von Willebrand disease (hereditary or acquired)

Summary

von Willebrand disease (hereditary or acquired) (MONDO:0024574) is a disease with 1 cohort gene and 84 clinical trials. Top therapeutic interventions include tranexamic acid, vonicog alfa, and octocog alfa.

At a glance

• Cohort genes: 1
• ClinVar variants: 62
• Clinical trials: 84

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	von Willebrand disease (hereditary or acquired)
Mondo ID	MONDO:0024574
MeSH	D014842
ICD-10-CM	D68.0
NCIT	C68677
SNOMED CT	128105004
UMLS	C0042974
MedGen	22686
GARD	0025434
Is cancer (heuristic)	no

Also known as: Von Willebrand Disease · von Willebrand disorder · von Willebrand’s disease · VWD

Data availability: 62 ClinVar variants · 1 cell line.

Disease family

An umbrella term covering 2 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › hematologic disorder › blood coagulation disease › coagulation protein disease › von Willebrand disease (hereditary or acquired)

Related subtypes (27): factor XIII deficiency, factor VII deficiency, factor X deficiency, thrombophilia due to activated protein C resistance, hypoplasminogenemia, congenital high-molecular-weight kininogen deficiency, congenital factor XII deficiency, alpha-2-plasmin inhibitor deficiency, Tatsumi factor deficiency, East Texas bleeding disorder, inherited prekallikrein deficiency, congenital plasminogen activator inhibitor type 1 deficiency, thrombomodulin-related bleeding disorder, congenital vitamin K-dependent coagulation factors deficiency, hemorrhagic disease due to alpha-1-antitrypsin Pittsburgh mutation, multiple sclerosis-ichthyosis-factor VIII deficiency syndrome, congenital fibrinogen deficiency, combined deficiency of factor V and factor VIII, hemophilia, factor V deficiency, acquired coagulation factor deficiency, factor V short isoforms-related bleeding disorder, factor V amsterdam bleeding disorder, factor V atlanta bleeding disorder, combined deficiency of factor VII and factor X, plasminogen deficiency, type II, dysplasminogenemia

Subtypes (2): hereditary von Willebrand disease, acquired von willebrand syndrome

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

62 retrieved; paginated sample, class counts are floors:

34 pathogenic, 15 pathogenic/likely pathogenic, 9 likely pathogenic, 3 conflicting classifications of pathogenicity, 1 conflicting classifications of pathogenicity; risk factor

ClinVar	Variant (HGVS)	Gene	Classification	Review
100225	NM_000552.5(VWF):c.2516del (p.Gly839fs)	VWF	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
100264	NM_000552.5(VWF):c.3467C>T (p.Thr1156Met)	VWF	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
100267	NM_000552.5(VWF):c.3538+1G>A	VWF	Pathogenic	criteria provided, single submitter
100281	NM_000552.5(VWF):c.3802C>G (p.His1268Asp)	VWF	Pathogenic	reviewed by expert panel
100310	NM_000552.5(VWF):c.3943C>T (p.Arg1315Cys)	VWF	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
100316	NM_000552.5(VWF):c.4021C>T (p.Arg1341Trp)	VWF	Pathogenic	reviewed by expert panel
100329	NM_000552.5(VWF):c.4120C>T (p.Arg1374Cys)	VWF	Pathogenic	criteria provided, multiple submitters, no conflicts
100337	NM_000552.5(VWF):c.4195C>T (p.Arg1399Cys)	VWF	Pathogenic	reviewed by expert panel
100344	NM_000552.5(VWF):c.4247T>A (p.Ile1416Asn)	VWF	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
100347	NM_000552.5(VWF):c.4309G>A (p.Ala1437Thr)	VWF	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
100382	NM_000552.5(VWF):c.4696C>T (p.Arg1566Ter)	VWF	Pathogenic	criteria provided, single submitter
100425	NM_000552.5(VWF):c.5335C>T (p.Arg1779Ter)	VWF	Pathogenic	criteria provided, multiple submitters, no conflicts
100427	NM_000552.5(VWF):c.5380A>G (p.Lys1794Glu)	VWF	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
100442	NM_000552.5(VWF):c.6536C>T (p.Ser2179Phe)	VWF	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
100467	NM_000552.5(VWF):c.7390C>T (p.Arg2464Cys)	VWF	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
100481	NM_000552.5(VWF):c.7664_7665insAG (p.Cys2557fs)	VWF	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
100512	NM_000552.5(VWF):c.970C>T (p.Arg324Ter)	VWF	Pathogenic	reviewed by expert panel
1065296	NM_000552.5(VWF):c.311_312del (p.Gln104fs)	VWF	Pathogenic	criteria provided, multiple submitters, no conflicts
1330038	NM_000552.5(VWF):c.5455+1G>A	VWF	Pathogenic	criteria provided, multiple submitters, no conflicts
2682118	NM_000552.5(VWF):c.5207del (p.Gly1736fs)	VWF	Pathogenic	criteria provided, multiple submitters, no conflicts
284	NM_000552.5(VWF):c.4883T>C (p.Ile1628Thr)	VWF	Pathogenic	reviewed by expert panel
288	NM_000552.5(VWF):c.3916C>T (p.Arg1306Trp)	VWF	Pathogenic	reviewed by expert panel
2920929	NM_000552.5(VWF):c.4413dup (p.Asp1472fs)	VWF	Pathogenic	criteria provided, multiple submitters, no conflicts
296	NM_000552.5(VWF):c.2561G>A (p.Arg854Gln)	VWF	Pathogenic	reviewed by expert panel
298	NM_000552.5(VWF):c.5557C>T (p.Arg1853Ter)	VWF	Pathogenic	criteria provided, multiple submitters, no conflicts
299	NM_000552.5(VWF):c.7603C>T (p.Arg2535Ter)	VWF	Pathogenic	criteria provided, multiple submitters, no conflicts
303	NM_000552.5(VWF):c.2435del (p.Pro812fs)	VWF	Pathogenic	criteria provided, multiple submitters, no conflicts
3032014	NM_000552.5(VWF):c.2438dup (p.Met814fs)	VWF	Pathogenic	criteria provided, multiple submitters, no conflicts
3332526	NM_000552.5(VWF):c.1147G>T (p.Glu383Ter)	VWF	Pathogenic	criteria provided, multiple submitters, no conflicts
3375311	NC_000012.11:g.(?6058042)(6233837_?)del	VWF	Pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 6 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
VWF	Orphanet:166078	Von Willebrand disease type 1
VWF	Orphanet:166084	Von Willebrand disease type 2A
VWF	Orphanet:166087	Von Willebrand disease type 2B
VWF	Orphanet:166090	Von Willebrand disease type 2M
VWF	Orphanet:166093	Von Willebrand disease type 2N
VWF	Orphanet:166096	Von Willebrand disease type 3

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
VWF	HGNC:12726	ENSG00000110799	P04275	von Willebrand factor	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
VWF	von Willebrand factor	Important in the maintenance of hemostasis, it promotes adhesion of platelets to the sites of vascular injury by forming a molecular bridge between sub-endothelial collagen matrix and platelet-surface receptor complex GPIb-IX-V.

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)
VWF	Other/Unknown	no		VWF_dom, VWF_type-D, VWF_A

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
apex of heart	1
tendon of biceps brachii	1
urethra	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
VWF	289	broad	marker	urethra, tendon of biceps brachii, apex of heart

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
VWF	5,204

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
VWF	P04275	48

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 25. 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 binding to von Willebrand factor	1	5710.0×	0.002	VWF
Defective F8 cleavage by thrombin	1	3806.7×	0.002	VWF
Defective VWF binding to collagen type I	1	3806.7×	0.002	VWF
Enhanced cleavage of VWF variant by ADAMTS13	1	2855.0×	0.002	VWF
Defective VWF cleavage by ADAMTS13 variant	1	2855.0×	0.002	VWF
Enhanced binding of GP1BA variant to VWF multimer:collagen	1	1631.4×	0.002	VWF
Defective binding of VWF variant to GPIb:IX:V	1	1631.4×	0.002	VWF
GP1b-IX-V activation signalling	1	951.7×	0.003	VWF
p130Cas linkage to MAPK signaling for integrins	1	761.3×	0.003	VWF
GRB2:SOS provides linkage to MAPK signaling for Integrins	1	713.8×	0.003	VWF
Platelet Adhesion to exposed collagen	1	671.8×	0.003	VWF
Amplification and propagation of coagulation cascade	1	634.4×	0.003	VWF
Initiation of coagulation cascade	1	475.8×	0.004	VWF
Platelet Aggregation (Plug Formation)	1	439.2×	0.004	VWF
Integrin signaling	1	423.0×	0.004	VWF
Signaling by high-kinase activity BRAF mutants	1	317.2×	0.005	VWF
MAP2K and MAPK activation	1	285.5×	0.005	VWF
Signaling by RAF1 mutants	1	278.5×	0.005	VWF
Signaling by moderate kinase activity BRAF mutants	1	253.8×	0.005	VWF
Paradoxical activation of RAF signaling by kinase inactive BRAF	1	253.8×	0.005	VWF
Signaling downstream of RAS mutants	1	253.8×	0.005	VWF
Regulation of clotting cascade	1	233.1×	0.005	VWF
Signaling by BRAF and RAF1 fusions	1	170.4×	0.006	VWF
Integrin cell surface interactions	1	134.3×	0.008	VWF
Platelet degranulation	1	87.8×	0.011	VWF

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
hemostasis	1	1685.2×	0.004	VWF
cell-substrate adhesion	1	766.0×	0.004	VWF
positive regulation of intracellular signal transduction	1	648.1×	0.004	VWF
platelet activation	1	267.5×	0.006	VWF
response to wounding	1	221.7×	0.006	VWF
blood coagulation	1	173.7×	0.007	VWF
cell adhesion	1	37.5×	0.027	VWF

Therapeutics

Drugs indicated for this disease

3 approved, 2 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Human Coagulation Factor Viii	Approved (phase 4)
Von Willebrand Factor Human	Approved (phase 4)
Vonicog Alfa	Approved (phase 4)
Octocog Alfa	Phase 3 (in late-stage trials)
Tranexamic Acid	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Oprelvekin.

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
VWF	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
VWF	17	Binding:17

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	VWF

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)
VWF	17	—

Clinical trials & evidence

Clinical trials

Clinical trials: 84.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	49
PHASE3	18
PHASE2	7
PHASE4	4
PHASE1	3
PHASE1/PHASE2	2
PHASE2/PHASE3	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00555555	PHASE4	ACTIVE_NOT_RECRUITING	Efficacy of Alphanate FVIII/VWF Concentrate in Type 3 Von Willebrand Patients
NCT00168090	PHASE4	COMPLETED	Study of Safety and Efficacy of Antihemophilic Factor/Von Willebrand Factor Complex in Surgical Subjects With Von Willebrand Disease (vWD)
NCT02472665	PHASE4	WITHDRAWN	Efficacy and Safety of Fanhdi®, a High-purity Von Willebrand Containing FVIII Concentrate, in Pediatric Patients With Von Willebrand Disease
NCT02552576	PHASE4	COMPLETED	Study of Voncento® in Subjects With Von Willebrand Disease
NCT05582993	PHASE3	RECRUITING	A Study of Vonicog Alfa (rVWF) in Children With Severe Von Willebrand Disease (vWD)
NCT06205095	PHASE3	RECRUITING	A Pilot Crossover Trial of Prophylactic Wilate Compared to Placebo for Heavy Menstrual Bleeding in Patients with VWD
NCT07115004	PHASE3	RECRUITING	Study to Evaluate Subcutaneous (SC) VGA039 in Patients With Von Willebrand Disease (VWD)
NCT07129343	PHASE3	RECRUITING	A Study of Recombinant Von Willebrand Factor (rVWF) in Chinese Participants With Von Willebrand Disease (vWD)
NCT00387192	PHASE3	TERMINATED	A Study With OPTIVATE® in People With Von Willebrand Disease
NCT00404300	PHASE3	TERMINATED	Optivate in People With Von Willebrand Disease Undergoing Surgery
NCT00941616	PHASE2/PHASE3	COMPLETED	Study of a pd VWF/FVIII Concentrate, Biostate®, in Subjects With Von Willebrand Disease
NCT01213446	PHASE3	COMPLETED	Study of Biostate® in Children With Von Willebrand Disease
NCT01224808	PHASE3	COMPLETED	Extension Study of Biostate in Subjects With Von Willebrand Disease
NCT01410227	PHASE3	COMPLETED	Pharmacokinetics, Safety and Efficacy of Recombinant Von Willebrand Factor (rVWF) in the Treatment of Bleeding Episodes in Von Willebrand Disease (VWD)
NCT02246881	PHASE3	COMPLETED	A Study to Compare the Pharmacokinetics and Safety of Current Factor VIII Concentrate and Optivate® in Haemophilia A.
NCT02283268	PHASE3	COMPLETED	Recombinant Von Willebrand Factor in Subjects With Severe Von Willebrand Disease Undergoing Surgery
NCT02606045	PHASE3	TERMINATED	Minimize Menorrhagia in Women With Von Willebrand Disease
NCT02932618	PHASE3	COMPLETED	A Study of Recombinant Von Willebrand Factor (rVWF) With or Without ADVATE in Children With Severe Von Willebrand Disease (VWD)
NCT02973087	PHASE3	COMPLETED	rVWF IN PROPHYLAXIS
NCT03879135	PHASE3	COMPLETED	A Study of Recombinant Von Willebrand Factor (rVWF) in Pediatric and Adult Participants With Severe Von Willebrand Disease (VWD)
NCT04052698	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of Wilate During Prophylaxis in Previously Treated Patients With VWD
NCT04344860	PHASE3	COMPLETED	Prevent Postpartum Hemorrhage in Women With Von Willebrand Disease: The VWD-WOMAN Trial
NCT04953884	PHASE3	COMPLETED	Efficacy, PK, Immunogenicity and Safety of Wilate in Severe Von Willebrand Disease (VWD) Patients <6 Years of Age
NCT05776069	PHASE1/PHASE2	RECRUITING	Study of VGA039 in Healthy Volunteers and Patients With Von Willebrand Disease (VIVID)
NCT06754852	PHASE1/PHASE2	RECRUITING	A Study Assessing HMB-002 in Participants With Von Willebrand Disease
NCT07575308	PHASE2	NOT_YET_RECRUITING	HMBeacon: A Phase 2 Study to Evaluate ALN-6400 in Adult and Adolescent Female Patients With VWD and HMB
NCT00151125	PHASE2	COMPLETED	Phase II Study of IL-11 (Neumega) in Von Willebrand Disease
NCT00524225	PHASE2	TERMINATED	IL-11 in Adults With Von Willebrand Disease Undergoing Surgery
NCT00524342	PHASE2	COMPLETED	IL-11 in Women With Von Willebrand Disease and Refractory Menorrhagia
NCT00694785	PHASE2	WITHDRAWN	A Study of the Pharmacokinetics, Pharmacodynamics, and Safety of ARC1779 Injection in Patients With Von Willebrand Disease Type 2B
NCT00994929	PHASE2	COMPLETED	Efficacy and Safety of IL-11 in DDAVP Unresponsive
NCT04677803	PHASE2	COMPLETED	BT200 in Hereditary Bleeding Disorders
NCT00004667	PHASE1	COMPLETED	Phase I Study of Human Von Willebrand Factor for Von Willebrand’s Disease
NCT00816660	PHASE1	COMPLETED	Pharmacokinetic, Safety and Tolerability Study of Recombinant Von Willebrand Factor / Recombinant Factor VIII Complex in Type 3 Von Willebrand Disease
NCT04770935	PHASE1	COMPLETED	To Assess the Pharmacokinetics and Safety and Tolerability of Efanesoctocog Alfa (BIVV001)in Adults With Type 2N and 3 Von Willebrand Disease (VWD)
NCT03327779	Not specified	RECRUITING	World Bleeding Disorders Registry
NCT03773159	Not specified	RECRUITING	Development of a Device for Evaluating Primary Hemostasis Under Whole Blood Flow Conditions
NCT03853486	Not specified	ACTIVE_NOT_RECRUITING	ATHN 9: Severe VWD Natural History Study
NCT04119908	Not specified	RECRUITING	Videomicroscopy for the Prediction of Bleeding in Constitutional Haemorrhagic Diseases
NCT04146376	Not specified	RECRUITING	Von Willebrand Factor in Pregnancy (VIP) Study

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
TRANEXAMIC ACID	4	4
VONICOG ALFA	4	4
OCTOCOG ALFA	4	2
DESMOPRESSIN ACETATE	4	1
EFANESOCTOCOG ALFA	4	1
NORETHINDRONE ACETATE	4	1
OPRELVEKIN	4	1
VON WILLEBRAND FACTOR HUMAN	4	1
EGAPTIVON PEGOL	2	1
RONDAPTIVON PEGOL	2	1
CHEMBL4091490	0	1
ADENOSINE DIPHOSPHATE	0	1