COL7A1 Gene: Type VII Collagen Alpha 1 Chain
Genetic insights into COL7A1, the gene encoding type VII collagen, crucial for skin integrity and implicated in dystrophic epidermolysis bullosa.
Gene Information Card
| Symbol | COL7A1 |
|---|---|
| Full Name | Collagen Type VII Alpha 1 Chain |
| Gene Type | Protein coding |
| Chromosomal Location | 3p21.31 |
| NCBI Gene ID | 1294 ncbi.nlm.nih.gov/gene/1294 |
| Ensembl ID | ENSG00000114270 |
| UniProt ID | Q02388 |
| OMIM ID | 120120 |
| HGNC ID | 2214 |
| Aliases | EBD1, EBDCT, EBR1 |
Description
The COL7A1 gene provides instructions for making the alpha-1 chain of type VII collagen (COL7A1). This protein is a major component of anchoring fibrils, which are structures that anchor the basement membrane to the underlying dermis in the skin and other epithelial tissues. These fibrils are essential for maintaining the integrity of the skin by attaching the epidermis to the dermis. Mutations in this gene disrupt the formation or function of anchoring fibrils, leading to skin fragility and blistering characteristic of dystrophic epidermolysis bullosa (DEB).
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Dystrophic Epidermolysis Bullosa (DEB), Autosomal Recessive (RDEB) | Biallelic loss-of-function mutations in COL7A1 lead to absent or severely reduced type VII collagen, resulting in a lack of functional anchoring fibrils. This causes severe skin and mucosal blistering with minimal trauma. | ClinVar, OMIM |
| Dystrophic Epidermolysis Bullosa (DEB), Autosomal Dominant (DDEB) | Heterozygous mutations, often missense or glycine substitutions in the collagenous domain, exert a dominant-negative effect. The mutant collagen chains interfere with the assembly of normal triple helices, leading to reduced but present anchoring fibrils and a milder phenotype. | ClinVar, OMIM |
| Epidermolysis Bullosa Pruriginosa | A clinical subtype of DEB, often associated with specific COL7A1 mutations, leading to intense pruritus (itching) and lichenified plaques. The mechanism is similar to other DEB forms but with a distinct clinical presentation. | OMIM, PubMed |
| Transient Bullous Dermolysis of the Newborn | A rare, self-limiting form of DEB where COL7A1 mutations cause temporary blistering in newborns. The mechanism involves abnormal intracellular accumulation of type VII collagen, which often resolves spontaneously. | OMIM, PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Skin | Not available | High expression in basal keratinocytes of the epidermis. |
| Esophagus | Not available | Expression in epithelial basement membrane zones. |
| Oral Mucosa | Not available | Expression in the basement membrane zone. |
| Cornea | Not available | Expression in the epithelial basement membrane. |
| Placenta | Not available | Expression in trophoblast basement membrane. |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Keratinocytes | Not available | Primary cell type expressing COL7A1. |
| Fibroblasts | Not available | Express COL7A1, contributing to the dermal side of the basement membrane. |
| A-431 (Epidermoid Carcinoma) | Not available | Cell line known to express COL7A1. |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.6527dupC (p.Gly2177fs) | Frameshift | Common in RDEB; leads to premature termination and absent protein. | Loss of function; severe phenotype. |
| c.425A>G (p.Lys142Arg) | Missense | Found in DDEB; affects triple helix stability. | Dominant negative; milder phenotype. |
| c.682+1G>A | Splice site | Causes aberrant splicing, leading to exon skipping and frameshift. | Loss of function; severe phenotype. |
| c.4939G>A (p.Gly1647Arg) | Missense | Glycine substitution in the collagenous domain, disrupting triple helix formation. | Dominant negative; moderate to severe phenotype. |
Mutation functional classification
Loss of Function (LOF)
Biallelic loss-of-function mutations (e.g., frameshift, nonsense, splice-site) result in the complete absence of functional type VII collagen, leading to severe recessive dystrophic epidermolysis bullosa (RDEB).
Gain of Function (GOF)
No classical gain-of-function mutations are described for COL7A1. The pathogenic mechanisms are primarily loss-of-function or dominant-negative.
Dominant Negative (DN)
Heterozygous missense mutations, particularly glycine substitutions within the collagenous domain, act in a dominant-negative manner. The mutant alpha-1 chain incorporates into the triple helix, destabilizing it and reducing the amount of functional collagen, leading to dominant dystrophic epidermolysis bullosa (DDEB).
View complete mutation data：
Gene Ontology (GO)
| • extracellular matrix structural constituent | • collagen binding |
| • integrin binding | • extracellular matrix organization |
| • cell adhesion | • skin development |
| • wound healing | • basement membrane assembly |
Pathways
• Collagen biosynthesis and modifying enzymes
• Extracellular matrix organization
• Integrin signaling pathway
• Focal adhesion
Protein Summary
The COL7A1 protein is a large, 2944-amino-acid polypeptide that forms homotrimers, creating the characteristic triple-helical structure of type VII collagen. These trimers assemble into anchoring fibrils, which are essential for dermal-epidermal adhesion. The protein contains a central collagenous domain with multiple Gly-X-Y repeats, flanked by non-collagenous NC1 and NC2 domains. The NC1 domain is crucial for the interaction with other extracellular matrix components like laminin-332 and type IV collagen. Mutations affecting any of these domains can disrupt fibril assembly and function, leading to skin fragility.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| COL7A1 Knockout HEK293 Cell Line | EDC90778 | Human | 1294 | Details Get a Quote |
| COL7A1 Knockout A-549 Cell Line | EDJ-KQ23068 | Human | 1294 | Details Get a Quote |
| COL7A1 Knockout HCT 116 Cell Line | EDJ-KQ23069 | Human | 1294 | Details Get a Quote |
| COL7A1 Knockout HeLa Cell Line | EDJ-KQ23070 | Human | 1294 | Details Get a Quote |
| COL7A1（c.5097+1G>A） Point Mutation in HaCaT Cell Line | EDC03258 | Human | 1294 | Details Get a Quote |
