F10

Summary

F10 (coagulation factor X, HGNC:3528) is a protein-coding gene on chromosome 13q34, encoding Coagulation factor X (P00742). Factor Xa is a vitamin K-dependent glycoprotein that converts prothrombin to thrombin in the presence of factor Va, calcium and phospholipid during blood clotting.

This gene encodes the vitamin K-dependent coagulation factor X of the blood coagulation cascade. This factor undergoes multiple processing steps before its preproprotein is converted to a mature two-chain form by the excision of the tripeptide RKR. Two chains of the factor are held together by 1 or more disulfide bonds; the light chain contains 2 EGF-like domains, while the heavy chain contains the catalytic domain which is structurally homologous to those of the other hemostatic serine proteases. The mature factor is activated by the cleavage of the activation peptide by factor IXa (in the intrisic pathway), or by factor VIIa (in the extrinsic pathway). The activated factor then converts prothrombin to thrombin in the presence of factor Va, Ca+2, and phospholipid during blood clotting. Mutations of this gene result in factor X deficiency, a hemorrhagic condition of variable severity. Alternative splicing results in multiple transcript variants encoding different isoforms that may undergo similar proteolytic processing to generate mature polypeptides.

Source: NCBI Gene 2159 — RefSeq curated summary.

At a glance

• Gene–disease (curated): congenital factor X deficiency (Definitive, ClinGen)
• GWAS associations: 6
• Clinical variants (ClinVar): 182 total — 17 pathogenic, 27 likely-pathogenic
• GTEx eGene: eQTL in 29 tissues, sQTL in 1 (q < 0.05)
• Phenotypes (HPO): 22
• Drug target: yes — 13 curated mechanism-of-action drugs, 1 via a complex or family; 23 molecules with ChEMBL bioactivity (top 2% of genes corpus-wide)
• Approved drugs (ChEMBL mechanism of action): 6 — Antithrombin Alfa, Apixaban, Betrixaban, +3 more
• Approved drugs acting on a complex or family including it: 1 — Emicizumab (Coagulation factor IX and X)
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 0.97 (unconstrained)
• MANE Select transcript: NM_000504

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3528
Approved symbol	F10
Name	coagulation factor X
Location	13q34
Locus type	gene with protein product
Status	Approved
Aliases	fX
Ensembl gene	ENSG00000126218
Ensembl biotype	protein_coding
OMIM	613872
Entrez	2159

Gene structure

Transcript identifiers

Ensembl transcripts: 18 — 13 protein_coding, 2 nonsense_mediated_decay, 2 retained_intron, 1 protein_coding_CDS_not_defined

MANE Select: ENST00000375559

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

ENST00000375559, ENST00000375551, ENST00000409306, ENST00000410083, ENST00000477269, ENST00000483537, ENST00000498455, ENST00000858581, ENST00000858582, ENST00000858583, ENST00000977588, ENST00000977589, ENST00001120110, ENST00001120111, ENST00001120112, ENST00001120113, ENST00001127694, ENST00001131518

RefSeq mRNA: 3 — MANE Select: NM_000504 NM_000504, NM_001312674, NM_001312675

CCDS: CCDS81783, CCDS9530

Canonical transcript exons

ENST00000375559 — 8 exons

Exon	Start	End
ENSE00000862534	113147379	113147496
ENSE00001616173	113148916	113149529
ENSE00001885902	113122799	113122925
ENSE00003500501	113129452	113129612
ENSE00003501032	113140919	113141050
ENSE00003650233	113139357	113139470
ENSE00003683329	113143851	113144095
ENSE00003683736	113138457	113138481

Expression profiles

Bgee: expression breadth ubiquitous, 176 present calls, max score 97.19.

FANTOM5 (CAGE): breadth broad, TPM avg 6.4809 / max 357.1279, expressed in 729 samples.

Highest expression (Bgee): lobe of liver, liver, stromal cell of endometrium, atrium auricular region, endocervix.

Genetic regulation across tissues (GTEx eQTL / sQTL)

F10 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 29 tissues and its splicing (sQTL) in 1 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 30 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Cells Cultured fibroblasts	eqtl	1.5e-32	-0.25	13:113122635:C:A
Artery Aorta	eqtl	8.5e-18	+0.67	13:113116562:G:A
Artery Tibial	eqtl	5.3e-13	+0.29	13:113121904:T:C
Lung	eqtl	8.6e-13	+0.31	13:113121904:T:C
Thyroid	eqtl	5.0e-12	+0.22	13:113121904:T:C
Heart Left Ventricle	eqtl	1.3e-10	-0.42	13:113235708:G:C
Nerve Tibial	eqtl	3.8e-08	+0.25	13:113119778:G:A
Breast Mammary Tissue	eqtl	5.4e-08	+0.27	13:113121904:T:C
Esophagus Muscularis	eqtl	4.0e-07	-0.20	13:113122635:C:A
Heart Atrial Appendage	eqtl	1.2e-06	-0.22	13:113240436:C:A
Adipose Subcutaneous	eqtl	1.6e-06	+0.18	13:113121904:T:C
Brain Frontal Cortex BA9	eqtl	3.5e-06	-0.41	13:113122635:C:A
Adrenal Gland	eqtl	3.5e-06	-0.44	13:113122635:C:A
Muscle Skeletal	eqtl	5.1e-06	-0.14	13:113122635:C:A
Pituitary	eqtl	5.7e-06	+0.32	13:113126596:T:C
Esophagus Gastroesophageal Junction	eqtl	8.3e-06	+0.26	13:113115325:T:G
Esophagus Mucosa	eqtl	3.0e-05	+0.18	13:113116562:G:A
Adipose Visceral Omentum	eqtl	4.7e-05	+0.22	13:113121904:T:C
Colon Transverse	eqtl	5.2e-04	-0.18	13:113175867:C:T
Artery Coronary	eqtl	7.0e-04	+0.36	13:113121904:T:C

FANTOM5 promoters

1 alternative TSS:

Promoter ID	TPM avg	Samples expressed
136199	6.4809	729

Top tissues by expression

showing 100 of 284 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	97.19	gold quality
liver	UBERON:0002107	93.73	gold quality
stromal cell of endometrium	CL:0002255	93.13	gold quality
right atrium auricular region	UBERON:0006631	90.97	gold quality
endocervix	UBERON:0000458	89.88	gold quality
ectocervix	UBERON:0012249	89.69	gold quality
mucosa of stomach	UBERON:0001199	89.13	gold quality
right ovary	UBERON:0002118	88.61	gold quality
cardiac atrium	UBERON:0002081	88.08	gold quality
left ovary	UBERON:0002119	87.33	gold quality
right coronary artery	UBERON:0001625	86.66	gold quality
left uterine tube	UBERON:0001303	86.49	gold quality
islet of Langerhans	UBERON:0000006	86.34	gold quality
skin of leg	UBERON:0001511	85.69	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.68	gold quality
apex of heart	UBERON:0002098	85.66	gold quality
right lung	UBERON:0002167	84.67	gold quality
left coronary artery	UBERON:0001626	83.26	gold quality
gall bladder	UBERON:0002110	82.89	gold quality
subcutaneous adipose tissue	UBERON:0002190	82.75	gold quality
vena cava	UBERON:0004087	82.62	silver quality
ascending aorta	UBERON:0001496	82.59	gold quality
coronary artery	UBERON:0001621	82.57	gold quality
thoracic aorta	UBERON:0001515	82.49	gold quality
aorta	UBERON:0000947	81.95	gold quality
omental fat pad	UBERON:0010414	81.85	gold quality
peritoneum	UBERON:0002358	81.82	gold quality
tibial artery	UBERON:0007610	81.77	gold quality
popliteal artery	UBERON:0002250	81.75	gold quality
body of uterus	UBERON:0009853	81.73	gold quality
zone of skin	UBERON:0000014	81.67	gold quality
skin of abdomen	UBERON:0001416	81.63	gold quality
right uterine tube	UBERON:0001302	81.52	gold quality
ovary	UBERON:0000992	81.50	gold quality
hindlimb stylopod muscle	UBERON:0004252	81.26	gold quality
upper lobe of left lung	UBERON:0008952	81.15	gold quality
adipose tissue of abdominal region	UBERON:0007808	81.13	gold quality
vagina	UBERON:0000996	81.05	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	81.00	gold quality
descending thoracic aorta	UBERON:0002345	80.43	gold quality
heart	UBERON:0000948	80.29	gold quality
upper lobe of lung	UBERON:0008948	80.03	gold quality
right adrenal gland	UBERON:0001233	79.83	gold quality
adipose tissue	UBERON:0001013	79.29	gold quality
tibial nerve	UBERON:0001323	79.08	gold quality
connective tissue	UBERON:0002384	78.47	gold quality
left adrenal gland	UBERON:0001234	77.99	gold quality
heart left ventricle	UBERON:0002084	77.33	gold quality
fundus of stomach	UBERON:0001160	77.27	gold quality
left adrenal gland cortex	UBERON:0035825	77.24	gold quality
duodenum	UBERON:0002114	77.17	gold quality
adrenal gland	UBERON:0002369	76.99	gold quality
uterine cervix	UBERON:0000002	76.97	gold quality
cardiac ventricle	UBERON:0002082	76.89	gold quality
right adrenal gland cortex	UBERON:0035827	76.67	gold quality
lower esophagus muscularis layer	UBERON:0035833	76.58	gold quality
lower esophagus	UBERON:0013473	76.51	gold quality
adrenal cortex	UBERON:0001235	76.08	gold quality
left testis	UBERON:0004533	75.97	gold quality
body of stomach	UBERON:0001161	75.95	gold quality
small intestine Peyer’s patch	UBERON:0003454	75.51	gold quality
female reproductive system	UBERON:0000474	75.50	gold quality
small intestine	UBERON:0002108	75.46	gold quality
testis	UBERON:0000473	75.26	gold quality
right testis	UBERON:0004534	75.26	gold quality
prostate gland	UBERON:0002367	75.15	gold quality
stomach	UBERON:0000945	75.09	gold quality
adrenal tissue	UBERON:0018303	75.01	gold quality
left lobe of thyroid gland	UBERON:0001120	74.61	gold quality
right lobe of thyroid gland	UBERON:0001119	74.47	gold quality
pancreas	UBERON:0001264	74.38	gold quality
esophagus	UBERON:0001043	73.84	gold quality
thyroid gland	UBERON:0002046	73.83	gold quality
urinary bladder	UBERON:0001255	73.35	gold quality
muscle of leg	UBERON:0001383	72.82	gold quality
uterus	UBERON:0000995	72.72	gold quality
muscle layer of sigmoid colon	UBERON:0035805	72.64	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	72.39	gold quality
minor salivary gland	UBERON:0001830	72.31	gold quality
mucosa of transverse colon	UBERON:0004991	72.16	gold quality
myometrium	UBERON:0001296	72.09	gold quality
gastrocnemius	UBERON:0001388	71.88	gold quality
saliva-secreting gland	UBERON:0001044	71.57	gold quality
metanephros cortex	UBERON:0010533	71.45	gold quality
lung	UBERON:0002048	71.40	gold quality
adenohypophysis	UBERON:0002196	71.39	gold quality
esophagus mucosa	UBERON:0002469	71.37	gold quality
colonic epithelium	UBERON:0000397	71.18	gold quality
lower esophagus mucosa	UBERON:0035834	70.78	gold quality
lymph node	UBERON:0000029	70.71	gold quality
transverse colon	UBERON:0001157	70.63	gold quality
saphenous vein	UBERON:0007318	70.63	gold quality
intestine	UBERON:0000160	70.61	gold quality
muscle organ	UBERON:0001630	70.33	gold quality
parotid gland	UBERON:0001831	70.25	gold quality
upper leg skin	UBERON:0004262	70.07	gold quality
pituitary gland	UBERON:0000007	69.98	gold quality
jejunal mucosa	UBERON:0000399	69.98	silver quality
mouth mucosa	UBERON:0003729	69.90	gold quality
fallopian tube	UBERON:0003889	69.89	gold quality

Single-cell (SCXA)

Detected in 9 experiment(s), a significant marker in 9.

Experiment	Marker?	Max mean expression
E-ENAD-27	yes	128.91
E-GEOD-134144	yes	37.82
E-MTAB-5061	yes	34.32
E-GEOD-81547	yes	33.57
E-HCAD-31	yes	31.12
E-GEOD-81608	yes	23.57
E-HCAD-1	yes	18.87
E-ANND-3	yes	14.61
E-GEOD-83139	yes	10.68

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 73 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM
Liver	tissue	116.4
Cervix	tissue	30.4
Vagina	tissue	24.1
Fallopian tube	tissue	20.2
Heart muscle	tissue	18.7
Ovary	tissue	17.0
Epididymis	tissue	15.5
Adipose tissue	tissue	13.5
Small intestine	tissue	11.2
Duodenum	tissue	10.2
Gallbladder	tissue	10.1
Prostate	tissue	9.5
Breast	tissue	8.3
Esophagus	tissue	8.3
Adrenal gland	tissue	8.0
Urinary bladder	tissue	7.6
Endometrium 1	tissue	7.4
Testis	tissue	7.3
Skin 1	tissue	6.8
Seminal vesicle	tissue	6.7
Pancreas	tissue	6.7
Skeletal muscle	tissue	6.3
Tongue	tissue	6.2
Lung	tissue	5.9
Stomach 1	tissue	4.4
Pituitary gland	tissue	4.2
Placenta	tissue	4.1
Colon	tissue	3.5
Lymph node	tissue	3.0
Salivary gland	tissue	2.9
Locus coeruleus	tissue	2.9
Choroid plexus	tissue	2.7
Postcentral gyrus	tissue	2.7
Spleen	tissue	2.6
Smooth muscle	tissue	2.5
Rectum	tissue	1.9
Kidney	tissue	1.8
Hippocampus	tissue	1.8
Nucleus accumbens	tissue	1.5
Thyroid gland	tissue	1.4
Corpus callosum	tissue	1.4
Appendix	tissue	1.4
Thymus	tissue	1.3
Tonsil	tissue	1.2
Pons	tissue	1.1
Spinal cord	tissue	1.1
Periaqueductal gray	tissue	1.1
Basal ganglia	tissue	1.0
Putamen	tissue	1.0
Medulla oblongata	tissue	1.0
Hypothalamus	tissue	1.0
Superior colliculi	tissue	1.0
Cerebellum	tissue	1.0
Substantia nigra	tissue	1.0
Hippocampal formation	tissue	1.0
Cerebral cortex	tissue	0.9
Amygdala	tissue	0.9
Midbrain	tissue	0.9
Thalamus	tissue	0.9
Ventral forebrain	tissue	0.9

Brain sub-regions (HPA Brain Atlas): detected in 189; highest nTPM — Blood vessel (15.3), Nucleus raphe magnus (5.2), Cerebellar nuclei (5.0), Nuclei of the trapezoid body (5.0), Lateral lemniscal nuclei (4.4).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): GATA4, HNF4A, PAX3, SP1, SP3, SPI1

Functional genomics

gnomAD constraint: pLI 9.9e-06, LOEUF 0.968, missense Z 2.06 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000375559 splits into 2 regions with different missense tolerance; 0 are missense-constrained. Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
13:113,122,856–113,139,379	130 / 120.0	1.08	no
13:113,139,380–113,149,514	409 / 547.9	0.75	no

Literature-anchored findings (GeneRIF, showing 40)

• A specific pentasaccharide sequence (H5) in high affinity heparin induces a conformational change in antithrombin that is particularly important for factor Xa (fXa) inhibition (factor Xa) (PMID:11854268)
• 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)
• Structure and dynamics of zymogen human blood coagulation factor X. (PMID:11867437)
• Activation of the prothrombinase complex could be a common step of the platelet response to distinct agonists (ADP, collagen, thrombin), which may be achieved at low levels of platelet stimulation by non-aggregant doses of platelet agonists. (PMID:11914651)
• Data suggesting a physical association between factor Xa and prothrombin, and that factor Xa has an increased affinity for prothrombin in the presence of factor Va. (PMID:11983337)
• used NAPc2 as a tight binding probe of human Xa to investigate protein substrate recognition by the human prothrombinase complex. (PMID:12011050)
• Exposure of human macrophages and smooth muscle cells (SMCs) to oxidized low-density lipoprotein (oxLDL) enhances their ability to support activity of 2 major complexes of the intrinsic pathway, Xase and prothrombinase. (PMID:12036878)
• Factor X activation is regulated by sequential occupancy of a pair of linked lipid binding sites: the first recognizes diacylglycerol as the simplest effective ligand, while the second recognizes glycerophosphoserine as the minimal binding structure. (PMID:12056907)
• Factor Xa induces mitogenesis of coronary artery smooth muscle cell via activation of PAR-2. (PMID:12123809)
• 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)
• There are two independent factor X binding sites on activated platelets: low affinity, high capacity (approximately 9000 sites per platelet; Kd approximately 380 nM) and low capacity, high affinity (1700 sites per platelet; Kd approximately 30 nM). (PMID:12220193)
• extended interactions between prothrombinase and substrate regions removed from the cleavage site drive substrate affinity and enforce the substrate specificity of this enzyme complex (PMID:12370181)
• A binding site for membrane-bound, activated factor X (Xa) is located on the heavy chain of factor Va; binding increases the catalytic efficiency of factor Xa toward prothrombin in the absence of factor Va. (PMID:12379114)
• prothrombinase formation is promoted by neutrophil cathepsin G in platelets (PMID:12524437)
• the Gla and first epidermal growth factor-like domains of factor X play a role in the prothrombinase and tissue factor-factor VIIa complexes. (PMID:12529356)
• A new FX mutation (Gly381Asp) in the structurally conserved serine protease active site was normally activated. It did not show detectable amidolytic activity. Mutations affecting FX activity may cause coagulation impairment & severe hemorrhage. (PMID:12574802)
• residues 404-418 in fXa provide fVa binding sites, whereas residues 557-571 in fII and 415-429 in fXa mediate interactions between fXa and fII in the prothrombinase complex (PMID:12805370)
• Factor Xa and thrombin, but not factor VIIa, induce expression of MCP-1, IL-8, IL-6 and VEGF, and expression of receptors implicated in signaling by these coagulation factors PAR-1, PAR-2 and PAR-3 in lung and dermal fibroblasts (PMID:12941034)
• findings suggest that antithrombin exosites responsible for enhancing the rates of factor Xa and factor IXa inhibition in the conformationally activated inhibitor lie in strand 3 of beta-sheet C of the serpin (PMID:14532267)
• results suggested a model by which platelet factor 4 bound to proximal (but distinct) sites to antithrombin (AT) resulting in steric interference of fXa binding to both polysaccharide and AT (PMID:14575696)
• the factor X cation-binding exosite-1 has a nonessential role in substrate and inhibitor interactions (PMID:14583605)
• FIXa/FVIIIa binding studies of coordinate binding of FVIIIa and FX to equivalent numbers of binding sites on activated platelets provide strong evidence that FVIIIa comprises the receptor that presents FX to FIXa for catalysis on the platelet membrane. (PMID:14629468)
• although charged residues of the 70-80 loop play an insignificant role in fX recognition by the factor VIIa-tissue factor complex, they are critical for the substrate recognition by factor IXa in the intrinsic Xase complex (PMID:14739327)
• model characterizes likely enzyme-binding exosites on FVIIa and Xa that may be involved in the ternary complex (sTF-VIIa-Xa) formation and the membrane binding region of the ternary complex. (PMID:14750502)
• factor X is initiated by factor IXabeta, which may play a significant role in producing Xa necessary for the procoagulant response following vascular damage (PMID:14963035)
• A new mutation (Arg251Trp) detected is responsible for defective activation via the extrinsic pathway; it may not affect protein folding and stability, but may be involved in the calcium binding site (PMID:14979399)
• direct activation of factor V by factor Xa at physiologically relevant concentrations does not appear to be a significant contributor to factor Va formation (PMID:14982929)
• The mutation Arg489Ala/Arg490Ala/Lys493Ala (489-3A) om factor VIIIa possessed near-normal affinity for FIXa and showed no effect on the Km for Factor X. (PMID:15009463)
• EGF-N of FX is required for the cofactor-dependent zymogen activation by both physiological activators, but it plays no apparent role in FXa recognition of the cofactor in the prothrombinase complex (PMID:15069066)
• the antithrombin hinge region extension is the activating conformational change for inhibition of factors IXa and Xa (PMID:15326167)
• residues Asn89, Ile90, and Val107 within loops 1 and 2 (Cys88-Cys109) of the EGF2 domain of factor IXa are essential for normal interactions with the platelet surface and for the assembly of the factor X-activating complex on activated platelets (PMID:15328360)
• These results suggest that factor Va interacts with 185-189-loop for fXa, which is energetically linked to the Na(+)-binding site of the protease. (PMID:15347660)
• propose that ordered bond cleavage results from the constraints associated with the binding of prothrombin substrates in one of two conformations to a single form of prothrombinase (PMID:15494418)
• FXa may contribute to proinflammatory changes in acute myocardial infarction by stimulation of IL-8 release. In vitro factor Xa stimulated IL-8 & monocyte chemoattractant protein-1 release & RNA expression by activation of protease-activated receptor 1. (PMID:15550696)
• thrombin formation by B16F10 melanoma cell-bound human factor Xa was enhanced approximately 10 fold in the presence of factor Va, indicating the assembly of prothrombinase complex. (PMID:15567463)
• EGF-like domains of factor Xa and factor IXa are important for the activation of the factor VII–tissue factor complex (PMID:15634274)
• Phosphatidylserine-induced formation of the coagulation factor Xa-factor Va (FVa) complex or its activity does not require occupancy of FVa C2-domain lipid binding pocket. (PMID:15641797)
• factor Xa can induce mesangial cell proliferation through the activation of ERK via PAR2 in mesangial cells. (PMID:15882255)
• analysis of molecular basis of FX deficiency in patients from the Indian subcontinent: six novel mutations including triple heterozygosity for Phe31Ser, 514delT and 516T–>G factor X gene mutations (PMID:15892863)
• the interaction of factor Xa with the heavy chain of factor Va strongly influences the catalytic activity of the enzyme resulting in increased rates for both prothrombin-activating cleavages. (PMID:15897196)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	f10	ENSDARG00000088581
mus_musculus	F10	ENSMUSG00000031444
rattus_norvegicus	F10	ENSRNOG00000033444

Paralogs (16): F7 (ENSG00000057593), F11 (ENSG00000088926), F9 (ENSG00000101981), HGFAC (ENSG00000109758), KLK10 (ENSG00000129451), F12 (ENSG00000131187), C1RL (ENSG00000139178), C1R (ENSG00000159403), KLKB1 (ENSG00000164344), C1S (ENSG00000182326), PRSS55 (ENSG00000184647), CFD (ENSG00000197766), CFI (ENSG00000205403), PRSS51 (ENSG00000253649), HP (ENSG00000257017), HPR (ENSG00000261701)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:103107) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 12 distinct phenotype terms.

Mouse phenotype (MP)	Records
internal hemorrhage	2
embryonic lethality during organogenesis, incomplete penetrance	2
decreased litter size	1
neonatal lethality	1
cardiac fibrosis	1
increased kidney weight	1
decreased circulating creatinine level	1
increased bleeding time	1
postnatal lethality, complete penetrance	1
neonatal lethality, incomplete penetrance	1
preweaning lethality, complete penetrance	1
increased heart iron level	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
Pan troglodytes	Q95ND7	99.8%	Diamond
Pongo abelii	Q5RCB6	99.5%	Diamond
Tropidechis carinatus	P81428	99.3%	Diamond
Notechis scutatus scutatus	P82807	99.3%	Diamond
Pan paniscus	Q2F9P4	98.7%	Diamond
Hoplocephalus stephensii	P83370	97.6%	Diamond
Bos taurus	P00741	96.8%	Diamond
Ovis aries	P16291	96.8%	Diamond
Macaca fascicularis	Q4R577	96.3%	Diamond
Macaca mulatta	Q28520	96.0%	Diamond
Oxyuranus microlepidotus	Q58L95	95.1%	Diamond
Oxyuranus scutellatus	Q58L96	95.1%	Diamond
Pseudonaja textilis	Q1L659	93.6%	Diamond
Capra hircus	Q28315	92.7%	Diamond
Cryptophis nigrescens	B5G6G5	89.2%	Diamond
Canis lupus familiaris	P19540	88.5%	Diamond
Felis catus	Q6SA95	88.5%	Diamond
Oryctolagus cuniculus	Q28661	86.3%	Diamond
Sus scrofa	P16293	86.1%	Diamond
Pseudechis porphyriacus	Q58L93	86.1%	Diamond
Demansia vestigiata	A6MFK7	85.8%	Diamond
Equus caballus	Q28380	84.7%	Diamond
Cavia porcellus	P16295	75.8%	Diamond
Strongylocentrotus purpuratus	P10079	74.9%	Diamond
Bombus ignitus	B5U2W0	67.2%	Diamond
Bombus pensylvanicus	Q7M4I3	67.2%	Diamond
Gallus gallus	Q804X6	58.1%	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
F10-AS2	protein-coding	102724474
F10-AS1	ncRNA	104413892
F7	protein-coding	2155
PCID2	protein-coding	55795
PROZ	protein-coding	8858
MCF2L	protein-coding	23263
MCF2L-AS1	ncRNA	100289410
MIR8075	ncRNA	102465874
CUL4A	protein-coding	8451
ATP11A	protein-coding	23250

Protein

Protein identifiers

Coagulation factor X — P00742 (reviewed: P00742)

Alternative names: Stuart factor, Stuart-Prower factor

All UniProt accessions (5): B7ZBK1, F8WBM7, P00742, Q5JVE7, Q5JVE8

UniProt curated annotations — full annotation on UniProt →

Function. Factor Xa is a vitamin K-dependent glycoprotein that converts prothrombin to thrombin in the presence of factor Va, calcium and phospholipid during blood clotting. Factor Xa activates pro-inflammatory signaling pathways in a protease-activated receptor (PAR)-dependent manner. Up-regulates expression of protease-activated receptors (PARs) F2R, F2RL1 and F2RL2 in dermal microvascular endothelial cells. Triggers the production of pro-inflammatory cytokines, such as MCP-1/CCL2 and IL6, in cardiac fibroblasts and umbilical vein endothelial cells in PAR-1/F2R-dependent manner. Triggers the production of pro-inflammatory cytokines, such as MCP-1/CCL2, IL6, TNF/TNF, IL-1beta/IL1B, IL8/CXCL8 and IL18, in endothelial cells and atrial tissues. Induces expression of adhesion molecules, such as ICAM1, VCAM1 and SELE, in endothelial cells and atrial tissues. Increases expression of phosphorylated ERK1/2 in dermal microvascular endothelial cells and atrial tissues. Triggers activation of the transcription factor NF-kappa-B in dermal microvascular endothelial cells and atrial tissues. Activates pro-inflammatory and pro-fibrotic responses in dermal fibroblasts and enhances wound healing probably via PAR-2/F2RL1-dependent mechanism. Activates barrier protective signaling responses in endothelial cells in PAR-2/F2RL1-dependent manner; the activity depends on the cleavage of PAR-2/F2RL1 by factor Xa. Up-regulates expression of plasminogen activator inhibitor 1 (SERPINE1) in atrial tissues.

Subunit / interactions. The two chains are formed from a single-chain precursor by the excision of two Arg residues and are held together by 1 or more disulfide bonds. Forms a heterodimer with SERPINA5. Interacts (inactive and activated) with ixolaris, an anticoagulant protein from Ixodes scapularis saliva. Interacts (activated) with iripin-8, a serine protease inhibitor from Ixodes ricinus saliva. Interacts (activated) with FXa-directed anticoagulant from Aedes albopictus saliva. Interacts (activated) with guianensin, an anticoagulant protein from Simulium guianense saliva. Interacts (activated) with simukunin, an anticoagulant protein from Simulium vittatum saliva. (Microbial infection) Interacts (via Gla domain) with Human adenovirus C serotype 5 hexon protein; this interaction allows the virus to be shielded from its host immune system.

Subcellular location. Secreted.

Tissue specificity. Plasma; synthesized in the liver.

Post-translational modifications. Carboxylated by vitamin K-dependent GGCX to form gamma-carboxyglutamate; these residues are essential for the binding of calcium. N- and O-glycosylated. O-glycosylated with core 1 or possibly core 8 glycans. Proteolytically cleaved and activated by cathepsin CTSG. The activation peptide is cleaved by factor IXa (in the intrinsic pathway), or by factor VIIa (in the extrinsic pathway). The iron and 2-oxoglutarate dependent 3-hydroxylation of aspartate and asparagine is (R) stereospecific within EGF domains.

Disease relevance. Factor X deficiency (FA10D) [MIM:227600] A hemorrhagic disease with variable presentation. Affected individuals can manifest prolonged nasal and mucosal hemorrhage, menorrhagia, hematuria, and occasionally hemarthrosis. Some patients do not have clinical bleeding diathesis. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Inhibited by SERPINA5 and SERPINA10.

Similarity. Belongs to the peptidase S1 family.

RefSeq proteins (3): NP_000495, NP_001299603, NP_001299604 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000152	EGF-type_Asp/Asn_hydroxyl_site	PTM
IPR000294	GLA_domain	Domain
IPR000742	EGF	Domain
IPR001254	Trypsin_dom	Domain
IPR001314	Peptidase_S1A	Family
IPR001881	EGF-like_Ca-bd_dom	Domain
IPR009003	Peptidase_S1_PA	Homologous_superfamily
IPR012224	Pept_S1A_FX	Family
IPR017857	Coagulation_fac-like_Gla_dom	Homologous_superfamily
IPR018097	EGF_Ca-bd_CS	Conserved_site
IPR018114	TRYPSIN_HIS	Active_site
IPR033116	TRYPSIN_SER	Active_site
IPR035972	GLA-like_dom_SF	Homologous_superfamily
IPR043504
IPR050442	Peptidase_S1_coag_factors	Family

Pfam: PF00008, PF00089, PF00594, PF14670

Enzyme classification (BRENDA)

• EC 3.4.21.6 — coagulation factor Xa (BRENDA: 13 organisms, 177 substrates, 1010 inhibitors, 101 Km, 85 kcat entries)

Substrate kinetics (BRENDA)

25 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
PROTHROMBIN	—	25
METHOXYCARBONYLCYCLOHEXYL-GLY-GLY-L-ARG-4-NITROA	0.072–1.38	8
N-ALPHA-BENZYLOXYCARBONYL-D-ARGINYL-GLYCYL-L-ARG	0.042–0.122	8
ARG-GLY-ARG-4-NITROANILIDE	0.0507–3.9	7
S2222	0.133–0.739	6
S2765	0.052–0.112	5
L-ARG-GLY-L-ARG-4-NITROANILIDE	0.036–0.24	4
PRETHROMBIN-1	0.0052–0.0069	4
BENZOYL-ILE-GLU(PIPERIDINEAMIDE)-GLY-ARG-P-NITRO	0.0867–0.0965	3
BENZOYL-ILE-GLU-(-H/OME)-GLY-ARG-P-NITROANILIDE	0.175–0.189	2
FRAGMENT 1.2:PRETHROMBIN-2	0.0006–0.0008	2
MEIZOTHROMBIN	0.0006–0.0009	2
RECOMBINANT PROTHROMBIN R155A/R284A/R271A MUTANT	0.0004	2
RECOMBINANT PROTHROMBIN R155A/R284A/R320A MUTANT	0.0004–0.0005	2
TOSYL-GLYCYL-PROLYL-D-ARGININE-4-NITROANILIDE	0.097–0.206	2

UniProt features (147 total): strand 35, sequence variant 33, mutagenesis site 14, helix 13, modified residue 12, disulfide bond 12, turn 6, domain 4, chain 4, glycosylation site 4, active site 3, propeptide 2, region of interest 2, sequence conflict 2, signal peptide 1

Structure

Experimental structures (PDB)

showing 30 of 192 structures by resolution:

PDB	Title	Method	Resolution (Å)
9I24	Coagulation factor Xa complex with a2-loop peptide	X-RAY DIFFRACTION	1.2
2JKH	Factor Xa - cation inhibitor complex	X-RAY DIFFRACTION	1.25
2Y5F	FACTOR XA - CATION INHIBITOR COMPLEX	X-RAY DIFFRACTION	1.29
2Y5G	FACTOR XA - CATION INHIBITOR COMPLEX	X-RAY DIFFRACTION	1.29
2Y5H	FACTOR XA - CATION INHIBITOR COMPLEX	X-RAY DIFFRACTION	1.33
3KL6	Discovery of Tetrahydropyrimidin-2(1H)-one derivative TAK-442: A potent, selective and …	X-RAY DIFFRACTION	1.45
2PR3	Factor XA inhibitor	X-RAY DIFFRACTION	1.5
6YYX	Aspartyl/Asparaginyl beta-hydroxylase (AspH) oxygenase and TPR domains in complex with …	X-RAY DIFFRACTION	1.53
3FFG	Factor XA in complex with the inhibitor (R)-6-(2’-((3- …	X-RAY DIFFRACTION	1.54
7YB9	Aspartyl/Asparaginyl beta-hydroxylase (AspH) oxygenase and TPR domains in complex with …	X-RAY DIFFRACTION	1.54
4Y6D	Factor Xa complex with GTC000101	X-RAY DIFFRACTION	1.55
2VWO	Aminopyrrolidine Factor Xa inhibitor	X-RAY DIFFRACTION	1.6
3CEN	Factor XA in complex with the inhibitor N-(2-(((5-chloro-2-pyridinyl) …	X-RAY DIFFRACTION	1.6
9FVV	Aspartyl/Asparaginyl beta-hydroxylase (AspH) in complex with Mn, 2OG, thiocyanate and …	X-RAY DIFFRACTION	1.6
2VWN	Aminopyrrolidine Factor Xa inhibitor	X-RAY DIFFRACTION	1.61
2P3U	Crystal structure of human factor XA complexed with …	X-RAY DIFFRACTION	1.62
6Q9F	Aspartyl/Asparaginyl beta-hydroxylase (AspH) H679A in complex with Mn, NOG and Factor X …	X-RAY DIFFRACTION	1.63
2BOK	Factor Xa - cation	X-RAY DIFFRACTION	1.64
2XBV	Factor Xa in complex with a pyrrolidine-3,4-dicarboxylic acid inhibitor	X-RAY DIFFRACTION	1.66
7BMI	Aspartyl/Asparaginyl beta-hydroxylase (AspH) oxygenase and TPR domains in complex with …	X-RAY DIFFRACTION	1.66
2XC4	Factor Xa in complex with a pyrrolidine-3,4-dicarboxylic acid inhibitor	X-RAY DIFFRACTION	1.67
7YBB	Aspartyl/Asparaginyl beta-hydroxylase (AspH) oxygenase and TPR domains in complex with …	X-RAY DIFFRACTION	1.68
2VH0	Structure and property based design of factor Xa inhibitors:biaryl pyrrolidin-2-ones …	X-RAY DIFFRACTION	1.7
2XC5	Factor Xa in complex with a pyrrolidine-3,4-dicarboxylic acid inhibitor	X-RAY DIFFRACTION	1.7
2Y81	Structure and property based design of factor Xa inhibitors: pyrrolidin-2-ones with …	X-RAY DIFFRACTION	1.7
8RE5	Aspartyl/Asparaginyl beta-hydroxylase (AspH) R735Q variant in complex with Mn …	X-RAY DIFFRACTION	1.7
9FVU	Aspartyl/Asparaginyl beta-hydroxylase (AspH) in complex with Fe, 2-oxoglutarate …	X-RAY DIFFRACTION	1.7
2XBW	Factor Xa in complex with a pyrrolidine-3,4-dicarboxylic acid inhibitor	X-RAY DIFFRACTION	1.72
2VVV	Aminopyrrolidine-related triazole Factor Xa inhibitor	X-RAY DIFFRACTION	1.73
2UWO	Selective and Dual Action Orally Active Inhibitors of Thrombin and Factor Xa	X-RAY DIFFRACTION	1.75

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P00742-F1	80.47	0.55

Antibody-complex structures (SAbDab)

3 antibodies co-crystallized with this protein: 7AHU, 9P0X, DENECIMIG

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Hydrolases, Peptidases, Serine-type peptidases, Predicted secreted proteins, Plasma proteins, Candidate cardiovascular disease genes, Disease related genes, FDA approved drug targets, Biotech drugs, Small molecule drugs, Human disease related genes

Protein evidence: Evidence at protein level

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 (3)

Position	Role
276	charge relay system
322	charge relay system
419	charge relay system

Post-translational modifications (12)

Type	Positions
4-carboxyglutamate	46, 47, 54, 56, 59, 60, 65, 66, 69, 72, 79
(3r)-3-hydroxyaspartate	103

Disulfide bonds (12)

Type	Positions
Disulfide bond	57–62, 90–101, 95–110, 112–121, 129–140, 136–149, 151–164, 241–246, 261–277, 390–404, 415–443
Interchain (between light and heavy chains)	172–342

Glycosylation sites (4)

Type	Positions
O-linked (galnac…) threonine	199, 211
N-linked (glcnac…) asparagine	221, 231

Mutagenesis-validated functional residues (14)

Position	Phenotype
255	reduces activity for cleavage of par-2/f2rl1. no significant effects on factor va (f5) binding and activity toward prothrombin in the …
256	reduces activity for cleavage of par-2/f2rl1. no significant effects on factor va (f5) binding and activity toward prothrombin in the …
258	reduces activity for cleavage of par-2/f2rl1. no significant effects on factor va (f5) binding and activity toward prothrombin in the …
282	reduces activity for cleavage of par-2/f2rl1. no significant effects on factor va (f5) binding and activity toward prothrombin in the …
283	reduces activity for cleavage of par-2/f2rl1. no significant effects on factor va (f5) binding and activity toward prothrombin in the …
306	no significant effects on activity for cleavage of par-2/f2rl1.
310	no significant effects on activity for cleavage of par-2/f2rl1.
345	no significant effects on activity for cleavage of par-2/f2rl1.
350	no significant effects on activity for cleavage of par-2/f2rl1.
366	reduces activity for cleavage of par-2/f2rl1.
372	reduces activity for cleavage of par-2/f2rl1.
376	reduces activity for cleavage of par-2/f2rl1.
387	reduces activity for cleavage of par-2/f2rl1.
391	reduces activity for cleavage of par-2/f2rl1.

Function

Pathways and Gene Ontology

Reactome pathways

9 curated (TAS) of 23; 7 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

23 pathways:

ID	Pathway	Evidence
R-HSA-9673202	Defective F9 variant does not activate FX ⚕	curated
R-HSA-9672396	Defective cofactor function of FVIIIa variant ⚕	curated
R-HSA-9672383	Defective factor IX causes thrombophilia ⚕	curated
R-HSA-9769743	Amplification and propagation of coagulation cascade	curated
R-HSA-159740	Gamma-carboxylation of protein precursors	curated
R-HSA-9769735	Initiation of coagulation cascade	curated
R-HSA-9769739	Regulation of clotting cascade	curated
R-HSA-159782	Removal of aminoterminal propeptides from gamma-carboxylated proteins	curated
R-HSA-159763	Transport of gamma-carboxylated protein precursors from the endoplasmic reticulum to the Golgi apparatus	curated
R-HSA-9668250	Defective factor IX causes hemophilia B ⚕	—
R-HSA-9662001	Defective factor VIII causes hemophilia A ⚕	—
R-HSA-1643685	Disease ⚕	—
R-HSA-9671793	Diseases of hemostasis ⚕	—
R-HSA-163841	Gamma carboxylation, hypusinylation, hydroxylation, and arylsulfatase activation	—
R-HSA-159854	Gamma-carboxylation, transport, and amino-terminal cleavage of proteins	—
R-HSA-109582	Hemostasis	—
R-HSA-392499	Metabolism of proteins	—
R-HSA-597592	Post-translational protein modification	—
R-HSA-140834		—
R-HSA-140837		—
R-HSA-140875		—
R-HSA-140877		—
R-HSA-9651496		—

MSigDB gene sets: 241 (showing top): MODULE_172, GOBP_PROTEIN_ACTIVATION_CASCADE, GNF2_GSTM1, GNF2_HPN, KAAB_HEART_ATRIUM_VS_VENTRICLE_UP, GOBP_POSITIVE_REGULATION_OF_TOR_SIGNALING, ACEVEDO_NORMAL_TISSUE_ADJACENT_TO_LIVER_TUMOR_DN, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, GOCC_CELL_SURFACE, GOBP_WOUND_HEALING, GOBP_PROTEIN_MATURATION, REACTOME_GAMMA_CARBOXYLATION_TRANSPORT_AND_AMINO_TERMINAL_CLEAVAGE_OF_PROTEINS, FOSTER_TOLERANT_MACROPHAGE_DN, MODULE_109, chr13q34

GO Biological Process (5): proteolysis (GO:0006508), blood coagulation (GO:0007596), positive regulation of cell migration (GO:0030335), positive regulation of TOR signaling (GO:0032008), hemostasis (GO:0007599)

GO Molecular Function (7): serine-type endopeptidase activity (GO:0004252), calcium ion binding (GO:0005509), phospholipid binding (GO:0005543), protein binding (GO:0005515), peptidase activity (GO:0008233), serine-type peptidase activity (GO:0008236), hydrolase activity (GO:0016787)

GO Cellular Component (5): extracellular region (GO:0005576), endoplasmic reticulum lumen (GO:0005788), Golgi lumen (GO:0005796), plasma membrane (GO:0005886), external side of plasma membrane (GO:0009897)

Reactome top-level categories

8 top-level categories:

Category	Pathways
Gamma-carboxylation, transport, and amino-terminal cleavage of proteins	3
Coagulation pathway	3
Defects of Coagulation cascade	1
Defective factor VIII causes hemophilia A	1
Defective factor IX causes hemophilia B	1
Gamma carboxylation, hypusinylation, hydroxylation, and arylsulfatase activation	1
Post-translational protein modification	1
Metabolism of proteins	1

GO top-level categories

30 GO namespaces:

Category	Terms
intracellular organelle lumen	2
protein metabolic process	1
hemostasis	1
wound healing	1
coagulation	1
cell migration	1
regulation of cell migration	1
positive regulation of cell motility	1
TOR signaling	1
regulation of TOR signaling	1
positive regulation of intracellular signal transduction	1
regulation of body fluid levels	1
endopeptidase activity	1
serine-type peptidase activity	1
metal ion binding	1
lipid binding	1
binding	1
hydrolase activity	1
catalytic activity, acting on a protein	1
peptidase activity	1
serine hydrolase activity	1
catalytic activity	1
cellular anatomical structure	1
endoplasmic reticulum	1
Golgi apparatus	1
membrane	1
cell periphery	1
plasma membrane	1
cell surface	1
side of membrane	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 3 of 18 annotations. The rest are phylogenetic / computational / electronic (IEA).

3 experimentally-supported GO terms:

GO term	NS	Evidence
positive regulation of TOR signaling	BP	direct assay
phospholipid binding	MF	direct assay
serine-type endopeptidase activity	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 1,096 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
F10	F3	P13726	945
F10	TFPI	P10646	858
F10	F8	P00451	857
F10	SERPINC1	P01008	741
F10	F2	P00734	728
F10	COL4A2	P08572	720
F10	EPRS1	P07814	717
F10	VWF	P04275	655
F10	F2R	P25116	655
F10	THBD	P07204	655
F10	ARAF	P07557	636
F10	PROCR	Q9UNN8	621
F10	SERPINA10	Q9UK55	621
F10	ZNF85	Q03923	610
F10	F5	P12259	606

IntAct

Human interaction partners of F10 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

10 partners by confidence:

Partner	Interaction type	MIscore	Records
NOTCH2NLC	physical association	0.560	3
UBQLN2	physical association	0.560	3
SERPINA10	direct interaction	0.560	2
L3	direct interaction	0.440	1
PCOLCE	direct interaction	0.440	1
IX	physical association	0.400	1
PIP4P1	association	0.350	1
H1-2	physical association	0.000	1
MGST3	physical association	0.000	1
PRKAB1	physical association	0.000	1

BioGRID (35 interactions; top human partners by supporting records): F2 (Affinity Capture-MS; 2 records), TFPI (Affinity Capture-Western; 2 records), APOC3 (Affinity Capture-MS), BTNL2 (Affinity Capture-MS), CAMP (Protein-peptide), CHAMP1 (Affinity Capture-MS), DNAJB9 (Affinity Capture-MS), F5 (Reconstituted Complex), F7 (Biochemical Activity), F8 (Reconstituted Complex), FIGF (Affinity Capture-MS), LY86 (Affinity Capture-MS), NBPF19 (Two-hybrid), NOTCH2NL (Two-hybrid), PARP3 (Proximity Label-MS)

SIGNOR signaling

showing 14 of 25 signaling interactions:

A	Effect	B	Mechanism
apixaban	down-regulates	F10	“chemical inhibition”
BMS-740808	down-regulates	F10	“chemical inhibition”
rivaroxaban	down-regulates	F10	“chemical inhibition”
F10	“up-regulates activity”	F7	cleavage
“Factor FVIIa:TF”	“up-regulates activity”	F10	binding
F7	“up-regulates activity”	F10	binding
GGCX	“up-regulates activity”	F10	carboxylation
“Factor VIIIa-IXa”	“up-regulates activity”	F10	cleavage
F10	“up-regulates activity”	F2	cleavage
betrixaban	“down-regulates activity”	F10	“chemical inhibition”
edoxaban	“down-regulates activity”	F10	“chemical inhibition”
F10	“form complex”	“Factor Va-Xa”	binding
SERPINC1	“down-regulates activity”	F10	cleavage
F10	“down-regulates activity”	APOH	cleavage

Protein complexes (CORUM) (4)

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

4 complexes by size:

Complex	Subunits	Members
★ F3-F7-F10-TFPI complex	4	TFPI, F10, F3, F7
★ F3-F7-F10 complex	3	F10, F3, F7
★ F10-SERPIN5A complex	2	F10, SERPINA5
★ F10-TFPI complex	2	TFPI, F10

Ligand–receptor pairs (CellPhoneDB) (1)

Curated ligand–receptor partners (cell-cell communication), distinct from the protein–protein interactions above.

1 ligand–receptor pairs:

Partner	This gene’s role	Signaling class
ITGB2;ITGAM	ligand	Adhesion by Prothrombin

Disease & clinical

Genetic variants

Variant evidence for F10: 182 ClinVar records (44 pathogenic / likely pathogenic); 6 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	17
Likely pathogenic	27
Uncertain significance	75
Likely benign	21
Benign	20

Top pathogenic / likely-pathogenic (15)

Showing the 15 best-reviewed of 44 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
12058	NM_000504.4(F10):c.61G>A (p.Gly21Arg)	Pathogenic	criteria provided, multiple submitters, no conflicts	3
626926	NM_000504.4(F10):c.1348G>A (p.Gly450Arg)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	4
627253	NM_000504.4(F10):c.161A>G (p.Glu54Gly)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	4
626966	NM_000504.4(F10):c.1087G>A (p.Gly363Ser)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	2
1098484	NM_000504.4(F10):c.513del (p.Cys172fs)	Pathogenic	criteria provided, single submitter	1
1341356	NM_000504.4(F10):c.1216G>A (p.Gly406Ser)	Pathogenic	criteria provided, single submitter	1
3340672	NM_000504.4(F10):c.1382G>A (p.Trp461Ter)	Pathogenic	criteria provided, single submitter	1
3765278	NM_000504.4(F10):c.730G>A (p.Gly244Arg)	Pathogenic	criteria provided, single submitter	1
4845820	NM_000504.4(F10):c.71-1G>C	Pathogenic	criteria provided, single submitter	1
1679953	NM_000504.4(F10):c.1073C>T (p.Thr358Met)	Likely pathogenic	criteria provided, single submitter	3
1684307	NM_000504.4(F10):c.205G>A (p.Glu69Lys)	Likely pathogenic	criteria provided, single submitter	2
1684309	NM_000504.4(F10):c.1252G>C (p.Asp418His)	Likely pathogenic	criteria provided, single submitter	2
626923	NM_000504.4(F10):c.1210T>C (p.Cys404Arg)	Likely pathogenic	criteria provided, single submitter	1
627495	NM_000504.4(F10):c.748-50_865+35del	Likely pathogenic	criteria provided, single submitter	1
1067302	NM_000504.4(F10):c.257-1G>C	Likely pathogenic	criteria provided, single submitter	1

Per-variant reference — Sugi Variant

Explore F10’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 27 predictions of 836):

Position(s)	Effect	Δscore	Sites
13:113129450–113129451	acceptor_loss	1.0000	6
13:113141051–113141052	donor_loss	1.0000	4
13:113144080	donor_gain	1.0000
13:113122920	donor_gain	0.9900
13:113139454	donor_gain	0.9900
13:113140917–113140918	acceptor_loss	0.9900	6
13:113141031	donor_gain	0.9900
13:113141051	donor_loss	0.9900
13:113143849–113143850	acceptor_loss	0.9900	5
13:113144051	donor_gain	0.9900

AlphaMissense

1,036 missense substitutions predicted likely pathogenic (of 3,253 scored), across 226 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
M402	9	0.942	0.987
D322	8	0.995	0.999
D418	8	0.994	0.998
D413	8	0.990	0.998
H276	8	0.985	0.994
S438	8	0.973	0.998
S419	8	0.964	0.994
F403	8	0.936	0.996
F260	8	0.920	0.993
D103	8	0.798	0.923
D86	8	0.746	0.897
C415	7	0.998	0.999
C277	7	0.997	0.999
C390	7	0.997	0.999
C404	7	0.997	0.999
C443	7	0.997	0.999
C261	7	0.995	0.999
C342	7	0.992	0.996
C136	7	0.991	0.996
C140	7	0.991	0.996

HPA cancer prognostics

RNA cancer specificity: Cancer enriched (Liver Hepatocellular Carcinoma)

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

2 prognostic cancer types:

Cancer	Prognostic	p-value
Pancreatic Adenocarcinoma (TCGA)	favorable	4.34e-05
Lung Squamous Cell Carcinoma (TCGA)	unfavorable	0.0004

Disease associations

OMIM: gene MIM:613872 | disease phenotypes: MIM:227600

GenCC curated gene-disease

1 curated gene-disease records:

Disease	Classification	Inheritance	Records
congenital factor X deficiency	Definitive	Autosomal recessive	4

ClinGen Gene-Disease Validity

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

1 validity classifications:

Disease	Classification	Inheritance
congenital factor X deficiency	Definitive	AR

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (3 panels, 3 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

3 panels:

Panel	Rating
Bleeding and platelet disorders	green
Factor X deficiency	green
Inherited bleeding disorders	green

Mondo (2): factor X deficiency (MONDO:0002247), congenital factor X deficiency (MONDO:0009212)

Orphanet (1): Congenital factor X deficiency (Orphanet:328)

HPO phenotypes

22 phenotypes (HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000132	Menorrhagia
HP:0000225	Gingival bleeding
HP:0000421	Epistaxis
HP:0000790	Hematuria
HP:0000978	Bruising susceptibility
HP:0002138	Subarachnoid hemorrhage
HP:0002170	Intracranial hemorrhage
HP:0002239	Gastrointestinal hemorrhage
HP:0003645	Prolonged partial thromboplastin time
HP:0004846	Prolonged bleeding after surgery
HP:0005261	Joint hemorrhage
HP:0006298	Prolonged bleeding after dental extraction
HP:0007420	Spontaneous hematomas
HP:0008151	Prolonged prothrombin time
HP:0008321	Reduced factor X activity
HP:0011854	Hemoperitoneum
HP:0011884	Abnormal umbilical stump bleeding
HP:0011891	Post-partum hemorrhage
HP:0012233	Intramuscular hematoma
HP:0025328	Antepartum hemorrhage
HP:0030140	Oral cavity bleeding

GWAS associations

6 associations:

Study	Trait	p-value
GCST000082_1	Factor VII	5e-16
GCST90002386_353	High light scatter reticulocyte percentage of red cells	3e-11
GCST90002385_443	High light scatter reticulocyte count	1e-9
GCST008103_61	Bipolar disorder	1e-6
GCST006585_1819	Blood protein levels	2e-6
GCST006585_1820	Blood protein levels	6e-6

EFO canonical traits (from GWAS)

2 canonical traits:

EFO ID	Trait name
EFO:0004619	factor VII measurement
EFO:0007986	reticulocyte count

MeSH disease descriptors

1 disease descriptors:

Descriptor	Name	Tree numbers
D005171	Factor X Deficiency	C15.378.100.100.320; C15.378.100.141.320; C15.378.463.320; C16.320.099.320

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (8): CHEMBL2111401 (SELECTIVITY GROUP), CHEMBL2111412 (SELECTIVITY GROUP), CHEMBL2111419 (SELECTIVITY GROUP), CHEMBL2111424 (SELECTIVITY GROUP), CHEMBL2111449 (PROTEIN COMPLEX), CHEMBL244 (SINGLE PROTEIN), CHEMBL5482991 (PROTEIN COMPLEX), CHEMBL6066543 (PROTEIN COMPLEX)

Drugs by curated mechanism of action (ChEMBL)

Drugs whose curated ChEMBL mechanism of action targets the F10 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.

13 curated-mechanism drugs:

Drug	Modality	Max phase
ANTITHROMBIN ALFA	Protein	4
APIXABAN	Small molecule	4
BETRIXABAN	Small molecule	4
COAGULATION FACTOR X HUMAN	Unknown	4
EDOXABAN TOSYLATE	Small molecule	4
RIVAROXABAN	Small molecule	4
BEMIPARIN	Oligosaccharide	3
DAREXABAN	Small molecule	3
IDRABIOTAPARINUX SODIUM	Oligosaccharide	3
IDRAPARINUX SODIUM	Oligosaccharide	3
OTAMIXABAN	Small molecule	3
PROTHROMBIN COMPLEX CONCENTRATE	Protein	3
LETAXABAN	Small molecule	2

Drugs acting on a complex or family that includes this protein

Curated ChEMBL mechanism-of-action drugs whose target is a protein complex or family of ≤10 members that includes F10 — the drug acts on the assembly or class, not necessarily on this subunit alone.

1 drugs via a complex or family:

Drug	Target (ChEMBL)	Members	Max phase
EMICIZUMAB	Coagulation factor IX and X	2	4

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 96,741 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

23 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL231779	APIXABAN	4	9,446
CHEMBL512351	BETRIXABAN	4	1,131
CHEMBL1269025	EDOXABAN	4	2,478
CHEMBL198362	RIVAROXABAN	4	11,700
CHEMBL1166	ARGATROBAN	4	233
CHEMBL1201202	FONDAPARINUX	4	144
CHEMBL1200644	FONDAPARINUX SODIUM	4	12,749
CHEMBL266349	MELAGATRAN	4	5,456
CHEMBL55	PENTAMIDINE	4	27,197
CHEMBL1922235	DAREXABAN	3	740
CHEMBL46618	OTAMIXABAN	3	548
CHEMBL48361	DABIGATRAN	3	13,643
CHEMBL87563	GABEXATE	3	2,044
CHEMBL273264	NAFAMOSTAT	3	7,150
CHEMBL1095032	LETAXABAN	2	390
CHEMBL273196	EFEGATRAN	2	1,040
CHEMBL476186	ERIBAXABAN	2	354
CHEMBL73193	FIDEXABAN	2	186
CHEMBL220050	GW813893	2	74
CHEMBL1271162	LY-517717	2	38
CHEMBL206335	RAZAXABAN	2
CHEMBL3139247	SEGATROXABAN	2
CHEMBL1270156	TANOGITRAN	2

PharmGKB: 1 entry (CPIC guideline: no)

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Blood coagulation components

Most potent curated ligand interactions (11 total), top 11:

Ligand	Action	Affinity	Parameter
apixaban	Inhibition	10.1	pKi
betrixaban	Inhibition	9.93	pKi
otamixaban	Inhibition	9.4	pKi
rivaroxaban	Inhibition	9.4	pKi
zifaxaban	Inhibition	9.3	pKi
edoxaban	Inhibition	9.25	pKi
eribaxaban	Inhibition	9.24	pIC50
BAY 3389934	Inhibition	9.15	pIC50
JTV-803	Inhibition	7.72	pKi
DX-9065a	Inhibition	7.39	pKi
emicizumab	Binding	5.73	pKd

Binding affinities (BindingDB)

5464 measured of 5961 human assays (6100 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
2-(3-Carbamimidoyl-phenyl)-5-trifluoromethyl-2H-pyrazole-3-carboxylic acid [5-(2-sulfamoyl-phenyl)-pyrimidin-2-yl]-amide	KI	0.001 nM
3-chloro-N-{4-chloro-2-[(5-chloropyridin-2-yl)carbamoyl]-6-methoxyphenyl}-4-{[3,4-dihydro-2H-pyrrol-5-yl(methyl)amino]methyl}thiophene-2-carboxamide	KI	0.004 nM
3-chloro-N-{4-chloro-2-[(5-chloropyridin-2-yl)carbamoyl]-6-methoxyphenyl}-4-{[2-(methylsulfanyl)-4,5-dihydro-1H-imidazol-1-yl]methyl}thiophene-2-carboxamide	KI	0.004 nM
3-chloro-N-{4-chloro-2-[(5-chloropyridin-2-yl)carbamoyl]-6-methoxyphenyl}-4-(4,5-dihydro-1H-imidazol-1-ylmethyl)thiophene-2-carboxamide	KI	0.004 nM
3-chloro-N-{4-chloro-2-[(5-chloropyridin-2-yl)carbamoyl]-6-methoxyphenyl}-4-{[2-(ethylamino)-1H-imidazol-1-yl]methyl}thiophene-2-carboxamide	KI	0.005 nM
2-(3-Carbamimidoyl-phenyl)-5-methyl-2H-pyrazole-3-carboxylic acid (3-fluoro-2’-sulfamoyl-biphenyl-4-yl)-amide	KI	0.005 nM
CHEMBL260160	KI	0.005 nM
4-[(2-amino-1H-imidazol-1-yl)methyl]-3-chloro-N-{4-chloro-2-[(5-chloropyridin-2-yl)carbamoyl]-6-methoxyphenyl}thiophene-2-carboxamide	KI	0.006 nM
2-(3-Carbamimidoyl-phenyl)-5-methyl-2H-pyrazole-3-carboxylic acid [5-(2-sulfamoyl-phenyl)-pyridin-2-yl]-amide	KI	0.007 nM
3-chloro-N-{4-chloro-2-[(5-chloropyridin-2-yl)carbamoyl]-6-methoxyphenyl}-4-{[2-(propan-2-ylamino)-1H-imidazol-1-yl]methyl}thiophene-2-carboxamide	KI	0.008 nM
2-(3-Carbamimidoyl-phenyl)-5-methyl-2H-pyrazole-3-carboxylic acid (2’-methanesulfonyl-biphenyl-4-yl)-amide	KI	0.008 nM
2-(3-Carbamimidoyl-phenyl)-5-trifluoromethyl-2H-pyrazole-3-carboxylic acid (2’-methanesulfonyl-biphenyl-4-yl)-amide	KI	0.008 nM
2-(3-Carbamimidoyl-phenyl)-5-methyl-2H-pyrazole-3-carboxylic acid (3-chloro-2’-sulfamoyl-biphenyl-4-yl)-amide	KI	0.009 nM
2-(3-Carbamimidoyl-phenyl)-5-trifluoromethyl-2H-pyrazole-3-carboxylic acid [5-(2-sulfamoyl-phenyl)-pyridin-2-yl]-amide	KI	0.009 nM
3-chloro-N-{4-chloro-2-[(5-chloropyridin-2-yl)carbamoyl]-6-methoxyphenyl}-4-[(2-imino-1,3-oxazolidin-3-yl)methyl]thiophene-2-carboxamide	KI	0.01 nM
3-chloro-N-{4-chloro-2-[(5-chloropyridin-2-yl)carbamoyl]-6-methoxyphenyl}-4-[(2-imino-1,3-thiazolidin-3-yl)methyl]thiophene-2-carboxamide	KI	0.01 nM
3-chloro-N-{4-chloro-2-[(5-chloropyridin-2-yl)carbamoyl]-6-methoxyphenyl}-4-[(2-iminoimidazolidin-1-yl)methyl]thiophene-2-carboxamide	KI	0.01 nM
3-chloro-N-{4-chloro-2-[(5-chloropyridin-2-yl)carbamoyl]-6-methoxyphenyl}-4-[(2-methyl-4,5-dihydro-1H-imidazol-1-yl)methyl]thiophene-2-carboxamide	KI	0.01 nM
3-chloro-N-{4-chloro-2-[(5-chloropyridin-2-yl)carbamoyl]-6-methoxyphenyl}-4-[(N-methylethanimidamido)methyl]thiophene-2-carboxamide	KI	0.01 nM
3-chloro-N-{4-chloro-2-[(5-chloropyridin-2-yl)carbamoyl]-6-methoxyphenyl}-4-(3-methylcarbamimidamidomethyl)thiophene-2-carboxamide	KI	0.01 nM
3-chloro-N-{4-chloro-2-[(5-chloropyridin-2-yl)carbamoyl]-6-methoxyphenyl}-4-[(2-methyl-1H-imidazol-1-yl)methyl]thiophene-2-carboxamide	KI	0.01 nM
2-(3-Carbamimidoyl-phenyl)-5-methyl-2H-pyrazole-3-carboxylic acid (3-bromo-2’-sulfamoyl-biphenyl-4-yl)-amide	KI	0.01 nM
3-chloro-N-{4-chloro-2-[(5-chloropyridin-2-yl)carbamoyl]-6-methoxyphenyl}-4-{[4,5-dihydro-1,3-oxazol-2-yl(ethyl)amino]methyl}thiophene-2-carboxamide	KI	0.012 nM
3-chloro-N-{4-chloro-2-[(5-chloropyridin-2-yl)carbamoyl]-6-methoxyphenyl}-4-{[5,6-dihydro-4H-1,3-oxazin-2-yl(methyl)amino]methyl}thiophene-2-carboxamide	KI	0.012 nM
CHEMBL270221	KI	0.013 nM
CHEMBL402980	KI	0.013 nM
2-(3-Carbamimidoyl-phenyl)-5-trifluoromethyl-2H-pyrazole-3-carboxylic acid (2’-sulfamoyl-biphenyl-4-yl)-amide	KI	0.015 nM
CHEMBL401958	KI	0.016 nM
3-chloro-N-{4-chloro-2-[(5-chloropyridin-2-yl)carbamoyl]-6-methoxyphenyl}-4-({methyl[2-(pyrrolidin-1-yl)ethyl]amino}methyl)thiophene-2-carboxamide	KI	0.019 nM
4-{[2-(4-{[1-(3-amino-1,2-benzoxazol-5-yl)-3-(trifluoromethyl)-1H-pyrazole-5-]amido}-3-fluorophenyl)phenyl]methyl}-4-methylmorpholin-4-ium bromide	KI	0.02 nM
3-chloro-N-{4-chloro-2-[(5-chloropyridin-2-yl)carbamoyl]-6-methoxyphenyl}-4-{[(ethylcarbamoyl)(methyl)amino]methyl}thiophene-2-carboxamide	KI	0.02 nM
3-chloro-N-{4-chloro-2-[(5-chloropyridin-2-yl)carbamoyl]-6-methoxyphenyl}-4-{[1H-imidazol-2-yl(methyl)amino]methyl}thiophene-2-carboxamide	KI	0.02 nM
2-(3-Carbamimidoyl-phenyl)-5-methyl-2H-pyrazole-3-carboxylic acid (3-fluoro-2’-methanesulfonyl-biphenyl-4-yl)-amide	KI	0.02 nM
1-(4-methoxyphenyl)-6-(4-(1-(pyrrolidin-1-ylmethyl)cyclopropyl)phenyl)-3-(trifluoromethyl)-5,6-dihydro-1H-pyrazolo[3,4-c]pyridin-7(4H)-one	KI	0.02 nM
6-(4-(1-(2-(dimethylamino)ethyl)cyclopropyl)phenyl)-1-(4-methoxyphenyl)-3-(trifluoromethyl)-5,6-dihydro-1H-pyrazolo[3,4-c]pyridin-7(4H)-one	KI	0.02 nM
1-(4-methoxyphenyl)-6-(4-(1-(2-(pyrrolidin-1-yl)ethyl)cyclopropyl)phenyl)-3-(trifluoromethyl)-5,6-dihydro-1H-pyrazolo[3,4-c]pyridin-7(4H)-one	KI	0.02 nM
6-(4-(1-(4,5-dihydro-1H-imidazol-2-yl)cyclopropyl)phenyl)-1-(4-methoxyphenyl)-3-(trifluoromethyl)-5,6-dihydro-1H-pyrazolo[3,4-c]pyridin-7(4H)-one	KI	0.02 nM
(2R,4S)-4-(2-Chlorophenyl)-N1-(4-chlorophenyl)-4-hydroxy-N2-(5-(2-oxopyridin-1(2H)-yl)pyridin-2-yl)pyrrolidine-1,2-dicarboxamide	IC50	0.02 nM
CHEMBL270862	KI	0.02 nM
3-[({[4-chloro-5-({4-chloro-2-[(5-chloropyridin-2-yl)carbamoyl]-6-methoxyphenyl}carbamoyl)thiophen-3-yl]methyl}(methyl)carbamoyl)amino]propanoic acid	KI	0.022 nM
3-chloro-N-{4-chloro-2-[(5-chloropyridin-2-yl)carbamoyl]-6-methoxyphenyl}-4-(1H-imidazol-1-ylmethyl)thiophene-2-carboxamide	KI	0.022 nM
3-(3-Carbamimidoyl-phenyl)-3H-[1,2,3]triazole-4-carboxylic acid (2’-sulfamoyl-biphenyl-4-yl)-amide; TFA	KI	0.023 nM
3-chloro-N-{4-chloro-2-[(5-chloropyridin-2-yl)carbamoyl]-6-methoxyphenyl}-4-({3-(dimethylamino)propylamino}methyl)thiophene-2-carboxamide	KI	0.024 nM
3-chloro-N-{4-chloro-2-[(5-chloropyridin-2-yl)carbamoyl]-6-methoxyphenyl}-4-{[4,5-dihydro-1,3-thiazol-2-yl(methyl)amino]methyl}thiophene-2-carboxamide	KI	0.024 nM
1-(4-methoxyphenyl)-6-(4-(1-((2-methyl-1H-imidazol-1-yl)methyl)cyclopropyl)phenyl)-3-(trifluoromethyl)-5,6-dihydro-1H-pyrazolo[3,4-c]pyridin-7(4H)-one	KI	0.025 nM
4-{[carbamoyl(methyl)amino]methyl}-3-chloro-N-{4-chloro-2-[(5-chloropyridin-2-yl)carbamoyl]-6-methoxyphenyl}thiophene-2-carboxamide	KI	0.026 nM
3-chloro-N-{4-chloro-2-[(5-chloropyridin-2-yl)carbamoyl]-6-methoxyphenyl}-4-{[methyl(4-oxo-4,5-dihydro-1,3-oxazol-2-yl)amino]methyl}thiophene-2-carboxamide	KI	0.026 nM
7-{6-[1-(1-Imino-ethyl)-piperidin-4-yloxy]-2-isopropyl-benzoimidazol-1-ylmethyl}-naphthalene-2-carboxamidine	KI	0.026 nM
1-(4-methoxyphenyl)-7-oxo-6-(4-(1-(pyrrolidin-1-ylmethyl)cyclopropyl)phenyl)-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carbonitrile 2,2,2-trifluoroacetate	KI	0.027 nM
3-(3-{2-Ethyl-6-[1-(1-imino-ethyl)-piperidin-4-yloxy]-benzoimidazol-1-yl}-propenyl)-phenylamine	KI	0.028 nM

ChEMBL bioactivities

6100 potent at pChembl≥5 of 6100 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
11.00	Ki	0.01	nM	CHEMBL37251
11.00	IC50	0.01	nM	CHEMBL507020
11.00	Ki	0.01	nM	CHEMBL152859
10.92	Ki	0.012	nM	CHEMBL387856
10.92	Ki	0.012	nM	CHEMBL226564
10.92	Ki	0.012	nM	CHEMBL174330
10.89	Ki	0.013	nM	CHEMBL37251
10.89	Ki	0.013	nM	CHEMBL270221
10.89	Ki	0.013	nM	CHEMBL402980
10.89	Ki	0.013	nM	CHEMBL152854
10.89	Ki	0.013	nM	CHEMBL352039
10.85	Ki	0.014	nM	CHEMBL414002
10.82	Ki	0.015	nM	CHEMBL347846
10.80	Ki	0.016	nM	CHEMBL401958
10.72	Ki	0.019	nM	CHEMBL441880
10.70	Ki	0.02	nM	CHEMBL183785
10.70	Ki	0.02	nM	CHEMBL185301
10.70	Ki	0.02	nM	CHEMBL380431
10.70	Ki	0.02	nM	CHEMBL389210
10.70	Ki	0.02	nM	CHEMBL226931
10.70	Ki	0.02	nM	CHEMBL270862
10.70	Ki	0.02	nM	CHEMBL256451
10.70	IC50	0.02	nM	CHEMBL507279
10.70	IC50	0.02	nM	CHEMBL475682
10.70	Ki	0.02	nM	CHEMBL422688
10.70	Ki	0.02	nM	CHEMBL456064
10.70	Ki	0.02	nM	CHEMBL540198
10.68	Ki	0.021	nM	CHEMBL461091
10.68	Ki	0.021	nM	CHEMBL456498
10.66	Ki	0.022	nM	CHEMBL226826
10.66	Ki	0.022	nM	CHEMBL390055
10.64	Ki	0.023	nM	CHEMBL157417
10.62	Ki	0.024	nM	CHEMBL449702
10.62	Ki	0.024	nM	CHEMBL376791
10.60	Ki	0.025	nM	CHEMBL471550
10.59	Ki	0.026	nM	CHEMBL226668
10.59	Ki	0.026	nM	CHEMBL227308
10.59	Ki	0.026	nM	CHEMBL177142
10.57	Ki	0.027	nM	CHEMBL446752
10.55	Ki	0.028	nM	CHEMBL257398
10.55	Ki	0.028	nM	CHEMBL24460
10.52	Ki	0.03	nM	CHEMBL426439
10.52	Ki	0.03	nM	CHEMBL378093
10.51	Ki	0.031	nM	CHEMBL226616
10.48	Ki	0.033	nM	CHEMBL228983
10.48	Ki	0.033	nM	CHEMBL252454
10.47	Ki	0.034	nM	CHEMBL389638
10.46	Ki	0.035	nM	CHEMBL461297
10.44	Ki	0.036	nM	CHEMBL227360
10.43	Ki	0.037	nM	CHEMBL270034

PubChem BioAssay actives

4311 with measured affinity, of 6100 total; 50 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
1-(3-carbamimidoylphenyl)-N-[4-(2-sulfamoylphenyl)phenyl]tetrazole-5-carboxamide	72496: Inhibition of human purified factor Xa	ki	<0.0001	uM
2-[(6-chloronaphthalen-2-yl)sulfonyl-[(3S)-1-[2-fluoro-4-(2-oxo-1-pyridinyl)phenyl]-2-oxopiperidin-3-yl]amino]-N-[2-(dimethylamino)ethyl]-N-methylacetamide	322035: Inhibition of human factor 10a	ki	<0.0001	uM
6-chloro-N-[1-[2-fluoro-4-(2-oxo-1-pyridinyl)phenyl]-2-oxopiperidin-3-yl]thieno[2,3-b]pyridine-2-sulfonamide	322035: Inhibition of human factor 10a	ki	<0.0001	uM
1-(3-carbamimidoylphenyl)-N-[5-(2-sulfamoylphenyl)pyrimidin-2-yl]-3-(trifluoromethyl)pyrazole-5-carboxamide	51646: Binding affinity against human coagulation factor X	ki	<0.0001	uM
N-(5-chloro-2-pyridinyl)-2-[[4-(N,N-dimethylcarbamimidoyl)benzoyl]amino]benzamide	527394: Inhibition of factor 10a	ki	<0.0001	uM
5-chloro-N-(5-chloro-2-pyridinyl)-3-methoxy-2-[[4-(2-oxo-1-pyridinyl)benzoyl]amino]benzamide	331785: Inhibition of human factor 10a	ki	<0.0001	uM
2-[(6-chlorothieno[2,3-b]pyridin-2-yl)sulfonyl-[1-[2-fluoro-4-(2-oxo-1-pyridinyl)phenyl]-2-oxopiperidin-3-yl]amino]-N-methylacetamide	322035: Inhibition of human factor 10a	ki	<0.0001	uM
2-[(6-chloronaphthalen-2-yl)sulfonyl-[1-[2-fluoro-4-(2-oxo-1-pyridinyl)phenyl]-2-oxopiperidin-3-yl]amino]-N-[2-(dimethylamino)ethyl]-N-methylacetamide	322035: Inhibition of human factor 10a	ki	<0.0001	uM
2-[(6-chlorothieno[2,3-b]pyridin-2-yl)sulfonyl-[1-[2-fluoro-4-(2-oxo-1-pyridinyl)phenyl]-2-oxopiperidin-3-yl]amino]-N-[2-(dimethylamino)ethyl]-N-methylacetamide	322035: Inhibition of human factor 10a	ki	<0.0001	uM
5-chloro-N-(5-chloro-2-pyridinyl)-2-[[4-(N,N-dimethylcarbamimidoyl)benzoyl]amino]benzamide	351693: Inhibition of Factor 10a	ki	<0.0001	uM
7-[[6-(1-ethanimidoylpiperidin-4-yl)oxy-2-propan-2-ylbenzimidazol-1-yl]methyl]naphthalene-2-carboximidamide	51686: In vitro inhibitory activity against human Coagulation factor X	ki	<0.0001	uM
6-[4-[1-[(dimethylamino)methyl]cyclopropyl]phenyl]-1-(4-methoxyphenyl)-3-(trifluoromethyl)-4,5-dihydropyrazolo[5,4-c]pyridin-7-one	343864: Inhibition of human factor 10a	ki	<0.0001	uM
6-[4-[1-(diethylaminomethyl)cyclopropyl]phenyl]-1-(4-methoxyphenyl)-3-(trifluoromethyl)-4,5-dihydropyrazolo[5,4-c]pyridin-7-one	343864: Inhibition of human factor 10a	ki	<0.0001	uM
methyl 2-[(6-chlorothieno[2,3-b]pyridin-2-yl)sulfonyl-[2-oxo-1-[4-(2-oxo-1-pyridinyl)phenyl]piperidin-3-yl]amino]acetate	322035: Inhibition of human factor 10a	ki	<0.0001	uM
6-[4-[1-[(dimethylamino)methyl]cyclopropyl]phenyl]-1-(4-methoxyphenyl)-7-oxo-4,5-dihydropyrazolo[5,4-c]pyridine-3-carboxamide	396701: Binding affinity to human coagulation factor 10a	ki	<0.0001	uM
2-(3-carbamimidoylphenyl)-N-[2-fluoro-4-(2-sulfamoylphenyl)phenyl]-5-methylpyrazole-3-carboxamide	51646: Binding affinity against human coagulation factor X	ki	<0.0001	uM
2-(3-carbamimidoylphenyl)-5-methyl-N-[4-(2-methylsulfonylphenyl)phenyl]pyrazole-3-carboxamide	51646: Binding affinity against human coagulation factor X	ki	<0.0001	uM
2-(3-carbamimidoylphenyl)-5-methyl-N-[4-[2-(trifluoromethyl)phenyl]phenyl]pyrazole-3-carboxamide	51646: Binding affinity against human coagulation factor X	ki	<0.0001	uM
1-(3-carbamimidoylphenyl)-N-[4-(2-methylsulfonylphenyl)phenyl]-3-(trifluoromethyl)pyrazole-5-carboxamide	51646: Binding affinity against human coagulation factor X	ki	<0.0001	uM
2-(3-carbamimidoylphenyl)-5-methyl-N-[5-(2-sulfamoylphenyl)-2-pyridinyl]pyrazole-3-carboxamide	51646: Binding affinity against human coagulation factor X	ki	<0.0001	uM
N-[2-bromo-4-(2-sulfamoylphenyl)phenyl]-2-(3-carbamimidoylphenyl)-5-methylpyrazole-3-carboxamide	51646: Binding affinity against human coagulation factor X	ki	<0.0001	uM
3-[[(3R)-3-[(7-methoxynaphthalen-2-yl)sulfonylamino]-2-oxopyrrolidin-1-yl]methyl]benzenecarboximidamide	52156: Compound was evaluated for the inhibition of human Coagulation factor Xa	ki	<0.0001	uM
2-(3-carbamimidoylphenyl)-N-[2-chloro-4-(2-sulfamoylphenyl)phenyl]-5-methylpyrazole-3-carboxamide	51646: Binding affinity against human coagulation factor X	ki	<0.0001	uM
2-(3-carbamimidoylphenyl)-N-[2-fluoro-4-(2-methylsulfonylphenyl)phenyl]-5-methylpyrazole-3-carboxamide	51646: Binding affinity against human coagulation factor X	ki	<0.0001	uM
1-[4-[2-[1-(3-amino-1,2-benzoxazol-5-yl)-3-(trifluoromethyl)pyrazol-5-yl]-2-oxoethyl]-3-fluorophenyl]pyridin-2-one	313675: Inhibition of human factor 10a	ki	<0.0001	uM
N-(5-chloro-2-pyridinyl)-5-methyl-2-[[4-(2-oxo-1-pyridinyl)benzoyl]amino]benzamide	331785: Inhibition of human factor 10a	ki	<0.0001	uM
3-chloro-N-[4-chloro-2-[(5-chloro-2-pyridinyl)carbamoyl]-6-methoxyphenyl]-4-[(2-imino-4-oxoimidazolidin-1-yl)methyl]thiophene-2-carboxamide	290948: Inhibition of human F10a	ki	<0.0001	uM
1-(3-carbamimidoylphenyl)-N-[4-(2-sulfamoylphenyl)phenyl]-3-(trifluoromethyl)pyrazole-5-carboxamide	51646: Binding affinity against human coagulation factor X	ki	<0.0001	uM
(2R)-N-[(2S)-1-[[2-(aminomethyl)-5-chlorophenyl]methylamino]-1-oxopropan-2-yl]-2-(benzylsulfonylamino)-4-(1-oxidopyridin-1-ium-2-yl)butanamide	290688: Inhibition of factor 10a	ki	<0.0001	uM
3-chloro-N-[4-chloro-2-[(5-chloro-2-pyridinyl)carbamoyl]-6-methoxyphenyl]-4-[[3-(dimethylamino)propyl-methylamino]methyl]thiophene-2-carboxamide	1797584: Enzyme Inhibition Assay from Article 10.1021/jm070125f: “Thiophene-anthranilamides as highly potent and orally available factor xa inhibitors”	ki	<0.0001	uM
3-chloro-N-[4-chloro-2-[(5-chloro-2-pyridinyl)carbamoyl]-6-methoxyphenyl]-4-[[methyl(2-pyrrolidin-1-ylethyl)amino]methyl]thiophene-2-carboxamide	1797584: Enzyme Inhibition Assay from Article 10.1021/jm070125f: “Thiophene-anthranilamides as highly potent and orally available factor xa inhibitors”	ki	<0.0001	uM
3-chloro-N-[4-chloro-2-[(5-chloro-2-pyridinyl)carbamoyl]-6-methoxyphenyl]-4-[[methyl(methylsulfonyl)amino]methyl]thiophene-2-carboxamide	1797584: Enzyme Inhibition Assay from Article 10.1021/jm070125f: “Thiophene-anthranilamides as highly potent and orally available factor xa inhibitors”	ki	<0.0001	uM
4-[[carbamoyl(methyl)amino]methyl]-3-chloro-N-[4-chloro-2-[(5-chloro-2-pyridinyl)carbamoyl]-6-methoxyphenyl]thiophene-2-carboxamide	1797584: Enzyme Inhibition Assay from Article 10.1021/jm070125f: “Thiophene-anthranilamides as highly potent and orally available factor xa inhibitors”	ki	<0.0001	uM
3-chloro-N-[4-chloro-2-[(5-chloro-2-pyridinyl)carbamoyl]-6-methoxyphenyl]-4-[[ethylcarbamoyl(methyl)amino]methyl]thiophene-2-carboxamide	1797584: Enzyme Inhibition Assay from Article 10.1021/jm070125f: “Thiophene-anthranilamides as highly potent and orally available factor xa inhibitors”	ki	<0.0001	uM
3-chloro-N-[4-chloro-2-[(5-chloro-2-pyridinyl)carbamoyl]-6-methoxyphenyl]-4-[[methyl(2-pyrrolidin-1-ylethylcarbamoyl)amino]methyl]thiophene-2-carboxamide	1797584: Enzyme Inhibition Assay from Article 10.1021/jm070125f: “Thiophene-anthranilamides as highly potent and orally available factor xa inhibitors”	ki	<0.0001	uM
3-[[[4-chloro-5-[[4-chloro-2-[(5-chloro-2-pyridinyl)carbamoyl]-6-methoxyphenyl]carbamoyl]thiophen-3-yl]methyl-methylcarbamoyl]amino]propanoic acid	1797584: Enzyme Inhibition Assay from Article 10.1021/jm070125f: “Thiophene-anthranilamides as highly potent and orally available factor xa inhibitors”	ki	<0.0001	uM
3-chloro-N-[4-chloro-2-[(5-chloro-2-pyridinyl)carbamoyl]-6-methoxyphenyl]-4-[[4,5-dihydro-1,3-oxazol-2-yl(ethyl)amino]methyl]thiophene-2-carboxamide	1797584: Enzyme Inhibition Assay from Article 10.1021/jm070125f: “Thiophene-anthranilamides as highly potent and orally available factor xa inhibitors”	ki	<0.0001	uM
3-chloro-N-[4-chloro-2-[(5-chloro-2-pyridinyl)carbamoyl]-6-methoxyphenyl]-4-[[ethyl-(4-methyl-4,5-dihydro-1,3-oxazol-2-yl)amino]methyl]thiophene-2-carboxamide	1797584: Enzyme Inhibition Assay from Article 10.1021/jm070125f: “Thiophene-anthranilamides as highly potent and orally available factor xa inhibitors”	ki	<0.0001	uM
3-chloro-N-[4-chloro-2-[(5-chloro-2-pyridinyl)carbamoyl]-6-methoxyphenyl]-4-[[5,6-dihydro-4H-1,3-oxazin-2-yl(methyl)amino]methyl]thiophene-2-carboxamide	1797584: Enzyme Inhibition Assay from Article 10.1021/jm070125f: “Thiophene-anthranilamides as highly potent and orally available factor xa inhibitors”	ki	<0.0001	uM
3-chloro-N-[4-chloro-2-[(5-chloro-2-pyridinyl)carbamoyl]-6-methoxyphenyl]-4-[[methyl-(4-oxo-1,3-oxazol-2-yl)amino]methyl]thiophene-2-carboxamide	290948: Inhibition of human F10a	ki	<0.0001	uM
3-chloro-N-[4-chloro-2-[(5-chloro-2-pyridinyl)carbamoyl]-6-methoxyphenyl]-4-[[4,5-dihydro-1,3-thiazol-2-yl(methyl)amino]methyl]thiophene-2-carboxamide	1797584: Enzyme Inhibition Assay from Article 10.1021/jm070125f: “Thiophene-anthranilamides as highly potent and orally available factor xa inhibitors”	ki	<0.0001	uM
3-chloro-N-[4-chloro-2-[(5-chloro-2-pyridinyl)carbamoyl]-6-methoxyphenyl]-4-[[3,4-dihydro-2H-pyrrol-5-yl(methyl)amino]methyl]thiophene-2-carboxamide	1797584: Enzyme Inhibition Assay from Article 10.1021/jm070125f: “Thiophene-anthranilamides as highly potent and orally available factor xa inhibitors”	ki	<0.0001	uM
3-chloro-N-[4-chloro-2-[(5-chloro-2-pyridinyl)carbamoyl]-6-methoxyphenyl]-4-[(2-imino-1,3-oxazolidin-3-yl)methyl]thiophene-2-carboxamide	1797584: Enzyme Inhibition Assay from Article 10.1021/jm070125f: “Thiophene-anthranilamides as highly potent and orally available factor xa inhibitors”	ki	<0.0001	uM
3-chloro-N-[4-chloro-2-[(5-chloro-2-pyridinyl)carbamoyl]-6-methoxyphenyl]-4-[(2-imino-1,3-thiazolidin-3-yl)methyl]thiophene-2-carboxamide	1797584: Enzyme Inhibition Assay from Article 10.1021/jm070125f: “Thiophene-anthranilamides as highly potent and orally available factor xa inhibitors”	ki	<0.0001	uM
4-[(2-amino-4,5-dihydroimidazol-1-yl)methyl]-3-chloro-N-[4-chloro-2-[(5-chloro-2-pyridinyl)carbamoyl]-6-methoxyphenyl]thiophene-2-carboxamide	1797584: Enzyme Inhibition Assay from Article 10.1021/jm070125f: “Thiophene-anthranilamides as highly potent and orally available factor xa inhibitors”	ki	<0.0001	uM
3-chloro-N-[4-chloro-2-[(5-chloro-2-pyridinyl)carbamoyl]-6-methoxyphenyl]-4-[(2-methylsulfanyl-4,5-dihydroimidazol-1-yl)methyl]thiophene-2-carboxamide	1797584: Enzyme Inhibition Assay from Article 10.1021/jm070125f: “Thiophene-anthranilamides as highly potent and orally available factor xa inhibitors”	ki	<0.0001	uM
3-chloro-N-[4-chloro-2-[(5-chloro-2-pyridinyl)carbamoyl]-6-methoxyphenyl]-4-[(2-methyl-4,5-dihydroimidazol-1-yl)methyl]thiophene-2-carboxamide	1797584: Enzyme Inhibition Assay from Article 10.1021/jm070125f: “Thiophene-anthranilamides as highly potent and orally available factor xa inhibitors”	ki	<0.0001	uM
3-chloro-N-[4-chloro-2-[(5-chloro-2-pyridinyl)carbamoyl]-6-methoxyphenyl]-4-(4,5-dihydroimidazol-1-ylmethyl)thiophene-2-carboxamide	1797584: Enzyme Inhibition Assay from Article 10.1021/jm070125f: “Thiophene-anthranilamides as highly potent and orally available factor xa inhibitors”	ki	<0.0001	uM
3-chloro-N-[4-chloro-2-[(5-chloro-2-pyridinyl)carbamoyl]-6-methoxyphenyl]-4-[[ethanimidoyl(methyl)amino]methyl]thiophene-2-carboxamide	1797584: Enzyme Inhibition Assay from Article 10.1021/jm070125f: “Thiophene-anthranilamides as highly potent and orally available factor xa inhibitors”	ki	<0.0001	uM
4-[[carbamimidoyl(methyl)amino]methyl]-3-chloro-N-[4-chloro-2-[(5-chloro-2-pyridinyl)carbamoyl]-6-methoxyphenyl]thiophene-2-carboxamide	1797584: Enzyme Inhibition Assay from Article 10.1021/jm070125f: “Thiophene-anthranilamides as highly potent and orally available factor xa inhibitors”	ki	<0.0001	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression, decreases methylation, increases expression, affects methylation	4
Cyclosporine	decreases expression	3
Aflatoxin B1	affects expression, decreases expression, increases methylation	3
Contraceptives, Oral	increases activity, increases expression	2
Ethinyl Estradiol	affects binding, increases expression, affects activity, affects cotreatment	2
Snake Venoms	decreases activity, increases activity	2
Viper Venoms	increases activity, affects binding, decreases activity	2
dicrotophos	decreases expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
bisphenol A	affects expression	1
kojic acid	increases expression	1
ethyl-p-hydroxybenzoate	decreases expression	1
mangiferin	decreases activity	1
beta-lapachone	decreases expression, increases expression	1
4-chloro-1,2-diaminobenzene	affects response to substance	1
sodium arsenite	decreases expression	1
ferrous sulfate	decreases activity	1
perfluorooctanoic acid	decreases expression	1
ferric citrate	decreases activity	1
Gestodene	affects activity, affects cotreatment	1
micrurus venom	affects reaction, decreases activity, decreases reaction	1
2,3-dimethoxy-1,4-naphthoquinone	decreases expression	1
(2S)-2-(4-(((3S)-1-acetimidoyl-3-pyrrolidinyl)oxy)phenyl)-3-(7-amidino-2-naphtyl)propanoic acid	decreases activity	1
reviparin	decreases activity	1
perfluoro-n-nonanoic acid	decreases expression	1
2-palmitoylglycerol	increases expression	1
varespladib	decreases activity, decreases reaction	1
estradiol, norethindrone drug combination	decreases expression	1
2-(3-bromo-2-hydroxy-5-methylphenyl)-1H-indole-5-carboxamidine	affects binding, decreases activity	1
2-(2-hydroxybiphenyl-3-yl)-1H-indole-5-carboxamidine	affects binding, decreases activity	1

ChEMBL screening assays

795 unique, capped per target: 779 binding, 9 functional, 7 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL832226	Binding	Ki ratio of human alpha thrombin to activated factor X	In-depth study of tripeptide-based alpha-ketoheterocycles as inhibitors of thrombin. Effective utilization of the S1’ subsite and its implications to structure-based drug design. — *J Med Chem*
CHEMBL883177	Functional	Anticoagulant potency against double prothrombin time	Investigation of factor Xa inhibitors containing non-amidine S1 elements. — *Bioorg Med Chem Lett*
CHEMBL4305262	ADMET	Inhibition of factor 10a (unknown origin) using spectrozyme as substrate preincubated for 5 mins followed by substrate addition	On the Process of Discovering Leads That Target the Heparin-Binding Site of Neutrophil Elastase in the Sputum of Cystic Fibrosis Patients. — *J Med Chem*

Clinical trials (associated diseases)

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

4 trials:

NCT	Phase	Status	Title
NCT00930176	Phase 3	COMPLETED	A Study Investigating Treatment Factor X in People With Factor X Deficiency
NCT01086852	Phase 3	TERMINATED	Safety & Efficacy of BPL’s High Purity FACTOR X in Treatment of Factor X Deficient Subjects Undergoing Surgery
NCT01721681	Phase 3	COMPLETED	A Study to Investigate Bio Product Laboratory Ltd (BPL’s) Factor X in the Prophylaxis of Bleeding in Children <12 Years
NCT03655223	Not specified	ACTIVE_NOT_RECRUITING	Early Check: Expanded Screening in Newborns

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for F10 across ~30M SureChEMBL compounds — explore on Sugi Predict.