Generalized dominant dystrophic epidermolysis bullosa

Summary

Generalized dominant dystrophic epidermolysis bullosa (MONDO:0007549) is a disease caused by COL7A1 (GenCC Strong), with 1 cohort gene and 4 clinical trials. Top therapeutic interventions include beremagene geperpavec.

At a glance

• Prevalence: Unknown (Worldwide)
• Causal gene: COL7A1 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 293
• Phenotypes (HPO): 15
• Clinical trials: 4

Clinical features

Signs & symptoms

Clinical features (HPO)

15 HPO clinical features (Orphanet curated; top 15 by frequency):

HPO ID	Term	Frequency
HP:0000987	Atypical scarring of skin	Very frequent (80-99%)
HP:0008066	Abnormal blistering of the skin	Very frequent (80-99%)
HP:0001030	Fragile skin	Frequent (30-79%)
HP:0001056	Milia	Frequent (30-79%)
HP:0001810	Dystrophic toenail	Frequent (30-79%)
HP:0008404	Nail dystrophy	Frequent (30-79%)
HP:0031045	Acral blistering	Frequent (30-79%)
HP:0001075	Atrophic scars	Occasional (5-29%)
HP:0001802	Absent toenail	Occasional (5-29%)
HP:0001817	Absent fingernail	Occasional (5-29%)
HP:0008390	Recurrent loss of toenails and fingernails	Occasional (5-29%)
HP:0008391	Dystrophic fingernails	Occasional (5-29%)
HP:0031446	Erosion of oral mucosa	Occasional (5-29%)
HP:0200041	Skin erosion	Occasional (5-29%)
HP:0200097	Oral mucosal blisters	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	generalized dominant dystrophic epidermolysis bullosa
Mondo ID	MONDO:0007549
OMIM	131750
Orphanet	231568
DOID	DOID:0080224
SNOMED CT	75875004
UMLS	C0432322
MedGen	140935
GARD	0002139
Is cancer (heuristic)	no

Also known as: autosomal dominant dystrophic epidermolysis bullosa, Pasini and Cockayne-Touraine types · DDEB · DDEB, generalised · DDEB, generalized · DDEB, Pasini and Cockayne-Touraine types · DDEB-gen · dominant dystrophic epidermolysis bullosa · dominant dystrophic epidermolysis bullosa, generalised · dominant dystrophic epidermolysis bullosa, generalized · epidermolysis bullosa dystrophica, AD · epidermolysis bullosa dystrophica, autosomal dominant · epidermolysis bullosa dystrophica, Cockayne-Touraine type (formerly) · epidermolysis bullosa dystrophica, Pasini type (formerly)

Data availability: 293 ClinVar variants · 3 GenCC gene-disease records · 1 cell line.

Disease family

Classification path: disease › human disease › disease by body system or component › integumentary system disorder › skin disorder › vesiculobullous skin disease › epidermolysis bullosa › inherited epidermolysis bullosa › epidermolysis bullosa dystrophica › generalized dominant dystrophic epidermolysis bullosa

Related subtypes (11): transient bullous dermolysis of the newborn, pretibial dystrophic epidermolysis bullosa, epidermolysis bullosa dystrophica Neurotrophica, recessive dystrophic epidermolysis bullosa, dystrophic epidermolysis bullosa pruriginosa, acral dystrophic epidermolysis bullosa, dystrophic epidermolysis bullosa, nails only, centripetalis recessive dystrophic epidermolysis bullosa, recessive dystrophic epidermolysis bullosa-generalized other, localized dystrophic epidermolysis bullosa, epidermolysis bullosa dystrophica with subcorneal cleavage

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

293 retrieved; paginated sample, class counts are floors:

72 pathogenic, 69 likely pathogenic, 61 pathogenic/likely pathogenic, 58 conflicting classifications of pathogenicity, 19 uncertain significance, 7 likely benign, 5 benign/likely benign, 2 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1032188	NM_000094.4(COL7A1):c.8304+1G>A	COL7A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1047934	NM_000094.4(COL7A1):c.58_70del (p.Arg20fs)	COL7A1	Pathogenic	criteria provided, multiple submitters, no conflicts
1047970	NM_000094.4(COL7A1):c.325_326insCG (p.Glu109fs)	COL7A1	Pathogenic	criteria provided, multiple submitters, no conflicts
1047979	NM_000094.4(COL7A1):c.6119G>A (p.Gly2040Asp)	COL7A1	Pathogenic	criteria provided, multiple submitters, no conflicts
1048001	NM_000094.4(COL7A1):c.2783_2784insGACAC (p.Gln929fs)	COL7A1	Pathogenic	criteria provided, multiple submitters, no conflicts
1048003	NM_000094.4(COL7A1):c.3130C>T (p.Gln1044Ter)	COL7A1	Pathogenic	criteria provided, multiple submitters, no conflicts
1048010	NM_000094.4(COL7A1):c.4012G>A (p.Gly1338Arg)	COL7A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1048045	NM_000094.4(COL7A1):c.7270C>T (p.Arg2424Trp)	COL7A1	Pathogenic	criteria provided, multiple submitters, no conflicts
1048050	NM_000094.4(COL7A1):c.7474C>T (p.Arg2492Ter)	COL7A1	Pathogenic	criteria provided, multiple submitters, no conflicts
1048054	NM_000094.4(COL7A1):c.7738C>T (p.Arg2580Cys)	COL7A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1066186	NM_000094.4(COL7A1):c.8020G>C (p.Gly2674Arg)	COL7A1	Pathogenic	criteria provided, multiple submitters, no conflicts
1070885	NM_000094.4(COL7A1):c.565C>T (p.Gln189Ter)	COL7A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1072343	NM_000094.4(COL7A1):c.3830del (p.Pro1277fs)	COL7A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1073113	NM_000094.4(COL7A1):c.4965C>T (p.Gly1655=)	COL7A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1074690	NM_000094.4(COL7A1):c.6501+1G>C	COL7A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1075255	NM_000094.4(COL7A1):c.1837C>T (p.Arg613Ter)	COL7A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1212890	NM_000094.4(COL7A1):c.6235G>A (p.Gly2079Arg)	COL7A1	Pathogenic	criteria provided, multiple submitters, no conflicts
1324153	NM_000094.4(COL7A1):c.6023G>A (p.Arg2008His)	COL7A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1393079	NM_000094.4(COL7A1):c.8219G>C (p.Gly2740Ala)	COL7A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1402177	NM_000094.4(COL7A1):c.3636del (p.Phe1213fs)	COL7A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1404275	NM_000094.4(COL7A1):c.6395G>A (p.Gly2132Asp)	COL7A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1404283	NM_000094.4(COL7A1):c.5108G>A (p.Gly1703Glu)	COL7A1	Pathogenic	criteria provided, multiple submitters, no conflicts
1409788	NM_000094.4(COL7A1):c.3850G>A (p.Gly1284Ser)	COL7A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1443361	NM_000094.4(COL7A1):c.2785C>T (p.Gln929Ter)	COL7A1	Pathogenic	criteria provided, multiple submitters, no conflicts
1453658	NM_000094.4(COL7A1):c.3832_3833del	COL7A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1458606	NM_000094.4(COL7A1):c.5532+5G>A	COL7A1	Pathogenic	criteria provided, multiple submitters, no conflicts
1459712	NM_000094.4(COL7A1):c.5107G>T (p.Gly1703Ter)	COL7A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1492815	NM_000094.4(COL7A1):c.5304_5307+1del	COL7A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1526043	NM_000094.4(COL7A1):c.5560G>A (p.Gly1854Arg)	COL7A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1676611	NM_000094.4(COL7A1):c.7104+3A>T	COL7A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 26 · Orphanet: 9 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
COL7A1	Definitive	Autosomal recessive	recessive dystrophic epidermolysis bullosa	26

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
COL7A1	Orphanet:158673	Localized dystrophic epidermolysis bullosa, acral form
COL7A1	Orphanet:158676	Localized dystrophic epidermolysis bullosa, nails only
COL7A1	Orphanet:231568	Autosomal dominant generalized dystrophic epidermolysis bullosa
COL7A1	Orphanet:79408	Autosomal recessive generalized dystrophic epidermolysis bullosa, severe form
COL7A1	Orphanet:79409	Recessive dystrophic epidermolysis bullosa inversa
COL7A1	Orphanet:79410	Localized dystrophic epidermolysis bullosa, pretibial form
COL7A1	Orphanet:79411	Self-improving dystrophic epidermolysis bullosa
COL7A1	Orphanet:89842	Autosomal recessive generalized dystrophic epidermolysis bullosa, intermediate form
COL7A1	Orphanet:89843	Dystrophic epidermolysis bullosa pruriginosa

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
COL7A1	HGNC:2214	ENSG00000114270	Q02388	Collagen alpha-1(VII) chain	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
COL7A1	Collagen alpha-1(VII) chain	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 c…

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Antibody/Immunoglobulin	1	29.2×	0.034

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
COL7A1	Antibody/Immunoglobulin	yes		VWF_A, Kunitz_BPTI, FN3_dom

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
skin of abdomen	1
skin of leg	1
stromal cell of endometrium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
COL7A1	267	ubiquitous	marker	stromal cell of endometrium, skin of abdomen, skin of leg

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
COL7A1	1,767

Structural data

PDB: 0 · AlphaFold-only: 1 · No structure: 0

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
COL7A1	Q02388

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 10. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Anchoring fibril formation	1	761.3×	0.007	COL7A1
Fibronectin matrix formation	1	571.0×	0.007	COL7A1
Laminin interactions	1	380.7×	0.007	COL7A1
Cargo concentration in the ER	1	335.9×	0.007	COL7A1
Collagen chain trimerization	1	259.6×	0.007	COL7A1
Assembly of collagen fibrils and other multimeric structures	1	200.3×	0.007	COL7A1
Collagen degradation	1	175.7×	0.007	COL7A1
Collagen biosynthesis and modifying enzymes	1	170.4×	0.007	COL7A1
COPII-mediated vesicle transport	1	163.1×	0.007	COL7A1
Integrin cell surface interactions	1	134.3×	0.007	COL7A1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
endodermal cell differentiation	1	495.6×	0.006	COL7A1
epidermis development	1	210.7×	0.007	COL7A1
cell adhesion	1	37.5×	0.027	COL7A1

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
COL7A1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	1	COL7A1
E	Difficult family or no structure, no drug	0

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
COL7A1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 4.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE3	3
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT07016750	PHASE3	RECRUITING	A Study Comparing KB803 and Matched Placebo in Patients With Dystrophic Epidermolysis Bullosa
NCT04491604	PHASE3	COMPLETED	Ph 3 Efficacy and Safety of B-VEC for the Treatment of DEB
NCT04917874	PHASE3	COMPLETED	A Long-term Treatment With B-VEC for Dystrophic Epidermolysis Bullosa
NCT04917887	Not specified	RECRUITING	Long-Term Follow-up Protocol

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
BEREMAGENE GEPERPAVEC	4	1