OMIA:000361-9615 : Factor VII deficiency in Canis lupus familiaris (dog)

In other species: Asiatic elephant

Categories: Haematopoietic system phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 227500 (trait) , 613878 (gene)

Links to relevant human diseases in MONDO:

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal recessive

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2005

Cross-species summary: Bleeding disorder due to deficiency of factor VII, a vitamin K–dependent glycoprotein

Molecular basis: By cloning and sequencing a very likely comparative candidate gene (based on the homologous human disorder), Callan et al. (2005, 2006) were the first to report a molecular basis for this disorder in dogs, as follows: "a G to A missense mutation in exon 5 in the affected Beagles, resulting in substitution of glycine 96 (GGA) to glutamic acid (GAA) in the second epidermal growth factor-like domain." The same variant (OMIAvariantID:40) was later later reported in several additional breeds (e.g., Kaae et al., 2007; Donner et al., 2016; Thorsrud and Huson, 2021). For some of these breeds affected dogs were reported to be homozygous for the variant. Scottish deerhounds have been reported with Factor VII deficiency (Keeshen et al. 2017), but Court et al. (2023) report that in their study of Scottish deerhounds with delayed postoperative hemorrhage (DEPOH) the F7 c.407 G>A variant was not associated with DEPOH". A missense SERPINF2 variant was associated with DEPOH in their study (see OMIA:002631-9615 : Delayed postoperative hemorrhage in Canis lupus familiaris).

Clinical features: Ramirez et al. (2019) report that the disease results in mild to moderate bleeding propensity, but in most cases it is identified by chance when regular coagulation screenings result in extended prothrombin times (PT). Kaae et al. (2008) report that clinical presentation includes subcutaneous hematoma formation, blood loss anemia, and a history of abnormal bleeding. IT thanks DVM student Rami Mazraani, who provided the basis of this contribution in May 2023.

Prevalence: Clark et al. (2022) genotyped "67 anticoagulant-negative autopsy cases with unexplained etiology for gross lesions of hemorrhage" for the c.407G>A variant (OMIA variant id 40), and reported that "All 67 cases tested homozygous for the wild-type allele, indicating that the common FVIID variant was not responsible for the observed unexplained bleeding."

Genetic testing: Ramirez et al. (2019) "identified 2 polymorphisms near the disease-causing F7 gene mutation, one of which interfered with testing in several Beagles by causing allele dropout of the normal, wild-type allele. In the absence of an external proficiency program among veterinary genetic testing laboratories, implementation of an internal proficiency program, which requires 2 independent methods for genotyping dogs at any given locus, was further enhanced by ensuring minimally non-overlapping primer pairs between the 2 assays. After redesign of our clinical tests, all dogs were re-examined, and the correct genotypes were identified. These changes ensure higher accuracy in future testing of the F7 mutation."

Breeds: Airedale Terrier (Dog) (VBO_0200008), Alaskan Klee Kai (Dog) (VBO_0200016), Alaskan Malamute (Dog) (VBO_0200017), American Foxhound (Dog) (VBO_0200047), Beagle (Dog) (VBO_0200131), Finnish Hound (Dog) (VBO_0200522), German Wirehaired Pointer (Dog) (VBO_0200602), Giant Schnauzer (Dog) (VBO_0200604), Irish Water Spaniel (Dog) (VBO_0200705), Japanese Spitz (Dog) (VBO_0200740), Miniature Schnauzer (Dog) (VBO_0200896), Mixed Breed (Dog) (VBO_0200902), obsolete Alaskan Sled Dog (Dog) (VBO_0200019), Papillon (Dog) (VBO_0200985), Scottish Deerhound (Dog) (VBO_0201195), Sealyham Terrier (Dog) (VBO_0201200), Welsh Springer Spaniel (Dog) (VBO_0201411).
Breeds in which the phene has been documented. (If a likely causal variant has been documented for the phene, see the variant table breeds in which the variant has been reported).

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
F7 coagulation factor VII (serum prothrombin conversion accelerator) Canis lupus familiaris 22 NC_051826.1 (61197920..61208435) F7 Homologene, Ensembl , NCBI gene


By default, variants are sorted chronologically by year of publication, to provide a historical perspective. Readers can re-sort on any column by clicking on the column header. Click it again to sort in a descending order. To create a multiple-field sort, hold down Shift while clicking on the second, third etc relevant column headers.

WARNING! Inclusion of a variant in this table does not automatically mean that it should be used for DNA testing. Anyone contemplating the use of any of these variants for DNA testing should examine critically the relevant evidence (especially in breeds other than the breed in which the variant was first described). If it is decided to proceed, the location and orientation of the variant sequence should be checked very carefully.

Since October 2021, OMIA includes a semiautomated lift-over pipeline to facilitate updates of genomic positions to a recent reference genome position. These changes to genomic positions are not always reflected in the ‘acknowledgements’ or ‘verbal description’ fields in this table.

OMIA Variant ID Breed(s) Variant Phenotype Gene Allele Type of Variant Source of Genetic Variant Reference Sequence Chr. g. or m. c. or n. p. Verbal Description EVA ID Year Published PubMed ID(s) Acknowledgements
40 Airedale Terrier (Dog) Alaskan Klee Kai (Dog) American Foxhound (Dog) Beagle (Dog) Finnish Hound (Dog) German Wirehaired Pointer (Dog) Giant Schnauzer (Dog) Irish Water Spaniel (Dog) Japanese Spitz (Dog) Miniature Schnauzer (Dog) obsolete Alaskan Sled Dog (Dog) Papillon (Dog) Scottish Deerhound (Dog) Sealyham Terrier (Dog) Welsh Springer Spaniel (Dog) Factor VII deficiency F7 missense Naturally occurring variant CanFam3.1 22 g.60578895G>A c.407G>A p.(G136E) 2006 16961583 Variant coordinates obtained from or confirmed by EBI's Some Effect Predictor (VEP) tool; variant initially identified in Beagle and later reported in additional breeds: PMID:17939552; PMID: 27525650; PMID:34544496

Cite this entry

Nicholas, F. W., Tammen, I., & Sydney Informatics Hub. (2023). OMIA:000361-9615: Online Mendelian Inheritance in Animals (OMIA) [dataset].


Note: the references are listed in reverse chronological order (from the most recent year to the earliest year), and alphabetically by first author within a year.

2023 Court, M.H., Kiser, J.N., Neibergs, H.L., Zhu, Z., Dillberger, J.E. :
Identification by whole genome sequencing of genes associated with delayed postoperative hemorrhage in Scottish deerhounds. J Vet Intern Med , 2023. Pubmed reference: 36780177. DOI: 10.1111/jvim.16643.
2022 Clark, J.A., Hooser, S.B., Dreger, D.L., Burcham, G.N., Ekenstedt, K.J. :
Investigation of a common canine factor VII deficiency variant in dogs with unexplained bleeding on autopsy. J Vet Diagn Invest 34:806-812, 2022. Pubmed reference: 35949113. DOI: 10.1177/10406387221118581.
2021 Thorsrud, J.A., Huson, H.J. :
Description of breed ancestry and genetic health traits in arctic sled dog breeds. Canine Med Genet 8:8, 2021. Pubmed reference: 34544496. DOI: 10.1186/s40575-021-00108-z.
2019 Ramirez, C.J., Krug, M., Zahand, A., Sundin, K., Shaffer, L.G., Ballif, B.C. :
Canine factor VII deficiency: lessons learned in applying methods-based laboratory proficiency testing. J Vet Diagn Invest 31:276-279, 2019. Pubmed reference: 30661469. DOI: 10.1177/1040638718825281.
2017 Keeshen, T.P., Case, J.B., Runge, J.J., Singh, A., Mayhew, P.D., Steffey, M.A., Culp, W.T.N. :
Outcome of laparoscopic ovariohysterectomy or ovariectomy in dogs with von Willebrand disease or factor VII deficiency: 20 cases (2012-2014). J Am Vet Med Assoc 251:1053-1058, 2017. Pubmed reference: 29035661. DOI: 10.2460/javma.251.9.1053.
2016 Donner, J., Kaukonen, M., Anderson, H., Möller, F., Kyöstilä, K., Sankari, S., Hytönen, M., Giger, U., Lohi, H. :
Genetic panel screening of nearly 100 mutations reveals new insights into the breed distribution of risk variants for canine hereditary disorders. PLoS One 11:e0161005, 2016. Pubmed reference: 27525650. DOI: 10.1371/journal.pone.0161005.
2011 Knudsen, T., Kjelgaard-Hansen, M., Tranholm, M., Wiinberg, B., Clausen, J.T., Hansen, J.J., Nichols, T.C., Kjalke, M., Jensen, A.L., Kristensen, A.T. :
Canine specific ELISA for coagulation factor VII. Vet J 190:352-8, 2011. Pubmed reference: 21216638. DOI: 10.1016/j.tvjl.2010.11.010.
Mischke, R. :
Determination of canine coagulation factor VII. Vet J 190:305-6, 2011. Pubmed reference: 22108258. DOI: 10.1016/j.tvjl.2011.10.005.
2009 Carlstrom, LP., Jens, JK., Dobyns, ME., Passage, M., Dickson, PI., Ellinwood, NM. :
Inadvertent propagation of factor VII deficiency in a canine mucopolysaccharidosis type I research breeding colony. Comp Med 59:378-82, 2009. Pubmed reference: 19712579.
Nichols, TC., Dillow, AM., Franck, HW., Merricks, EP., Raymer, RA., Bellinger, DA., Arruda, VR., High, KA. :
Protein replacement therapy and gene transfer in canine models of hemophilia A, hemophilia B, von willebrand disease, and factor VII deficiency. ILAR J 50:144-67, 2009. Pubmed reference: 19293459.
2007 Daly, M.L., Giger, U. :
A rodenticide exposed and bleeding beagle dog with hereditary factor VII deficiency J Vet Emerg Crit Care 17:170-174, 2007.
Kaae, JA., Callan, MB., Brooks, MB. :
Hereditary factor VII deficiency in the Alaskan Klee Kai dog. J Vet Intern Med 21:976-81, 2007. Pubmed reference: 17939552.
2006 Callan, MB., Aljamali, MN., Margaritis, P., Griot-Wenk, ME., Pollak, ES., Werner, P., Giger, U., High, KA. :
A novel missense mutation responsible for factor VII deficiency in research Beagle colonies. J Thromb Haemost 4:2616-22, 2006. Pubmed reference: 16961583. DOI: 10.1111/j.1538-7836.2006.02203.x.
Withnall, E., Giger, U. :
Effects of recombinant human activated factor VII and canine fresh frozen plasma in Beagles with hereditary coagulation factor VII deficiency Journal of Veterinary Internal Medicine 20:766 only, 2006.
2005 Callan, M. B., Aljamali, M. N., Griot-Wenkl, M. E., Pollak, E. S., Werner, P., Giger, U., High, K. A. :
Molecular characterization of hereditary factor VII deficiency in the beagle Journal of Veterinary Internal Medicine 19:448-449 (abstract), 2005.
2003 Mischke, R., Diedrich, M., Nolte, I. :
Sensitivity of different prothrombin time assays to factor VII deficiency in canine plasma Veterinary Journal 166:79-85, 2003.
1999 Macpherson, R., Scherer, J., Ross, M.L., Gentry, P.A. :
Factor VII deficiency in a mixed breed dog Canadian Veterinary Journal - Revue Veterinaire Canadienne 40:503-505, 1999.
1997 Mills, J.N., Labuc, R.H., Lawley, M.J. :
Factor VII deficiency in an Alaskan Malamute Australian Veterinary Journal 75:320-322, 1997. Pubmed reference: 9196814.
1993 Brooks, M., Catalfamo, J. :
Buccal mucosa bleeding time is prolonged in canine models of primary hemostatic disorders. Thrombosis and Haemostasis 70:777-780, 1993. Pubmed reference: 8128434.
1991 Ferguson, J.M., MacGregor, I.R., McLaughlin, L.F., Prowse, C.V. :
Use of factor VII-deficient beagles bred by artificial insemination to evaluate mechanisms of thrombosis associated with prothrombin complex concentrates. Blood Coagul Fibrinolysis 2:731-4, 1991. Pubmed reference: 1799659.
Prydz, H., Spurling, N.W., Boyce, A.J., Mifsud, C.V.J. :
Phospholipase-C-sensitive factor-VII complexes in dog plasma. Thrombosis Research 64:387-394, 1991. Pubmed reference: 1788825.
1988 Fogh, J.M., Fogh, I.T. :
Inherited coagulation disorders. Vet Clin North Am Small Anim Pract 18:231-43, 1988. Pubmed reference: 3282382.
Spurling, N.W. :
Hereditary blood coagulation factor-VII deficiency: a comparison of the defect in Beagles from several sources Comparative Biochemistry and Physiology. A. Comparative Physiology 89:461-464, 1988. Pubmed reference: 2896576.
Vander Velden, P., Giles, A.R. :
A detailed morphological evaluation of the evolution of the haemostatic plug in normal, factor VII and factor VIII deficient dogs. Br J Haematol 70:345-55, 1988. Pubmed reference: 3207628.
1987 Noguchi, M., Fujii, T., Michizono, A. :
[Congenital deficiency of factor VII in a canine family] [Japanese] Experimental Animals 36:423-430, 1987. Pubmed reference: 3436375.
1986 Spurling, N.W. :
Hereditary blood coagulation factor-VII deficiency in the Beagle: immunological characterisation of the defect Comparative Biochemistry and Physiology. A. Comparative Physiology 83:755-760, 1986. Pubmed reference: 2870866.
1984 Wheeler, S.L., Weingand, K.W., Thrall, M.A., Berg, R.J., Schwarz, P.D. :
Persistent uterine and vaginal hemorrhage in a Beagle with factor-VII deficiency Journal of the American Veterinary Medical Association 185:447-448, 1984. Pubmed reference: 6469849.
1980 Spurling, N.W. :
Hereditary disorders of haemostasis in dogs: a critical review of the literature Veterinary Bulletin 50:151-173, 1980.
1974 Dodds, W.J. :
Hereditary and acquired hemorrhagic disorders in animals. Prog Hemost Thromb 2:215-47, 1974. Pubmed reference: 4604529.
Spurling, N.W., Burton, L.K., Pilling, T. :
Canine factor-VII deficiency: experience with a modified thrombotest method in distinguishing between the genotypes. Res Vet Sci 16:228-39, 1974. Pubmed reference: 4830986.
Spurling, N.W., Peacock, R., Pilling, T. :
The clinical aspects of canine factor-VII deficiency including some case histories. J Small Anim Pract 15:229-39, 1974. Pubmed reference: 4449220.
1972 Spurberg, N.W., Burton, L.K., Peacock, R., Pilling, T. :
Hereditary factor VII deficiency in the Beagle British Journal of Haematology 23:59-67, 1972. Pubmed reference: 5045961.
von Schaewen, H. :
[Thromboplastic activity of brain extracts from various species in normal plasma and in congenital factor VII deficient plasma from dogs]. Berl Munch Tierarztl Wochenschr 85:149-52, 1972. Pubmed reference: 5027610.
1970 Garner, R., Conning, D.M. :
The assay of human factor VII by means of modified factor VII deficient dog plasma British Journal of Maematology 18:57-66, 1970. Pubmed reference: 5416591.
Hall, D.E. :
Sensitivity of different thromboplastin reagents to factor VII deficiency in the blood of beagle dogs. Lab Anim 4:55-9, 1970. Pubmed reference: 5527820.
1968 Gaston, L.W., Spivack, A.R. :
Preparation of canine factor VII deficient substrate plasma. J Lab Clin Med 72:548-55, 1968. Pubmed reference: 5677303.
1967 Garner, R., Hermoso-Perez, C., Conning, D.M. :
Factor VII deficiency in Beagle dog plasma and its use in the assay of human factor VII Nature 216:1130-1131, 1967. Pubmed reference: 6075264.
1962 Mustard, J.F., Secord, D., Hoeksema, T.D., Downie, H.G., Rowsell, H.C. :
Canine factor-VII deficiency. Br J Haematol 8:43-7, 1962. Pubmed reference: 14477610.

Edit History

  • Created by Frank Nicholas on 14 Jul 2006
  • Changed by Frank Nicholas on 10 Aug 2011
  • Changed by Frank Nicholas on 12 Dec 2011
  • Changed by Frank Nicholas on 21 Oct 2012
  • Changed by Frank Nicholas on 26 Jan 2017
  • Changed by Frank Nicholas on 27 Apr 2019
  • Changed by Imke Tammen2 on 03 Oct 2021
  • Changed by Frank Nicholas on 17 Aug 2022
  • Changed by Imke Tammen2 on 05 Jun 2023