Encyclopedia
FKBP prolyl isomerase 14: The FKBP14 gene provides instructions for making a protein called FKBP prolyl isomerase 14 (also known as FKBP22).
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1. Normal Function
This protein is found in a cell structure called the endoplasmic reticulum (ER), which is involved in protein processing and transport. Among its many functions, the endoplasmic reticulum folds and modifies newly formed proteins so they have the 3-dimensional shape they need to function properly. FKBP prolyl isomerase 14 is thought to assist with protein folding, particularly the folding of procollagens. Procollagens are the precursors of collagens, which are complex molecules found in the spaces between cells (the extracellular matrix) that add strength, support, and stretchiness (elasticity) to organs and tissues throughout the body. Studies suggest that FKBP prolyl isomerase 14 may also play a role in processing other components of the extracellular matrix.
2. Health Conditions Related to Genetic Changes
2.1 Ehlers-Danlos Syndrome
Mutations in the FKBP14 gene are one cause of a rare form of Ehlers-Danlos syndrome called the kyphoscoliotic type (kEDS-FKBP14). Ehlers-Danlos syndrome is a group of disorders that affect the connective tissues supporting the skin, bones, blood vessels, and many other organs and tissues. The kyphoscoliotic type is characterized by an unusually large range of joint movement (hypermobility); weak muscle tone (hypotonia); severe, progressive curvature of the spine (kyphoscoliosis) that can interfere with breathing; and fragile blood vessels that can tear (rupture), leading to internal bleeding. When the kyphoscoliotic type is caused by FKBP14 gene mutations, affected individuals may also have muscle wasting (atrophy) and hearing loss that is present from birth.
At least four FKBP14 gene mutations have been found to cause the kyphoscoliotic type of Ehlers-Danlos syndrome. These mutations, which affect both copies of the gene in each cell, abnormally copy (duplicate) or delete a small amount of DNA from the gene. The extra or missing genetic material prevents the gene from making functional FKBP prolyl isomerase 14. A loss of this protein disrupts the activities of the endoplasmic reticulum, including folding procollagens and processing other components of the extracellular matrix. As a result, the extracellular matrix becomes disorganized, which weakens connective tissues throughout the body and leads to the signs and symptoms of the disorder.
3. Other Names for This Gene
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22 kDa FK506-binding protein
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22 kDa FKBP
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EDSKMH
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FK506 binding protein 14
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FK506 binding protein 14, 22 kDa
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FKBP-22
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FKBP22
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FLJ20731
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IPBP12
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peptidyl-prolyl cis-trans isomerase FKBP14 precursor
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PPIase FKBP14
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rotamase
This entry is adapted from the peer-reviewed paper https://medlineplus.gov/genetics/gene/fkbp14
References
- Aldeeri AA, Alazami AM, Hijazi H, Alzahrani F, Alkuraya FS. Excessivelyredundant umbilical skin as a potential early clinical feature of Morquiosyndrome and FKBP14-related Ehlers-Danlos syndrome. Clin Genet. 2014Nov;86(5):469-72. doi: 10.1111/cge.12414.
- Baumann M, Giunta C, Krabichler B, Rüschendorf F, Zoppi N, Colombi M, Bittner RE, Quijano-Roy S, Muntoni F, Cirak S, Schreiber G, Zou Y, Hu Y, Romero NB,Carlier RY, Amberger A, Deutschmann A, Straub V, Rohrbach M, Steinmann B, RostásyK, Karall D, Bönnemann CG, Zschocke J, Fauth C. Mutations in FKBP14 cause avariant of Ehlers-Danlos syndrome with progressive kyphoscoliosis, myopathy, and hearing loss. Am J Hum Genet. 2012 Feb 10;90(2):201-16. doi:10.1016/j.ajhg.2011.12.004.
- Brady AF, Demirdas S, Fournel-Gigleux S, Ghali N, Giunta C, Kapferer-SeebacherI, Kosho T, Mendoza-Londono R, Pope MF, Rohrbach M, Van Damme T, Vandersteen A,van Mourik C, Voermans N, Zschocke J, Malfait F. The Ehlers-Danlos syndromes,rare types. Am J Med Genet C Semin Med Genet. 2017 Mar;175(1):70-115. doi:10.1002/ajmg.c.31550. Review.
- Dordoni C, Ciaccio C, Venturini M, Calzavara-Pinton P, Ritelli M, Colombi M.Further delineation of FKBP14-related Ehlers-Danlos syndrome: A patient withearly vascular complications and non-progressive kyphoscoliosis, and literaturereview. Am J Med Genet A. 2016 Aug;170(8):2031-8. doi: 10.1002/ajmg.a.37728.
- Ishikawa Y, Bächinger HP. A substrate preference for the rough endoplasmicreticulum resident protein FKBP22 during collagen biosynthesis. J Biol Chem. 2014Jun 27;289(26):18189-201. doi: 10.1074/jbc.M114.561944.
- Malfait F, Francomano C, Byers P, Belmont J, Berglund B, Black J, Bloom L,Bowen JM, Brady AF, Burrows NP, Castori M, Cohen H, Colombi M, Demirdas S, DeBacker J, De Paepe A, Fournel-Gigleux S, Frank M, Ghali N, Giunta C, Grahame R,Hakim A, Jeunemaitre X, Johnson D, Juul-Kristensen B, Kapferer-Seebacher I,Kazkaz H, Kosho T, Lavallee ME, Levy H, Mendoza-Londono R, Pepin M, Pope FM,Reinstein E, Robert L, Rohrbach M, Sanders L, Sobey GJ, Van Damme T, Vandersteen A, van Mourik C, Voermans N, Wheeldon N, Zschocke J, Tinkle B. The 2017international classification of the Ehlers-Danlos syndromes. Am J Med Genet CSemin Med Genet. 2017 Mar;175(1):8-26. doi: 10.1002/ajmg.c.31552.
- Murray ML, Yang M, Fauth C, Byers PH. FKBP14-related Ehlers-Danlos syndrome:expansion of the phenotype to include vascular complications. Am J Med Genet A.2014 Jul;164A(7):1750-5. doi: 10.1002/ajmg.a.36492.
