In other species: lorises , coyote , dog , red fox , American black bear , domestic cat , jaguar , ass (donkey) , domestic horse , Przewalski's horse , pig , Arabian camel , reindeer , taurine cattle , indicine cattle (zebu) , goat , sheep , rabbit , Mongolian gerbil , domestic guinea pig , domestic yak , fallow deer , alpaca , gray squirrel , raccoon dog , antarctic fur seal , woolly mammoth , rock pocket mouse , oldfield mouse , lesser earless lizard , Geoffroy's cat , jaguarundi , little striped whiptail , water buffalo , Arctic fox , Colocolo

Categories: Pigmentation phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 266300 (trait) , 155555 (gene)

Single-gene trait/disorder: yes

Disease-related: no

Key variant known: yes

Year key variant first reported: 2025

Cross-species summary: The extension locus encodes the melanocyte-stimulating hormone receptor (MSHR; now known as MC1R). This receptor controls the level of tyrosinase within melanocytes. Tyrosinase is the limiting enzyme involved in synthesis of melanins: high levels of tyrosinase result in the production of eumelanin (dark colour, e.g. brown or black), while low levels result in the production of phaeomelanin (light colour, e.g. red or yellow). When melanocyte-stimulating hormone (MSH) binds to its receptor, the level of tyrosinase is increased, leading to production of eumelanin. The wild-type allele at the extension locus corresponds to a functional MSHR, and hence to dark pigmentation in the presence of MSH. As explained by Schneider et al. (PLoS Genet 10(2): e1004892; 2015), "The most common causes of melanism (black coat) mutations are gain-of-function alterations in MC1R, or loss-of function alterations in ASIP, which encodes Agouti signaling protein, a paracrine signaling molecule that inhibits MC1R signaling". Mutations in MC1R have been associated with white colouring in several species.

Molecular basis: Sauerman et al. (2025) investigated the normal coat colour of marsupial moles, who all have a cream to pale-yellow coat, lacking dark eumelanin deposition. The authors aligned the southern marsupial mole MC1R amino acid sequences against other marsupial orthologues and identified a likely causal southern marsupial mole specific "in-frame stop codon at position 160, in place of a highly conserved arginine residue (R160X) ... ." 

Associated gene: