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Genetics Home Reference: your guide to understanding genetic conditions
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KRT5

Reviewed May 2013

What is the official name of the KRT5 gene?

The official name of this gene is “keratin 5.”

KRT5 is the gene's official symbol. The KRT5 gene is also known by other names, listed below.

What is the normal function of the KRT5 gene?

The KRT5 gene provides instructions for making a protein called keratin 5. Keratins are a group of tough, fibrous proteins that form the structural framework of certain cells, particularly cells that make up the skin, hair, and nails. Keratin 5 is produced in cells called keratinocytes found in the outer layer of the skin (the epidermis).

Keratin 5 partners with a similar protein, keratin 14 (produced from the KRT14 gene), to form molecules called keratin intermediate filaments. These filaments assemble into strong networks that help attach keratinocytes together and anchor the epidermis to underlying layers of skin. The network of keratin intermediate filaments provides strength and resiliency to the skin and protects it from being damaged by friction and other everyday physical stresses.

Researchers believe that keratin 5 may also play a role in transporting melanosomes, which are cellular structures that produce a pigment called melanin. The transport of these structures into keratinocytes is important for normal skin coloration (pigmentation).

Does the KRT5 gene share characteristics with other genes?

The KRT5 gene belongs to a family of genes called KRT (keratins).

A gene family is a group of genes that share important characteristics. Classifying individual genes into families helps researchers describe how genes are related to each other. For more information, see What are gene families? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genefamilies) in the Handbook.

How are changes in the KRT5 gene related to health conditions?

Dowling-Degos disease - caused by mutations in the KRT5 gene

At least four mutations in the KRT5 gene have been found to cause Dowling-Degos disease. This condition is characterized by various skin abnormalities, particularly a lacy pattern of abnormally dark skin coloring (hyperpigmentation) that occurs most often in the body's folds and creases. Most of these mutations lead to the production of a keratin 5 protein that is abnormally small and nonfunctional or prevent any protein from being produced from the gene. A reduced amount of functional keratin 5 can impair the formation of keratin intermediate filaments. As a result, the organization of the epidermis is altered, leading to the development of different types of skin abnormalities. Additionally, a shortage of keratin 5 may disrupt the movement of pigment-carrying melanosomes into keratinocytes, where they are needed for normal skin pigmentation. This disruption of melanosome transport is thought to cause the pigmentation abnormalities seen in individuals with Dowling-Degos disease.

epidermolysis bullosa simplex - caused by mutations in the KRT5 gene

More than 100 mutations in the KRT5 gene have been identified in people with epidermolysis bullosa simplex, a condition that causes the skin to be very fragile and to blister easily. Most of these mutations alter single protein building blocks (amino acids) used to make keratin 5. The most severe form of epidermolysis bullosa simplex, the Dowling-Meara type, usually results from changes in regions of keratin 5 that are essential for the normal assembly of keratin intermediate filaments. Milder forms of the disorder, including the localized type (formerly called the Weber-Cockayne type) and a form known as the other generalized type (formerly called the Koebner type), are often caused by changes affecting less critical regions of the protein. Another form of the disorder called epidermis bullosa simplex with mottled pigmentation typically results from a particular KRT5 mutation. This mutation replaces the amino acid proline with the amino acid leucine at protein position 25 (written as Pro25Leu or P25L).

The KRT5 gene mutations responsible for epidermolysis bullosa simplex change the structure and function of keratin 5, preventing it from working effectively with keratin 14 and interfering with the assembly of the keratin intermediate filament network. Mutations that cause severe forms of the disorder severely disrupt the assembly of keratin intermediate filaments, while mutations that result in milder forms impair keratin filament assembly to a lesser degree. A disruption in this network makes keratinocytes fragile and prone to rupture. Minor trauma to the skin, such as rubbing or scratching, can cause these cells to break down, resulting in the formation of painful, fluid-filled blisters.

Where is the KRT5 gene located?

Cytogenetic Location: 12q13.13

Molecular Location on chromosome 12: base pairs 52,514,574 to 52,520,458

The KRT5 gene is located on the long (q) arm of chromosome 12 at position 13.13.

The KRT5 gene is located on the long (q) arm of chromosome 12 at position 13.13.

More precisely, the KRT5 gene is located from base pair 52,514,574 to base pair 52,520,458 on chromosome 12.

See How do geneticists indicate the location of a gene? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genelocation) in the Handbook.

Where can I find additional information about KRT5?

You and your healthcare professional may find the following resources about KRT5 helpful.

You may also be interested in these resources, which are designed for genetics professionals and researchers.

What other names do people use for the KRT5 gene or gene products?

  • 58 kda cytokeratin
  • CK5
  • cytokeratin 5
  • EBS2
  • K2C5_HUMAN
  • K5
  • Keratin-5
  • keratin, type II cytoskeletal 5
  • KRT5A

See How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What glossary definitions help with understanding KRT5?

acids ; amino acid ; blister ; cytokeratin ; epidermis ; gene ; intermediate filaments ; keratin ; leucine ; melanin ; melanosome ; mutation ; pigment ; pigmentation ; proline ; protein ; reticulate ; rupture ; skin pigmentation ; trauma

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

  • Arin MJ, Grimberg G, Schumann H, De Almeida H Jr, Chang YR, Tadini G, Kohlhase J, Krieg T, Bruckner-Tuderman L, Has C. Identification of novel and known KRT5 and KRT14 mutations in 53 patients with epidermolysis bullosa simplex: correlation between genotype and phenotype. Br J Dermatol. 2010 Jun;162(6):1365-9. doi: 10.1111/j.1365-2133.2010.09657.x. Epub 2010 Feb 25. (http://www.ncbi.nlm.nih.gov/pubmed/20199538?dopt=Abstract)
  • Betz RC, Planko L, Eigelshoven S, Hanneken S, Pasternack SM, Bussow H, Van Den Bogaert K, Wenzel J, Braun-Falco M, Rutten A, Rogers MA, Ruzicka T, Nöthen MM, Magin TM, Kruse R. Loss-of-function mutations in the keratin 5 gene lead to Dowling-Degos disease. Am J Hum Genet. 2006 Mar;78(3):510-9. Epub 2006 Jan 19. (http://www.ncbi.nlm.nih.gov/pubmed/16465624?dopt=Abstract)
  • Bolling MC, Lemmink HH, Jansen GH, Jonkman MF. Mutations in KRT5 and KRT14 cause epidermolysis bullosa simplex in 75% of the patients. Br J Dermatol. 2011 Mar;164(3):637-44. doi: 10.1111/j.1365-2133.2010.10146.x. Epub 2011 Feb 17. (http://www.ncbi.nlm.nih.gov/pubmed/21375516?dopt=Abstract)
  • Gene Review: Epidermolysis Bullosa Simplex (http://www.ncbi.nlm.nih.gov/books/NBK1369)
  • Liao H, Zhao Y, Baty DU, McGrath JA, Mellerio JE, McLean WH. A heterozygous frameshift mutation in the V1 domain of keratin 5 in a family with Dowling-Degos disease. J Invest Dermatol. 2007 Feb;127(2):298-300. Epub 2006 Aug 17. (http://www.ncbi.nlm.nih.gov/pubmed/16917491?dopt=Abstract)
  • Müller FB, Küster W, Wodecki K, Almeida H Jr, Bruckner-Tuderman L, Krieg T, Korge BP, Arin MJ. Novel and recurrent mutations in keratin KRT5 and KRT14 genes in epidermolysis bullosa simplex: implications for disease phenotype and keratin filament assembly. Hum Mutat. 2006 Jul;27(7):719-20. (http://www.ncbi.nlm.nih.gov/pubmed/16786515?dopt=Abstract)
  • NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/3852)
  • Pfendner EG, Sadowski SG, Uitto J. Epidermolysis bullosa simplex: recurrent and de novo mutations in the KRT5 and KRT14 genes, phenotype/genotype correlations, and implications for genetic counseling and prenatal diagnosis. J Invest Dermatol. 2005 Aug;125(2):239-43. (http://www.ncbi.nlm.nih.gov/pubmed/16098032?dopt=Abstract)
  • Planko L, Böhse K, Höhfeld J, Betz RC, Hanneken S, Eigelshoven S, Kruse R, Nöthen MM, Magin TM. Identification of a keratin-associated protein with a putative role in vesicle transport. Eur J Cell Biol. 2007 Dec;86(11-12):827-39. Epub 2007 Mar 29. (http://www.ncbi.nlm.nih.gov/pubmed/17397964?dopt=Abstract)
  • Schuilenga-Hut PH, Vlies Pv, Jonkman MF, Waanders E, Buys CH, Scheffer H. Mutation analysis of the entire keratin 5 and 14 genes in patients with epidermolysis bullosa simplex and identification of novel mutations. Hum Mutat. 2003 Apr;21(4):447. Review. (http://www.ncbi.nlm.nih.gov/pubmed/12655565?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: May 2013
Published: December 22, 2014