D-locus - MLPH

The melanophilin gene (MLPH) has some recessive alleles which cause a diluted version of the original coat colour.

Working mechanism

The protein that is encoded by the MLPH gene plays an important role in the distribution of pigment particles in the cell. It binds the melanosomes (pigment particles) to the actin skeleton in the cell. This skeleton makes sure that the pigment is distributed throughout the cell. The mutations disrupt this and the colour looks diluted. Melanocytes are stretched out through the tissue. If the pigment is concentrated in a single location then it looks like a small dot. On a larger scale this looks like a diluted colour.


The first mutation that was discovered, termed d1 is a change in a single nucleotide. It makes it very likely that translation to mRNA is cut off very early, resulting in a very short and non-functional peptide. Homozygous dd dogs have only about 25% of functional MLPH compared to homozygous DD dogs.

A second variant (d2)is a mutation of a single nucleotide but more to the end of the protein. Nevertheless it disrupts the function of the protein in such a way that the phenotype is the same as with d1d1 dogs.

The most recent discovery is the d3 variant which is caused by an insertion of a nucleotide. This also causes an early stop to the DNA sequence and thus the MLPH protein is approximately half the original size.


D : normal colour (wild type)
d1 : dilute
d2 : dilute
d3 : dilute

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. https://doi.org/10.1111/age.13154

Weizmann Institute of Science (2020c) MLPH Gene, Weizmann Institute of Science, viewed 22 Dec 2023, https://www.genecards.org/cgi-bin/carddisp.pl?gene=MLPH

Drögemüller, C., Ute Philipp, Bianca Haase, Anne-Rose Günzel-Apel, Tosso Leeb, A Noncoding Melanophilin Gene (MLPH) SNP at the Splice Donor of Exon 1 Represents a Candidate Causal Mutation for Coat Color Dilution in Dogs, Journal of Heredity, Volume 98, Issue 5, July/August 2007, Pages 468–473, https://doi.org/10.1093/jhered/esm021

Van Buren SL, Minor KM, Grahn RA, Mickelson JR, Grahn JC, Malvick J, Colangelo JR, Mueller E, Kuehnlein P, Kehl A. A Third MLPH Variant Causing Coat Color Dilution in Dogs. Genes. 2020; 11(6):639. https://doi.org/10.3390/genes11060639