In other species: cattle , dog , horse , pig , sheep , jaguar , jaguarundi , American black bear , woolly mammoth , domestic cat , rabbit , domestic guinea pig , goat , Arctic fox , rock pocket mouse , oldfield mouse , gray squirrel , lesser earless lizard , little striped whiptail , water buffalo , domestic yak , alpaca , , coyote , reindeer , Geoffroy's cat , Kodkod , Colocolo , ass , Arabian camel , Mongolian gerbil

Possibly relevant human trait(s) and/or gene(s) (MIM number): 266300

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal

Considered a defect: no

Key variant known: yes

Year key variant first reported: 1997

Cross-species summary: The extension locus encodes the melanocyte-stimulating hormone receptor (MSHR; also 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.

Molecular basis: By cloning and sequencing a very likely comparative candidate gene (based on extensive evidence in other mammal species that the Extension (E) locus corresponds to the MC1R gene), Vage et al. (1997) cloned and characterized the fox extension locus, providing strong evidence that the Alaska Silver allele, E(A), which confers dark pigmentation, is due to a C125R amino-acid substitution in the melanocyte-stimulating hormone receptor.

Liu et al. (2016) reported that "SNP c.373T>C in the coding region of the MC1R gene is probably associated with the brown phenotype of chocolate foxes".

Associated gene: