In other species: dog , domestic cat , horse , llama , taurine cattle , domestic guinea pig

Categories: Pigmentation phene , Hearing / vestibular / ear phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 193510 (trait) , 103500 (trait) , 156845 (gene)

Single-gene trait/disorder: yes

Disease-related: no

Key variant known: yes

Year key variant first reported: 2015

Cross-species summary: Variable degree of white spotting ranging from tiny white spots up to completely white animals. The absence of pigment is caused by the absence of skin melanocytes ("leucism, leucistic"), not by failure in the biochemical reactions required for pigment synthesis.

Molecular basis: Yusnizar et al. (2015): "Two independent loss-of-function mutations, a premature stop codon (c.328C>T, p.Arg110*) and a donor splice-site mutation (c.840+2T>A, p.Glu281_Leu282Ins8), both of which cause white-spotted coat color in swamp buffaloes, were identified. The nonsense mutation leads to a premature stop codon in exon 3, and likely removal of the resulting mRNA via nonsense-mediated decay pathway, whereas the donor splice-site mutation leads to aberrant splicing of exon 8 that encodes part of a highly conserved region of MITF. The resulting insertion of eight amino acid residues is expected to perturb the leucine zipper part in the basic helix-loop-helix leucine zipper (bHLH-Zip) domain and will most likely influence dimerization and DNA binding capacity."
Dai et al. (2024) "successfully validated these two previously identified mutations in MITF [Yusnizar et al., 2015] and detected the KIT gene as another candidate responsible for the manifestation of the white spotting in swamp buffaloes [see OMIA:001737-89462 for details]. ... These mutations jointly explained 95% of the white spotting in swamp buffaloes .... [The authors]  also found evidence for other candidate genes relevant to the white spotting."

Associated gene: