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.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes the alpha chain of type VII collagen. The type VII collagen fibril, composed of three identical alpha collagen chains, is restricted to the basement zone beneath stratified squamous epithelia. It functions as an anchoring fibril between the external epithelia and the underlying stroma. Mutations in this gene are associated with all forms of dystrophic epidermolysis bullosa. In the absence of mutations, however, an acquired form of this disease can result from an autoimmune response made to type VII collagen. [provided by RefSeq, Jul 2008]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Epidermolysis bullosa dystrophica inversaMIM #226600

Epidermolysis bullosa dystrophica, autosomal dominantMIM #131750

Epidermolysis bullosa dystrophica, autosomal recessiveMIM #226600

Epidermolysis bullosa dystrophica, Bart typeMIM #132000

Epidermolysis bullosa dystrophica, localisata variantMIM #226600

Epidermolysis bullosa pruriginosaMIM #604129

ADAR

Epidermolysis bullosa, pretibialMIM #131850

ADAR

Nail disorder, nonsyndromic congenital, 8MIM #607523

Transient bullous of the newbornMIM #131705

ADAR

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · recessive dystrophic epidermolysis bullosa · AR · ClinGen 2022

Interpreting a novel variant

The dominant disease is caused by dominant-negative changes and the recessive disease by loss of function (Gene2Phenotype). A single heterozygous truncating variant therefore fits the recessive disease and does not by itself explain a dominant presentation; a novel missense has to be read against the dominant mechanism.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

103

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.59

LOEUF

Multiple*

Mechanism· G2P

📖

GeneReview available — COL7A1

Authoritative clinical overview · Recommended first read

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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 OE?0.50 (0.43–0.59)

0≤0.351.4

Missense OE?0.89 (0.86–0.93)

0≤0.61.4

Synonymous OE?0.98

0≤1.21.6

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

Background carrier burden — how many people carry a rare variant somewhere in COL7A1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 14

3,708 rare PASS variants

Rare truncating (LoF)

1 in 240

602 rare PASS variants

Rare synonymous (reference)

1 in 28

1,548 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for COL7A1. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 17	1 in 200
South Asian	~43k	1 in 12	1 in 190
Remaining (unassigned)	~30k	1 in 12	1 in 270
European (Finnish)	~27k	1 in 37	1 in 480
Admixed American	~22k	1 in 13	1 in 240
African / African American	~21k	1 in 11	1 in 390
East Asian	~20k	1 in 13	1 in 210
Ashkenazi Jewish	~13k	1 in 57	1 in 380
Middle Eastern	~2,884	1 in 13	≈ 1 in 720

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 118 coding exons well covered in gnomAD exomes and genomes.? see exons ↓