Inherited thrombophilia

Summary

Inherited thrombophilia (MONDO:0100240) is a disease (an umbrella term covering 12 Mondo subtypes) with 1 cohort gene and 1 clinical trial.

At a glance

• Umbrella term: 12 Mondo subtypes
• Cohort genes: 1
• ClinVar variants: 1
• Clinical trials: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	inherited thrombophilia
Mondo ID	MONDO:0100240
OMIM	188050
UMLS	C2584620
MedGen	391721
GARD	0026094
Is cancer (heuristic)	no

Also known as: hereditary hypercoagulable disorder · hereditary thrombophilia · thrombophilia, hereditary

Data availability: 1 ClinVar variant.

Disease family

An umbrella term covering 12 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › hematologic disorder › blood coagulation disease › thrombophilia › inherited thrombophilia

Related subtypes (3): disseminated intravascular coagulation, protein S deficiency, thrombotic thrombocytopenic purpura

Subtypes (12): factor 5 excess with spontaneous thrombosis, thrombophilia due to thrombin defect, thrombophilia due to activated protein C resistance, thrombophilia, X-linked, due to factor 9 defect, thrombophilia, familial, due to decreased release of tissue plasminogen activator, heparin cofactor 2 deficiency, hereditary thrombophilia due to congenital histidine-rich (poly-L) glycoprotein deficiency, hereditary antithrombin deficiency, thrombomodulin-related bleeding disorder, hereditary thrombophilia due to congenital protein S deficiency, hereditary thrombophilia due to congenital protein C deficiency, thrombophilia, X-linked, due to factor 8 defect

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

1 retrieved; paginated sample, class counts are floors:

1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
4282514	NM_000132.4(F8):c.1770G>T (p.Arg590Ser)	F8	Pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 4 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
F8	Orphanet:169802	Severe hemophilia A
F8	Orphanet:169805	Moderate hemophilia A
F8	Orphanet:169808	Mild hemophilia A
F8	Orphanet:177926	Bleeding disorder in hemophilia A carriers

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
F8	HGNC:3546	ENSG00000185010	P00451	Coagulation factor VIII	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
F8	Coagulation factor VIII	Factor VIII, along with calcium and phospholipid, acts as a cofactor for F9/factor IXa when it converts F10/factor X to the activated form, factor Xa.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

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
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
F8	Other/Unknown	no		FA58C, Cupredoxin, Galactose-bd-like_sf

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
heart right ventricle	1
left ventricle myocardium	1
myocardium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
F8	266	broad	marker	left ventricle myocardium, heart right ventricle, myocardium

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
F8	1,900

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
F8	P00451	25

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 16. 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
Defective F8 accelerates dissociation of the A2 domain	1	11420.0×	5e-04	F8
Defective F8 binding to the cell membrane	1	11420.0×	5e-04	F8
Defective F8 secretion	1	11420.0×	5e-04	F8
Defective F8 binding to von Willebrand factor	1	5710.0×	5e-04	F8
Defective factor IX causes thrombophilia	1	3806.7×	5e-04	F8
Defective F8 cleavage by thrombin	1	3806.7×	5e-04	F8
Defective cofactor function of FVIIIa variant	1	3806.7×	5e-04	F8
Defective F9 variant does not activate FX	1	3806.7×	5e-04	F8
Defective F8 sulfation at Y1699	1	3806.7×	5e-04	F8
Amplification and propagation of coagulation cascade	1	634.4×	0.003	F8
Initiation of coagulation cascade	1	475.8×	0.003	F8
Gamma carboxylation, hypusinylation, hydroxylation, and arylsulfatase activation	1	423.0×	0.003	F8
Cargo concentration in the ER	1	335.9×	0.004	F8
Regulation of clotting cascade	1	233.1×	0.005	F8
COPII-mediated vesicle transport	1	163.1×	0.007	F8
Platelet degranulation	1	87.8×	0.011	F8

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
blood coagulation, intrinsic pathway	1	2106.5×	0.001	F8
acute-phase response	1	421.3×	0.004	F8
blood coagulation	1	173.7×	0.006	F8

Therapeutics

Drug target analysis

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

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

Top cohort targets by molecule count

Symbol	Molecules	Max phase
F8	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
F8	8	Binding:8

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

0 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.

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
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	1	F8

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
F8	8	—

Clinical trials & evidence

Clinical trials

Clinical trials: 1.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00721591	Not specified	COMPLETED	Pharmacokinetics of Low Molecular Weight and Unfractionated Heparin in Pregnancy