Links to possible relevant human trait(s) and/or gene(s) in OMIM: 607206 (gene) , 606545 (trait)

Links to relevant human diseases in MONDO:

• MONDO:0011680: autosomal recessive congenital ichthyosis 3

Single-gene trait/disorder: yes

Mode of inheritance: Probably autosomal recessive

Disease-related: yes

Key variant known: yes

Year key variant first reported: 2025

Molecular basis: Vinberg et al. (2025) "sequenced the genome of the affected [Chihuahua] dog and compared the data to 1567 control genomes. Filtering for private variants identified a homozygous missense variant in ALOXE3, XP_038392720.1:p.(Gly460Asp). ALOXE3 is a known candidate gene for ichthyosis in humans and encodes arachidonate epidermal lipoxygenase 3."

Clinical features: Vinberg et al. (2025) "investigated a Chihuahua with severe scaling since age 12 weeks. The scaling was generalized and involved the entire body and legs. The paw pads were mildly hyperkeratotic."

Pathology: Vinberg et al. (2025) reported histopathological findings in skin biopsies of an affected Chihuahua which showed "markedly increased amounts of keratin in the stratum corneum (marked lamellar orthokeratotic hyperkeratosis), with keratin lifting and flaking, explaining the clinical scaling ... . Mildly increased amounts of keratin in the infundibular hair follicle lumen were also observed (infundibular hyperkeratosis)."

Breed: Chihuahua (Dog) (VBO_0200338).
Breeds in which the phene or likely causal variants have been documented. If a likely causal variant has been documented, see variant-specific breed information in the variant table. (Breed information may be incomplete).

Associated gene: