Pregnancy loss, recurrent, susceptibility to, 2

Summary

Pregnancy loss, recurrent, susceptibility to, 2 (MONDO:0013728) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 11

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	pregnancy loss, recurrent, susceptibility to, 2
Mondo ID	MONDO:0013728
OMIM	614390
UMLS	C3280672
MedGen	482302
Is cancer (heuristic)	no

Also known as: F2 pregnancy loss, recurrent, susceptibility · pregnancy loss, recurrent, susceptibility caused by mutation in F2 · pregnancy loss, recurrent, susceptibility to, 2 · pregnancy loss, recurrent, susceptibility to, type 2 · RPRGL2

Data availability: 11 ClinVar variants.

Disease family

Classification path: disease susceptibility › inherited disease susceptibility › pregnancy loss, recurrent, susceptibility › pregnancy loss, recurrent, susceptibility to, 2

Related subtypes (3): pregnancy loss, recurrent, susceptibility to, 1, pregnancy loss, recurrent, susceptibility to, 3, pregnancy loss, recurrent, 4

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

11 retrieved; paginated sample, class counts are floors:

3 conflicting classifications of pathogenicity, 3 uncertain significance, 1 conflicting classifications of pathogenicity; risk factor, 1 pathogenic/likely pathogenic/pathogenic, low penetrance/established risk allele; risk factor, 1 benign, 1 pathogenic, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
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
2706763	NM_000506.5(F2):c.1499G>A (p.Arg500Gln)	F2	Pathogenic	criteria provided, multiple submitters, no conflicts
3599612	NM_000506.5(F2):c.317-1G>A	F2	Likely pathogenic	criteria provided, single submitter
13302	NM_000506.3(F2):c.598G>A (p.Glu200Lys)	F2	Conflicting classifications of pathogenicity; risk factor	criteria provided, conflicting classifications
2697011	NM_000506.5(F2):c.1542C>A (p.Asn514Lys)	F2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2868567	NM_000506.5(F2):c.316+16G>A	F2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
627262	NM_000506.5(F2):c.1814_1815del (p.His605fs)	F2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3599613	NM_000506.5(F2):c.1762G>A (p.Val588Ile)	F2	Uncertain significance	criteria provided, single submitter
3891630	NM_000506.5(F2):c.49G>T (p.Ala17Ser)	F2	Uncertain significance	criteria provided, multiple submitters, no conflicts
3891636	NM_000506.5(F2):c.706G>A (p.Ala236Thr)	F2	Uncertain significance	criteria provided, single submitter
143996	NM_000506.5(F2):c.1726-59G>A	F2	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

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

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	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: 0.