COL17A1: Collagen Type XVII Alpha 1 Chain
A critical hemidesmosomal structural protein involved in epidermal adhesion, skin integrity, and epithelial-mesenchymal transition; mutations cause epidermolysis bullosa and contribute to cancer progression.
Gene Information Card
| Symbol | COL17A1 |
|---|---|
| Full Name | Collagen type XVII alpha 1 chain |
| Gene Type | protein-coding |
| Chromosomal Location | 10q25.1 |
| NCBI Gene ID | 1308 ncbi.nlm.nih.gov/gene/1308 |
| Ensembl ID | ENSG00000065618 |
| UniProt ID | Q9UMD6 |
| OMIM ID | 113811 |
| HGNC ID | 2194 |
| Aliases | BP180, BPAG2, BA16H23.2, collagen XVII, 180 kDa bullous pemphigoid antigen |
Description
The COL17A1 gene encodes the alpha 1 chain of type XVII collagen, a transmembrane protein that is a key component of hemidesmosomes in basal keratinocytes. It plays a crucial role in maintaining the integrity of the dermal-epidermal junction by anchoring the epidermis to the underlying basement membrane. The protein is also known as BP180 or BPAG2 and is a major autoantigen in bullous pemphigoid. Mutations in COL17A1 lead to junctional epidermolysis bullosa, a severe skin fragility disorder. Additionally, COL17A1 has been implicated in cancer progression, particularly in squamous cell carcinoma, where its expression is often altered.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Junctional epidermolysis bullosa (JEB) | Loss-of-function mutations (nonsense, frameshift, splice-site) lead to truncated or absent collagen XVII, causing defective hemidesmosome assembly and dermal-epidermal separation. | ClinVar; OMIM #226650 |
| Bullous pemphigoid (BP) | Autoantibodies target the NC16A domain of collagen XVII, triggering complement activation and inflammatory blistering; not a genetic disease but COL17A1 is the autoantigen. | UniProt; OMIM #113811 |
| Squamous cell carcinoma (SCC) | Altered COL17A1 expression (often downregulation) promotes epithelial-mesenchymal transition and invasion; loss of collagen XVII disrupts hemidesmosomes, enhancing cell motility. | COSMIC; PubMed studies |
| Oral squamous cell carcinoma (OSCC) | Reduced COL17A1 expression correlates with poor differentiation and metastasis; functional studies show collagen XVII suppresses tumor growth. | COSMIC; PubMed studies |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Skin | High (e.g., 100-200 nTPM) | Highest expression in basal keratinocytes |
| Oral mucosa | Moderate | Epithelial layers |
| Esophagus | Moderate | Squamous epithelium |
| Breast | Low | Basal/myoepithelial cells |
| Lung | Low | Bronchial epithelium |
| Kidney | Low | Tubular cells |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HaCaT (keratinocyte) | High | Immortalized keratinocyte line; used as model for skin |
| A431 (epidermoid carcinoma) | High | Derived from skin; expresses COL17A1 |
| MCF7 (breast cancer) | Low | Low expression; not a major site |
| HeLa (cervical cancer) | Low | Minimal expression |
| A549 (lung cancer) | Low | Minimal expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1706delC (p.Pro569LeufsTer5) | Frameshift | Rare (found in JEB patients) | Loss of function; premature termination codon; nonsense-mediated decay |
| c.3061C>T (p.Arg1021Ter) | Nonsense | Rare | Loss of function; truncated protein |
| c.3466G>A (p.Gly1156Ser) | Missense | Rare | Likely affects triple helix stability; may be pathogenic |
| c.3676C>T (p.Arg1226Ter) | Nonsense | Rare | Loss of function; JEB |
| c.4150G>A (p.Gly1384Arg) | Missense | Rare | Glycine substitution in collagenous domain; disrupts triple helix |
Mutation functional classification
Loss of Function (LOF)
Most COL17A1 mutations in JEB are loss-of-function, leading to absent or non-functional collagen XVII, resulting in skin fragility and blistering.
Gain of Function (GOF)
No clear gain-of-function mutations reported; overexpression in some cancers may promote tumor progression, but this is not due to mutations.
Dominant Negative (DN)
Some missense mutations in the collagenous domain may exert dominant-negative effects by disrupting triple helix formation, but this is less common; autosomal recessive inheritance is typical.
View complete mutation data：
Gene Ontology (GO)
| • extracellular matrix structural constituent | • integrin binding |
| • protein binding | • collagen binding |
| • cell adhesion | • hemidesmosome assembly |
| • cell-matrix adhesion | • epidermis development |
| • skin morphogenesis | • response to wound healing |
Pathways
• Hemidesmosome assembly
• Cell-extracellular matrix adhesion
• Integrin signaling
• Epithelial-mesenchymal transition (EMT)
• Wound healing
Protein Summary
Collagen XVII is a homotrimeric transmembrane protein with a collagenous extracellular domain and a cytoplasmic domain that interacts with integrins and plectin. It is a structural component of hemidesmosomes, anchoring basal keratinocytes to the basement membrane. The protein undergoes proteolytic cleavage, releasing a soluble ectodomain that may have signaling roles. Mutations cause junctional epidermolysis bullosa, and autoantibodies against it cause bullous pemphigoid. In cancer, loss of collagen XVII promotes invasion and metastasis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| COL17A1 Knockout HEK293 Cell Line | EDC90455 | Human | 1308 | Details Get a Quote |
| COL17A1 Knockout A-549 Cell Line | EDJ-KQ22883 | Human | 1308 | Details Get a Quote |
| COL17A1 Knockout HCT 116 Cell Line | EDJ-KQ22884 | Human | 1308 | Details Get a Quote |
| COL17A1 Knockout HeLa Cell Line | EDJ-KQ52957 | Human | 1308 | Details Get a Quote |
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