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), endoplasmic reticulum lumen (GO:0005788), plasma membrane (GO:0005886), membrane (GO:0016020), COPII-coated ER to Golgi transport vesicle (GO:0030134), platelet alpha granule (GO:0031091), platelet alpha granule lumen (GO:0031093), endoplasmic reticulum-Golgi intermediate compartment membrane (GO:0033116), extracellular vesicle (GO:1903561)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
Coagulation pathway	3
ER to Golgi Anterograde Transport	2
Defective FV causes thrombophilia	2
Response to elevated platelet cytosolic Ca2+	1
Metabolism of proteins	1
Post-translational protein modification	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
hemostasis	1
wound healing	1
coagulation	1
circulatory system process	1
response to vitamin	1
response to ketone	1
regulation of body fluid levels	1
transition metal ion binding	1
binding	1
cation binding	1
endoplasmic reticulum	1
intracellular organelle lumen	1
membrane	1
cell periphery	1
coated vesicle	1
secretory granule	1
platelet alpha granule	1
secretory granule lumen	1
endoplasmic reticulum-Golgi intermediate compartment	1
bounding membrane of organelle	1
extracellular region	1
vesicle	1
extracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1692 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
F5	F2	P00734	887
F5	MTHFR	P42898	822
F5	F10	P00742	797
F5	STOX1	Q6ZVD7	672
F5	MCFD2	Q8NI22	665
F5	TFPI	P10646	642
F5	SELE	P16111	615
F5	C4BPB	P20851	605
F5	SELP	P16109	605
F5	PGA4	P00790	605
F5	SELL	P14151	603
F5	PGA4	P00790	600
F5	LMAN1	P49257	596
F5	A2M	P01023	592
F5	SERPINC1	P01008	587

IntAct

25 interactions, top by confidence:

A	B	Type	Score
MED4	MED19	psi-mi:“MI:0914”(association)	0.900
TNFSF8	TOR1B	psi-mi:“MI:0914”(association)	0.640
DKKL1	DENND11	psi-mi:“MI:0914”(association)	0.640
OLR1	F5	psi-mi:“MI:0915”(physical association)	0.590
KLRG2	GXYLT2	psi-mi:“MI:0914”(association)	0.530
MMRN1	CTSV	psi-mi:“MI:0914”(association)	0.530
TNFSF8	LGALS8	psi-mi:“MI:0914”(association)	0.530
	BIN1	psi-mi:“MI:0914”(association)	0.460
F5	FAM20C	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
	CD5L	psi-mi:“MI:0915”(physical association)	0.400
SDC1	ILVBL	psi-mi:“MI:0915”(physical association)	0.400
F5		psi-mi:“MI:0915”(physical association)	0.370
F5	BJLF1	psi-mi:“MI:0915”(physical association)	0.370
TNFSF8	NME4	psi-mi:“MI:0914”(association)	0.350
ITM2B	ILVBL	psi-mi:“MI:0914”(association)	0.350
RYK	TNFRSF10B	psi-mi:“MI:0914”(association)	0.350
FGF4	QSOX1	psi-mi:“MI:0914”(association)	0.350
CLU	SERPINC1	psi-mi:“MI:0914”(association)	0.350
INSR	BLTP3B	psi-mi:“MI:0914”(association)	0.350
INSR	RIMOC1	psi-mi:“MI:0914”(association)	0.350

BioGRID (37): F5 (Affinity Capture-MS), F5 (Affinity Capture-MS), F5 (Affinity Capture-MS), F5 (Biochemical Activity), F5 (Affinity Capture-MS), F5 (Affinity Capture-MS), F5 (Affinity Capture-MS), F5 (Affinity Capture-MS), F5 (Reconstituted Complex), F5 (Affinity Capture-MS), F5 (Affinity Capture-Western), F5 (Reconstituted Complex), PROS1 (Reconstituted Complex), F5 (Reconstituted Complex), F5 (Affinity Capture-MS)

ESM2 similar proteins: A2RUV9, F8W3R9, O18738, O43278, O54858, O88393, O97827, P00734, P00735, P0C5J5, P12259, P18292, P26342, P35054, P51511, Q08629, Q08E66, Q09101, Q14118, Q24567, Q24568, Q28685, Q29243, Q5R537, Q5RD69, Q62165, Q62288, Q640N1, Q66K79, Q701R2, Q7TQN3, Q80TS3, Q8BKV0, Q8IUX7, Q8N436, Q8R4V4, Q8TEU8, Q91ZV2, Q91ZV3, Q92563

Diamond homologs: A2RUV9, A5A6K7, O14786, O17754, O18806, O35276, O35375, O35474, O43854, O54858, O54991, O60462, O75976, O88783, O89001, P00451, P02886, P02887, P02888, P04836, P12259, P12263, P14384, P15087, P15169, P16870, P21956, P28824, P29068, P37892, P39041, P42787, P70490, P78357, P79385, P79795, P83852, P97333, P97846, P98092

SIGNOR signaling

19 interactions.

A	Effect	B	Mechanism
PROC	“down-regulates activity”	F5	cleavage
F2	“up-regulates activity”	F5
CSNK2A1	“down-regulates activity”	F5	phosphorylation
F5	“form complex”	“Factor Va-Xa”	binding
F2	“up-regulates activity”	F5	cleavage
ELANE	“up-regulates activity”	F5	cleavage
ELANE	“down-regulates activity”	F5	cleavage
“Factor FVIIa:TF”	“down-regulates activity”	F5	cleavage

Disease & clinical

Clinical variants and AI predictions

ClinVar

1463 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	60
Likely pathogenic	38
Uncertain significance	523
Likely benign	549
Benign	116

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1098461	NM_000130.5(F5):c.2615del (p.Arg872fs)	Pathogenic
1452773	NM_000130.5(F5):c.1600C>T (p.Arg534Ter)	Pathogenic
1703833	NM_000130.5(F5):c.5403del (p.Lys1801fs)	Pathogenic
2444143	NM_000130.5(F5):c.2521C>T (p.Gln841Ter)	Pathogenic
2578588	NM_000130.5(F5):c.4647dup (p.Tyr1550fs)	Pathogenic
2701935	NM_000130.5(F5):c.3322del (p.Thr1108fs)	Pathogenic
2702927	NM_000130.5(F5):c.987C>A (p.Cys329Ter)	Pathogenic
2711546	NM_000130.5(F5):c.3532G>T (p.Glu1178Ter)	Pathogenic
2728317	NM_000130.5(F5):c.5261del (p.Gly1754fs)	Pathogenic
2734021	NM_000130.5(F5):c.3088C>T (p.Arg1030Ter)	Pathogenic
2734022	NM_000130.5(F5):c.2743_2744del (p.Thr915fs)	Pathogenic
2734024	NM_000130.5(F5):c.1258G>T (p.Gly420Cys)	Pathogenic
2734025	NM_000130.5(F5):c.653T>C (p.Phe218Ser)	Pathogenic
2734026	NM_000130.5(F5):c.286G>C (p.Asp96His)	Pathogenic
2745996	NM_000130.5(F5):c.4465C>T (p.Gln1489Ter)	Pathogenic
2746047	NM_000130.5(F5):c.4317_4318del (p.Pro1440fs)	Pathogenic
2761343	NM_000130.5(F5):c.2228C>A (p.Ser743Ter)	Pathogenic
2766288	NM_000130.5(F5):c.4705_4706delinsTA (p.Ala1569Ter)	Pathogenic
2845595	NM_000130.5(F5):c.4083dup (p.Ser1362fs)	Pathogenic
2860268	NM_000130.5(F5):c.2521del (p.Gln841fs)	Pathogenic
2884086	NM_000130.5(F5):c.5143C>T (p.Arg1715Ter)	Pathogenic
2884844	NM_000130.5(F5):c.3646G>T (p.Glu1216Ter)	Pathogenic
2885367	NM_000130.5(F5):c.155C>G (p.Ser52Ter)	Pathogenic
2896674	NM_000130.5(F5):c.5793C>G (p.Tyr1931Ter)	Pathogenic
2904412	NM_000130.5(F5):c.597_598del (p.Glu200fs)	Pathogenic
2956469	NM_000130.5(F5):c.5645G>A (p.Trp1882Ter)	Pathogenic
2971118	NM_000130.5(F5):c.2946G>A (p.Trp982Ter)	Pathogenic
2979682	NM_000130.5(F5):c.2780del (p.Pro927fs)	Pathogenic
3247627	NC_000001.10:g.(?169497133)(169497352_?)del	Pathogenic
3339457	NM_000130.5(F5):c.6604C>T (p.Arg2202Cys)	Pathogenic

SpliceAI

4029 predictions. Top by Δscore:

Variant	Effect	Δscore
1:169515626:CCTA:C	acceptor_gain	1.0000
1:169515629:A:C	acceptor_gain	1.0000
1:169518437:C:A	donor_gain	1.0000
1:169520660:AAATA:A	acceptor_gain	1.0000
1:169520661:AATA:A	acceptor_gain	1.0000
1:169520662:ATA:A	acceptor_gain	1.0000
1:169520663:TA:T	acceptor_gain	1.0000
1:169520664:ACTA:A	acceptor_loss	1.0000
1:169520665:C:CC	acceptor_gain	1.0000
1:169520665:C:T	acceptor_loss	1.0000
1:169523192:CAAA:C	donor_gain	1.0000
1:169523195:A:AC	donor_gain	1.0000
1:169523196:C:CC	donor_gain	1.0000
1:169523196:C:CT	donor_loss	1.0000
1:169523201:ACATT:A	donor_gain	1.0000
1:169523202:CATTC:C	donor_gain	1.0000
1:169523203:ATT:A	donor_gain	1.0000
1:169523205:T:TA	donor_gain	1.0000
1:169523218:C:A	donor_gain	1.0000
1:169523348:TCCAC:T	acceptor_gain	1.0000
1:169523349:CCAC:C	acceptor_gain	1.0000
1:169523349:CCACC:C	acceptor_gain	1.0000
1:169523350:CAC:C	acceptor_gain	1.0000
1:169523350:CACC:C	acceptor_gain	1.0000
1:169523350:CACCT:C	acceptor_loss	1.0000
1:169523352:CCTGC:C	acceptor_loss	1.0000
1:169523353:C:T	acceptor_loss	1.0000
1:169523354:T:A	acceptor_loss	1.0000
1:169524911:A:C	acceptor_gain	1.0000
1:169525864:T:A	donor_gain	1.0000

AlphaMissense

14814 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:169518423:A:G	W2112R	0.999
1:169518423:A:T	W2112R	0.999
1:169544443:A:G	W610R	0.999
1:169544443:A:T	W610R	0.999
1:169549959:A:G	W485R	0.999
1:169549959:A:T	W485R	0.999
1:169518421:C:A	W2112C	0.998
1:169518421:C:G	W2112C	0.998
1:169520549:C:G	R2055P	0.998
1:169514344:C:G	R2215P	0.997
1:169530866:A:G	W1710R	0.997
1:169530866:A:T	W1710R	0.997
1:169550732:A:G	F435S	0.997
1:169514347:A:G	L2214P	0.996
1:169518469:C:A	W2096C	0.996
1:169518469:C:G	W2096C	0.996
1:169543109:A:G	W661R	0.996
1:169543109:A:T	W661R	0.996
1:169549834:A:C	C526W	0.996
1:169549914:A:G	C500R	0.996
1:169549957:C:A	W485C	0.996
1:169549957:C:G	W485C	0.996
1:169514383:C:G	R2202P	0.995
1:169523851:A:G	W1948R	0.995
1:169523851:A:T	W1948R	0.995
1:169531021:A:T	V1658D	0.995
1:169544441:C:A	W610C	0.995
1:169544441:C:G	W610C	0.995
1:169552567:T:A	D429V	0.995
1:169555237:C:G	A355P	0.995

dbSNP variants (sampled 300 via entrez): RS1000105215 (1:169546595 G>A), RS1000142005 (1:169530429 A>G,T), RS1000182448 (1:169558032 T>C), RS1000189450 (1:169581087 T>G), RS1000229220 (1:169568841 G>A), RS1000304832 (1:169533928 G>A), RS1000353300 (1:169546161 C>G), RS1000356608 (1:169533485 C>A,T), RS1000438514 (1:169527580 C>G), RS1000488925 (1:169556961 G>A,C,T), RS1000489077 (1:169527315 C>T), RS1000518397 (1:169587750 T>C), RS1000610470 (1:169533763 A>G), RS1000708750 (1:169556652 A>G), RS1000726290 (1:169513910 T>C,G)

Disease associations

OMIM: gene MIM:612309 | disease phenotypes: MIM:227400, MIM:188055, MIM:600880, MIM:614389, MIM:188050, MIM:192600, MIM:227300, MIM:142623

GenCC curated gene-disease

Disease	Classification	Inheritance
thrombophilia due to activated protein C resistance	Strong	Autosomal dominant
congenital factor V deficiency	Strong	Autosomal recessive
East Texas bleeding disorder	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (2)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
thrombophilia due to activated protein C resistance	Definitive	AD
congenital factor V deficiency	Definitive	AR

Mondo (14): congenital factor V deficiency (MONDO:0009210), factor V deficiency (MONDO:0020586), cholesteatoma (MONDO:0006530), prostate cancer (MONDO:0008315), thrombophilia due to activated protein C resistance (MONDO:0008560), Budd-Chiari syndrome (MONDO:0010947), pregnancy loss, recurrent, susceptibility to, 1 (MONDO:0013727), ischemic stroke (MONDO:1060198), thrombophilia due to thrombin defect (MONDO:0008559), thrombocytopenia (MONDO:0002049), familial hypertrophic cardiomyopathy (MONDO:0024573), factor V and factor VIII, combined deficiency of, type 1 (MONDO:0009206), Hirschsprung disease (MONDO:0018309), East Texas bleeding disorder (MONDO:0011615)

Orphanet (7): Congenital factor V deficiency (Orphanet:326), Familial prostate cancer (Orphanet:1331), Budd-Chiari syndrome (Orphanet:131), Rare familial disorder with hypertrophic cardiomyopathy (Orphanet:99739), Combined deficiency of factor V and factor VIII (Orphanet:35909), Hirschsprung disease (Orphanet:388), NON RARE IN EUROPE: Familial isolated hypertrophic cardiomyopathy (Orphanet:155)

HPO phenotypes

60 total (30 of 60 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000083	Renal insufficiency
HP:0000132	Menorrhagia
HP:0000225	Gingival bleeding
HP:0000421	Epistaxis
HP:0000790	Hematuria
HP:0000952	Jaundice
HP:0000978	Bruising susceptibility
HP:0001082	Cholecystitis
HP:0001297	Stroke
HP:0001394	Cirrhosis
HP:0001402	Hepatocellular carcinoma
HP:0001409	Portal hypertension
HP:0001426	Non-Mendelian inheritance
HP:0001541	Ascites
HP:0001744	Splenomegaly
HP:0001824	Weight loss
HP:0001892	Abnormal bleeding
HP:0001934	Persistent bleeding after trauma
HP:0001945	Fever
HP:0002024	Malabsorption
HP:0002027	Abdominal pain
HP:0002040	Esophageal varix
HP:0002105	Hemoptysis
HP:0002170	Intracranial hemorrhage
HP:0002239	Gastrointestinal hemorrhage
HP:0002240	Hepatomegaly
HP:0002480	Hepatic encephalopathy
HP:0002573	Hematochezia

GWAS associations

40 associations (top):

Study	Trait	p-value
GCST001049_7	D-dimer levels	2.000000e-14
GCST001253_1	Venous thromboembolism	2.000000e-26
GCST001378_2	Hemostatic factors and hematological phenotypes	4.000000e-80
GCST001530_6	Hippocampal atrophy	1.000000e-09
GCST001557_1	Venous thromboembolism	2.000000e-22
GCST001574_2	Activated partial thromboplastin time	3.000000e-09
GCST001801_2	Uric acid levels	3.000000e-06
GCST002012_1	Venous thromboembolism	4.000000e-51
GCST002763_11	Optic disc area	2.000000e-06
GCST002763_2	Optic disc area	3.000000e-09
GCST002808_4	Venous thromboembolism	1.000000e-96
GCST002808_5	Venous thromboembolism	3.000000e-11
GCST003324_1	Ischemic stroke	2.000000e-06
GCST003390_4	Thrombosis	4.000000e-137
GCST004075_38	Vertical cup-disc ratio	2.000000e-09
GCST004075_39	Vertical cup-disc ratio	2.000000e-09
GCST004256_1	Venous thromboembolism	7.000000e-50
GCST004428_28	Stem cell growth factor beta levels	1.000000e-15
GCST006017_7	Prothrombin time	2.000000e-87
GCST006018_6	Activated partial thromboplastin time	4.000000e-39
GCST007924_11	Medication use (antithrombotic agents)	3.000000e-11
GCST008461_2	Plasma factor V levels in venous thrombosis	8.000000e-12
GCST008474_3	Peripheral artery disease	2.000000e-12
GCST009030_26	Venous thromboembolism	1.000000e-188
GCST009030_27	Venous thromboembolism	3.000000e-29
GCST009097_1	Venous thromboembolism	1.000000e-300
GCST009244_5	Cytokine network levels (multivariate analysis)	7.000000e-12
GCST009411_2	Optic disc area	1.000000e-12
GCST009412_16	Vertical cup-disc ratio	2.000000e-09
GCST009462_8	Optic disc size	2.000000e-10

EFO canonical traits (19, from GWAS)

EFO ID	Trait name
EFO:0004507	D dimer measurement
EFO:0004503	hematological measurement
EFO:0005039	hippocampal atrophy
EFO:0004761	uric acid measurement
EFO:0003907	deep vein thrombosis
EFO:0006939	cup-to-disc ratio measurement
EFO:0008390	prothrombin time measurement
EFO:0009925	Antithrombotic agent use measurement
EFO:0004750	interleukin 10 measurement
EFO:0004753	interleukin 12 measurement
EFO:0004810	interleukin-6 measurement
EFO:0008165	interferon gamma measurement
EFO:0008174	interleukin 17 measurement
EFO:0008184	interleukin 4 measurement
EFO:0008293	stromal cell-derived factor 1 alpha measurement
EFO:0010977	macrovascular complications of diabetes
EFO:0006334	total iron binding capacity
EFO:0004459	ferritin measurement
EFO:0004872	inflammatory biomarker measurement

MeSH disease descriptors (9)

Descriptor	Name	Tree numbers
D020016	Activated Protein C Resistance	C15.378.100.100.037; C15.378.100.141.036; C15.378.925.050; C16.320.099.037
D006502	Budd-Chiari Syndrome	C06.552.347; C14.907.355.830.925.275
D024741	Cardiomyopathy, Hypertrophic, Familial	C14.280.238.100.500; C14.280.484.048.750.070.160.500; C16.320.160
D002781	Cholesteatoma	C17.800.428.260
D005166	Factor V Deficiency	C15.378.100.100.300; C15.378.100.141.300; C15.378.463.300; C16.320.099.300
D006627	Hirschsprung Disease	C06.198.439; C06.405.469.158.701.439; C16.131.314.439
D011471	Prostatic Neoplasms	C04.588.945.440.770; C12.100.500.260.750; C12.100.500.565.625; C12.200.294.260.750; C12.200.294.565.625; C12.200.758.409.750; C12.900.619.750
D013921	Thrombocytopenia	C15.378.140.855; C15.378.243.937
C565275	Bleeding Disorder, East Texas Type (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL3618 (SINGLE PROTEIN), CHEMBL5482991 (PROTEIN COMPLEX), CHEMBL6066543 (PROTEIN COMPLEX)

Molecules with ChEMBL bioactivity

2 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 2,657 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1269025	EDOXABAN	4	2,356
CHEMBL206335	RAZAXABAN	2	301

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs6025	Toxicity	2B	hormonal contraceptives for systemic use	Thrombotic disease

PharmGKB variants

12 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs6018	F5		0.00	0
rs6025	F5	2B	8.50	1	hormonal contraceptives for systemic use
rs7542281	F5		0.00	0
rs4524	F5		0.00	0
rs6020	F5		0.00	0
rs200157005	F5		0.00	0
rs9332695	F5		0.00	0
rs149389480	F5		0.00	0
rs143509841	F5		0.00	0
rs6019	F5		0.00	0
rs140530655	F5		0.00	0
rs368967198	F5		0.00	0

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — Blood coagulation components

Binding affinities (BindingDB)

5 measured of 19 human assays (19 total across all organisms); most potent 5 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
1-(4-methoxyphenyl)-7-oxo-6-[4-(2-oxopiperidin-1-yl)phenyl]-1H,4H,5H,6H,7H-pyrazolo[3,4-c]pyridine-3-carboxamide	KI	0.075 nM
1-(4-methoxyphenyl)-7-oxo-6-[1-(2-oxopyrrolidin-3-yl)piperidin-4-yl]-4,5-dihydropyrazolo[5,4-c]pyridine-3-carboxamide	KI	30 nM	US-9938272: Hydrazine compound as blood coagulation factor Xa inhibitor
1-(4-Methoxyphenyl)-N5-(1-(3-oxomorpholino)piperidin-4-yl)-1H-pyrazole-3,5-dicarboxamide	KI	30 nM	US-9938272: Hydrazine compound as blood coagulation factor Xa inhibitor
3-(7-Oxo-6-(1-(3-oxomorpholino)piperidin-4-yl)-3-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridin-1-yl)benzamide	KI	30 nM	US-9938272: Hydrazine compound as blood coagulation factor Xa inhibitor
7-Oxo-6-(1-(3-oxomorpholino)piperidin-4-yl)-1-(4-(trifluoromethoxy)phenyl)-4,5,6,7-tetr a hydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide	KI	525 nM	US-9938272: Hydrazine compound as blood coagulation factor Xa inhibitor

ChEMBL bioactivities

18 potent at pChembl≥5 of 32 total, top 18 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.53	Ki	2.98	nM	EDOXABAN
7.52	Ki	30	nM	CHEMBL5919505
7.52	Ki	30	nM	CHEMBL5912703
7.52	Ki	30	nM	CHEMBL6013950
6.28	Ki	525	nM	CHEMBL5877639
5.74	IC50	1810	nM	CHEMBL1162108
5.60	IC50	2500	nM	CHEMBL259312
5.46	IC50	3510	nM	CHEMBL259312
5.42	IC50	3800	nM	CHEMBL1162109
5.32	IC50	4800	nM	CHEMBL410427
5.26	IC50	5530	nM	CHEMBL410427
5.24	Ki	5700	nM	CHEMBL436766
5.17	IC50	6710	nM	CHEMBL265687
5.13	IC50	7400	nM	CHEMBL410426
5.07	IC50	8550	nM	CHEMBL410426
5.07	IC50	8560	nM	CHEMBL265687
5.05	IC50	8950	nM	CHEMBL410426
5.04	IC50	9190	nM	CHEMBL265687

PubChem BioAssay actives

14 with measured affinity, of 47 total; 8 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
Edoxaban	2033260: Inhibition of activated human factor X/activated human factor V complex derived prothrombinase using S-2238 as substrate	ki	0.0030	uM
3-[5-[(E)-[1-(4-bromophenyl)-3-methyl-5-oxopyrazol-4-ylidene]methyl]furan-2-yl]benzoic acid	328629: Inhibition of factor 5a-mediated prothrombin activation in human plasma by prothrombinase assay	ic50	1.8100	uM
4-[[2-ethoxy-4-[(E)-[1-[(2-fluorophenyl)methyl]-2,5-dioxoimidazolidin-4-ylidene]methyl]phenoxy]methyl]benzoic acid	328628: Inhibition of human factor 5a light chain binding to immobilized phospholipid by surface plasmon resonance assay	ic50	2.5000	uM
(2R)-1-(3-phenyl-4,5-dihydropyrazolo[4,5-a]carbazol-10-yl)-3-(propan-2-ylamino)propan-2-ol	328629: Inhibition of factor 5a-mediated prothrombin activation in human plasma by prothrombinase assay	ic50	3.8000	uM
(5E)-1-(1,3-benzodioxol-5-yl)-5-[[5-(2-methoxy-4-nitrophenyl)furan-2-yl]methylidene]-1,3-diazinane-2,4,6-trione	328628: Inhibition of human factor 5a light chain binding to immobilized phospholipid by surface plasmon resonance assay	ic50	4.8000	uM
1-(3-amino-1,2-benzoxazol-5-yl)-N-[2-fluoro-4-[2-[[(3R)-3-hydroxypyrrolidin-1-yl]methyl]phenyl]phenyl]-3-(trifluoromethyl)pyrazole-5-carboxamide	263266: Binding affinity to human aPC	ki	5.7000	uM
3-[(4Z)-3-methyl-4-[[5-(4-nitrophenyl)furan-2-yl]methylidene]-5-oxopyrazol-1-yl]benzoic acid	328630: Inhibition of human recombinant factor 5a C2 domain binding to immobilized phospholipid by surface plasmon resonance assay	ic50	6.7100	uM
(4Z)-1-(3-chlorophenyl)-4-[[5-(4,5-dimethyl-2-nitrophenyl)furan-2-yl]methylidene]pyrazolidine-3,5-dione	328630: Inhibition of human recombinant factor 5a C2 domain binding to immobilized phospholipid by surface plasmon resonance assay	ic50	7.4000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, affects cotreatment, increases expression	5
mercuric bromide	increases expression, affects cotreatment	2
entinostat	increases expression, affects cotreatment	2
Cadmium	decreases expression, increases abundance, affects binding	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Tretinoin	decreases response to substance, affects expression	2
Cyclosporine	decreases expression	2
Aflatoxin B1	affects expression, decreases methylation	2
p-Chloromercuribenzoic Acid	affects cotreatment, increases expression	2
ginger extract	decreases reaction, increases abundance, increases expression	1
dicrotophos	increases expression	1
2,4,6-tribromophenol	increases expression	1
propionaldehyde	decreases expression	1
bisphenol A	increases expression, decreases reaction, increases abundance	1
decabromobiphenyl ether	increases expression	1
trichostatin A	increases expression	1
beta-lapachone	decreases expression	1
sodium arsenite	decreases expression	1
butyraldehyde	decreases expression	1
nickel chloride	decreases expression	1
ochratoxin A	decreases expression	1
pentanal	decreases expression	1
2,3-dimethoxy-1,4-naphthoquinone	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
2-palmitoylglycerol	increases expression	1
ethinyl estradiol-desogestrel combination	decreases expression, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
abrine	decreases expression	1
dorsomorphin	increases expression, affects cotreatment	1

ChEMBL screening assays

10 unique, capped per target: 10 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5355154	Binding	Inhibition of activated protein C (unknown origin) using S-2366 as chromogenic substrate preincubated for 10 mins followed by substrate addition and measured after 10 mins	Discovery of novel N-acylpyrazoles as potent and selective thrombin inhibitors. — Eur J Med Chem

Cellosaurus cell lines

9 cell lines: 8 transformed cell line, 1 finite cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_4W10	GM16028	Transformed cell line	Female
CVCL_5B01	GM14650	Transformed cell line	Female
CVCL_8A57	GM14899	Transformed cell line	Male
CVCL_8A58	GM20833	Transformed cell line	Male
CVCL_BT38	GM16643	Transformed cell line	Female
CVCL_BX21	GM25285	Transformed cell line	Male
CVCL_C7LI	GM27968	Finite cell line	Male
CVCL_C7LJ	GM27980	Transformed cell line	Male
CVCL_N218	GM14641	Transformed cell line	Female

Clinical trials (associated diseases)

302 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00029224	PHASE4	COMPLETED	Treatment With Zoledronic Acid in Patients With Breast Cancer, Multiple Myeloma, and Prostate Cancer With Cancer Related Bone Lesions
NCT00035997	PHASE4	COMPLETED	Open-label Trial on the Effect of I.V. Zoledronic Acid 4 mg on Bone Density in Hormone Sensitive Prostate Cancer Patients With Bone Metastasis
NCT00063609	PHASE4	COMPLETED	The Effect of Zoledronic Acid on Bone Loss in Prostate Cancer Patients Undergoing Androgen Deprivation Therapy
NCT00103623	PHASE4	SUSPENDED	The Plenaxis® Experience Study
NCT00106392	PHASE4	COMPLETED	A Safety and Efficacy Study of Prograf in the Prevention of Erectile Dysfunction After Radical Prostatectomy
NCT00185029	PHASE4	UNKNOWN	MR-Lymphography and Lymph Node Staging in Prostate Cancer
NCT00199485	PHASE4	COMPLETED	Angelica Sinensis for the Treatment of Hot Flashes in Men Undergoing LHRH Therapy for Prostate Cancer
NCT00219219	PHASE4	COMPLETED	Zoledronic Acid in the Prevention of Skeletal-related Events in Hormone Refractory and Hormone-sensitive Prostate Cancer Patients With Bone Metastases
NCT00219271	PHASE4	COMPLETED	Effect Of Zoledronic Acid On Circulating And Bone Marrow-Residing Prostate Cancer Cells In Patients With Clinically Localized Prostate Cancer
NCT00237146	PHASE4	COMPLETED	Study to Evaluate Zoledronic Acid on Quality of Life and Skeletal-related Events as Adjuvant Treatment in Patients With Hormone-naïve Prostate Cancer and Bone Metastasis Who Have Undergone Orchiectomy
NCT00242554	PHASE4	COMPLETED	Open-label Phase IV Clinical Trial to Evaluate the Safety and Tolerability of Zoledronic Acid in Patients With Prostate Cancer and Bone Metastases
NCT00280098	PHASE4	COMPLETED	Docetaxel in the Treatment of Hormone Refractory Prostate Cancer
NCT00293696	PHASE4	COMPLETED	Casodex/Zoladex Biomarkers in Localised Prostate Cancer
NCT00334139	PHASE4	COMPLETED	Effect of Zoledronic Acid on Bone Metabolism in Patients With Bone Metastasis and Prostate or Breast Cancer
NCT00375765	PHASE4	COMPLETED	Effects On Dihydrotestosterone Regulated Gene Expression In Benign Prostatic Hyperplasia Or Prostate Cancer
NCT00391690	PHASE4	COMPLETED	Evaluation of Bone Markers as Diagnostic Tools for Early Detection of Bone Metastases in Patients With High Risk Prostate Cancer
NCT00422708	PHASE4	COMPLETED	Local Anesthesia for Prostate Biopsy
NCT00526331	PHASE4	COMPLETED	Evaluation of Arterial Pressure Based Cardiac Output for Goal-Directed Perioperative Therapy
NCT00590213	PHASE4	COMPLETED	Compare the Value of Prophylactic Versus Therapeutic Breast Radiotherapy in CASODEX
NCT00629330	PHASE4	TERMINATED	Dissemination of Prostate Cancer Screening to PCP’s in African American Communities
NCT00771966	PHASE4	COMPLETED	Radical Prostatectomy and Perioperative Fluid Therapy
NCT00805701	PHASE4	COMPLETED	Study Assessing The Efficacy And Safety Of Avodart (Dutasteride) At Improving Urinary Symptoms In Men With Prostate Cancer Who Are Undergoing Seed Implantation
NCT00859027	PHASE4	COMPLETED	Effect Of Risedronate On Bone Mass In Older Men Receiving Neoadjuvant Therapy For Prostate Cancer
NCT00906269	PHASE4	UNKNOWN	Can Hyperbaric Oxygen Improve Erectile Function Following Surgery for Prostate Cancer
NCT00953277	PHASE4	COMPLETED	Study of Nerve Reconstruction Using AVANCE in Subjects Who Undergo Robotic Assisted Prostatectomy for Treatment of Prostate Cancer
NCT00982800	PHASE4	COMPLETED	Does Postoperative Gabapentin Reduce Pain, Opioid Consumption and Anxiety and Have a Positive Effect on Health Related Quality of Life After Radical Prostatectomy?
NCT01083199	PHASE4	COMPLETED	Global Performance Evaluation of the AMS CONTINUUM™ Device
NCT01136226	PHASE4	COMPLETED	Evaluate Recovery of Testosterone for Patients Using Eligard
NCT01161563	PHASE4	COMPLETED	Randomized Crossover Trial to Assess the Tolerability of Gonadotropin Releasing Hormone (GnRH) Analogue Administration
NCT01230905	PHASE4	COMPLETED	Study to Monitor the Effects of Androgen Suppression Treatment on the Heart
NCT01296672	PHASE4	COMPLETED	3 Month Finasteride Challenge Test Can Significantly Improve the Performance of Screening for Prostate Cancer
NCT01365143	PHASE4	TERMINATED	Prospective Randomized Trial Comparing Robotic Versus Open Radical Prostatectomy
NCT01379742	PHASE4	UNKNOWN	Comparison of Between ThinSeed™ and OncoSeed™ for Permanent Prostate Brachytherapy
NCT01486563	PHASE4	COMPLETED	Hydroxyethyl Starch and Renal Function After Radical Prostatectomy
NCT01511874	PHASE4	COMPLETED	Efficacy and Safety Study of ELIGARD 22.5mg With Prostate Cancer
NCT01512472	PHASE4	TERMINATED	Firmagon (Degarelix) Intermittent Therapy
NCT01547416	PHASE4	COMPLETED	The Effect of Combined General/Epidural Anesthesia Versus General Anesthesia on Diaphragmatic Function
NCT01571544	PHASE4	COMPLETED	The Use of Thermal Suits as Preventing Hypothermia During Surgery
NCT01581749	PHASE4	UNKNOWN	Evaluation of Truebeam for Low-Intermediate Risk Prostate Cancer
NCT01649635	PHASE4	COMPLETED	Study of Cabazitaxel Combined With Prednisone and Prophylaxis of Neutropenia Complications in the Treatment of Patients With Metastatic Castration-resistant Prostate Cancer