Epidermolysis bullosa dystrophica

Summary

Epidermolysis bullosa dystrophica (MONDO:0006543) is a disease (an umbrella term covering 12 Mondo subtypes) with 1 cohort gene and 20 clinical trials. Top therapeutic interventions include rigosertib and vehicle.

At a glance

• Prevalence: 1-9 / 1 000 000 (Europe) [Orphanet-validated]
• Umbrella term: 12 Mondo subtypes
• Cohort genes: 1
• ClinVar variants: 891
• Clinical trials: 20

Clinical features

Epidemiology

Prevalence records

7 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	1-9 / 1 000 000	0.572	Europe	Validated
Annual incidence	1-9 / 100 000	1.41	Netherlands	Validated
Point prevalence	1-9 / 1 000 000	0.6	Spain	Validated
Point prevalence	1-9 / 1 000 000	0.39	Australia	Validated
Point prevalence	1-9 / 1 000 000	0.14	United States	Validated
Point prevalence	1-9 / 1 000 000	0.28	Romania	Validated
Point prevalence	1-9 / 1 000 000	0.83	Netherlands	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	epidermolysis bullosa dystrophica
Mondo ID	MONDO:0006543
EFO	EFO:1000692
MeSH	D016108
Orphanet	303
DOID	DOID:4959
ICD-10-CM	Q81.2
ICD-11	1060981106
NCIT	C84691
SNOMED CT	254185007
UMLS	C0079294
MedGen	37179
GARD	0002150
Is cancer (heuristic)	no

Also known as: DEB · dermolytic epidermolysis bullosa · epidermolysis bullosa dystrophica · epidermolysis bullosa, dermolytic

Data availability: 891 ClinVar variants · 41 cell lines.

Disease family

An umbrella term covering 12 Mondo subtypes.

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

Related subtypes (3): Kindler syndrome, epidermolysis bullosa simplex, junctional epidermolysis bullosa

Subtypes (12): transient bullous dermolysis of the newborn, generalized dominant dystrophic epidermolysis bullosa, 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

600 retrieved; paginated sample, class counts are floors:

173 uncertain significance, 147 pathogenic, 91 conflicting classifications of pathogenicity, 72 pathogenic/likely pathogenic, 45 likely benign, 37 likely pathogenic, 23 benign, 12 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1012377	NC_000003.12:g.48595347G>A	COL7A1	Pathogenic	criteria provided, single submitter
1032184	NM_000094.4(COL7A1):c.2587+1G>A	COL7A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
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
1047935	NM_000094.4(COL7A1):c.5440C>T (p.Arg1814Cys)	COL7A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1047936	NM_000094.4(COL7A1):c.5449C>T (p.Gln1817Ter)	COL7A1	Pathogenic	criteria provided, single submitter
1047937	NM_000094.4(COL7A1):c.5532+1G>T	COL7A1	Pathogenic	criteria provided, multiple submitters, no conflicts
1047938	NM_000094.4(COL7A1):c.5532+6T>C	COL7A1	Pathogenic	criteria provided, single submitter
1047939	NM_000094.4(COL7A1):c.5569-11_5569-3del	COL7A1	Pathogenic	criteria provided, single submitter
1047940	NM_000094.4(COL7A1):c.5576_5577del (p.Lys1859fs)	COL7A1	Pathogenic	criteria provided, multiple submitters, no conflicts
1047941	NM_000094.4(COL7A1):c.5755G>A (p.Gly1919Arg)	COL7A1	Pathogenic	criteria provided, single submitter
1047942	NM_000094.4(COL7A1):c.5771A>G (p.Gln1924Arg)	COL7A1	Pathogenic	criteria provided, single submitter
1047943	NM_000094.4(COL7A1):c.5892_5905del (p.Asp1964fs)	COL7A1	Pathogenic	criteria provided, single submitter
1047944	NM_000094.4(COL7A1):c.5944_5945delinsTA (p.Gly1982Ter)	COL7A1	Pathogenic	criteria provided, single submitter
1047945	NM_000094.4(COL7A1):c.6034G>A (p.Gly2012Ser)	COL7A1	Pathogenic	criteria provided, single submitter
1047946	NM_000094.4(COL7A1):c.6041_6042del (p.Gln2014fs)	COL7A1	Pathogenic	criteria provided, single submitter
1047947	NM_000094.4(COL7A1):c.7930-1G>C	COL7A1	Pathogenic	criteria provided, multiple submitters, no conflicts
1047948	NM_000094.4(COL7A1):c.8103_8104dup (p.Glu2702fs)	COL7A1	Pathogenic	criteria provided, single submitter
1047950	NM_000094.4(COL7A1):c.8165G>T (p.Gly2722Val)	COL7A1	Pathogenic	criteria provided, multiple submitters, no conflicts
1047951	NM_000094.4(COL7A1):c.8209G>C (p.Gly2737Arg)	COL7A1	Pathogenic	criteria provided, multiple submitters, no conflicts
1047952	NM_000094.4(COL7A1):c.8537_8565del (p.Pro2846fs)	COL7A1	Pathogenic	criteria provided, single submitter
1047953	NM_000094.4(COL7A1):c.8572T>C (p.Tyr2858His)	COL7A1	Pathogenic	criteria provided, single submitter
1047954	NM_000094.4(COL7A1):c.8717del (p.Pro2906fs)	COL7A1	Pathogenic	criteria provided, single submitter
1047968	NM_000094.4(COL7A1):c.86-8C>A	COL7A1	Pathogenic	criteria provided, single submitter
1047969	NM_000094.4(COL7A1):c.267-3C>G	COL7A1	Pathogenic	criteria provided, single submitter
1047970	NM_000094.4(COL7A1):c.325_326insCG (p.Glu109fs)	COL7A1	Pathogenic	criteria provided, multiple submitters, no conflicts
1047971	NM_000094.4(COL7A1):c.336C>G (p.Tyr112Ter)	COL7A1	Pathogenic	criteria provided, single submitter
1047972	NM_000094.4(COL7A1):c.448G>C (p.Gly150Arg)	COL7A1	Pathogenic	criteria provided, single submitter
1047973	NM_000094.4(COL7A1):c.1423C>T (p.Gln475Ter)	COL7A1	Pathogenic	criteria provided, multiple submitters, no conflicts
1047974	NM_000094.4(COL7A1):c.1507G>A (p.Gly503Arg)	COL7A1	Pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

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

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	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

Drugs indicated for this disease

2 approved, 2 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Beremagene Geperpavec	Approved (phase 4)
Birch Triterpenes	Approved (phase 4)
Dabocemagene Autoficel	Phase 3 (in late-stage trials)
Prademagene Zamikeracel	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Epigalocatechin Gallate, Filgrastim, Timbetasin Acetate.

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: 20.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	13
PHASE2	2
PHASE1/PHASE2	2
PHASE4	1
PHASE3	1
EARLY_PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT07596927	PHASE4	ACTIVE_NOT_RECRUITING	Curcumin-Based Photodynamic Therapy in Epidermolysis Bullosa: Wound Healing, Quality of Life, and Salivary Biomarkers
NCT00587223	PHASE3	TERMINATED	Safety and Efficacy of Apligraf in Nonhealing Wounds of Subjects With Junctional or Dystrophic Epidermolysis Bullosa (EB)
NCT00951964	PHASE2	COMPLETED	Treatment of Epidermolysis Bullosa Dystrophica by Polyphenon E (Epigallocatechin 3 Gallate)
NCT01263379	PHASE1/PHASE2	COMPLETED	Gene Transfer for Recessive Dystrophic Epidermolysis Bullosa
NCT03786237	PHASE1/PHASE2	COMPLETED	Rigosertib for RDEB-SCC
NCT04908215	PHASE2	COMPLETED	INM-755 (Cannabinol) Cream for Treatment of Epidermolysis Bullosa
NCT04171661	EARLY_PHASE1	ACTIVE_NOT_RECRUITING	Self-Assembled Skin Substitute for the Treatment of Epidermolysis Bullosa
NCT01019148	Not specified	RECRUITING	Characteristics of Patients With Recessive Dystrophic Epidermolysis Bullosa
NCT05843994	Not specified	ACTIVE_NOT_RECRUITING	Artificial Intelligence Patient App for RDEB SCCs
NCT06177353	Not specified	RECRUITING	Study of the Blood and Skin Immunological Profile of Patients With Recessive Dystrophic Epidermolysis Bullosa: in Vivo Analysis and the Impact of Placental Stem Cells in Vitro
NCT06563414	Not specified	RECRUITING	A Natural History Study of Corneal Abrasions in Patients With Dystrophic Epidermolysis Bullosa (DEB)
NCT00533572	Not specified	TERMINATED	Recessive Dystrophic Epidermolysis Bullosa Screening for Possible Gene Transfer
NCT00904163	Not specified	COMPLETED	Characteristics of Adult Patients With Recessive Dystrophic Epidermolysis Bullosa
NCT01716169	Not specified	COMPLETED	Treatment of Chronic and Non-Chronic Wounds in Patients With Recessive Dystrophic Epidermolysis Bullosa Using Helicoll Collagen Dressings Versus Standard of Care
NCT03241628	Not specified	COMPLETED	Proof of Concept Study for a Dressing Glove
NCT03269474	Not specified	UNKNOWN	Computational Drug Repurposing for All EBS Cases
NCT04213703	Not specified	WITHDRAWN	A Pilot Study to Explore the Role of Gut Flora in Epidermolysis Bullosa
NCT05033574	Not specified	UNKNOWN	The State of Sexual Development in Children With Inherited Epidermolysis Bullosa
NCT05390073	Not specified	UNKNOWN	Growth Hormone in EB
NCT06007235	Not specified	UNKNOWN	CACIPLIQ20 in Wound Healing in Subjects With Epidermolysis Bullosa

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
RIGOSERTIB	3	2
VEHICLE	0	1