Defective F8 binding to von Willebrand factor

Stable Identifier
Homo sapiens
Locations in the PathwayBrowser
SVG |   | PPTX  | SBGN
Click the image above or here to open this pathway in the Pathway Browser
Upon secretion from the cell, FVIII circulates in a tight complex with the multimeric glycoprotein von Willebrand Factor (vWF), which is essential for maintaining stable levels of FVIII in the circulation (reviewed by Pipe SW et al. 2016). Genetic mutations in the F8 gene can compromise FVIII binding to vWF thus decreasing FVIII values in the plasma causing hemophilia A (HA), an X-linked recessive bleeding disorder.
Literature References
PubMed ID Title Journal Year
15471879 Surface-exposed hemophilic mutations across the factor VIII C2 domain have variable effects on stability and binding activities

Spiegel, PC, Stoddard, BL, Murphy, P

J. Biol. Chem. 2004
12969981 Deletion of alanine 2201 in the FVIII C2 domain results in mild hemophilia A by impairing FVIII binding to VWF and phospholipids and destroys a major FVIII antigenic determinant involved in inhibitor development

d'Oiron, R, Lavend'homme, R, Lavergne, JM, Jacquemin, M, Vermylen, J, Negrier, C, Bordet, JC, Benhida, A, Saint-Remy, JM, Peerlinck, K

Blood 2004
10910910 A novel cause of mild/moderate hemophilia A: mutations scattered in the factor VIII C1 domain reduce factor VIII binding to von Willebrand factor

Saint-Remy, JM, Gilles, JG, Schwaab, R, Jacquemin, M, Peerlinck, K, Vanzieleghem, B, Benhida, A, Chuah, MK, d'Oiron, R, Lavergne, JM, Brackmann, HH, Vermylen, J, Hoylaerts, M, VandenDriessche, T, Lavend'homme, R

Blood 2000
21909383 Storage of factor VIII variants with impaired von Willebrand factor binding in Weibel-Palade bodies in endothelial cells

Voorberg, J, Bouwens, EA, van den Biggelaar, M, Mertens, K

PLoS ONE 2011
Name Identifier Synonyms
factor VIII deficiency DOID:12134 Congenital factor VIII disorder, Subhemophilia, Hemophilia A
Cite Us!