COL7A1

Chr 3ARAD

collagen type VII alpha 1 chain

Also known as: EBD1, EBDCT, EBR1, NDNC8

NCBI Gene: 1294 ENSG00000114270 UniProt: Q02388 OMIM: 120120

The type VII collagen alpha chain forms anchoring fibrils that secure stratified squamous epithelia to the underlying basement membrane. Mutations cause dystrophic epidermolysis bullosa, a group of blistering disorders affecting skin and mucous membranes that can present from birth with varying severity depending on inheritance pattern. The gene shows both autosomal dominant and autosomal recessive inheritance patterns, with recessive forms typically more severe.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

MultiplemechanismAR/ADLOEUF 0.599 OMIM phenotypes

Clinical Summary— COL7A1

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Gene-Disease Validity (ClinGen)

recessive dystrophic epidermolysis bullosa · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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Clinical Trials

6 active or recruiting trials — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint

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

1.59Z-score

OE missense 0.89 (0.86–0.93)

1594 obs / 1782.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios

LoF OE0.50 (0.43–0.59)

0≤0.351.4

Missense OE0.89 (0.86–0.93)

0≤0.61.4

Synonymous OE0.98

0≤1.21.6

LoF obs/exp: 100 / 198.6Missense obs/exp: 1594 / 1782.9Syn Z: 0.41

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveCOL7A1-related epidermolysis bullosa dystrophicaLOFAR

definitiveCOL7A1-related epidermolysis bullosa dystrophicaDNAD

definitiveCOL7A1-related epidermolysis bullosa pruriginosaDNAD

definitiveCOL7A1-related epidermolysis bullosa, Bart typeDNAD

0.73top 25%

GOF

0.6736th %ile

LOF

0.3648th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median · 1 literature citation

GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Literature Evidence

DNThese data demonstrate that collagen VII presents a remarkable exception among collagens in that not all glycine substitutions within the triple helix exert dominant-negative interference and that the biological consequences of the substitutions probably depend on their position within the triple hePMID:9668111

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.