von Willebrand disease type 2B

Summary

von Willebrand disease type 2B (MONDO:0015629) is a disease with 1 cohort gene and 2 clinical trials. Top therapeutic interventions include egaptivon pegol.

At a glance

• Prevalence: Unknown (Worldwide)
• Cohort genes: 1
• ClinVar variants: 18
• Clinical trials: 2

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	von Willebrand disease type 2B
Mondo ID	MONDO:0015629
Orphanet	166087
ICD-11	1383884415
NCIT	C131687
SNOMED CT	359717002, 359721009
UMLS	C1282971
MedGen	224831
GARD	0017022
Is cancer (heuristic)	no

Also known as: von Willebrand disease type 2B · von Willebrand disease, type 2B

Data availability: 18 ClinVar variants · 14 ClinGen variant curations · 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by body system or component › hematologic disorder › hemorrhagic disease › hereditary von Willebrand disease › von Willebrand disease 2 › von Willebrand disease type 2B

Related subtypes (3): von Willebrand disease type 2A, von Willebrand disease type 2M, von Willebrand disease type 2N

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

18 retrieved; paginated sample, class counts are floors:

10 pathogenic, 5 likely pathogenic, 2 conflicting classifications of pathogenicity, 1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
100281	NM_000552.5(VWF):c.3802C>G (p.His1268Asp)	VWF	Pathogenic	reviewed by expert panel
100305	NM_000552.5(VWF):c.3925A>G (p.Ile1309Val)	VWF	Pathogenic	reviewed by expert panel
100308	NM_000552.5(VWF):c.3940G>T (p.Val1314Phe)	VWF	Pathogenic	reviewed by expert panel
100309	NM_000552.5(VWF):c.3941T>A (p.Val1314Asp)	VWF	Pathogenic	reviewed by expert panel
100316	NM_000552.5(VWF):c.4021C>T (p.Arg1341Trp)	VWF	Pathogenic	reviewed by expert panel
288	NM_000552.5(VWF):c.3916C>T (p.Arg1306Trp)	VWF	Pathogenic	reviewed by expert panel
289	NM_000552.5(VWF):c.3922C>T (p.Arg1308Cys)	VWF	Pathogenic	reviewed by expert panel
290	NM_000552.5(VWF):c.3946G>A (p.Val1316Met)	VWF	Pathogenic	reviewed by expert panel
291	NM_000552.5(VWF):c.4022G>A (p.Arg1341Gln)	VWF	Pathogenic	reviewed by expert panel
302	NM_000552.5(VWF):c.3940G>C (p.Val1314Leu)	VWF	Pathogenic	reviewed by expert panel
100306	NM_000552.5(VWF):c.3929C>T (p.Ser1310Phe)	VWF	Likely pathogenic	reviewed by expert panel
100314	NM_000552.5(VWF):c.4010C>T (p.Pro1337Leu)	VWF	Likely pathogenic	reviewed by expert panel
1684483	NM_000552.5(VWF):c.3926T>A (p.Ile1309Asn)	VWF	Likely pathogenic	reviewed by expert panel
1803174	NM_000552.5(VWF):c.573G>C (p.Trp191Cys)	VWF	Likely pathogenic	criteria provided, single submitter
287	NM_000552.5(VWF):c.3939G>C (p.Trp1313Cys)	VWF	Likely pathogenic	reviewed by expert panel
1695346	NM_000552.5(VWF):c.7987C>T (p.Arg2663Cys)	VWF	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1695355	NM_000552.5(VWF):c.3845T>C (p.Leu1282Pro)	VWF	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
314	NM_000552.5(VWF):c.3797C>T (p.Pro1266Leu)	VWF	Likely benign	reviewed by expert panel

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 13 · Orphanet: 6 · 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
VWF	Definitive	Autosomal dominant	von Willebrand disease 2	13

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	gencc,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

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: 2.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE2	1
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00632242	PHASE2	COMPLETED	ARC1779 Injection in Patients With Von Willebrand Factor-Related Platelet Function Disorders
NCT05015244	Not specified	UNKNOWN	Impact of Von Willebrand Factor-platelet Aggregates in Patients With Type 2B Disease

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
EGAPTIVON PEGOL	2	1