Coat color in Holstein dairy cattle is primarily controlled by the melanocortin 
1 receptor (MC1R) gene, a central determinant of black (eumelanin) vs. red/brown 
pheomelanin synthesis across animal species. The major MC1R alleles in Holsteins 
are Dominant Black (MC1RD) and Recessive Red (MC1Re). A novel form of dominant 
red coat color was first observed in an animal born in 1980. The mutation 
underlying this phenotype was named Dominant Red and is epistatic to the 
constitutively activated MC1RD. Here we show that a missense mutation in the 
coatomer protein complex, subunit alpha (COPA), a gene with previously no known 
role in pigmentation synthesis, is completely associated with Dominant Red in 
Holstein dairy cattle. The mutation results in an arginine to cysteine 
substitution at an amino acid residue completely conserved across eukaryotes. 
Despite this high level of conservation we show that both heterozygotes and 
homozygotes are healthy and viable. Analysis of hair pigment composition shows 
that the Dominant Red phenotype is similar to the MC1R Recessive Red phenotype, 
although less effective at reducing eumelanin synthesis. RNA-seq data similarly 
show that Dominant Red animals achieve predominantly pheomelanin synthesis by 
downregulating genes normally required for eumelanin synthesis. COPA is a 
component of the coat protein I seven subunit complex that is involved with 
retrograde and cis-Golgi intracellular coated vesicle transport of both protein 
and RNA cargo. This suggests that Dominant Red may be caused by aberrant MC1R 
protein or mRNA trafficking within the highly compartmentalized melanocyte, 
mimicking the effect of the Recessive Red loss of function MC1R allele.