Inherited epidermolysis bullosa

Summary

Inherited epidermolysis bullosa (MONDO:0019276) is a disease caused by JUP (GenCC Strong), with 1 cohort gene and 5 clinical trials. Top therapeutic interventions include diacerein and vehicle.

At a glance

• Prevalence: 1-9 / 1 000 000 (Europe) [Orphanet-validated]
• Causal gene: JUP (GenCC Strong)
• Cohort genes: 1
• Clinical trials: 5

Clinical features

Epidemiology

Prevalence records

6 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	1-9 / 1 000 000	0.8	Europe	Validated
Prevalence at birth	1-9 / 100 000	1.9	Europe	Validated
Point prevalence	1-9 / 1 000 000	0.96	Croatia	Validated
Point prevalence	1-9 / 1 000 000	0.8	United States	Validated
Point prevalence	1-9 / 1 000 000	0.59	China	Validated
Prevalence at birth	1-9 / 100 000	1.9	United States	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	inherited epidermolysis bullosa
Mondo ID	MONDO:0019276
Orphanet	79361
SNOMED CT	402781004
UMLS	C1274224
MedGen	697573
GARD	0018992
Is cancer (heuristic)	no

Also known as: epidermolysis bullosa hereditaria · hereditary epidermolysis bullosa

Data availability: 1 GenCC gene-disease record · 4 cell lines.

Disease family

An umbrella term covering 4 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

Related subtypes (1): acquired epidermolysis bullosa

Subtypes (4): epidermolysis bullosa dystrophica, Kindler syndrome, epidermolysis bullosa simplex, junctional epidermolysis bullosa

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

No tiered GWAS variants or ClinVar records for this disease.

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 9 · Orphanet: 5 · 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
JUP	Strong	Autosomal recessive	inherited epidermolysis bullosa	9

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
JUP	Orphanet:158687	Lethal acantholytic erosive disorder
JUP	Orphanet:293888	Inherited isolated arrhythmogenic cardiomyopathy, dominant-left variant
JUP	Orphanet:293899	Inherited isolated arrhythmogenic ventricular dysplasia, biventricular variant
JUP	Orphanet:293910	Inherited isolated arrhythmogenic cardiomyopathy, dominant-right variant
JUP	Orphanet:34217	Naxos disease

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
JUP	HGNC:6207	ENSG00000173801	P14923	Junction plakoglobin	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
JUP	Junction plakoglobin	Common junctional plaque protein.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

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
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
JUP	Other/Unknown	no		Armadillo, ARM-like, Beta-catenin

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
lower esophagus mucosa	1
skin of abdomen	1
skin of leg	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
JUP	287	ubiquitous	marker	lower esophagus mucosa, skin of leg, skin of abdomen

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
JUP	4,618

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
JUP	P14923	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 20. 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
CDH11 homotypic and heterotypic interactions	1	1631.4×	0.005	JUP
Regulation of CDH19 Expression and Function	1	1427.5×	0.005	JUP
Regulation of CDH11 function	1	1038.2×	0.005	JUP
Regulation of CDH1 Function	1	951.7×	0.005	JUP
SRC activates STAT3 in a quantitative manner, through Cadherin-11 (CDH11), RAC1 and gp130 (IL6ST)	1	496.5×	0.008	JUP
VEGFR2 mediated vascular permeability	1	407.9×	0.008	JUP
Regulation of CDH1 posttranslational processing and trafficking to plasma membrane	1	335.9×	0.008	JUP
RHOH GTPase cycle	1	308.6×	0.008	JUP
Adherens junctions interactions	1	248.3×	0.009	JUP
RHOJ GTPase cycle	1	200.3×	0.009	JUP
Degradation of CDH1	1	196.9×	0.009	JUP
RHOQ GTPase cycle	1	181.3×	0.009	JUP
Activation of STAT3 by cadherin engagement	1	163.1×	0.009	JUP
RHOB GTPase cycle	1	154.3×	0.009	JUP
RHOC GTPase cycle	1	146.4×	0.009	JUP
Formation of the cornified envelope	1	87.8×	0.014	JUP
RHOA GTPase cycle	1	74.6×	0.015	JUP
CDC42 GTPase cycle	1	72.3×	0.015	JUP
Keratinization	1	55.7×	0.019	JUP
Neutrophil degranulation	1	23.1×	0.043	JUP

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
endothelial cell-cell adhesion	1	4213.0×	0.002	JUP
cellular response to indole-3-methanol	1	3370.4×	0.002	JUP
desmosome assembly	1	2407.4×	0.002	JUP
bundle of His cell-Purkinje myocyte adhesion involved in cell communication	1	2407.4×	0.002	JUP
regulation of ventricular cardiac muscle cell action potential	1	1404.3×	0.003	JUP
detection of mechanical stimulus	1	1203.7×	0.003	JUP
negative regulation of blood vessel endothelial cell migration	1	732.7×	0.004	JUP
positive regulation of cell-matrix adhesion	1	674.1×	0.004	JUP
skin development	1	443.5×	0.005	JUP
positive regulation of protein import into nucleus	1	421.3×	0.005	JUP
regulation of heart rate by cardiac conduction	1	374.5×	0.005	JUP
positive regulation of canonical Wnt signaling pathway	1	154.6×	0.010	JUP
canonical Wnt signaling pathway	1	153.2×	0.010	JUP
regulation of cell population proliferation	1	115.4×	0.011	JUP
positive regulation of angiogenesis	1	115.4×	0.011	JUP
protein localization to plasma membrane	1	108.7×	0.011	JUP
cell-cell adhesion	1	101.5×	0.011	JUP
cell migration	1	61.5×	0.017	JUP
positive regulation of transcription by RNA polymerase II	1	14.9×	0.067	JUP

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
JUP	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
JUP	1	Binding:1

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	0
E	Difficult family or no structure, no drug	1	JUP

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)
JUP	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 5.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE2	3
Not specified	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01294241	PHASE2	COMPLETED	Oleogel-S10 in Wound Healing of Inherited Epidermolysis Bullosa (BEB-10)
NCT03468322	PHASE2	COMPLETED	A Double-blind, Intra-individual Comparison, POC Trial of AC-203 in EB Patients
NCT05651607	PHASE2	COMPLETED	Evaluation of the Efficacy of CANNABIDIOL on the Pruritus in Children With Hereditary Epidermolysis Bullosa
NCT05954416	Not specified	RECRUITING	FARD (RaDiCo Cohort) (RaDiCo-FARD)
NCT05248503	Not specified	COMPLETED	Impact of Complex Care Training of Hereditary Epidermolysis Bullosa on Caregiver Burden (FIREB)

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
DIACEREIN	3	1
VEHICLE	0	1