Congenital prothrombin deficiency

Summary

Congenital prothrombin deficiency (MONDO:0013361) is a disease caused by F2 (GenCC Strong), with 1 cohort gene and 1 clinical trial.

At a glance

• Prevalence: <1 / 1 000 000 (Europe) [Orphanet-validated]
• Causal gene: F2 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 368
• Phenotypes (HPO): 21
• Clinical trials: 1

Clinical features

Epidemiology

Prevalence records

1 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	<1 / 1 000 000	0.05	Europe	Validated

Signs & symptoms

Clinical features (HPO)

21 HPO clinical features (Orphanet curated; top 21 by frequency):

HPO ID	Term	Frequency
HP:0003645	Prolonged partial thromboplastin time	Very frequent (80-99%)
HP:0008151	Prolonged prothrombin time	Very frequent (80-99%)
HP:0040250	Reduced prothrombin antigen	Very frequent (80-99%)
HP:0000421	Epistaxis	Frequent (30-79%)
HP:0001892	Abnormal bleeding	Frequent (30-79%)
HP:0002170	Intracranial hemorrhage	Frequent (30-79%)
HP:0005261	Joint hemorrhage	Frequent (30-79%)
HP:0000132	Menorrhagia	Occasional (5-29%)
HP:0001903	Anemia	Occasional (5-29%)
HP:0002907	Microscopic hematuria	Occasional (5-29%)
HP:0006298	Prolonged bleeding after dental extraction	Occasional (5-29%)
HP:0011884	Abnormal umbilical stump bleeding	Occasional (5-29%)
HP:0011890	Prolonged bleeding following procedure	Occasional (5-29%)
HP:0011891	Post-partum hemorrhage	Occasional (5-29%)
HP:0012233	Intramuscular hematoma	Occasional (5-29%)
HP:0012541	Cephalohematoma	Occasional (5-29%)
HP:0030137	Prolonged bleeding following circumcision	Occasional (5-29%)
HP:0030138	Excessive bleeding from superficial cuts	Occasional (5-29%)
HP:0030140	Oral cavity bleeding	Occasional (5-29%)
HP:0004420	Arterial thrombosis	Excluded (0%)
HP:0004936	Venous thrombosis	Excluded (0%)

Identifiers

Disease identifiers

Field	Value
Canonical name	congenital prothrombin deficiency
Mondo ID	MONDO:0013361
MeSH	D007020
OMIM	613679
Orphanet	325
DOID	DOID:2235
NCIT	C131737
SNOMED CT	73975000
UMLS	C0272317
MedGen	124425
GARD	0002926
Is cancer (heuristic)	no

Also known as: congenital prothrombin deficiency · Dysprothrombinemia · factor 2 deficiency · factor II deficiency · hereditary prothrombin deficiency · hypoprothrombinemia · prothrombin deficiency

Data availability: 368 ClinVar variants · 4 GenCC gene-disease records · 2 cell lines.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › autosomal genetic disease › autosomal recessive disease › congenital prothrombin deficiency

Related subtypes (218): immunodeficiency-centromeric instability-facial anomalies syndrome, hypercalcemia, infantile, Ochoa syndrome, autosomal recessive Ehlers-Danlos syndrome, vascular type, hydrolethalus syndrome, 3-M syndrome, isolated hyperchlorhidrosis, dacryocystitis-osteopoikilosis syndrome, Hutchinson-Gilford progeria syndrome, achalasia microcephaly syndrome, acrorenal syndrome, autosomal recessive, beta-ketothiolase deficiency, autosomal recessive Alport syndrome, Alstrom syndrome, microphthalmia with limb anomalies, camptodactyly-arthropathy-coxa vara-pericarditis syndrome, Behr syndrome, bifid nose, autosomal recessive, Bloom syndrome, Bowen-Conradi syndrome, camptodactyly with fibrous tissue hyperplasia and skeletal dysplasia, heart defects-limb shortening syndrome, autosomal recessive palmoplantar keratoderma and congenital alopecia, COFS syndrome, craniometaphyseal dysplasia, autosomal recessive, Fraser syndrome, cystic fibrosis, polycystic lipomembranous osteodysplasia with sclerosing leukoencephaly, persistent hyperplastic primary vitreous, autosomal recessive, Donnai-Barrow syndrome, Schöpf-Schulz-Passarge syndrome, cleft lip/palate-ectodermal dysplasia syndrome, Ellis-van Creveld syndrome, Wolcott-Rallison syndrome, autosomal recessive faciodigitogenital syndrome, acromesomelic dysplasia 2B, brittle cornea syndrome, triple-A syndrome, autosomal recessive humeroradial synostosis, multinucleated neurons-anhydramnios-renal dysplasia-cerebellar hypoplasia-hydranencephaly syndrome, hydrocephalus, nonsyndromic, autosomal recessive 1, autosomal recessive hydrocephalus due to congenital stenosis of aqueduct of Sylvius, hypertelorism, microtia, facial clefting syndrome, hypoparathyroidism-retardation-dysmorphism syndrome, Vici syndrome, Johanson-Blizzard syndrome, autosomal recessive Kenny-Caffey syndrome, Papillon-Lefevre disease, Haim-Munk syndrome, Laurence-Moon syndrome, Donohue syndrome, lipase deficiency, combined, autosomal recessive familial Mediterranean fever, thiamine-responsive megaloblastic anemia syndrome, cartilage-hair hypoplasia, Nijmegen breakage syndrome, pseudo-TORCH syndrome, Galloway-Mowat syndrome, mulibrey nanism, myotonia congenita, autosomal recessive, Schwartz-Jampel syndrome, proteosome-associated autoinflammatory syndrome, Netherton syndrome, Niemann-Pick disease type A, oculodentodigital dysplasia, autosomal recessive, odonto-onycho-dermal dysplasia, autosomal recessive omodysplasia, osteoporosis-pseudoglioma syndrome, Shwachman-Diamond syndrome, phenylketonuria, Bjornstad syndrome, Laron syndrome, autosomal recessive polycystic kidney disease, autosomal recessive inherited pseudoxanthoma elasticum, autosomal recessive multiple pterygium syndrome, rapadilino syndrome, short-rib thoracic dysplasia 9 with or without polydactyly, autosomal recessive Robinow syndrome, Sjogren-Larsson syndrome, scapuloperoneal spinal muscular atrophy, autosomal recessive, spondyloepiphyseal dysplasia tarda, autosomal recessive, inherited threoninemia, Pendred syndrome, autosomal recessive spondylocostal dysostosis, Werner syndrome, ABCD syndrome, Naxos disease, autosomal recessive amelia, human HOXA1 syndromes, sickle cell disease, autosomal recessive proximal renal tubular acidosis, hyper-IgM syndrome type 2, temtamy preaxial brachydactyly syndrome, TH-deficient dopa-responsive dystonia, craniosynostosis syndrome, autosomal recessive, Niemann-Pick disease type B, skin fragility-woolly hair-palmoplantar keratoderma syndrome, CoQ-responsive OXPHOS deficiency, familial adenomatous polyposis 2, Pierson syndrome, palmoplantar keratoderma-XX sex reversal-predisposition to squamous cell carcinoma syndrome, cardiomyopathy-hypotonia-lactic acidosis syndrome, PHARC syndrome, Kahrizi syndrome, cutis laxa with severe pulmonary, gastrointestinal and urinary anomalies, immunodeficiency 31B, dyskeratosis congenita, autosomal recessive 2, dyskeratosis congenita, autosomal recessive 3, Nestor-Guillermo progeria syndrome, leukoencephalopathy with calcifications and cysts, mitochondrial pyruvate carrier deficiency, branched-chain keto acid dehydrogenase kinase deficiency, dyskeratosis congenita, autosomal recessive 5, hypohidrosis-enamel hypoplasia-palmoplantar keratoderma-intellectual disability syndrome, alacrima, achalasia, and intellectual disability syndrome, hyperlipoproteinemia, type 1D, microcephaly and chorioretinopathy 2, congenital stationary night blindness 1G, combined oxidative phosphorylation deficiency 29, hypermanganesemia with dystonia 2, growth retardation, intellectual developmental disorder, hypotonia, and hepatopathy, gnb5-related intellectual disability-cardiac arrhythmia syndrome, autosomal recessive spastic paraplegia type 78, autosomal recessive limb-girdle muscular dystrophy, Bardet-Biedl syndrome, autosomal recessive cerebellar ataxia, neuronopathy, distal hereditary motor, autosomal recessive, UV-sensitive syndrome, Ehlers-Danlos syndrome, kyphoscoliotic type 1, Cockayne syndrome, hyperphenylalaninemia due to tetrahydrobiopterin deficiency, leukoencephalopathy-palmoplantar keratoderma syndrome, autosomal recessive hypohidrotic ectodermal dysplasia, Warburg micro syndrome, autosomal recessive primary microcephaly, autosomal recessive progressive external ophthalmoplegia, Meier-Gorlin syndrome, autosomal recessive sideroblastic anemia, autosomal recessive intermediate Charcot-Marie-Tooth disease, Perrault syndrome, autosomal recessive hypophosphatemic rickets, de Barsy syndrome, leukocyte adhesion deficiency, Senior-Loken syndrome, autosomal recessive spastic ataxia, childhood-onset autosomal recessive myopathy with external ophthalmoplegia, autosomal recessive cerebral atrophy, GM3 synthase deficiency, autosomal recessive distal renal tubular acidosis, pigmentation defects-palmoplantar keratoderma-skin carcinoma syndrome, autosomal recessive brachyolmia, Aicardi-Goutieres syndrome, homocystinuria without methylmalonic aciduria, Niemann-Pick disease type C, nephronophthisis, autosomal recessive osteopetrosis, peroxisome biogenesis disorder, congenital non-bullous ichthyosiform erythroderma, Seckel syndrome, Usher syndrome, autosomal recessive cutis laxa type 1, autosomal recessive cutis laxa type 2, hearing loss, autosomal recessive, microcephaly, growth restriction, and increased sister chromatid exchange 2, encephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathy, 1, congenital vertebral-cardiac-renal anomalies syndrome, hair defect with photosensitivity and intellectual disability syndrome, autosomal recessive severe congenital neutropenia, severe combined immunodeficiency due to CARMIL2 deficiency, extraoral halitosis due to methanethiol oxidase deficiency, neurodevelopmental disorder with microcephaly, impaired language, epilepsy, and gait abnormalities, mitochondrial complex 2 deficiency, nuclear type 3, mitochondrial complex 2 deficiency, nuclear type 4, mismatch repair cancer syndrome, spondyloepimetaphyseal dysplasia with joint laxity, type 3, Kilquist syndrome, Duane anomaly-myopathy-scoliosis syndrome, autosomal recessive axonal charcot-marie-tooth disease due to copper metabolism defect, immune dysregulation-inflammatory bowel disease-arthritis-recurrent infections-lymphopenia syndrome, optic atrophy-ataxia-peripheral neuropathy-global developmental delay syndrome, congenital myopathy with reduced type 2 muscle fibers, NAD(P)HX dehydratase deficiency, autosomal recessive ocular albinism, ichthyosis linearis circumflexa, eosinophil peroxidase deficiency, hyperphenylalaninemia due to DNAJC12 deficiency, autosomal recessive epidermolytic ichthyosis, Ehlers-Danlos syndrome, classic-like, 2, joint laxity, short stature, and myopia, HELIX syndrome, auditory neuropathy-optic atrophy syndrome, glycosylphosphatidylinositol biosynthesis defect 15, neurodegeneration, childhood-onset, stress-induced, with variable ataxia and seizures, SCN4A-related myopathy, autosomal recessive, Uner Tan Syndrome, nephropathic cystinosis, Imerslund-Grasbeck syndrome type 1, Imerslund-Grasbeck syndrome type 2, permanent neonatal diabetes mellitus 1, growth hormone insensitivity with immune dysregulation 1, autosomal recessive, Rajab interstitial lung disease with brain calcifications 1, Roberts-SC phocomelia syndrome, neurodevelopmental disorder with microcephaly, impaired language, and gait abnormalities, RPE65-related recessive retinopathy, GUCY2D-related recessive retinopathy, autosomal recessive titinopathy, intellectual disability, autosomal recessive, ALPL-related autosomal recessive hypophosphatasia, spastic paraplegia 18b, autosomal recessive, CEP164-related ciliopathy, RP1-related recessive retinopathy, pseudohypoaldosteronism, type IB2, autosomal recessive, pseudohypoaldosteronism, type IB3, autosomal recessive, spastic paraplegia 30B, autosomal recessive, cerebral arteriopathy, autosomal recessive, with subcortical infarcts and leukoencephalopathy 1, brain small vessel disease 2B, autosomal recessive, IMPG1-related recessive retinopathy, PROM1-related recessive retinopathy

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

368 retrieved; paginated sample, class counts are floors:

238 likely benign, 53 uncertain significance, 27 conflicting classifications of pathogenicity, 19 pathogenic, 13 likely pathogenic, 7 benign/likely benign, 6 benign, 3 pathogenic/likely pathogenic, 1 conflicting classifications of pathogenicity; risk factor, 1 pathogenic/likely pathogenic/pathogenic, low penetrance/established risk allele; risk factor

ClinVar	Variant (HGVS)	Gene	Classification	Review
1324366	NM_000506.5(F2):c.1159C>T (p.Gln387Ter)	F2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
13303	NM_000506.3(F2):c.940C>T (p.Arg314Cys)	F2	Pathogenic	criteria provided, single submitter
13304	NM_000506.3(F2):c.1381C>T (p.Arg461Trp)	F2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
13306	NM_000506.3(F2):c.1802G>T (p.Gly601Val)	F2	Pathogenic	no assertion criteria provided
13307	NM_000506.3(F2):c.1139T>C (p.Met380Thr)	F2	Pathogenic	no assertion criteria provided
13309	NM_000506.5(F2):c.462_463insT (p.Asn155Ter)	F2	Pathogenic	no assertion criteria provided
13310	NM_000506.5(F2):c.*97G>A	F2	Pathogenic/Likely pathogenic/Pathogenic, low penetrance/Established risk allele; risk factor	criteria provided, multiple submitters, no conflicts
13311	NM_000506.3(F2):c.1027G>A (p.Glu343Lys)	F2	Pathogenic	no assertion criteria provided
13312	NM_000506.3(F2):c.1054G>A (p.Glu352Lys)	F2	Pathogenic	no assertion criteria provided
13313	NM_000506.5(F2):c.1274G>A (p.Arg425His)	F2	Pathogenic	no assertion criteria provided
13314	NM_000506.3(F2):c.1785C>G (p.Asp595Glu)	F2	Pathogenic	no assertion criteria provided
2706763	NM_000506.5(F2):c.1499G>A (p.Arg500Gln)	F2	Pathogenic	criteria provided, multiple submitters, no conflicts
2735585	NM_000506.5(F2):c.1015C>T (p.Arg339Ter)	F2	Pathogenic	criteria provided, single submitter
2735586	NM_000506.5(F2):c.1786C>T (p.Arg596Trp)	F2	Pathogenic	criteria provided, single submitter
2806215	NM_000506.5(F2):c.13C>T (p.Arg5Ter)	F2	Pathogenic	criteria provided, single submitter
2872207	NM_000506.5(F2):c.923_926del (p.Asp308fs)	F2	Pathogenic	criteria provided, single submitter
2884504	NM_000506.5(F2):c.392dup (p.Trp132fs)	F2	Pathogenic	criteria provided, single submitter
2957927	NM_000506.5(F2):c.349C>T (p.Arg117Ter)	F2	Pathogenic	criteria provided, single submitter
2966946	NM_000506.5(F2):c.954dup (p.Glu319Ter)	F2	Pathogenic	criteria provided, single submitter
3015914	NM_000506.5(F2):c.1678C>T (p.Arg560Ter)	F2	Pathogenic	criteria provided, single submitter
3721020	NM_000506.5(F2):c.1741C>T (p.Arg581Cys)	F2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
4686696	NM_000506.5(F2):c.552del (p.Val185fs)	F2	Pathogenic	criteria provided, single submitter
692073	NM_000506.5(F2):c.1787G>A (p.Arg596Gln)	F2	Pathogenic	criteria provided, multiple submitters, no conflicts
1098519	NM_000506.5(F2):c.995G>C (p.Gly332Ala)	F2	Likely pathogenic	criteria provided, single submitter
1098520	NM_000506.5(F2):c.1070A>G (p.Glu357Gly)	F2	Likely pathogenic	criteria provided, single submitter
1098522	NM_000506.5(F2):c.1270G>A (p.Val424Met)	F2	Likely pathogenic	criteria provided, single submitter
1098523	NM_000506.5(F2):c.1496G>A (p.Gly499Glu)	F2	Likely pathogenic	criteria provided, single submitter
13305	NM_000506.3(F2):c.1273C>T (p.Arg425Cys)	F2	Likely pathogenic	criteria provided, single submitter
1684489	NM_000506.5(F2):c.1094T>A (p.Val365Glu)	F2	Likely pathogenic	no assertion criteria provided
2735584	NM_000506.5(F2):c.422+1G>A	F2	Likely pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 8 · Orphanet: 2 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
F2	Strong	Autosomal recessive	congenital prothrombin deficiency	8

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
F2	Orphanet:325	Congenital factor II deficiency
F2	Orphanet:329217	Cerebral sinovenous thrombosis

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
F2	HGNC:3535	ENSG00000180210	P00734	Prothrombin	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
F2	Prothrombin	Thrombin, which cleaves bonds after Arg and Lys, converts fibrinogen to fibrin and activates factors V, VII, VIII, XIII, and, in complex with thrombomodulin, protein C.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Protease	1	36.6×	0.027

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
F2	Protease	yes	3.4.21.5	Kringle, GLA_domain, Trypsin_dom

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
liver	1
male germ line stem cell (sensu Vertebrata) in testis	1
right lobe of liver	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
F2	117	tissue_specific	marker	right lobe of liver, liver, male germ line stem cell (sensu Vertebrata) in testis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
F2	2,709

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
F2	P00734	475

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 38. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Gamma-carboxylation, transport, and amino-terminal cleavage of proteins	1	11420.0×	0.002	F2
Defective factor VIII causes hemophilia A	1	11420.0×	0.002	F2
R-HSA-9651496	1	3806.7×	0.002	F2
Defective F8 cleavage by thrombin	1	3806.7×	0.002	F2
R-HSA-140875	1	2855.0×	0.002	F2
Defective factor XII causes hereditary angioedema	1	2855.0×	0.002	F2
Diseases of hemostasis	1	2855.0×	0.002	F2
R-HSA-140837	1	1427.5×	0.003	F2
Transport of gamma-carboxylated protein precursors from the endoplasmic reticulum to the Golgi apparatus	1	1268.9×	0.003	F2
Gamma-carboxylation of protein precursors	1	1142.0×	0.003	F2
Removal of aminoterminal propeptides from gamma-carboxylated proteins	1	1142.0×	0.003	F2
R-HSA-140877	1	951.7×	0.003	F2
Fibrin formation	1	878.5×	0.003	F2
Complement cascade	1	634.4×	0.004	F2
Amplification and propagation of coagulation cascade	1	634.4×	0.004	F2
Initiation of coagulation cascade	1	475.8×	0.005	F2
Platelet Aggregation (Plug Formation)	1	439.2×	0.005	F2
Gamma carboxylation, hypusinylation, hydroxylation, and arylsulfatase activation	1	423.0×	0.005	F2
Thrombin signalling through proteinase activated receptors (PARs)	1	356.9×	0.006	F2
Regulation of clotting cascade	1	233.1×	0.008	F2
Regulation of Complement cascade	1	233.1×	0.008	F2
Platelet activation, signaling and aggregation	1	105.7×	0.016	F2
Cell surface interactions at the vascular wall	1	95.2×	0.017	F2
Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)	1	86.5×	0.018	F2
Class A/1 (Rhodopsin-like receptors)	1	74.2×	0.020	F2
Peptide ligand-binding receptors	1	74.2×	0.020	F2
GPCR ligand binding	1	64.2×	0.022	F2
G alpha (q) signalling events	1	57.4×	0.024	F2
Dengue Virus-Host Interactions	1	45.7×	0.029	F2
GPCR downstream signalling	1	43.4×	0.029	F2

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
neutrophil-mediated killing of gram-negative bacterium	1	3370.4×	0.002	F2
thrombin-activated receptor signaling pathway	1	2407.4×	0.002	F2
positive regulation of phospholipase C-activating G protein-coupled receptor signaling pathway	1	2407.4×	0.002	F2
obsolete cytolysis by host of symbiont cells	1	2106.5×	0.002	F2
negative regulation of platelet activation	1	1872.4×	0.002	F2
regulation of blood coagulation	1	1872.4×	0.002	F2
ligand-gated ion channel signaling pathway	1	1872.4×	0.002	F2
blood coagulation, fibrin clot formation	1	1685.2×	0.002	F2
negative regulation of astrocyte differentiation	1	1532.0×	0.002	F2
negative regulation of fibrinolysis	1	1404.3×	0.002	F2
negative regulation of blood coagulation	1	1203.7×	0.002	F2
positive regulation of blood coagulation	1	1123.5×	0.002	F2
fibrinolysis	1	842.6×	0.003	F2
negative regulation of proteolysis	1	674.1×	0.003	F2
positive regulation of collagen biosynthetic process	1	648.1×	0.003	F2
positive regulation of reactive oxygen species metabolic process	1	510.7×	0.004	F2
positive regulation of release of sequestered calcium ion into cytosol	1	495.6×	0.004	F2
positive regulation of receptor signaling pathway via JAK-STAT	1	432.1×	0.004	F2
acute-phase response	1	421.3×	0.004	F2
negative regulation of cytokine production involved in inflammatory response	1	421.3×	0.004	F2
positive regulation of protein localization to nucleus	1	391.9×	0.004	F2
regulation of cytosolic calcium ion concentration	1	383.0×	0.004	F2
platelet activation	1	267.5×	0.005	F2
positive regulation of insulin secretion	1	255.3×	0.005	F2
response to wounding	1	221.7×	0.006	F2
positive regulation of cell growth	1	183.2×	0.007	F2
blood coagulation	1	173.7×	0.007	F2
antimicrobial humoral immune response mediated by antimicrobial peptide	1	162.0×	0.007	F2
regulation of cell shape	1	123.0×	0.009	F2
positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	1	78.4×	0.014	F2

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 0

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
F2	INDIGOTINDISULFONATE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
F2	48	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
INDIGOTINDISULFONATE	4	F2
ARGATROBAN	4	F2
BENZOYL PEROXIDE	4	F2
SUCCIMER	4	F2
EDOXABAN	4	F2
METHYLPREDNISOLONE ACETATE	4	F2
LIOTHYRONINE	4	F2
CAPTOPRIL	4	F2
RIVAROXABAN	4	F2
TELOTRISTAT	4	F2
LUSUTROMBOPAG	4	F2
APIXABAN	4	F2
HEXAMIDINE	4	F2
MELAGATRAN	4	F2
CIANIDANOL	4	F2
BORTEZOMIB	4	F2
DEQUALINIUM	4	F2
SULFAGUANIDINE	4	F2
BETRIXABAN	4	F2
XIMELAGATRAN	4	F2
BIVALIRUDIN	4	F2
DABIGATRAN ETEXILATE	4	F2
PENTAMIDINE	4	F2
GENTIAN VIOLET	4	F2
NAFAMOSTAT	3	F2
MILVEXIAN	3	F2
DABIGATRAN	3	F2
QUERCETIN	3	F2
CAMOSTAT	3	F2
CAMOSTAT MESILATE	3	F2

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
F2	1,269	Binding:1216, Functional:38, ADMET:13, Toxicity:2

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
F2	3.4.21.5	thrombin

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
F2	1,269

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

30 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Compound	Max phase	Cohort target (bioactivity)
INDIGOTINDISULFONATE	4	F2
ARGATROBAN	4	F2
BENZOYL PEROXIDE	4	F2
SUCCIMER	4	F2
EDOXABAN	4	F2
METHYLPREDNISOLONE ACETATE	4	F2
LIOTHYRONINE	4	F2
CAPTOPRIL	4	F2
RIVAROXABAN	4	F2
TELOTRISTAT	4	F2
LUSUTROMBOPAG	4	F2
APIXABAN	4	F2
HEXAMIDINE	4	F2
MELAGATRAN	4	F2
CIANIDANOL	4	F2
BORTEZOMIB	4	F2
DEQUALINIUM	4	F2
SULFAGUANIDINE	4	F2
BETRIXABAN	4	F2
XIMELAGATRAN	4	F2
BIVALIRUDIN	4	F2
DABIGATRAN ETEXILATE	4	F2
PENTAMIDINE	4	F2
GENTIAN VIOLET	4	F2
NAFAMOSTAT	3	F2
MILVEXIAN	3	F2
DABIGATRAN	3	F2
QUERCETIN	3	F2
CAMOSTAT	3	F2
CAMOSTAT MESILATE	3	F2

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	F2
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

0 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Clinical trials & evidence

Clinical trials

Clinical trials: 1.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE1/PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT02267408	PHASE1/PHASE2	TERMINATED	Randomized Controlled Feasibility Trial of the Fearon Algorithm to Improve Management of Unstable Warfarin