COL7A1

Chr 3ARAD

collagen type VII alpha 1 chain

NCBI Gene: 1294ENSG00000114270UniProt: Q02388

Stratified squamous epithelial basement membrane protein that forms anchoring fibrils which may contribute to epithelial basement membrane organization and adherence by interacting with extracellular matrix (ECM) proteins such as type IV collagen

Primary Disease Associations & Inheritance

Epidermolysis bullosa dystrophica inversaMIM #226600
AR
Epidermolysis bullosa dystrophica, autosomal dominantMIM #131750
AD
Epidermolysis bullosa dystrophica, autosomal recessiveMIM #226600
AR
Epidermolysis bullosa dystrophica, Bart typeMIM #132000
AD
Epidermolysis bullosa dystrophica, localisata variantMIM #226600
AR
Epidermolysis bullosa pruriginosaMIM #604129
ADAR
Epidermolysis bullosa, pretibialMIM #131850
ADAR
Nail disorder, nonsyndromic congenital, 8MIM #607523
AD
Transient bullous of the newbornMIM #131705
ADAR
661
ClinVar variants
58
Pathogenic / LP
0.00
pLI score
6
Active trials
Clinical Summary— COL7A1
🧬
Gene-Disease Validity (ClinGen)
recessive dystrophic epidermolysis bullosa · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
58 Pathogenic / Likely Pathogenic· 402 VUS of 661 total submissions
💊
Clinical Trials
6 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.59LOEUF
pLI 0.000
Z-score 6.48
OE 0.50 (0.43–0.59)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.59Z-score
OE missense 0.89 (0.86–0.93)
1594 obs / 1782.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.50 (0.43–0.59)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.89 (0.86–0.93)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.98
0≤1.21.6
LoF obs/exp: 100 / 198.6Missense obs/exp: 1594 / 1782.9Syn Z: 0.41

ClinVar Variant Classifications

661 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic29
Likely Pathogenic29
VUS402
Likely Benign195
Benign4
Conflicting2
29
Pathogenic
29
Likely Pathogenic
402
VUS
195
Likely Benign
4
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
14
8
7
0
29
Likely Pathogenic
18
8
3
0
29
VUS
1
302
72
27
402
Likely Benign
0
4
131
60
195
Benign
0
1
3
0
4
Conflicting
—2
Total3332321687661

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

COL7A1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

COL7A1-related epidermolysis bullosa dystrophica

definitive
ARLoss Of FunctionAbsent Gene Product
EyeSkin
G2P ↗

COL7A1-related epidermolysis bullosa dystrophica

definitive
ADDominant NegativeAltered Gene Product Structure
Skin
G2P ↗

COL7A1-related epidermolysis bullosa pruriginosa

definitive
ADDominant NegativeAltered Gene Product Structure
Skin
G2P ↗

COL7A1-related epidermolysis bullosa, Bart type

definitive
ADDominant NegativeAltered Gene Product Structure
Skin
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Epidermolysis bullosa dystrophica inversa

MIM #226600

Molecular basis of disorder known

Autosomal recessive

Epidermolysis bullosa dystrophica, autosomal dominant

MIM #131750

Molecular basis of disorder known

Autosomal dominant

Epidermolysis bullosa dystrophica, autosomal recessive

MIM #226600

Molecular basis of disorder known

Autosomal recessive

Epidermolysis bullosa dystrophica, Bart type

MIM #132000

Molecular basis of disorder known

Autosomal dominant

Epidermolysis bullosa dystrophica, localisata variant

MIM #226600

Molecular basis of disorder known

Autosomal recessive

Epidermolysis bullosa pruriginosa

MIM #604129

Molecular basis of disorder known

Autosomal dominantAutosomal recessive

Epidermolysis bullosa, pretibial

MIM #131850

Molecular basis of disorder known

Autosomal dominantAutosomal recessive

Nail disorder, nonsyndromic congenital, 8

MIM #607523

Molecular basis of disorder known

Autosomal dominant

Transient bullous of the newborn

MIM #131705

Molecular basis of disorder known

Autosomal dominantAutosomal recessive
📖
GeneReview available — COL7A1
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Genotype and phenotype correlations in 441 patients with epidermolysis bullosa from China.
Chen F et al.·J Eur Acad Dermatol Venereol
2023Cohort
Epidermolysis bullosa. II. Type VII collagen mutations and phenotype-genotype correlations in the dystrophic subtypes.
Varki R et al.·J Med Genet
2007
In vivo topical gene therapy for recessive dystrophic epidermolysis bullosa: a phase 1 and 2 trial.
Gurevich I et al.·Nat Med
2022Clinical trial
Practical considerations relevant to treatment with the gene therapy beremagene geperpavec-svdt for dystrophic epidermolysis bullosa.
Paller AS et al.·J Dermatolog Treat
2024Review
Analysis of COL7A1 pathogenic variants in a large cohort of dystrophic epidermolysis bullosa patients from Argentina reveals a new genotype-phenotype correlation.
Natale MI et al.·Am J Med Genet A
2022Cohort
Identical glycine substitution mutations in type VII collagen may underlie both dominant and recessive forms of dystrophic epidermolysis bullosa.
Almaani N et al.·Acta Derm Venereol
2011
Prademagene zamikeracel for recessive dystrophic epidermolysis bullosa wounds (VIITAL): a two-centre, randomised, open-label, intrapatient-controlled phase 3 trial.
Tang JY et al.·Lancet
2025Clinical trial
Long-Term Safety and Tolerability of Beremagene Geperpavec-svdt (B-VEC) in an Open-Label Extension Study of Patients with Dystrophic Epidermolysis Bullosa.
Marinkovich MP et al.·Am J Clin Dermatol
2025Clinical trial
Exploring potential genes and mechanisms linking erectile dysfunction and depression.
Yuan P et al.·Front Endocrinol (Lausanne)
2023Functional
A scalable and cGMP-compatible autologous organotypic cell therapy for Dystrophic Epidermolysis Bullosa.
Neumayer G et al.·Nat Commun
2024
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Expression profiling, functional characterization, and potential functional variants of the COL7A1 gene in sheep horn development.
Zhang S et al.·Genomics
2025Functional
SERPINH1 promotes malignant progression of laryngeal squamous cell carcinoma via COL7A1-mediated Wnt/β-catenin signaling.
He F et al.·Cell Signal
2025
Restoration of Hair Luster via Novel Biomarker COL7A1 by Minoxidil, Caffeine, and Biotin.
Nguyen NH et al.·Curr Issues Mol Biol
2025🔓 Open Access
Safe and Efficacious Permanent Removal of Large COL7A1 Exons for Gene Reframing as a Reliable Therapeutic Strategy for Recessive Dystrophic Epidermolysis Bullosa.
López-Manzaneda S et al.·Hum Gene Ther
2025
Dystrophic epidermolysis bullosa caused by novel frameshift mutation in the COL7A1 gene: A case report.
Yang Y et al.·World J Clin Cases
2025🔓 Open AccessCase report
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
RDEBRecessive Dystrophic Epidermolysis BullosaEpidermolysis Bullosa Dystrophica, Recessive

GMEB-SASS: A Gene-Modified Skin Substitute for RDEB Treatment

RECRUITING
NCT07193134Phase PHASE1, PHASE2CHU de Quebec-Universite LavalStarted 2026-01
Genetically Modified Epidermolysis Bullosa Self-Assembled Skin Substitute (GMEB-SASS)
Epidermolysis BullosaRecessive Dystrophic Epidermolysis BullosaRDEB

A Phase 3b Study for the Treatment of Dystrophic Epidermolysis Bullosa (DEB) in New and Previously EB-101 Treated Patients

ACTIVE NOT RECRUITING
NCT05725018Phase PHASE3Abeona Therapeutics, IncStarted 2023-04-02
EB-101 Surgical application of RDEB wounds
Dystrophic Epidermolysis Bullosa

Evaluation of D-Fi for the Treatment of Wounds Due to DEB

RECRUITING
NCT06892639Phase PHASE3Castle Creek Biosciences, LLC.Started 2025-03-27
D-Fi
Squamous Cell Carcinoma

Impact of COL7A1 Gene Therapy on SCC Recurrence in RDEB Skin

RECRUITING
NCT06731933Phase PHASE2Stanford UniversityStarted 2025-03-28
BVEC
Recessive Dystrophic Epidermolysis Bullosa

A Study of FCX-007 for Recessive Dystrophic Epidermolysis Bullosa

ACTIVE NOT RECRUITING
NCT04213261Phase PHASE3Castle Creek Biosciences, LLC.Started 2020-06-09
FCX-007 (dabocemagene autoficel; see below for FCX-007 description)
Epidermolysis Bullosa Dystrophica, Recessive

Ex Vivo Gene Therapy Clinical Trial for RDEB Using Genetically Corrected Autologous Skin Equivalent Grafts

ACTIVE NOT RECRUITING
NCT04186650Phase PHASE1, PHASE2Institut National de la Santé Et de la Recherche Médicale, FranceStarted 2020-01-10
COL7A1-SIN retroviral vector engineered autologous tissue-engineered skin

External Resources

Links to major genomics databases and tools