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Normal Function
The FERMT1 gene provides instructions for making a protein called kindlin-1. This protein is found in epithelial cells, which are the cells that line the surfaces and cavities of the body. In the skin, kindlin-1 plays a critical role in specialized cells called keratinocytes, which are the major component of the outer layer of the skin (the epidermis).
Kindlin-1 is part of cell structures called focal adhesions. These structures contain many different kinds of proteins, which are involved in linking the cell's internal framework (the cytoskeleton) to the intricate lattice of proteins and other molecules that surrounds cells (the extracellular matrix). This linking is known as cell-matrix adhesion. Kindlin-1 attaches (binds) to and turns on (activates) proteins called integrins, which directly connect the cytoskeleton with the extracellular matrix and help transmit chemical signals into the cell.
As part of focal adhesions, Kindlin-1 is involved in several important cell functions, including cell growth and division (proliferation) and the movement (migration) of cells.
Health Conditions Related to Genetic Changes
Kindler epidermolysis bullosa
More than 70 variants (also known as mutations) in the FERMT1 gene have been identified in people with Kindler epidermolysis bullosa (EB). This disorder is a rare type of epidermolysis bullosa, which is a group of genetic conditions that cause the skin to be very fragile and to blister easily. Kindler EB also affects the moist lining (mucosae) of the mouth, eyes, esophagus, intestines, genitals, and urinary system, causing these tissues to be very fragile. In addition, people with Kindler EB have an increased risk of developing a form of cancer called squamous cell carcinoma.
Most variants in the FERMT1 gene prevent the production of any functional kindlin-1. A lack of this protein disrupts many essential cell functions. For example, keratinocytes without kindlin-1 have an abnormal structure and cannot grow or divide normally. They are also less able to attach the epidermis to the underlying layer of skin (the dermis). These changes make the skin fragile and prone to blistering. Similarly, a lack of kindlin-1 in epithelial cells of the mucosae causes damage that makes these tissues extremely fragile. It is unclear how a shortage of kindlin-1 is related to squamous cell carcinoma in people with Kindler EB.
More About This Health ConditionOther Names for This Gene
- C20orf42
- DTGCU2
- fermitin family homolog 1
- FLJ20116
- KIND1
- kindlerin
- kindlin 1
- kindlin syndrome protein
- unc-112-related protein 1
- UNC112 related protein 1
- UNC112A
- URP1
Additional Information & Resources
Tests Listed in the Genetic Testing Registry
Scientific Articles on PubMed
Catalog of Genes and Diseases from OMIM
References
- Ashton GH, McLean WH, South AP, Oyama N, Smith FJ, Al-Suwaid R, Al-Ismaily A, Atherton DJ, Harwood CA, Leigh IM, Moss C, Didona B, Zambruno G, Patrizi A, Eady RA, McGrath JA. Recurrent mutations in kindlin-1, a novel keratinocyte focal contact protein, in the autosomal recessive skin fragility and photosensitivity disorder, Kindler syndrome. J Invest Dermatol. 2004 Jan;122(1):78-83. doi: 10.1046/j.0022-202X.2003.22136.x. Citation on PubMed
- Has C, Castiglia D, del Rio M, Diez MG, Piccinni E, Kiritsi D, Kohlhase J, Itin P, Martin L, Fischer J, Zambruno G, Bruckner-Tuderman L. Kindler syndrome: extension of FERMT1 mutational spectrum and natural history. Hum Mutat. 2011 Nov;32(11):1204-12. doi: 10.1002/humu.21576. Epub 2011 Sep 20. Citation on PubMed
- Heinemann A, He Y, Zimina E, Boerries M, Busch H, Chmel N, Kurz T, Bruckner-Tuderman L, Has C. Induction of phenotype modifying cytokines by FERMT1 mutations. Hum Mutat. 2011 Apr;32(4):397-406. doi: 10.1002/humu.21449. Epub 2011 Mar 1. Citation on PubMed
- Herz C, Aumailley M, Schulte C, Schlotzer-Schrehardt U, Bruckner-Tuderman L, Has C. Kindlin-1 is a phosphoprotein involved in regulation of polarity, proliferation, and motility of epidermal keratinocytes. J Biol Chem. 2006 Nov 24;281(47):36082-90. doi: 10.1074/jbc.M606259200. Epub 2006 Oct 1. Citation on PubMed
- Jobard F, Bouadjar B, Caux F, Hadj-Rabia S, Has C, Matsuda F, Weissenbach J, Lathrop M, Prud'homme JF, Fischer J. Identification of mutations in a new gene encoding a FERM family protein with a pleckstrin homology domain in Kindler syndrome. Hum Mol Genet. 2003 Apr 15;12(8):925-35. doi: 10.1093/hmg/ddg097. Citation on PubMed
- Lai-Cheong JE, McGrath JA. Kindler syndrome. Dermatol Clin. 2010 Jan;28(1):119-24. doi: 10.1016/j.det.2009.10.013. Citation on PubMed
- Margadant C, Kreft M, Zambruno G, Sonnenberg A. Kindlin-1 regulates integrin dynamics and adhesion turnover. PLoS One. 2013 Jun 11;8(6):e65341. doi: 10.1371/journal.pone.0065341. Print 2013. Citation on PubMed or Free article on PubMed Central
- Siegel DH, Ashton GH, Penagos HG, Lee JV, Feiler HS, Wilhelmsen KC, South AP, Smith FJ, Prescott AR, Wessagowit V, Oyama N, Akiyama M, Al Aboud D, Al Aboud K, Al Githami A, Al Hawsawi K, Al Ismaily A, Al-Suwaid R, Atherton DJ, Caputo R, Fine JD, Frieden IJ, Fuchs E, Haber RM, Harada T, Kitajima Y, Mallory SB, Ogawa H, Sahin S, Shimizu H, Suga Y, Tadini G, Tsuchiya K, Wiebe CB, Wojnarowska F, Zaghloul AB, Hamada T, Mallipeddi R, Eady RA, McLean WH, McGrath JA, Epstein EH. Loss of kindlin-1, a human homolog of the Caenorhabditis elegans actin-extracellular-matrix linker protein UNC-112, causes Kindler syndrome. Am J Hum Genet. 2003 Jul;73(1):174-87. doi: 10.1086/376609. Epub 2003 Jun 3. Citation on PubMed or Free article on PubMed Central
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