How Epidermolysis Bullosa Simplex [EBS] is caused due to mutation in the KRT14 gene?

EBS is caused by mutations in the KRT14 gene.

More than 60 mutations in the KRT14 gene have been identified in people with EBS. Most of the mutation alters single protein building blocks — amino acids — used to make ‘keratin 14’.

The most severe form of EBS — the Dowling-Meara type —  usually results from mutations in regions of the KRT14 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.

The mutations in the KRT14 gene change the structure and function of ‘keratin 14’, preventing it from working effectively with ‘keratin 5’ 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 in the formation of painful, fluid-filled blisters.

KRT14 Gene : Location

Location

Cytogenetic Location        : 17q12-q21

Molecular Location       : Base pairs 39,738,530 — 39,743,146 on chromosome 17.

The KRT14 gene is located on the long (q) arm of chromosome 17 at position 12 and 21, precisely, from base pair 39,738,530 to base pair 39,743,146.

KRT14 Gene : Function

Function of the KRT14 gene...

The KRT14 gene provides instructions for making a protein called ‘keratin 14’.

As we already discussed in KRT5 gene ‘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 14 is specifically produced in cells called keratinocytes in the outer layer of the skin (the epidermis).

Keratin 14 partners with a similar protein, ‘keratin 5’, 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 resiliency to the skin and protects it from being damaged by friction and other everyday physical stresses.

Researchers believe that keratin 14 may also play a role in the formation of sweat glands and the development of patterned ridges on the skin of the hands and feet. These ridges, called ‘dermatoglyphs’, are the basis for each person's unique fingerprints.

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