UC Davis School of Veterinary Medicine Veterinary Genetics Laboratory

Intensity Dilution

Quick Summary: The intensity coat color gene variant causes an extreme dilution of phaeomelanin (red or yellow pigment), resulting in a cream to white coat in dogs.

Phenotype: Red and yellow pigment is diluted to cream or white hair. Black and brown pigment, if present, will remain undiluted.

Mode of Inheritance: Autosomal Recessive

Explanation of Results:

  • Dogs with the N/N genotype are not likely to show the extreme dilution phenotype and cannot transmit the intensity dilution variant to their offspring.
  • Dogs with the N/In genotype are carriers and likely will not show extreme dilution of phaeomelanin. They are predicted to transmit the variant to 50% of their offspring, and 25% of pups produced by mating of two carriers are predicted to have the extreme dilution phenotype caused by the intensity allele.
  • Dogs with the In/In genotype have two Intensity dilution variants and will likely show dilution of phaeomelanin resulting in a cream to white phenotype. They will transmit the variant to all of their offspring.

Allow 3-6 business days for results.

Additional Details: Mammals produce two kinds of pigment; eumelanin (black and/or brown in color) and phaeomelanin (red and/or yellow in color). Many genes contribute to the type and amount of pigment produced. Several breeds of dogs have an extreme dilution phenotype that has been shown to only affect the red pigment phaeomelanin. Hédan et al (2019) identified a single nucleotide change (c.151C>T predicted) in the first exon of the Major Facilitator Superfamily Domain Containing 12 gene (MFSD12) associated with the dilution phenotype. This change in the DNA results in an amino acid difference in the protein where cysteine replaces the normal arginine at amino acid 51 (p.Arg51Cys). This mutation is predicted to have damaging effect on protein function. MFSD12 is a gene identified to have a conserved role in vertebrate pigmentation with variants identified to impact pigmentation in zebrafish, human, mouse, and horse. MFSD12 is believed to function as a lysosomal transmembrane solute transporter directly affecting the production of phaeomleanin. In humans and horses decreased and/or non-functional MFSD12 has been implicated in reducing red/yellow pigment while increasing black/brown pigment. In dogs, the MFSD12 In variant has only been shown to decrease red/yellow pigment leaving black/brown pigment unaffected.

The degree of dilution varies within and between breeds with coat color ranging from cream to solid white. Population studies demonstrate that 10% of dogs homozygous for the In allele do not show the extreme dilution phenotype and 10% of extreme dilution phenotype dogs do not have two copies of the In allele. Additionally, roughly 2% of dogs with 0 or 1 copies of the In variant have the extreme dilution phenotype, and the extreme dilution variant does not appear to affect breeds fixed for phaeomelanin such as Irish Setters. Taken together, these results suggest the phenotype may be impacted by variants at additional genes. These additional genes are currently unknown.

Note: Because studies indicate additional unknown genes influence the effects of this mutation, it is possible that the phenotype (physical appearance) of the dog may not be predictable by the genetic results. In other words, the polygenic nature of pigmentation makes it possible for discordant phenotypic and genotypic results.

Testing is recommended for: Leonberger, French Bulldog, German Shepherd, Puli, Saluki, Afghan Hound, and Scottish Terrier. This variant may be present in other breeds with the extreme dilution phenotype.

Results reported as:


No copies of intensity dilution. Dog is unlikely to exhibit the intensity dilution phenotype.


Carrier of intensity dilution. Dog is unlikely to exhibit the intensity dilution phenotype.


2 copies of intensity dilution. Red pigment is likely to be diluted to cream or white.


Hédan, B., Cadieu, E., Botherel, N., Dufaure de Citres, C., Letko, A., Rimbault, M., Drögemüller, C., Jagannathan, V., Derrien, T., Schmutz, S.,Leeb T., André, C. (2019) Identification of a Missense Variant in MFSD12 Involved in Dilution of Phaeomelanin Leading to White or Cream Coat Color in Dogs. Genes, 10(5):386. doi: 10.3390/genes10050386.

Veterinary Genetics Laboratory, Tel 530-752-2211, Email VGL