OMIA:002081-9913 : Epidermolysis bullosa simplex, KRT5-related in Bos taurus (taurine cattle)

In other species: dog

Categories: Integument (skin) phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 131760 (trait) , 131900 (trait) , 601001 (trait) , 131800 (trait) , 131960 (trait) , 609352 (trait) , 148040 (gene)

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal dominant

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2005

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).

Molecular basis: In a textbook example of how to make use of clinical information to identify a comparative candidate gene (based on the homologous human disorder) namely KRT5 (keratin 5), Ford et al. (2005) showed that this disorder in the offspring of a Friesian-Jersey bull is due to a 4051G>A base substitution in the bovine KRT5 gene, leading to an E478K amino-acid substitution. The bull turned out to be mosaic for a de novo mutation. Jacinto et al. (2020): "Whole‐genome sequencing [of a "6‐day‐old Belgian Blue‐Holstein calf . . . [with] a syndrome resembling epidermolysis bullosa simplex"] revealed a heterozygous disruptive in‐frame deletion variant in KRT5 (c.534_536delCAA). Genotyping of both parents confirmed the variant as de novo mutation."

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
KRT5 keratin 5, type II Bos taurus 5 NC_037332.1 (27367078..27372929) KRT5 Homologene, Ensembl , NCBI gene


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WARNING! Inclusion of a variant in this table does not automatically mean that it should be used for DNA testing. Anyone contemplating the use of any of these variants for DNA testing should examine critically the relevant evidence (especially in breeds other than the breed in which the variant was first described). If it is decided to proceed, the location and orientation of the variant sequence should be checked very carefully.

Since October 2021, OMIA includes a semiautomated lift-over pipeline to facilitate updates of genomic positions to a recent reference genome position. These changes to genomic positions are not always reflected in the ‘acknowledgements’ or ‘verbal description’ fields in this table.

OMIA Variant ID Breed(s) Variant Phenotype Gene Allele Type of Variant Source of Genetic Variant Reference Sequence Chr. g. or m. c. or n. p. Verbal Description EVA ID Year Published PubMed ID(s) Acknowledgements
1265 Epidermolysis bullosa, simplex, KRT5-related` KRT5 deletion, small (<=20) Naturally occurring variant ARS-UCD1.2 5 g.27367604_27367606del c.534_536del p.(N178del) "27367604delCAA (NM_001008663.1:c.534_536delCAA), leading to a loss of an asparagine amino acid at residue 178 of the encoded KRT5 protein (NP_001008663.1:p.Asn178del)" (Jacinto et al., 2020). 2020 33135329 In an email dated 5 November 2020, Cord Drögemüller confirmed that the genomic specification for this variant is g.27367604_27367606delCAA
192 Friesian cross (Cattle) Jersey cross Epidermolysis bullosa KRT5 missense Naturally occurring variant ARS-UCD1.2 5 g.27371128G>A c.1432G>A p.(E478K) 2005 15955091 Variant coordinates obtained from or confirmed by EBI's Some Effect Predictor (VEP) tool

Cite this entry

Nicholas, F. W., Tammen, I., & Sydney Informatics Hub. (2020). OMIA:002081-9913: Online Mendelian Inheritance in Animals (OMIA) [dataset].


Note: the references are listed in reverse chronological order (from the most recent year to the earliest year), and alphabetically by first author within a year.

2020 Has, C., Bauer, J.W., Bodemer, C., Bolling, M.C., Bruckner-Tuderman, L., Diem, A., Fine, J.D., Heagerty, A., Hovnanian, A., Marinkovich, M.P., Martinez, A.E., McGrath, J.A., Moss, C., Murrell, D.F., Palisson, F., Schwieger-Briel, A., Sprecher, E., Tamai, K., Uitto, J., Woodley, D.T., Zambruno, G., Mellerio, J.E. :
Consensus reclassification of inherited epidermolysis bullosa and other disorders with skin fragility. Br J Dermatol 183:614-627, 2020. Pubmed reference: 32017015. DOI: 10.1111/bjd.18921.
Jacinto, J.G.P., Häfliger, I.M., Veiga, I.M.B., Drögemüller, C., Agerholm, J.S. :
A de novo mutation in KRT5 in a crossbred calf with epidermolysis bullosa simplex. J Vet Intern Med 34:2800-07, 2020. Pubmed reference: 33135329. DOI: 10.1111/jvim.15943.
2015 Bray, D.J., Walsh, T.R., Noro, M.G., Notman, R. :
Complete structure of an epithelial keratin dimer: Implications for intermediate filament assembly. PLoS One 10:e0132706, 2015. Pubmed reference: 26181054. DOI: 10.1371/journal.pone.0132706.
2012 Coulombe, P.A., Lee, C.H. :
Defining keratin protein function in skin epithelia: epidermolysis bullosa simplex and its aftermath. J Invest Dermatol 132:763-75, 2012. Pubmed reference: 22277943. DOI: 10.1038/jid.2011.450.
2005 Ford, CA., Stanfield, AM., Spelman, RJ., Smits, B., Ankersmidt-Udy, AE., Cottier, K., Holloway, H., Walden, A., Al-Wahb, M., Bohm, E., Snell, RG., Sutherland, GT. :
A mutation in bovine keratin 5 causing epidermolysis bullosa simplex, transmitted by a mosaic sire. J Invest Dermatol 124:1170-6, 2005. Pubmed reference: 15955091. DOI: 10.1111/j.0022-202X.2005.23610.x.

Edit History

  • Created by Frank Nicholas on 29 Nov 2016
  • Changed by Frank Nicholas on 04 Nov 2020
  • Changed by Frank Nicholas on 05 Nov 2020