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GeneBe

VWF

von Willebrand factor, the group of Receptor ligands

Basic information

Region (hg38): 12:5948876-6124770

Previous symbols: [ "F8VWF" ]

Links

ENSG00000110799 ∙ NCBI:7450 ∙ OMIM:613160 ∙ HGNC:12726 ∙ Uniprot:P04275 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

  • von Willebrand disease 2 (Definitive), mode of inheritance: AD
  • von Willebrand disease 1 (Supportive), mode of inheritance: AD
  • von Willebrand disease type 2A (Supportive), mode of inheritance: AD
  • von Willebrand disease type 2B (Supportive), mode of inheritance: AD
  • von Willebrand disease type 2M (Supportive), mode of inheritance: AD
  • von Willebrand disease type 2N (Supportive), mode of inheritance: AR
  • von Willebrand disease 3 (Supportive), mode of inheritance: AR
  • von Willebrand disease 1 (Strong), mode of inheritance: AD
  • von Willebrand disease 2 (Strong), mode of inheritance: AR
  • hereditary von Willebrand disease (Definitive), mode of inheritance: AD
  • von Willebrand disease type 2B (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
von Willebrand disease, type 1; von Willebrand disease, type 2A; von Willebrand disease, type 3ADHematologic; PharmacogenomicThere are a number of treatments depending on the subtype of disease; Treatments include control of severe bleeding episodes (eg, with IV infusion of plasma-derived clotting factor, or IV/SQ desmopressin), as well as fibrinolytic inhibitors and hormones for menorrhagia; Primary prevention can be instituted via prophylactic VWF/FVIII infusions; Among a number of important preventive measures, specific medications should be avoided, including ASA, clopidogrel, NSAIDSHematologic315519; 6972630; 6412139; 3116703; 3033024; 3257148; 3258663; 2895123; 2297569; 8456431; 8456432; 8367445; 8052974; 8839833; 9253800; 10444292; 10669167; 11756169; 12649144; 15306670; 17080221; 16889557; 16985174; 17190853; 19085649; 20409624; 22428722; 22458923; 22482515; 22531022; 22530576; 22722677; 22726101; 22823000; 22906074; 22957493; 23034827; 23109357; 23109385

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the VWF gene.

  • not provided (771 variants)
  • von Willebrand disorder (266 variants)
  • von Willebrand disease type 1 (218 variants)
  • not specified (216 variants)
  • von Willebrand disease type 2 (175 variants)
  • von Willebrand disease type 3 (122 variants)
  • Inborn genetic diseases (83 variants)
  • VWF-related condition (37 variants)
  • Abnormality of coagulation (16 variants)
  • von Willebrand disease type 1;von Willebrand disease type 3;von Willebrand disease type 2 (13 variants)
  • Thrombocytopenia (11 variants)
  • Von Willebrand disease type 2B (8 variants)
  • von Willebrand disease type 2;von Willebrand disease type 1;von Willebrand disease type 3 (7 variants)
  • Thrombocytopenia;Abnormal bleeding (5 variants)
  • Von Willebrand disease type 2A (5 variants)
  • Abnormal bleeding (4 variants)
  • von Willebrand disease type 2N (3 variants)
  • von Willebrand disease type 2M (3 variants)
  • von Willebrand disease type 3;von Willebrand disease type 1;von Willebrand disease type 2 (3 variants)
  • Reduced quantity of Von Willebrand factor;Reduced von Willebrand factor activity (2 variants)
  • Hemorrhage (2 variants)
  • Reduced von Willebrand factor activity (1 variants)
  • Thrombus (1 variants)
  • See cases (1 variants)
  • Von Willebrand disease type 2A;von Willebrand disease type 1;von Willebrand disease type 2M (1 variants)
  • Abnormal bleeding;Prolonged bleeding time (1 variants)
  • VWF-related disorders (1 variants)
  • von Willebrand disease, type 1, susceptibility to (1 variants)
  • VON WILLEBRAND FACTOR POLYMORPHISM (1 variants)
  • von Willebrand factor Vicenza (1 variants)
  • Hereditary factor VIII deficiency disease (1 variants)
  • Abnormality of blood and blood-forming tissues (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the VWF gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type Pathogenic Likely pathogenic VUS Likely benign Benign Sum
synonymous
3
clinvar
28
clinvar
76
clinvar
1
clinvar
 108
missense
30
clinvar
79
clinvar
416
clinvar
24
clinvar
1
clinvar
 550
nonsense
21
clinvar
13
clinvar
1
clinvar
 35
start loss
0
frameshift
30
clinvar
19
clinvar
1
clinvar
 50
inframe indel
1
clinvar
5
clinvar
4
clinvar
 10
splice donor/acceptor (+/-2bp)
10
clinvar
12
clinvar
3
clinvar
 25
splice region
?
    Intron variants in splice region, excluding donor/acceptor (+/-2bp)
1
29
9
2
 41
non coding
?
    UTR, intron and other, non coding variants
23
clinvar
16
clinvar
78
clinvar
 117
Total 92 131 476 116 80

Highest pathogenic variant AF is 0.0000985

Variants in VWF

This is a list of pathogenic ClinVar variants found in the VWF region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position Type Phenotype Significance ClinVar
12-5949017-A-C Uncertain significance (Nov 17, 2022)2683177
12-5949023-T-TGCAC Hereditary von Willebrand disease Uncertain significance (-)1684477
12-5949034-G-GGGGA VWF-related disorder Pathogenic (Apr 19, 2023)2628675
12-5949039-G-C Thrombocytopenia Uncertain significance (-)2572116
12-5949041-A-G Uncertain significance (Jan 04, 2023)100509
12-5949044-T-TGGGGA not provided (-)100508
12-5949046-C-T not provided (-)100507
12-5949055-G-T not provided (-)100506
12-5949056-C-T von Willebrand disease type 1 Uncertain significance (Apr 28, 2021)1098541
12-5949079-A-G not specified • VWF-related disorder Uncertain significance (Feb 22, 2024)437264
12-5949091-G-C Hereditary von Willebrand disease • not specified Uncertain significance (Jan 05, 2024)310031
12-5949091-G-T Inborn genetic diseases Uncertain significance (Nov 08, 2022)2396469
12-5949112-A-G Uncertain significance (Feb 09, 2021)1330075
12-5949116-G-A not provided (-)100505
12-5949121-G-A Inborn genetic diseases Uncertain significance (Feb 23, 2023)2465535
12-5949122-T-C Uncertain significance (Feb 18, 2021)1200719
12-5949124-C-T Uncertain significance (Jan 09, 2020)993044
12-5949125-G-A Uncertain significance (Jan 25, 2018)619762
12-5949130-G-A not provided (-)100504
12-5949131-G-A Uncertain significance (Nov 07, 2022)2501503
12-5949132-A-G Likely benign (May 31, 2023)619761
12-5949134-A-G von Willebrand disease type 3 Uncertain significance (Nov 01, 2020)1065227
12-5949139-C-G not provided (-)100503
12-5949140-A-G Von Willebrand disease type 2A Pathogenic (May 01, 2010)306
12-5949140-AG-A not provided (-)100502

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
VWFprotein_codingprotein_codingENST00000261405 51175897
pLI Probability
LOF Intolerant 		pRec Probability
LOF Recessive 		Individuals with
no LOFs 		Individuals with
Homozygous LOFs 		Individuals with
Heterozygous LOFs 		Defined p
3.22e-251.0012550102471257480.000983
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense0.99014911.60e+30.9300.00010218429
Missense in Polyphen538608.650.883926920
Synonymous-1.887286661.090.00004585440
Loss of Function5.54641330.4810.000006951590

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.001310.00130
Ashkenazi Jewish0.0004000.000397
East Asian0.002720.00272
Finnish0.0008360.000832
European (Non-Finnish)0.0009730.000959
Middle Eastern0.002720.00272
South Asian0.0009150.000915
Other0.001640.00163

dbNSFP

Source: dbNSFP

Function
FUNCTION: 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. Also acts as a chaperone for coagulation factor VIII, delivering it to the site of injury, stabilizing its heterodimeric structure and protecting it from premature clearance from plasma.;
Disease
DISEASE: von Willebrand disease 1 (VWD1) [MIM:193400]: 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. {ECO:0000269|PubMed:10887119, ECO:0000269|PubMed:11698279}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: von Willebrand disease 2 (VWD2) [MIM:613554]: A hemorrhagic disorder due to defects in von Willebrand factor protein and resulting in altered platelet aggregation. Von Willebrand disease type 2 is characterized by qualitative deficiency and functional anomalies of von Willebrand factor. It is divided in different subtypes including 2A, 2B, 2M and 2N (Normandy variant). The mutant VWF protein in types 2A, 2B and 2M are defective in their platelet-dependent function, whereas the mutant protein in type 2N is defective in its ability to bind factor VIII. Clinical manifestations are mucocutaneous bleeding, such as epistaxis and menorrhagia, and prolonged bleeding after surgery or trauma. {ECO:0000269|PubMed:12406074, ECO:0000269|PubMed:1409710, ECO:0000269|PubMed:1419803, ECO:0000269|PubMed:1419804, ECO:0000269|PubMed:1420817, ECO:0000269|PubMed:1429668, ECO:0000269|PubMed:1672694, ECO:0000269|PubMed:1673047, ECO:0000269|PubMed:1729889, ECO:0000269|PubMed:1761120, ECO:0000269|PubMed:1832934, ECO:0000269|PubMed:1906179, ECO:0000269|PubMed:2010538, ECO:0000269|PubMed:2011604, ECO:0000269|PubMed:21592258, ECO:0000269|PubMed:2786201, ECO:0000269|PubMed:7620154, ECO:0000269|PubMed:7734373, ECO:0000269|PubMed:7789955, ECO:0000269|PubMed:8011991, ECO:0000269|PubMed:8123843, ECO:0000269|PubMed:8123844, ECO:0000269|PubMed:8338947, ECO:0000269|PubMed:8348943, ECO:0000269|PubMed:8376405, ECO:0000269|PubMed:8435341, ECO:0000269|PubMed:8486782, ECO:0000269|PubMed:8547152, ECO:0000269|PubMed:8622978}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: von Willebrand disease 3 (VWD3) [MIM:277480]: A severe hemorrhagic disorder due to a total or near total absence of von Willebrand factor in the plasma and cellular compartments, also leading to a profound deficiency of plasmatic factor VIII. Bleeding usually starts in infancy and can include epistaxis, recurrent mucocutaneous bleeding, excessive bleeding after minor trauma, and hemarthroses. {ECO:0000269|PubMed:10887119, ECO:0000269|PubMed:7989040, ECO:0000269|PubMed:8088787}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway
PI3K-Akt signaling pathway - Homo sapiens (human);Complement and coagulation cascades - Homo sapiens (human);Platelet activation - Homo sapiens (human);ECM-receptor interaction - Homo sapiens (human);Focal adhesion - Homo sapiens (human);Human papillomavirus infection - Homo sapiens (human);Platelet Aggregation Inhibitor Pathway, Pharmacodynamics;Blood Clotting Cascade;Focal Adhesion;Dengue-2 Interactions with Complement and Coagulation Cascades;Dengue-2 Interactions with Blood Clotting Cascade;Focal Adhesion-PI3K-Akt-mTOR-signaling pathway;PI3K-Akt Signaling Pathway;Complement and Coagulation Cascades;MAP2K and MAPK activation;Disease;Signal Transduction;GRB2:SOS provides linkage to MAPK signaling for Integrins ;p130Cas linkage to MAPK signaling for integrins;Integrin alphaIIb beta3 signaling;GP1b-IX-V activation signalling;Platelet Adhesion to exposed collagen;Platelet Aggregation (Plug Formation);Platelet degranulation ;Response to elevated platelet cytosolic Ca2+;Platelet activation, signaling and aggregation;Intrinsic Pathway of Fibrin Clot Formation;Integrin signaling;Hemostasis;RAF/MAP kinase cascade;MAPK1/MAPK3 signaling;MAPK family signaling cascades;Formation of Fibrin Clot (Clotting Cascade);Signaling by RAS mutants;Signaling by high-kinase activity BRAF mutants;Signaling by moderate kinase activity BRAF mutants;Paradoxical activation of RAF signaling by kinase inactive BRAF;Signaling by BRAF and RAF fusions;Oncogenic MAPK signaling;Diseases of signal transduction (Consensus)

Recessive Scores

pRec
0.808

Intolerance Scores

loftool
0.0306
rvis_EVS
1.04
rvis_percentile_EVS
91.14

Haploinsufficiency Scores

pHI
0.238
hipred
Y
hipred_score
0.603
ghis
0.505

Essentials

essential_gene_CRISPR
N
essential_gene_CRISPR2
S
essential_gene_gene_trap
N
gene_indispensability_pred
E
gene_indispensability_score
0.867

Gene Damage Prediction

AllRecessiveDominant
MendelianHighHighHigh
Primary ImmunodeficiencyHighHighHigh
CancerHighHighHigh

Mouse Genome Informatics

Gene name
Vwf
Phenotype
digestive/alimentary phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); immune system phenotype; hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); homeostasis/metabolism phenotype; cellular phenotype;

Zebrafish Information Network

Gene name
vwf
Affected structure
head
Phenotype tag
abnormal
Phenotype quality
hemorrhagic

Gene ontology

Biological process
platelet degranulation;cell adhesion;blood coagulation;blood coagulation, intrinsic pathway;hemostasis;response to wounding;platelet activation;extracellular matrix organization;cell-substrate adhesion;protein homooligomerization
Cellular component
extracellular region;endoplasmic reticulum;platelet alpha granule;platelet alpha granule lumen;Weibel-Palade body;collagen-containing extracellular matrix;extracellular exosome
Molecular function
protease binding;integrin binding;extracellular matrix structural constituent;protein binding;collagen binding;immunoglobulin binding;identical protein binding;protein homodimerization activity;protein N-terminus binding;chaperone binding