KRT14 Gene : Gene Family

The Gene Family…

Like KRT5, the KRT14 gene belongs to the same family of genes called KRT (keratins).

KRT14 Gene : The name...

The official name of the KRT14 Gene…

Official Name  : ‘keratin 14’

Official Symbol : KRT14 is the gene's official symbol

Other Names used for the KRT14 gene or gene products…

@ CK14

@ cytokeratin 14

@ EBS3

@ EBS4

@ K1C14_HUMAN

@ K14

@ Keratin-14

@ Keratin 14

@ keratin, type I cytoskeletal 14

How Epidermolysis Bullosa Simplex [EBS] cause?

EBS is caused by mutations in the KRT5 gene.

More than 100 mutations in the KRT5 gene have been identified in people suffering with EBS. Most of the mutation alters single protein building blocks — amino acids — used to make ‘keratin 5’.

The most severe form of EBS — the Dowling-Meara type— usually caused by the mutations in the regions of keratin 5 gene which are essential for the normal assembly of keratin intermediate filaments.

Milder forms of the disorder — the Weber-Cockayne and Koebner types — are often caused by mutations in less critical regions of the protein.

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 (expressed as Pro25Leu or P25L).

The mutations in the gene KRT5 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. 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 the formation of painful, fluid-filled blisters.

KRT5 Gene : Location

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Location

Cytogenetic Location     : 12q13.13

Molecular Location   : Base pairs 52,908,358 — 52,914,242 on chromosome 12.

The KRT5 gene is located on the long (q) arm of chromosome 12 at position 13.13, precisely, from base pair 52,908,358 to base pair 52,914,242.

KRT5 Gene : Function

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 which form the structural framework for the cells which 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, to form molecules called keratin intermediate filaments. These filaments assemble into strong networks which help keratinocytes to attach together and anchor the epidermis to underlying layers of skin. The network of keratin intermediate filaments provides strength and resilience to the skin and protects it from being damaged by friction and other everyday physical stresses.

Researchers also 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).

KRT5 Gene : Gene Family

The Gene Family…

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

^ëA gene family is a group of genes which share important characteristics

KRT5 Gene : The Name

The official name of the KRT5 Gene…

Official Name of KRT5 gene is ‘keratin 5’.

Official Symbol: KRT5 is the gene's official symbol. 

Other Names used for the KRT5 gene or gene products…

@ CK5

@ cytokeratin 5

@ EBS2

@ K2C5_HUMAN

@ K5

@ 58 kda cytokeratin

@ Keratin-5

@ keratin, type II cytoskeletal 5

@ KRT5A

The Gene...

Genes related to Epidermolysis Bullosa Simplex [EBS]...

Mutations in the KRT5 and KRT14 genes are responsible for the 4 major types of Epidermolysis Bullosa Simplex. These genes provide instructions for making proteins — ‘keratin 5’ and ‘keratin 14’. These tough, fibrous proteins work together to provide strength and resiliency to the outer layer of the skin (the epidermis).

Mutations in either the KRT5 or KRT14 gene make the epidermis cells fragile and easily damageable. As a result, the skin becomes less resistant to friction & minor trauma and blisters easily.

In rare cases of EBS, no mutation in the KRT5 or KRT14 have been identified. Mutations in another gene, PLEC, have been associated with the uncommon Ogna type of the condition. The PLEC gene provides instructions for making a protein called plectin, which helps the epidermis to attach with the underlying layers of skin. Researchers continue to search for PLEC gene mutations in people with epidermolysis bullosa simplex. They are also working to determine how these mutations lead to the major features of the condition.

Prevalence

How common is Epidermolysis Bullosa Simplex?

The exact prevalence of epidermolysis bullosa simplex is unknown, but it is estimated that EBS affect 1 in 30,000 — 50,000 people. The Weber-Cockayne type is the most common form of EBS.

Genetics .....[EBS]

Epidermolysis Bullosa Simplex [EBS]

We already discussed the basic and the symptoms for Epidermolysis Bullosa Simplex [EBS]. Now let’s take a look in details on the genetic patterns and possible mutational analysis.

Researchers have identified 4 major types of EBS. Although the types differ in severity, their features overlap significantly and they are caused by mutations in the same genes.

The mildest form of EBS, known as the Weber-Cockayne type — is characterized by skin blistering mainly in hands and feet which begins anytime between childhood and adulthood. Later in life, skin on the palms and soles of the feet may thicken and harden (hyperkeratosis).

In the Koebner type — blisters appear at birth or in early infancy and are more widespread.

Another form of the disorder — epidermolysis bullosa simplex with mottled pigmentation, is characterized by patches of darker skin on the trunk, arms and legs which fade in adulthood — this form of the disorder also involves skin blistering from early infancy, hyperkeratosis of the palms and soles and abnormal nail growth.

The Dowling-Meara type is the most severe form of epidermolysis bullosa simplex. Extensive, severe blistering can occur anywhere on the body, including the inside of the mouth and in clusters. Blisters are present from birth and tends to improve with age. Affected individuals also experience abnormal nail growth and hyperkeratosis of the palms and soles.

Researchers have identified another skin condition characteristic of epidermolysis bullosa simplex — Ogna type — it is caused by mutations in a gene that is not associated with the other types of epidermolysis bullosa simplex. Researchers are still not sure whether Ogna type is a subtype of epidermolysis bullosa simplex or represents a separate form of epidermolysis bullosa.