In other species: dog , taurine cattle

Categories: Integument (skin) phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 131960 (trait) , 609352 (trait) , 148040 (gene) , 619555 (trait) , 619599 (trait) , 619594 (trait) , 619588 (trait) , 179850 (trait)

Single-gene trait/disorder: yes

Mode of inheritance: Autosomal recessive

Disease-related: yes

Key variant known: yes

Year key variant first reported: 2020

Cross-species summary: Keratins form heterodimers comprising an acidic and a neutral keratin monomer. The two subunits intertwine in-parallel and in-register to give a central rod domain comprising, from the N- to the C-terminus, the 1A-L1-1B-L12-2A-L2-2B subdomains. 1A, 1B, 2A and 2B are coiled-coil subdomains, and L1, L12, L2 are the intervening linkers (Bray et al. 2015).
Keratin 5 (KRT5) heterodimerizes with keratin 14 (KRT14). The KRT5/KRT14 heterodimer forms intermediate filaments required for the integrity of the epidermis. The KRT5 and KRT14 genes are almost exclusively transcribed in the basal layer of the epidermis, but the proteins may persist during keratinocyte differentiation and also be found in higher layers of the epidermis (Coulombe & Lee, 2012).
Variants in KRT5 (or KRT14) may lead to various subtypes of epidermolysis bullosa simplex (EBS). The genotype-phenotype correlation is largely determined by the specific variant. Missense variants and in frame deletions often show a dominant negative effect on heterodimer formation and consequently a dominant mode of inheritance. Variants affecting the highly conserved helical subdomains within the central rod domain result in more severe generalized forms of EBS, while variants affecting the linker domains typically result in milder localized forms of EBS that may be restricted to the palmoplantar epidermis. Nonsense or frameshift variants typically result in autosomal recessive and very severe/lethal forms of EBS (Coulombe & Lee, 2012; Has et al. 2020).

Species summary:   [IT thanks Alexandra Schaening for contributions to this entry in September 2026]

Species-specific name: Epidermolysis Bullosa Simplex

Species-specific symbol: EBS

Molecular basis: Johnson et al. (2020) report two affected rhesus macaques and identified and identified a KRT5 34 bp insertion variant (KRT5:c.1087_1088insGTCTTGGTACCAGCTTGGTCTTGGTACCAGACCA; p.Lys363fs; omia.variant:1933) as likely causal variant. 

Clinical features: Johnson et al. (2020): "Animals that were homozygous for the KRT5 insertion variant were stillborn and had widespread loss of the epidermis." 

Pathology: Johnson et al. (2020): "Microscopic examination [of skin of affected animals] confirmed severe ulceration and basal cell vacuolation, with basilar vesicle formation in the remaining intact epidermis. Immunohistochemistry for cytokeratin 5 demonstrated lack of epidermal immunoreactivity in homozygotes."

Associated gene: