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COL17A1
collagen type XVII alpha 1 chain
The COL17A1 gene provides instructions for making type XVII collagen, a crucial protein for the structural integrity and stability of the skin. COL17A1 is vital for assembling type XVII collagen, which helps anchor the epidermis to the underlying layers of the skin through structures called hemidesmosomes.
COL17A1 is located on the long (q) arm of chromosome 10, at band 10q25.1. Arm ratio per GRCh38 - banding schematic.
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Overview
The COL17A1 gene, also known as collagen type XVII alpha 1 chain, encodes a protein that forms type XVII collagen. Collagens are a family of structural proteins essential for strengthening and supporting connective tissues throughout the body, including the skin, bones, tendons, and ligaments. Specifically, type XVII collagen is critical for maintaining the strength and stability of the skin, preventing separation of its layers.
What the gene does
The protein produced by the COL17A1 gene is a pro-α1(XVII) chain. Three identical pro-α1(XVII) chains combine to form a triple-stranded procollagen molecule. These molecules are then processed and assembled into long, thin bundles of mature type XVII collagen outside the cell. Type XVII collagen is a primary component of hemidesmosomes, microscopic structures located on the inner surface of the epidermis, the skin's outermost layer. Hemidesmosomes are responsible for anchoring the epidermis to the underlying dermal layers, and type XVII collagen's presence within these structures is essential for holding the skin layers together effectively. The protein's nonhelical region (NC16), specifically amino acids 145-230, is necessary for interacting with the DST protein and recruiting it to the hemidesmosome.
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Chromosome location
The COL17A1 gene is located on chromosome 10 at position 10q25.1. This specific genomic location indicates where the gene can be found within the human genome.
Protein structure
The COL17A1 protein consists of 1497 amino acids and features distinct structural regions. The Nonhelical region (NC16) spans amino acids 1-566, with a Disordered segment from amino acids 1-154. A critical functional region, necessary for interaction with DST and for the recruitment of DST to hemidesmosome, is located between amino acids 145-230. Further Disordered segments are found at amino acids 167-186 and 562-1011. The core structural component is the Triple-helical region, spanning amino acids 567-1482. Additional Disordered regions are present at amino acids 1209-1234, 1261-1316, and 1434-1497. The Nonhelical region (NC1) is found at the C-terminus, from amino acids 1483-1497.
Key variants
Variants in the COL17A1 gene can alter the production or function of type XVII collagen. More than 100 variants have been identified, primarily involving additions or removals of DNA building blocks or the introduction of premature stop signals. These genetic changes typically lead to a reduced amount of functional type XVII collagen within the skin.
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.1696C>T | p.Arg566Ter | Pathogenic | ★★☆☆ | not provided |
c.2551+1G>T | - | Pathogenic/Likely pathogenic | ★★☆☆ | Epidermolysis bullosa, junctional 4, intermediate |
c.2635C>T | p.Arg879Ter | Pathogenic | ★★☆☆ | not provided |
c.3198C>T | p.Ser1066= | Pathogenic | ★★☆☆ | Epidermolysis bullosa, junctional 4, intermediate |
c.340del | p.Ser114fs | Pathogenic/Likely pathogenic | ★★☆☆ | Epithelial recurrent erosion dystrophy |
c.3613_3616del | p.Leu1205fs | Pathogenic | ★★☆☆ | Epidermolysis bullosa, junctional 4, intermediate |
c.3672del | p.Pro1225fs | Pathogenic | ★★☆☆ | not provided |
c.3686dup | p.Val1231fs | Pathogenic | ★★☆☆ | Epidermolysis bullosa, junctional 4, intermediate |
c.3800dup | p.Gly1268fs | Pathogenic | ★★☆☆ | COL17A1-related disorders |
c.380-1G>A | - | Pathogenic | ★★☆☆ | not provided |
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 COL17A1 gene are associated with inherited conditions that primarily affect skin integrity. The most commonly linked condition is junctional epidermolysis bullosa (JEB), a group of rare genetic disorders characterised by extreme skin fragility and blistering. These conditions arise due to the compromised anchoring function of type XVII collagen within the skin layers.
No disease links recorded for this gene in our reference set.
Inheritance pattern
Conditions caused by pathogenic COL17A1 variants typically follow autosomal recessive inheritance.
When both parents are carriers, each child has a 25% chance of being affected, 50% of being a carrier, and 25% of being unaffected.
UK clinical status
The COL17A1 gene is part of several NHS Genomic Medicine Service national test panels. These include panels for Amelogenesis imperfecta (R340), Corneal dystrophy (R262), and Epidermolysis bullosa (R164), indicating its relevance in diagnosing these conditions within the UK healthcare system.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What is the primary function of the COL17A1 gene?
The COL17A1 gene provides instructions for making type XVII collagen, a protein crucial for strengthening and stabilising the skin. It helps to anchor the top layer of skin (epidermis) to the layers beneath it.
What happens if there are variants in the COL17A1 gene?
Variants in the COL17A1 gene can reduce the amount of functional type XVII collagen. This can lead to conditions where the skin is fragile and prone to blistering, such as junctional epidermolysis bullosa.
Is COL17A1 relevant to NHS testing in the UK?
Yes, COL17A1 is included in several NHS Genomic Medicine Service national test panels. This indicates its importance for diagnosing conditions like Amelogenesis imperfecta, Corneal dystrophy, and Epidermolysis bullosa within the UK healthcare system.
References
- Pasmooij AM, Pas HH, Jansen GH. Localized and generalized forms of blistering in junctional epidermolysis bullosa due to COL17A1 mutations in the Netherlands. The British journal of dermatology. 2007. PMID: 17263807
- Fu CL, Giudice GJ, Van den Bergh F. Protein structural analysis of BP180 mutant isoforms linked to non-Herlitz junctional epidermolysis bullosa. The Journal of investigative dermatology. 2006. PMID: 16417243
- Varki R, Sadowski S, Pfendner E. Epidermolysis bullosa. I. Molecular genetics of the junctional and hemidesmosomal variants. Journal of medical genetics. 2006. PMID: 16473856
- Nakamura H, Sawamura D, Goto M. Analysis of the COL17A1 in non-Herlitz junctional epidermolysis bullosa and amelogenesis imperfecta. International journal of molecular medicine. 2006. PMID: 16820943
- Franzke CW, Has C, Schulte C. C-terminal truncation impairs glycosylation of transmembrane collagen XVII and leads to intracellular accumulation. The Journal of biological chemistry. 2006. PMID: 16899459
- Bauer JW, Lanschuetzer C. Type XVII collagen gene mutations in junctional epidermolysis bullosa and prospects for gene therapy. Clinical and experimental dermatology. 2003. PMID: 12558632
- Ruzzi L, Pas H, Posteraro P. A homozygous nonsense mutation in type XVII collagen gene (COL17A1) uncovers an alternatively spliced mRNA accounting for an unusually mild form of non-Herlitz junctional epidermolysis bullosa. The Journal of investigative dermatology. 2001. PMID: 11168815
- Pulkkinen L, Uitto J. Mutation analysis and molecular genetics of epidermolysis bullosa. Matrix biology : journal of the International Society for Matrix Biology. 1999. PMID: 10367729
- Gatalica B, Pulkkinen L, Li K. Cloning of the human type XVII collagen gene (COL17A1), and detection of novel mutations in generalized atrophic benign epidermolysis bullosa. American journal of human genetics. 1997. PMID: 9012408