I-locus (MSFD12) and others

In the other pages about coat colour genes there was a single gene responsible for a certain colour or pattern or group of colour variations. Unfortunately this is not the case (yet?) for the intensity of pheomelanin (red/yellow pigment).

MSFD12 (Major Facilitator Superfamily Domain Containing 12)

This gene produces a protein that is located in the cell membrane and regulates pheomelanin production. The gene is known in many species.

A change in one nucleotide reduces the pheomelanin production to a level that the coat becomes cream or white.


In some breeds it was found that close to the KIT Ligand gene a block determines the saturation of pheomelanin. This block can be repeated and the more copies there are the darker the colour looks. It turned out that individuals with a low number of copies have a paler root of each hair and a darker colour at the tip. Animals with a high number of copies have an equal pigmentation at the root and at the tip of each hair.

In other breeds the saturation of pheomelanin pigmentation could not be explained by the number of copies of that block.

Other genes

Further research with a large number of dogs from various breeds identified five locations in the DNA where changes would influence the pheomelanin colour intensity. These included MSDF12 and KITLG but also three locations which were previously not identified. A mathematical model was created which could predict the correct saturation in 70% of the dogs in a separate test group.

A lot more research is needed to find the working mechanisms of the three new locations and to identify alleles and develop DNA tests.

Because not all variants are found in all breeds the exact situation for the Border Collie is far from clear.

Little, Clarence C., The Inheritance of Coat Color in Dogs, Ithaca, New York, Comstock Pub. Associates, 1957.

Brancalion, L., Haase, B. and Wade, C.M. (2022), Canine coat pigmentation genetics: a review. Anim Genet, 53: 3-34.

Hédan B, Cadieu E, Botherel N, Dufaure de Citres C, Letko A, Rimbault M, Drögemüller C, Jagannathan V, Derrien T, Schmutz S, et al. Identification of a Missense Variant in MFSD12 Involved in Dilution of Phaeomelanin Leading to White or Cream Coat Color in Dogs. Genes. 2019; 10(5):386.

Weich, K., Affolter, V., York, D., Rebhun, R., Grahn, R., Kallenberg, A., & Bannasch, D. (2020). Pigment Intensity in Dogs is Associated with a Copy Number Variant Upstream of KITLG. Genes, 11(1), 75.

Slavney, A. J., Kawakami, T., Jensen, M. K., Nelson, T. C., Sams, A. J., & Boyko, A. R. (2021). Five genetic variants explain over 70% of hair coat pheomelanin intensity variation in purebred and mixed breed domestic dogs. PloS one, 16(5), e0250579.