VWD1
MCID: VNW005
MIFTS: 49

Von Willebrand Disease, Type 1 (VWD1)

Categories: Blood diseases, Genetic diseases, Immune diseases, Rare diseases

Aliases & Classifications for Von Willebrand Disease, Type 1

MalaCards integrated aliases for Von Willebrand Disease, Type 1:

Name: Von Willebrand Disease, Type 1 56 13 43 39 71
Von Willebrand Disease Type 1 12 58 29 6
Vwd1 56 12 73
Von Willebrand Disease Type I 12 73
Von Willebrand's Disease 1 12 15
Von Willebrand Disease, Type 1, Susceptibility to 6
Von Willebrand Factor Deficiency Type 1 73
Von Willebrand Disease, Type I 56
Von Willebrand Disease 1 73
Vwd, Type 1 56
Vwd Type 1 12

Characteristics:

Orphanet epidemiological data:

58
von willebrand disease type 1
Inheritance: Autosomal dominant; Age of onset: All ages;

OMIM:

56
Miscellaneous:
incomplete penetrance
highly variable phenotype
variably expressivity
most common inherited bleeding disorder

Inheritance:
autosomal dominant


HPO:

31
von willebrand disease, type 1:
Inheritance autosomal dominant inheritance
Onset and clinical course incomplete penetrance


Classifications:

Orphanet: 58  
Rare haematological diseases


External Ids:

Disease Ontology 12 DOID:0060573
OMIM 56 193400
MeSH 43 D056725
NCIt 49 C131685
MESH via Orphanet 44 D056725
ICD10 via Orphanet 33 D68.0
UMLS via Orphanet 72 C1264039
Orphanet 58 ORPHA166078
MedGen 41 C1264039
UMLS 71 C1264039

Summaries for Von Willebrand Disease, Type 1

OMIM : 56 Von Willebrand disease is the most common inherited bleeding disorder. It is characterized clinically by mucocutaneous bleeding, such as epistaxis and menorrhagia, and prolonged bleeding after surgery or trauma. The disorder results from a defect in platelet aggregation due to defects in the von Willebrand factor protein. Von Willebrand factor is a large, multimeric protein that plays a role in platelet adhesion and also serves as a carrier for the thrombotic protein factor VIII (F8; 300841). F8 is mutated in hemophilia A (summary by Goodeve, 2010). For a review of the various forms of von Willebrand disease, see Leebeek and Eikenboom (2016). (193400)

MalaCards based summary : Von Willebrand Disease, Type 1, also known as von willebrand disease type 1, is related to von willebrand disease, type 2 and factor xii deficiency. An important gene associated with Von Willebrand Disease, Type 1 is VWF (Von Willebrand Factor), and among its related pathways/superpathways are Response to elevated platelet cytosolic Ca2+ and ECM-receptor interaction. The drugs Tranexamic Acid and Hemostatics have been mentioned in the context of this disorder. Affiliated tissues include bone, whole blood and testes, and related phenotypes are gastrointestinal hemorrhage and gastrointestinal angiodysplasia

Disease Ontology : 12 A von Willebrand's disease characterized by quantitative partial deficiency of circulating VWF that has material basis in heterozygous mutation in the VWF gene on chromosome 12p13.

UniProtKB/Swiss-Prot : 73 von Willebrand disease 1: A common hemorrhagic disorder due to defects in von Willebrand factor protein and resulting in impaired platelet aggregation. Von Willebrand disease type 1 is characterized by partial quantitative deficiency of circulating von Willebrand factor, that is otherwise structurally and functionally normal. Clinical manifestations are mucocutaneous bleeding, such as epistaxis and menorrhagia, and prolonged bleeding after surgery or trauma.

Related Diseases for Von Willebrand Disease, Type 1

Diseases in the Von Willebrand's Disease family:

Pseudo-Von Willebrand Disease Von Willebrand Disease, Type 1
Von Willebrand Disease, Type 3 Von Willebrand Disease, Type 2
Acquired Von Willebrand Syndrome

Diseases related to Von Willebrand Disease, Type 1 via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 147)
# Related Disease Score Top Affiliating Genes
1 von willebrand disease, type 2 31.1 VWF SIGLEC5 GP1BA F8 ATAT1
2 factor xii deficiency 30.4 VWF F3
3 angiodysplasia 29.4 VWF SIGLEC5 F8 F3 ATAT1
4 hemorrhagic disease 29.1 VWF GP6 GP1BA F8 F3 F2
5 von willebrand disease, type 3 28.9 VWF SIGLEC5 GP1BA F8 ATAT1
6 von willebrand's disease 28.8 VWF STXBP5 GP6 GP1BA F8 F3
7 fainting 10.4 VWF F8
8 pediatric angiosarcoma 10.4 VWF F8
9 breast hemangioma 10.4 VWF F8
10 lymphangiosarcoma 10.4 VWF F8
11 thyroid angiosarcoma 10.3 VWF F8
12 acquired hemophilia 10.3 F8 F3
13 acquired hemophilia a 10.3 F8 F3
14 retinal vein occlusion 10.3 F3 F2
15 brachydactyly, type d 10.3 VWF F8
16 grange syndrome 10.3 VWF F3
17 gastric hemangioma 10.3 F3 F2
18 renal pelvis squamous cell carcinoma 10.3 F3 F2
19 blue toe syndrome 10.3 F3 F2
20 retinal artery occlusion 10.3 F8 F2
21 emphysematous cholecystitis 10.3 F3 F2
22 dic in newborn 10.2 F3 F2
23 hepatic infarction 10.2 F3 F2
24 giant hemangioma 10.2 F3 F2
25 femoral neuropathy 10.2 F3 F2
26 lemierre's syndrome 10.2 F3 F2
27 alpha-2-plasmin inhibitor deficiency 10.2 F8 F2
28 occlusion precerebral artery 10.2 GP6 F3
29 intracranial sinus thrombosis 10.2 F3 F2
30 cerebral sinovenous thrombosis 10.2 F3 F2
31 hemopericardium 10.2 F3 F2
32 volkmann contracture 10.2 F3 F2
33 sagittal sinus thrombosis 10.2 F3 F2
34 branch retinal artery occlusion 10.2 F3 F2
35 sneddon syndrome 10.2 F8 F2
36 intracranial hypotension 10.2 F3 F2
37 intracranial embolism 10.2 F3 F2
38 multicentric castleman disease 10.2 F8 F3
39 splenic infarction 10.2 F3 F2
40 cardiovascular cancer 10.2 VWF F8
41 hantavirus pulmonary syndrome 10.2 F3 F2
42 analbuminemia 10.2 F3 F2
43 intracranial hypertension, idiopathic 10.2 F3 F2
44 intermediate coronary syndrome 10.2 VWF F3
45 esophageal varix 10.2 F3 F2
46 spotted fever 10.2 VWF F2
47 papilledema 10.2 F3 F2
48 anuria 10.2 F3 F2
49 peripheral vertigo 10.2 F3 F2
50 tricuspid valve insufficiency 10.2 F3 F2

Graphical network of the top 20 diseases related to Von Willebrand Disease, Type 1:



Diseases related to Von Willebrand Disease, Type 1

Symptoms & Phenotypes for Von Willebrand Disease, Type 1

Human phenotypes related to Von Willebrand Disease, Type 1:

31 (show all 13)
# Description HPO Frequency HPO Source Accession
1 gastrointestinal hemorrhage 31 HP:0002239
2 gastrointestinal angiodysplasia 31 HP:0000471
3 mitral valve prolapse 31 HP:0001634
4 epistaxis 31 HP:0000421
5 bruising susceptibility 31 HP:0000978
6 prolonged bleeding time 31 HP:0003010
7 reduced factor viii activity 31 HP:0003125
8 joint hemorrhage 31 HP:0005261
9 menorrhagia 31 HP:0000132
10 aortic valve stenosis 31 HP:0001650
11 abnormality of the genitourinary system 31 HP:0000119
12 impaired platelet aggregation 31 HP:0003540
13 prolonged whole-blood clotting time 31 HP:0005542

Symptoms via clinical synopsis from OMIM:

56
Head And Neck Nose:
epistaxis

Hematology:
menorrhagia
prolonged bleeding time due to quantitative decrease of vwf protein
defect in platelet aggregation
mucocutaneous bleeding

Laboratory Abnormalities:
decreased levels of plasma vwf antigen
decreased levels of plasma factor viii

Genitourinary Internal Genitalia Female:
menorrhagia

Skin Nails Hair Skin:
easy bruisability

Clinical features from OMIM:

193400

MGI Mouse Phenotypes related to Von Willebrand Disease, Type 1:

45
# Description MGI Source Accession Score Top Affiliating Genes
1 hematopoietic system MP:0005397 9.17 ATAT1 F2 F3 F8 GP1BA GP6

Drugs & Therapeutics for Von Willebrand Disease, Type 1

Drugs for Von Willebrand Disease, Type 1 (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):


# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Tranexamic Acid Approved Phase 3 1197-18-8 5526
2 Hemostatics Phase 3
3 Coagulants Phase 3
4 Antifibrinolytic Agents Phase 3

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Prospective, Randomized, Crossover Trial Comparing Recombinant Von Willebrand Factor (rVWF) vs. Tranexamic Acid (TA) to Minimize Menorrhagia in Women With Type 1 Von Willebrand Disease: The VWD Minimize Study Recruiting NCT02606045 Phase 3 recombinant von Willebrand factor;tranexamic acid
2 Protocol for the Determination of Menstrual Losses Using a System for the Quantitative Determination of Menses (Quantitative Evaluation of Menses [QUEM] Method) and Its Application to Healthy Women With Apparently Normal Cycles Unknown status NCT01276964
3 Protocol for the Determination of Menstrual Blood Losses in Women Affected by Congenital Bleeding Disorders Unknown status NCT01261936
4 Assessing the Bleeding Severity in Type I Von Willebrand Patients Using the International Society on Thrombosis and Hemostasis Bleeding Assessment Tool ( ISTH-BAT) Questionnaire Not yet recruiting NCT03915873

Search NIH Clinical Center for Von Willebrand Disease, Type 1

Cochrane evidence based reviews: von willebrand disease, type 1

Genetic Tests for Von Willebrand Disease, Type 1

Genetic tests related to Von Willebrand Disease, Type 1:

# Genetic test Affiliating Genes
1 Von Willebrand Disease Type 1 29 VWF

Anatomical Context for Von Willebrand Disease, Type 1

MalaCards organs/tissues related to Von Willebrand Disease, Type 1:

40
Bone, Whole Blood, Testes, Endothelial, Bone Marrow, Heart, Thyroid

Publications for Von Willebrand Disease, Type 1

Articles related to Von Willebrand Disease, Type 1:

(show top 50) (show all 152)
# Title Authors PMID Year
1
The genetic basis of von Willebrand disease. 56 6
20409624 2010
2
A novel deletion mutation is recurrent in von Willebrand disease types 1 and 3. 56 6
19372260 2009
3
An investigation of the von Willebrand factor genotype in UK patients diagnosed to have type 1 von Willebrand disease. 56 6
17080221 2006
4
Inherited and de novo von Willebrand disease 'Vicenza' in UK families with the R1205H mutation: diagnostic pitfalls and new insights. 56 6
16925796 2006
5
Update on the pathophysiology and classification of von Willebrand disease: a report of the Subcommittee on von Willebrand Factor. 56 6
16889557 2006
6
An amino acid polymorphism in von Willebrand factor correlates with increased susceptibility to proteolysis by ADAMTS13. 56 6
14525793 2004
7
Founder von Willebrand factor haplotype associated with type 1 von Willebrand disease. 56 6
12649144 2003
8
The elusive pathogenesis of von Willebrand disease Vicenza. 56 6
12043692 2002
9
Reduced von Willebrand factor survival in type Vicenza von Willebrand disease. 56 6
11756169 2002
10
Von Willebrand Disease type 2M "Vicenza" in Italian and German patients: identification of the first candidate mutation (G3864A; R1205H) in 8 families. 56 6
10669167 2000
11
New families with von Willebrand disease type 2M (Vicenza). 56 6
9253800 1997
12
Dominant type 1 von Willebrand disease caused by mutated cysteine residues in the D3 domain of von Willebrand factor. 56 6
8839833 1996
13
The genetic defect of type I von Willebrand disease "Vicenza" is linked to the von Willebrand factor gene. 56 6
8456430 1993
14
Identification of two point mutations in the von Willebrand factor gene of three families with the 'Normandy' variant of von Willebrand disease. 56 6
1832934 1991
15
von Willebrand disease "Vicenza" with larger-than-normal (supranormal) von Willebrand factor multimers. 56 6
3257148 1988
16
Type 1 von Willebrand disease mutation Cys1149Arg causes intracellular retention and degradation of heterodimers: a possible general mechanism for dominant mutations of oligomeric proteins. 61 6
11698279 2001
17
Von Willebrand's Disease. 56
27959741 2016
18
Characterization of W1745C and S1783A: 2 novel mutations causing defective collagen binding in the A3 domain of von Willebrand factor. 6
19687512 2009
19
Genotype/phenotype association in von Willebrand disease: is the glass half full or empty? 56
19630771 2009
20
von Willebrand Disease 6
20301765 2009
21
The role of molecular genetics in diagnosing von Willebrand disease. 56
19085649 2008
22
The mutational spectrum of type 1 von Willebrand disease: Results from a Canadian cohort study. 56
17190853 2007
23
Phenotype and genotype of a cohort of families historically diagnosed with type 1 von Willebrand disease in the European study, Molecular and Clinical Markers for the Diagnosis and Management of Type 1 von Willebrand Disease (MCMDM-1VWD). 56
16985174 2007
24
The prevalence of the cysteine1584 variant of von Willebrand factor is increased in type 1 von Willebrand disease: co-segregation with increased susceptibility to ADAMTS13 proteolysis but not clinical phenotype. 6
15755288 2005
25
Expression of two type 2N von Willebrand disease mutations identified in exon 18 of von Willebrand factor gene. 6
15461624 2004
26
Treatment of von Willebrand's Disease. 56
15306670 2004
27
Significant linkage and non-linkage of type 1 von Willebrand disease to the von Willebrand factor gene. 56
11736956 2001
28
Type 1 von Willebrand disease - a clinical retrospective study of the diagnosis, the influence of the ABO blood group and the role of the bleeding history. 56
10691852 2000
29
Inconsistency of association between type 1 von Willebrand disease phenotype and genotype in families identified in an epidemiological investigation. 56
10494765 1999
30
Molecular genetics of von Willebrand disease. 56
10605755 1999
31
Mvwf, a dominant modifier of murine von Willebrand factor, results from altered lineage-specific expression of a glycosyltransferase. 56
9989502 1999
32
A mouse model of severe von Willebrand disease: defects in hemostasis and thrombosis. 56
9689113 1998
33
von Willebrand factor. 56
9045854 1997
34
von Willebrand disease. 56
9064484 1997
35
A novel modifier gene for plasma von Willebrand factor level maps to distal mouse chromosome 11. 56
8986815 1996
36
Linkage disequilibrium patterns vary with chromosomal location: a case study from the von Willebrand factor region. 56
7913583 1994
37
Von Willebrand's disease, digestive angiodysplasia, and estrogen-progesterone treatment. 56
8192164 1994
38
von Willebrand disease in the RIIIS/J mouse is caused by a defect outside of the von Willebrand factor gene. 56
8193357 1994
39
A revised classification of von Willebrand disease. For the Subcommittee on von Willebrand Factor of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. 56
8052974 1994
40
Mutations of von Willebrand factor gene in families with von Willebrand disease in the Aland Islands. 56
8367445 1993
41
von Willebrand disease: a database of point mutations, insertions, and deletions. For the Consortium on von Willebrand Factor Mutations and Polymorphisms, and the Subcommittee on von Willebrand Factor of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. 56
8456431 1993
42
A database of polymorphisms in the von Willebrand factor gene and pseudogene. For the Consortium on von Willebrand Factor Mutations and Polymorphisms and the Subcommittee on von Willebrand Factor of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. 56
8456432 1993
43
A single cytosine deletion in exon 18 of the von Willebrand factor gene is the most common mutation in Swedish vWD type III patients. 6
1302613 1992
44
Nonsense mutations of the von Willebrand factor gene in patients with von Willebrand disease type III and type I. 6
1415226 1992
45
Aortic stenosis and bleeding gastrointestinal angiodysplasia: is acquired von Willebrand's disease the link? 56
1351610 1992
46
Polymerase chain reaction amplification of two polymorphic simple repeat sequences within the von Willebrand factor gene: application to family studies in von Willebrand disease. 56
1587530 1992
47
The inheritance of type I and type III von Willebrand's disease in Israel: linkage analysis, carrier detection and prenatal diagnosis using three intragenic restriction fragment length polymorphisms. 56
1351407 1992
48
Identification of a new nonsense mutation in the von Willebrand factor gene in patients with von Willebrand disease type III. 6
1301136 1992
49
A patient with von Willebrand's disease characterized by a compound heterozygosity for a substitution of Arg854 by Gln in the putative factor-VIII-binding domain of von Willebrand factor (vWF) on one allele and very low levels of mRNA from the second vWF allele. 6
1581215 1992
50
Analysis of the relationship of von Willebrand disease (vWD) and hereditary hemorrhagic telangiectasia and identification of a potential type IIA vWD mutation (IIe865 to Thr). 56
1673047 1991

Variations for Von Willebrand Disease, Type 1

ClinVar genetic disease variations for Von Willebrand Disease, Type 1:

6 (show all 17) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 VWF NM_000552.4(VWF):c.4975C>T (p.Arg1659Ter)SNV Pathogenic 297 rs61750595 12:6127609-6127609 12:6018443-6018443
2 VWF NM_000552.4(VWF):c.5557C>T (p.Arg1853Ter)SNV Pathogenic 298 rs61750612 12:6122710-6122710 12:6013544-6013544
3 VWF NM_000552.4(VWF):c.3614G>A (p.Arg1205His)SNV Pathogenic 308 rs121964895 12:6131126-6131126 12:6021960-6021960
4 VWF NM_000552.4(VWF):c.3445T>C (p.Cys1149Arg)SNV Pathogenic 309 rs61748511 12:6131999-6131999 12:6022833-6022833
5 VWF VWF, 8.6-KB DEL, EX4-5deletion Pathogenic 31008
6 VWF NM_000552.4(VWF):c.2279G>A (p.Arg760His)SNV Pathogenic 31011 rs61748467 12:6155891-6155891 12:6046725-6046725
7 VWF NM_000552.4(VWF):c.2561G>A (p.Arg854Gln)SNV Pathogenic/Likely pathogenic 296 rs41276738 12:6143978-6143978 12:6034812-6034812
8 VWF NM_000552.4(VWF):c.3390C>T (p.Cys1130=)SNV Likely pathogenic 627186 12:6132054-6132054 12:6022888-6022888
9 VWF NM_000552.4(VWF):c.2060G>A (p.Cys687Tyr)SNV Likely pathogenic 627034 12:6161835-6161835 12:6052669-6052669
10 VWF NM_000552.4(VWF):c.7730-1G>TSNV Likely pathogenic 627375 12:6077334-6077334 12:5968168-5968168
11 VWF NM_000552.4(VWF):c.5520dup (p.Gly1841fs)duplication Likely pathogenic 800868 12:6122746-6122747 12:6013580-6013581
12 VWF NM_000552.4(VWF):c.1625C>G (p.Ala542Gly)SNV Conflicting interpretations of pathogenicity 381621 rs141649383 12:6167119-6167119 12:6057953-6057953
13 VWF NM_000552.4(VWF):c.1922C>T (p.Ala641Val)SNV Conflicting interpretations of pathogenicity 100196 rs61754019 12:6166046-6166046 12:6056880-6056880
14 VWF NM_000552.4(VWF):c.4751A>G (p.Tyr1584Cys)SNV Conflicting interpretations of pathogenicity 310 rs1800386 12:6127833-6127833 12:6018667-6018667
15 VWF NM_000552.4(VWF):c.6859C>T (p.Arg2287Trp)SNV Uncertain significance 100450 rs61750625 12:6094771-6094771 12:5985605-5985605
16 VWF NM_000552.4(VWF):c.7940C>T (p.Thr2647Met)SNV Uncertain significance 100487 rs61751302 12:6062708-6062708 12:5953542-5953542
17 VWF NM_000552.4(VWF):c.2570A>G (p.Asn857Ser)SNV Uncertain significance 417966 rs765163545 12:6143969-6143969 12:6034803-6034803

UniProtKB/Swiss-Prot genetic disease variations for Von Willebrand Disease, Type 1:

73
# Symbol AA change Variation ID SNP ID
1 VWF p.Arg273Trp VAR_010242 rs61753997
2 VWF p.Cys1149Arg VAR_064925 rs61748511

Expression for Von Willebrand Disease, Type 1

Search GEO for disease gene expression data for Von Willebrand Disease, Type 1.

Pathways for Von Willebrand Disease, Type 1

GO Terms for Von Willebrand Disease, Type 1

Biological processes related to Von Willebrand Disease, Type 1 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 platelet activation GO:0030168 9.65 VWF GP6 GP1BA F8 F2
2 blood coagulation GO:0007596 9.63 VWF GP6 GP1BA F8 F3 F2
3 acute-phase response GO:0006953 9.4 F8 F2
4 fibrinolysis GO:0042730 9.37 GP1BA F2
5 regulation of blood coagulation GO:0030193 9.32 GP1BA F2
6 blood coagulation, intrinsic pathway GO:0007597 9.26 VWF GP1BA F8 F2
7 hemostasis GO:0007599 9.1 VWF GP6 GP1BA F8 F3 F2

Sources for Von Willebrand Disease, Type 1

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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