OMIA:000209-494514 : Coat colour, dominant white in Vulpes lagopus (Arctic fox)

In other species: dog , domestic cat , ass (donkey) , horse , pig , llama , taurine cattle , goat , rabbit , domestic yak , alpaca , raccoon dog

Categories: Pigmentation phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 172800 (trait) , 164920 (gene)

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal dominant

Considered a defect: no

Key variant known: yes

Year key variant first reported: 2013

Cross-species summary: The dominant white gene is one of a number of genes that regulate normal growth and proliferation of cells. In fact, it encodes a protein that protrudes through the cell membrane, relaying 'messages' across the membrane, from outside to inside the cell. The transmembrane domain of the protein is a receptor for a growth factor (a protein produced by one type of cell, that acts on another type of cell). The domain inside the cell has tyrosine kinase activity. When a growth factor binds to the receptor on the outside of the cell, this stimulates tyrosine kinase activity inside the cell, which sets off a cascade of phosphorylations, resulting in activation of transcription factors, which in turn activate genes, resulting in multiplication of stem cells, including melanocyte precursor cells, in the developing embryo. This whole process is known as a signal transduction pathway. During embryonic development, the melanosome precursor cells migrate from the neural crest down either side of the body. Under normal circumstances, they eventually meet at the centre of the belly. The cells then proliferate in all directions until they meeting neighbouring cells, thereby filling up all available areas, resulting in a solid mass of melanocytes over the entire body. The dominant white allele produces a defective transmembrane protein which is unable to relay 'messages', resulting in a lack of melanocytes, and hence white coat colour. An interesting aspect of the dominant white gene is that if it is activated at the wrong time, the result can be excess and uncontrolled proliferation of stem cells; in other words, cancer. In fact, at some time in the past, a feline retrovirus (the Hardy-Zuckerman 4 feline sarcoma virus) 'picked up' (by transduction) a copy of the dominant white gene from a cat, and incorporated this gene into its own genome. When this retrovirus infects cats, it activates its own copy of the gene at inappropriate times, causing sarcoma - a malignant tumour of cells derived from connective tissue. Retroviral genes that cause cancer are called oncogenes. The original host version of an oncogene is called a proto-oncogene. Thus, the dominant white gene is actually a proto-oncogene. In this particular case, the oncogene was discovered and named v-kit (where 'v' indicates a viral version of the gene) long before its association with white coat colour was established. The corresponding proto-oncogene is called c-kit, where 'c' stands for cellular. After the discovery and cloning of v-kit in the feline retrovirus by Besmer et al. (1986; Nature 320:415-421), c-kit was identified and mapped first in humans, by Mattei et al. (1987; Cytogenetics and Cell Genetics 46:657 only), and then in mice (Chabot et al., 1988; Nature 335:88-89, 1988), where it was shown to be identical with the long-recognised white-spotting (W) locus. Three years later, Giebel and Spritz (1991; Proceedings of the National Academy of Sciences 88:8696-8699) showed that mutations at the c-kit gene in humans cause piebaldism, which is the human homologue of white spotting (see the MIM entry at the top of this page)

Species-specific name: Note that the official (NCBI Taxonomy) name for Alopex lagopus (blue fox) is now Vulpes lagopus (Arctic fox)

Inheritance: As summarised by Yan et al. (2013), "dominant white in blue fox is inherited as a monogenic autosomal dominant trait and is suggested to be embryonic lethal in the homozygous state (Filistowicz et al. 1997)."

Molecular basis: Adopting the candidate-gene strategy, Yan et al. (2013) cloned and sequenced the KIT gene in blue foxes, and compared sequence between dominant white and normal blue phenotypic variants, discovering that "dominant white coat colour of blue fox results from an exon 12 skipping caused by a c.1867+1G>T substitution in the first nucleotide of intron 12 of the KIT gene".

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
KIT Vulpes lagopus 12 NC_054835.1 (69187489..69270919) KIT Homologene, Ensembl , NCBI gene


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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
403 Coat colour, dominant white KIT splicing Naturally occurring variant c.1867+1G>T 2013 24308634

Cite this entry

Nicholas, F. W., Tammen, I., & Sydney Informatics Hub. (2017). OMIA:000209-494514: 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.

2013 Yan, S.Q., Hou, J.N., Bai, C.Y., Jiang, Y., Zhang, X.J., Ren, H.L., Sun, B.X., Zhao, Z.H., Sun, J.H. :
A base substitution in the donor site of intron 12 of KIT gene is responsible for the dominant white coat colour of blue fox (Alopex lagopus). Anim Genet , 2013. Pubmed reference: 24308634. DOI: 10.1111/age.12105.
1997 Filistowicz, A., Wierzbicki, H., Przysiecki, P. :
Preliminary studies on the inheritance of white coat color in Arctic foxes (Alopex lagopus L.). Journal of Applied Genetics 38:57-64, 1997.

Edit History

  • Created by Frank Nicholas on 08 Dec 2013
  • Changed by Frank Nicholas on 08 Dec 2013
  • Changed by Frank Nicholas on 11 Dec 2017