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The official name of this gene is “FK506 binding protein 10, 65 kDa.”
FKBP10 is the gene's official symbol. The FKBP10 gene is also known by other names, listed below.
The FKBP10 gene provides instructions for making a protein called FK506-binding protein 65 (FKBP65). This protein is found in a cell structure called the endoplasmic reticulum, which is involved in protein production, processing, and transport. FKBP65 is important for the correct processing of complex molecules called collagen and elastin, which are part of the intricate lattice of proteins and other molecules that forms in the spaces between cells (the extracellular matrix). This matrix provides structure and strength to connective tissues that support the body's joints and organs.
In the extracellular matrix, collagen molecules are cross-linked to one another to form long, thin fibrils. The formation of cross-links results in very strong collagen fibrils. The FKBP65 protein attaches to collagen molecules and plays a role in their cross-linking. It is thought to be involved in a reaction called hydroxylation that modifies a particular region of the collagen molecule and is necessary for cross-linking of the molecules.
The FKBP65 protein is also involved in the formation of elastin. In particular, FKBP65 helps with the proper folding of a protein called tropoelastin. Multiple copies of tropoelastin attach to one another to make elastin. Elastin is the major component of elastic fibers, which provide strength and elasticity to connective tissues as part of the extracellular matrix.
The FKBP10 gene belongs to a family of genes called EF-hand domain containing (EF-hand domain containing).
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.
At least one mutation in the FKBP10 gene causes Kuskokwim syndrome, a rare condition that affects a small number of people from the Yup'ik Eskimo population in southwest Alaska. This condition is characterized by joint deformities called contractures, particularly in the knees, ankles, and elbows. The contractures restrict the movement of affected joints.
The FKBP10 gene mutation involved in Kuskokwim syndrome deletes a single protein building block (amino acid) from the FKBP65 protein. The mutation, written as Tyr293del, removes the amino acid tyrosine at position 293. This genetic change leads to production of a protein that is unstable and easily broken down. As a result, people with Kuskokwim syndrome have only about 5 percent of the normal amount of FKBP65 protein. Although the mechanism is unclear, the reduction of FKBP65 protein leads to a severe decrease in collagen hydroxylation, which interferes with collagen cross-linking. The network of collagen molecules in affected individuals is disorganized. It is unclear how changes in the collagen matrix are involved in the development of joint contractures in people with Kuskokwim syndrome. It is unknown whether elastin abnormalities also contribute to the features of this disorder.
Mutations in the FKBP10 gene are also associated with other connective tissue disorders. Changes in this gene can cause a rare form of osteogenesis imperfecta classified as type XI. People with osteogenesis imperfecta type XI have thin, brittle bones that are prone to fracture. Another condition caused by FKBP10 gene mutations is Bruck syndrome 1, which has features similar to both osteogenesis imperfecta XI and Kuskokwim syndrome (described above): affected individuals have fragile bones as well as joint contractures that typically affect the knees, ankles, and elbows.
The mutations that cause osteogenesis imperfecta type XI and Bruck syndrome 1 lead to the production of little to no FKBP65 protein. While people with Kuskokwim syndrome have some residual collagen hydroxylation, it is nearly absent in people with osteogenesis imperfecta type XI and Bruck syndrome 1. As a result, collagen cross-linking is severely impaired: there are very few collagen fibrils in the extracellular matrix, and the network is sparse and disorganized. How these changes in collagen lead to the signs and symptoms of osteogenesis imperfecta type XI and Bruck syndrome 1 is unclear. In addition, it is unknown whether abnormalities in elastin are also involved in development of these conditions. Researchers are unsure why some people with these more severe gene mutations have joint deformities in addition to fragile bones and others do not.
Cytogenetic Location: 17q21.2
Molecular Location on chromosome 17: base pairs 41,812,261 to 41,823,216
The FKBP10 gene is located on the long (q) arm of chromosome 17 at position 21.2.
More precisely, the FKBP10 gene is located from base pair 41,812,261 to base pair 41,823,216 on chromosome 17.
See How do geneticists indicate the location of a gene? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genelocation) in the Handbook.
You and your healthcare professional may find the following resources about FKBP10 helpful.
You may also be interested in these resources, which are designed for genetics professionals and researchers.
See How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.
amino acid ; cell ; chaperone ; collagen ; connective tissue ; elastic ; endoplasmic reticulum ; extracellular ; extracellular matrix ; gene ; joint ; molecule ; mutation ; osteogenesis ; population ; precursor ; protein ; syndrome ; tissue ; tyrosine
You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://ghr.nlm.nih.gov/glossary).
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.