In other species: dog

Categories: Pigmentation phene

Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 606574 (trait) , 227240 (trait) , 606202 (gene)

Links to MONDO diseases: No links.

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal

Considered a defect: no

Key variant known: yes

Year key variant first reported: 2003

Species-specific name: Palomino

Species-specific description: In 2003, Mariat et al. showed that this classic coat-colour locus encodes membrane-associated transporter protein (MATP), now renamed SLC45A2, and that the first reported dilution allele in horses is due to a missense mutation [FN 16 Oct 2003].

Inheritance: Holl et al. (2019): "Cream dilution is inherited in an incomplete dominant manner, diluting only red in the heterozygous state but both red and black pigments when two alleles are present. The pearl dilution is recessive and dilutes only the red and black pigment in the homozygous state or when paired with a cream allele. Horses that inherit one copy of pearl (C^prl) and one copy of the dominant cream allele (C^Cr) display a dilution phenotype similar to that of homozygous cream, suggesting that pearl is the result of a different variation in the same gene responsible for cream".

Mapping: Mariat et al. (2003) showed that the candidate gene MATP (now called SLC45A2) is completely linked (theta = 0) to the equine cream locus.

Molecular basis: Building on the strong evidence from mapping (see Mapping section above), Mariat et al. (2003) identified a missense G457A transition (OMIAvariantID:153) in the equine MATP gene (now called SLC45A2), giving rise to a D153N amino acid substitution in cream horses. Sevane et al. (2019) reported a "missense variation in exon 4 [SLC45A2:c.985G>A; SLC45A2:p.(Ala329Thr), OMIAvariantID:1069] as the causative mutation for the pearl coat colour". These authors also explained "the cremello, perlino and smoky cream like phenotypes associated with the compound C^Cr and C^prl heterozygous genotype (known as cream pearl in the Purebred Spanish horse breed)" Having sequenced a "'false double dilute'" horse (one that is "phenotypically homozygous cream but tested as possessing only a single C^Cr allele") and a non-dilute offspring, Holl et al. (2019) reported that both horses were "heterozygous for a novel missense variant ECA21:SLC45A2:c.568G>A (p.Gly190Arg) [OMIAvariantID:1074], the proposed C^sun variant (for the name of the horse). This variant produces a recessive dilution similar to pearl and indicates that multiple alleles of SLC45A2 result in dilution phenotypes in the domestic horse." Bisbee et al. (2020) identified an SLC45A2 variant in exon 1 (c.305G>A; p.(Arg102Gln); ENSECAT00000026240.1 in the Ensembl EquCab2.0 assembly; OMIAvariantID:1140) as the likely causal variant for an autosomal recessive coat colour of "a Gypsy breed mare that appeared phenotypically cremello (light creamy white) but tested negative for any known dilution or spotting alleles, including sabino, W20, tobiano, PATN1 and SW1‐4". They named this variant snowdrop (C^sno).

Genetic engineering: Unknown
Have human generated variants been created, e.g. through genetic engineering and gene editing

Breeds: American Paint (Horse) (VBO_0000897), Lusitanian (Horse) (VBO_0001017), Purebred Spanish (Horse) (VBO_0001056), Quarter Horse (Horse) (VBO_0001057), Standardbred x Tennessee Walking Horse cross (Horse) (VBO_0016849), Traditional Gypsy Cob, United Kingdom of Great Britain and Northern Ireland (Horse) (VBO_0011496).
Breeds in which the phene has been documented. For breeds in which a likely causal variant has been documented, see the variant table below

Associated gene: