OMIA:001199-9685 : Coat colour, extension in Felis catus (domestic cat)
In other species: lorises , coyote , dog , red fox , American black bear , jaguar , ass (donkey) , 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 , Colocolo , little striped whiptail , water buffalo , Arctic fox
Categories: Pigmentation phene
Links to MONDO diseases: No links.
Mendelian trait/disorder: yes
Mode of inheritance: Autosomal recessive
Considered a defect: no
Key variant known: yes
Year key variant first reported: 2009
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: Peterschmitt et al. (2009): amber in Norwegian Forest cats: c.250G>A; p.Asp84Asn
Gustafson et al. (2017): russet in Burmese cats: 3-bp deletion (c.439_441del; p.Phe146del)
Abitbol and Gache (2019) reported "a c.640_669del in‐frame deletion that is predicted to cause a p.(Ala214_Ala223del) deletion of 10 amino acids in the protein" as the likely causal variant for an autosomal recessive orange coat colour that develops with age in the Kurilian Bobtail breed. The authors names this the Copal variant. As the authors describe, the phenotype was reported in "brown tabby cats born with a warm reddish tone and exhibiting a modification of their original colour during their first year of life. Kittens brighten and adults show an apricot‐red colour. Eumelanin disappears from hairs and cats become very similar to red cats (X‐linked orange locus . . .)". In a personal communication of 6 August 2019, Dr Abitbol advises that "homozygous cats for the variant become red but heterozygous tabby cats are referenced as "golden" by breeders (due to their warm coat colour). It seems that the variant has slight effect on heterozygous tabby cats. But the variant seems to have no effect on heterozygous solid cats."
Bychkova et al. (2020) confirmed the existence and effect of the c.640_669del variant.
Have human generated variants been created, e.g. through genetic engineering and gene editing
Burmese (Cat) (VBO_0100053),
Kurilian Bobtail (Cat) (VBO_0100146),
Norwegian Forest Cat (Cat) (VBO_0100178).
Breeds in which the phene has been documented. For breeds in which a likely causal variant has been documented, see the variant table below
|Symbol||Description||Species||Chr||Location||OMIA gene details page||Other Links|
|MC1R||melanocortin 1 receptor (alpha melanocyte stimulating hormone receptor)||Felis catus||E2||NC_058382.1 (61570045..61570998)||MC1R||Homologene, Ensembl , NCBI gene|
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WARNING! Inclusion of a variant in this table does not automatically mean that it should be used for DNA testing. Anyone contemplating the use of any of these variants for DNA testing should examine critically the relevant evidence (especially in breeds other than the breed in which the variant was first described). If it is decided to proceed, the location and orientation of the variant sequence should be checked very carefully.
Since October 2021, OMIA includes a semiautomated lift-over pipeline to facilitate updates of genomic positions to a recent reference genome position. These changes to genomic positions are not always reflected in the ‘acknowledgements’ or ‘verbal description’ fields in this table.
|OMIA Variant ID||Breed(s)||Variant Phenotype||Gene||Allele||Type of Variant||Source of Genetic Variant||Reference Sequence||Chr.||g. or m.||c. or n.||p.||Verbal Description||EVA ID||Inferred EVA rsID||Year Published||PubMed ID(s)||Acknowledgements|
|123||Norwegian Forest Cat (Cat)||Coat colour, amber||MC1R||e||missense||Naturally occurring variant||Felis_catus_9.0||E2||g.63829934G>A||c.250G>A||p.(D84N)||NM_001009324.1; NP_001009324.1||2009||19422360||Variant coordinates obtained from or confirmed by EBI's Some Effect Predictor (VEP) tool|
|561||Burmese (Cat)||Coat colour, russet||MC1R||e^r||deletion, small (<=20)||Naturally occurring variant||Felis_catus_9.0||E2||g.63830124_63830126del||c.440_442del||p.(F147del)||NM_001009324.1; NP_001009324.1; published as c.439_441del and p.(F146del); coordinates in the table have been updated to a recent reference genome and / or transcript||2017||27671997||Genomic position in Felis_catus_9.0 provided by Leslie Lyons and Reuben Buckley.|
|1090||Kurilian Bobtail (Cat)||Coat colour, copal||MC1R||e^c||deletion, small (<=20)||Naturally occurring variant||Felis_catus_9.0||E2||g.63830324_63830353del||c.640_669del||p.(A214_R223del)||NM_001009324.1; NP_001009324.1||2019||31361350|
Cite this entry
Note: the references are listed in reverse chronological order (from the most recent year to the earliest year), and alphabetically by first author within a year.
|2020||Bychkova, E.O., Golubeva, N.A., Filippova, E.A., Sangina, L.O., Markov, A.V. :|
|A new mutation in the MC1R gene leads to unique carnelian color in Kurilian Bobtails. Russian Journal of Genetics 56:108-111, 2020. DOI: 10.1134/S1022795420010020.|
|2019||Abitbol, M., Gache, V. :|
|Copal, a new MC1R allele in the domestic cat. Anim Genet 50:553-554, 2019. Pubmed reference: 31361350. DOI: 10.1111/age.12829.|
|2017||Gustafson, N.A., Gandolfi, B., Lyons, L.A. :|
|Not another type of potato: MC1R and the russet coloration of Burmese cats. Anim Genet 48:116-120, 2017. Pubmed reference: 27671997. DOI: 10.1111/age.12505.|
|2009||Peterschmitt, M., Grain, F., Arnaud, B., Deléage, G., Lambert, V. :|
|Mutation in the melanocortin 1 receptor is associated with amber colour in the Norwegian Forest Cat. Anim Genet 40:547-52, 2009. Pubmed reference: 19422360. DOI: 10.1111/j.1365-2052.2009.01864.x.|
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