What is the human equivalent of Von Willebrand's Disease, Type 3 (Discovered in the Shetland Sheepdog; vWD 3)?

OMIA links Von Willebrand's Disease, Type 3 (Discovered in the Shetland Sheepdog; vWD 3) to its human counterpart in OMIM (OMIM 277480), the bridge to the deeper human-medicine literature for the same underlying biology.

Canine Mendelian disease record

Von Willebrand's Disease, Type 3 (Discovered in the Shetland Sheepdog; vWD 3)

Q: How well studied is Von Willebrand's Disease, Type 3 (Discovered in the Shetland Sheepdog; vWD 3) in dogs?

OMIA curates 22 peer-reviewed references for Von Willebrand's Disease, Type 3 (Discovered in the Shetland Sheepdog; vWD 3). The full, linked citation list is on this page.

Von Willebrand's Disease, Type 3 (Discovered in the Shetland Sheepdog; vWD 3). Autosomal recessive. Observed in 3 of 266 breeds tested in the Sniff Atlas, with measured carrier frequencies drawn from 242,665 dogs (Donner 2023). Per-dog phenotype outcome depends on penetrance, modifiers, and environment; the carrier frequencies below describe variant prevalence, not disease incidence.

OMIA identifier: OMIA:001058-9615
Inheritance: Autosomal recessive
Source dataset: Sniff Atlas v1.0.1 / DOI

The human connection

A model of human von Willebrand disease 3

Dogs with this condition carry a change in VWF. In people, changes in the same gene cause von Willebrand disease 3. That makes affected dogs a naturally-occurring model of the human disease, and it is part of why studying dogs moves medicine forward for everyone. It does not mean your dog has the human disease. It means the two share an underlying biology.

In people, the disease is described as: Type 3 von Willebrand disease (type 3 VWD) is the most severe form of VWD characterized by a bleeding disorder associated with a total or near-total absence of Willebrand factor (von Willebrand factor; VWF) in the plasma and cellular compartments, also leading to a profound deficiency of plasmatic factor VIII (FVIII).

In humans it is also called: VWD3, von Willebrand disease type 3, VON WILLEBRAND disease, type 3, von Willebrand's disease 3, von Willebrand's disease type 3.

MONDO:0010191 OMIM 277480

Mapped from OMIA via the human disease's OMIM entry to the Mondo Disease Ontology (Monarch Initiative, CC-BY 4.0). Sniff renders this as a model-of link; the canine disease remains the subject of this page.

About this disease

From OMIA's curated record

Documented in OMIA (Online Mendelian Inheritance in Animals). This describes the disease as recorded in the published literature, not a prediction for any individual dog. As of 2026-06-03.

Summary

The von Willebrand factor (vWF) is a large multimeric plasma glycoprotein required for platelet adhesion and aggregation. A deficiency or defective vWF results in von Willebrand disease (vWD). vWD are often classified in 3 different types based on the clinical severity and quantity and multimere size of von Willebrand factor. Type I is characterized by low plasma vWF concentrations and mild to moderate bleeding symptoms. Type II disorder is characterised by qualitative abnormalities of the vWF protein and moderate to severe bleeding. Type III is the most severe form of vWD with no detectable or a severe quantitative deficiency of vWF.

Molecular genetics

By cloning and sequencing a very likely comparative candidate gene (based on the homologous human disorder), Rieger et al. (1998) showed the molecular basis for this disorder in Dutch Kooiker dogs to be a frameshift mutation in the gene encoding von Willebrand factor. Specifically, a G>A base substition at the first position of the donor splice site sequence of intron 16 results in a transcript containing 46 bases of intron, and creates a stop codon at amino acid position 729 (omia.variant:371).
Venta et al. (2000) reported "a single base deletion in the codon for amino acid 85 of the prepro-vWF cDNA" (omia.variant:479) as a causal mutation in Scottish Terriers.
As reported by Boudreaux (2012), a causal mutation (omia.variant:968) in the Shetland Sheepdog breed was reported in US Patent 6074832 by Brewer et al. (Michigan State University) in 2000. To FN's knowledge, this discovery has not been published in the peer-reviewed literature. If anyone knows of a relevant publication, please contact FN.
Armas-Jimenez et al. (2025) "investigated the cause of type 3 VWD in a family of purebred Havanese dogs. ... [The authors] performed whole genome sequencing of the parents and relatives of two affected siblings, revealing a novel missense variant in the VWF gene. The variant causes a cysteine to glycine substitution at residue 2571 (NP_001002932.1:p.(Cys2571Gly) [omia.variant:1813]) within the VWF C4 domain."

Inheritance

Venta et al. (2000) report that type 3 von Willebrand's disease is inherited as an autosomal recessive trait in Scottish terriers. Armas-Jimenez (2025) also reported an autosomal recessive mode of inheritance for type 3 von Willebrand's disease in Havanese dogs.

Human analog

OMIA links this condition to its human counterpart in OMIM (Mendelian Inheritance in Man), the place to read across to the deeper human literature for the same biology.

Disease · OMIM 277480 Gene · OMIM 613160

Source: OMIA (Nicholas, Tammen & the Sydney Informatics Hub), entry OMIA:001058-9615, doi:10.25910/2AMR-PV70 (CC-BY 4.0).

The evidence

Published references

The peer-reviewed papers behind this disease, curated by OMIA. Starred entries are OMIA-designated landmark papers. Showing 6 of 22.

A VWF missense variant in Havanese dogs with type 3 von Willebrand disease. · Anim Genet · 2025 · PMID 40504041
Diagnosis of type III von Willebrand disease in a standard dachshund. · J Small Anim Pract · 2024 · PMID 39435623
Clinical assessment of primary hemostasis: A review. · Top Companion Anim Med · 2023 · PMID 37673175
Gene therapy for inherited bleeding disorders. · Semin Thromb Hemost · 2021 · PMID 33636747
Canine models of inherited bleeding disorders in the development of coagulation assays, novel protein replacement and gene therapies. · J Thromb Haemost · 2016 · PMID 26924758
Inherited platelet disorders. · J Vet Emerg Crit Care (San Antonio) · 2012 · PMID 22316339

References curated by OMIA (Nicholas, Tammen & the Sydney Informatics Hub), doi:10.25910/2AMR-PV70 (CC-BY 4.0). Full list at the OMIA entry.

Predict a litter

Set each parent's status for Von Willebrand's Disease, Type 3 (Discovered in the Shetland Sheepdog; vWD 3) and see the odds for their puppies. Single recessive variant, exact Mendelian math.

Parent A

Parent B

NNClear

NmCarrier

mmAffected

Clear25%

Carrier50%

Affected25%

These are the genetic odds for one known variant, not a promise: a real litter varies around them, and penetrance or other genes can change whether the condition ever appears. Use it to avoid pairing two carriers and to keep a line healthy, not to engineer a dog. Inheritance mode per OMIA.

Your breed

See what Von Willebrand's Disease, Type 3 (Discovered in the Shetland Sheepdog; vWD 3) looks like in your dog's breed.

Carrier frequency by breed

Top 3 well-sampled breeds (n ≥ 50)

Maximum carrier frequency per breed across variants in the Donner 2023 cohort, with Wilson 95% confidence intervals. The list below is split into well-sampled breeds (n ≥ 50 tested) and small-sample breeds (n < 50, where the Wilson CI typically spans more than 20 percentage points and frequencies should not be compared directly to the well-sampled entries). Frequencies are population-level, not per-litter or per-line.

0%3%5%

Scottish Terrier1.3% · n 237

1.3%n 237

Shetland Sheepdog1.1% · n 945

1.1%n 945

Chihuahua<0.1% · n 4,273

<0.1%n 4,273

n = 5,455 dogs · Donner et al. 2023 carrier-screening cohort · Sniff Atlas

Each bar is one well-sampled breed; the whisker is its Wilson 95% CI, and fainter bars have wider intervals. Frequencies are population-level, not per-litter. Carrier status for Von Willebrand's Disease, Type 3 (Discovered in the Shetland Sheepdog; vWD 3) is measured; phenotype outcome depends on penetrance and modifiers.

▸ Full table with Wilson 95% confidence intervals

Breed	Carrier frequency	Wilson 95% CI	n tested
Scottish Terrier	1.3%	[0.4%, 3.7%]	237
Shetland Sheepdog	1.1%	[0.6%, 2.0%]	945
Chihuahua	<0.1%	[0.0%, 0.1%]	4,273

263 additional breeds in the Donner 2023 cohort were tested but showed no carriers.

Scope of this record

This record carries the breed-level carrier frequencies from the Donner 2023 cohort. Penetrance data (the fraction of at-risk dogs that develop the phenotype) is not yet quantified for this disease in the Sniff Atlas v1.0.1. The OMIA entry is the authoritative reference for the clinical phenotype, inheritance pattern, and gene assignment.

Predicted disease relevance at the per-dog level is UNPROVEN. The carrier frequency is measured; phenotype outcome depends on penetrance, environment, and modifier loci. Consult a veterinarian for clinical interpretation.

How to cite this record

If you use this record in published work, cite the Sniff Atlas (the published dataset that carries the breed-level carrier frequencies) and the upstream sources:

Sniff Atlas v1.0.1 for the per-breed carrier frequencies:
Gehring, M. (2026). Sniff Atlas v1.0.1. Zenodo. https://doi.org/10.5281/zenodo.20566358. CC-BY 4.0.
OMIA for the disease definition, inheritance, and gene assignment:
Nicholas, F. W., & Tammen, I. (2024). OMIA. Sydney Informatics Hub, The University of Sydney. https://doi.org/10.25910/2AMR-PV70. Entry: OMIA:001058-9615.
Donner et al. 2023 for the breed × variant carrier-frequency cohort:
Donner, J., Freyer, J., Davison, S., Anderson, H., Blades, M., Honkanen, L., et al. (2023). Genetic prevalence and clinical relevance of canine Mendelian disease variants in over one million dogs. PLOS Genetics, 19(2), e1010651. https://doi.org/10.1371/journal.pgen.1010651.

Full citation formats (BibTeX, RIS, CITATION.cff) at sniff.world/cite.

Sniff Atlas v1.0.1, the source dataset for these frequencies.
Browse breeds, per-breed Mendelian profiles, including this disease in context.
OMIA entry OMIA:001058-9615, authoritative clinical reference.
About OMIA, the catalogue this record comes from, and how Sniff uses it.

Last updated June 20, 2026

Sources: Sniff Atlas v1.0.1 · OMIA OMIA:001058-9615 · Donner et al. 2023