Categories: Integument (skin) phene

Possibly relevant human trait(s) and/or gene(s) (MIM number): 608613 (gene)

Links to MONDO diseases: No links.

Mendelian trait/disorder: no

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2018

Inheritance: Thomer et al. (2018) reported that genotypes at two genes, KRT25 and SP6, each with two alleles, could explain all combinations of curly +/- and hypotrichosis +/-: "Horses heterozygous or homozygous only for KRT25 variant [see below] showed curly coat and hypotrichosis, whereas horses with SP6 variant [see below] only, exhibited curly coat without hypotrichosis. Horses with mutant alleles in both variants developed curly hair and hypotrichosis. Thus, mutant KRT25 allele is masking SP6 allele effect, indicative for epistasis of KRT25 variant over SP6 variant."

Molecular basis: Thomer et al. (2018) identified two likely causal variants: g.21891160G>A; p.R89H in the KRT25 gene, and g. 24022045C>T; p.G364S in the SP6 gene. An independent discovery of the KRT25 variant in relation to Curly coat (see OMIA 000245-9796) was published while the MS by Thomer et al. was undergoing peer review. As explained in the Inheritance section, Tomer et al. (2018) "demonstrated an epistatic effect of KRT25 variant on SP6 variant due to its pleiotropy on hair structure and hair loss."

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

Breeds: Bashkir Curly (Horse) (VBO_0000913), Missouri Fox Trotter, Germany (Horse) (VBO_0011358).
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: