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FKBP10
FKBP prolyl isomerase 10
The FKBP10 gene provides instructions for a protein crucial in processing collagen and elastin, vital components for the strength and elasticity of connective tissues. The FKBP10 gene encodes a protein (formerly FKBP65) located in the endoplasmic reticulum, playing a key role in the proper formation of collagen and elastin molecules.
FKBP10 is located on the long (q) arm of chromosome 17, at band 17q21.2. Arm ratio per GRCh38 - banding schematic.
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Overview
The FKBP10 gene, also known as FKBP prolyl isomerase 10, is essential for synthesising and processing complex structural proteins within the body. It produces a protein involved in the correct assembly of collagen and elastin, which are critical for the extracellular matrix. This matrix provides the framework and mechanical strength to connective tissues throughout the body, including joints and organs. Disruptions in FKBP10 function can lead to conditions affecting bone and connective tissue integrity.
What the gene does
The protein encoded by the FKBP10 gene (formerly FKBP65) resides within the endoplasmic reticulum, a cellular compartment involved in protein production, modification, and transport. This protein is particularly important for the accurate processing of collagen and elastin, both of which are foundational components of the extracellular matrix. For collagen, FKBP10 facilitates cross-linking between molecules by contributing to a hydroxylation reaction, which strengthens collagen fibrils. It also assists in the proper folding of tropoelastin, the precursor protein to elastin. Multiple tropoelastin copies then assemble to form elastin, providing elasticity and strength to connective tissues. Therefore, FKBP10 is integral to the structural integrity and flexibility of connective tissues.
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Chromosome location
The FKBP10 gene is situated on chromosome 17 at position q21.2. This genomic location specifies its precise address within the human genome. Understanding the gene's chromosomal position can be important for genetic mapping and identifying its proximity to other genes.
Protein structure
The FKBP10 protein is 582 amino acids long and contains several distinct functional regions. It features four PPIase FKBP-type domains: PPIase FKBP-type 1 (amino acids 62-150), PPIase FKBP-type 2 (amino acids 174-262), PPIase FKBP-type 3 (amino acids 286-374), and PPIase FKBP-type 4 (amino acids 399-486). Additionally, the protein includes two EF-hand domains: EF-hand 1 (amino acids 497-532) and EF-hand 2 (amino acids 542-577). A disordered region is present from amino acids 533-582, and a specific motif (amino acids 579-582) prevents its secretion from the endoplasmic reticulum.
Key variants
Variants within the FKBP10 gene can lead to alterations in the protein's structure or function, impacting its ability to correctly process collagen and elastin. These genetic changes are typically inherited and can result in a spectrum of connective tissue disorders. The clinical presentation often depends on the specific variant and its effect on protein activity.
Sample of pathogenic variants
10 pathogenic / likely-pathogenic variants from ClinVar, ranked by review status (expert-panel-reviewed first). This is a sample; recurrent founder variants in a specific population may not appear here - see the full ClinVar listing via the link above.
| Variant (HGVS) | Protein change | Classification | Evidence | Associated condition |
|---|---|---|---|---|
c.1256+1G>A | - | Pathogenic/Likely pathogenic | ★★☆☆ | Osteogenesis imperfecta |
c.1276del | p.Gln426fs | Pathogenic/Likely pathogenic | ★★☆☆ | Bruck syndrome 1 |
c.1373dup | p.His459fs | Pathogenic | ★★☆☆ | Osteogenesis imperfecta |
c.1563+1G>A | - | Pathogenic/Likely pathogenic | ★★☆☆ | Bruck syndrome 1 |
c.1621C>T | p.Gln541Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Bruck syndrome 1 |
c.21dup | p.Ser8fs | Pathogenic/Likely pathogenic | ★★☆☆ | Osteogenesis imperfecta type 11 |
c.343C>T | p.Arg115Ter | Pathogenic | ★★☆☆ | not provided |
c.612C>G | p.Tyr204Ter | Pathogenic | ★★☆☆ | Osteogenesis imperfecta type 11 |
c.829_841del | p.Pro277fs | Pathogenic/Likely pathogenic | ★★☆☆ | Bruck syndrome 1 |
c.918-3C>A | - | Pathogenic/Likely pathogenic | ★★☆☆ | Osteogenesis imperfecta |
Evidence stars indicate ClinVar review status. Individual variant interpretation should always be performed by a qualified clinical laboratory - many variants remain classified as Variants of Uncertain Significance (VUS) pending more research.
Associated conditions
Variants in the FKBP10 gene are associated with several inherited conditions that primarily affect connective tissues. These include osteogenesis imperfecta, characterised by fragile bones, and Kuskokwim syndrome, which presents with joint contractures, particularly in the knees, ankles, and elbows. FKBP10 variants are also linked to Bruck syndrome 1, a condition with features resembling both osteogenesis imperfecta type XI and Kuskokwim syndrome, leading to fragile bones and joint contractures.
No disease links recorded for this gene in our reference set.
UK clinical status
The FKBP10 gene is included on several NHS Genomic Medicine Service clinical panels in the UK, reflecting its recognised role in inherited conditions. It is part of panels for Arthrogryposis (R83), Foetal anomalies (R21), Osteogenesis imperfecta (R102), and Skeletal dysplasia (R104), and is also listed in DDG2P.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What is the main function of the FKBP10 gene?
The FKBP10 gene provides instructions for a protein that is crucial for the proper processing and folding of collagen and elastin. These structural proteins are vital components of the extracellular matrix, which gives strength and elasticity to the body's connective tissues.
What conditions are associated with FKBP10 gene variants?
Variants in the FKBP10 gene are linked to several inherited connective tissue disorders, including osteogenesis imperfecta, Kuskokwim syndrome, and Bruck syndrome 1. These conditions primarily affect bone strength and joint mobility.
Where is the FKBP10 protein found within the cell?
The protein produced by the FKBP10 gene is located in the endoplasmic reticulum, a cellular organelle responsible for synthesising, processing, and transporting proteins within the cell.
References
- Schwarze U, Cundy T, Pyott SM. Mutations in FKBP10, which result in Bruck syndrome and recessive forms of osteogenesis imperfecta, inhibit the hydroxylation of telopeptide lysines in bone collagen. Human molecular genetics. 2013. PMID: 22949511
- Miao M, Reichheld SE, Muiznieks LD. Elastin binding protein and FKBP65 modulate in vitro self-assembly of human tropoelastin. Biochemistry. 2013. PMID: 24106871
- Barnes AM, Cabral WA, Weis M. Absence of FKBP10 in recessive type XI osteogenesis imperfecta leads to diminished collagen cross-linking and reduced collagen deposition in extracellular matrix. Human mutation. 2012. PMID: 22718341
- Ishikawa Y, Vranka J, Wirz J. The rough endoplasmic reticulum-resident FK506-binding protein FKBP65 is a molecular chaperone that interacts with collagens. The Journal of biological chemistry. 2008. PMID: 18786928