In other species: lorises , coyote , dog , red fox , American black bear , domestic cat , jaguar , ass (donkey) , 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 , Colocolo , little striped whiptail , water buffalo , Arctic fox

Categories: Pigmentation phene

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

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal recessive

Considered a defect: no

Key variant known: no

Year key variant first reported: 2016

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.

Species-specific description: See 'OMIA:001199-9796 : Coat colour, extension in Equus caballus (horse)' for additional details.

Molecular basis: Reichmann et al. (2016) "tested 12 coat-color-associated alleles in 55 breeds (n= 1093) and 20 specimens of Przewalski’s horse for five genes (MC1R – E/e, ASIP – A/a, SLC45A2/MATP – C/c cr, Pmel17/SILV – Z/ z, KIT – SB1/sb1 and KM0/KM1) ... ." Only the the recessive chestnut allele e (15.0 %) was detecctd in Przewalski’s horses. The authors speculated that it was either inherited from their ancestors or from historic cross-breeding with domestic horses.
Musiał et al. (2023) investigated the presence of two equine TBX3 variants (see OMIA:001972-9796 : Coat colour, dun in Equus caballus) and a MC1R variant associated with 'fox' colour in 23 Przewalski horses: "The coat color genes analyses indicated only native, wild genotypes. ... The results assigned all horses to the [TBX3] genotype with G/G alleles in both SNP loci, and deletions were not observed. ... none of Przewalski horses presented C to T missense mutation associated with an unfavorable [MC1R] ‘fox’ color variant for this species."

Associated gene: