Late-onset junctional epidermolysis bullosa

Summary

Late-onset junctional epidermolysis bullosa (MONDO:0019309) is a disease with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 1
• ClinVar variants: 1
• Phenotypes (HPO): 27

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		37	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

27 HPO clinical features (Orphanet curated; top 27 by frequency):

HPO ID	Term	Frequency
HP:0001030	Fragile skin	Frequent (30-79%)
HP:0001798	Anonychia	Frequent (30-79%)
HP:0006297	Enamel hypoplasia	Frequent (30-79%)
HP:0007455	Adermatoglyphia	Frequent (30-79%)
HP:0008066	Abnormal blistering of the skin	Frequent (30-79%)
HP:0008404	Nail dystrophy	Frequent (30-79%)
HP:0000670	Carious teeth	Occasional (5-29%)
HP:0000975	Hyperhidrosis	Occasional (5-29%)
HP:0011355	Localized skin lesion	Occasional (5-29%)
HP:0020117	Hypoplastic dermoepidermal hemidesmosomes	Occasional (5-29%)
HP:0200097	Oral mucosal blisters	Occasional (5-29%)
HP:0000079	Abnormality of the urinary system	Excluded (0%)
HP:0000478	Abnormality of the eye	Excluded (0%)
HP:0000982	Palmoplantar keratoderma	Excluded (0%)
HP:0001056	Milia	Excluded (0%)
HP:0001075	Atrophic scars	Excluded (0%)
HP:0001510	Growth delay	Excluded (0%)
HP:0001903	Anemia	Excluded (0%)
HP:0001965	Abnormality of the scalp	Excluded (0%)
HP:0002671	Basal cell carcinoma	Excluded (0%)
HP:0002860	Squamous cell carcinoma	Excluded (0%)
HP:0004057	Mitten deformity	Excluded (0%)
HP:0004386	Gastrointestinal inflammation	Excluded (0%)
HP:0010562	Keloids	Excluded (0%)
HP:0012056	Cutaneous melanoma	Excluded (0%)
HP:0012252	Abnormal respiratory system morphology	Excluded (0%)
HP:0031464	Genital blistering	Excluded (0%)

Identifiers

Disease identifiers

Field	Value
Canonical name	late-onset junctional epidermolysis bullosa
Mondo ID	MONDO:0019309
Orphanet	79406
SNOMED CT	719432000
UMLS	C4304724
MedGen	930393
GARD	0012921
Is cancer (heuristic)	no

Also known as: EB progressive · JEB-lo

Data availability: 1 ClinVar variant · 1 GenCC gene-disease record.

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 › junctional epidermolysis bullosa › late-onset junctional epidermolysis bullosa

Related subtypes (14): late-onset localized junctional epidermolysis bullosa-intellectual disability syndrome, junctional epidermolysis bullosa, non-Herlitz type, junctional epidermolysis bullosa Herlitz type, junctional epidermolysis bullosa with pyloric atresia, laryngo-onycho-cutaneous syndrome, epidermolysis bullosa, junctional 7, with interstitial lung disease and nephrotic syndrome, junctional epidermolysis bullosa inversa, epidermolysis bullosa, junctional 2A, intermediate, epidermolysis bullosa, junctional 2B, severe, epidermolysis bullosa, junctional 3A, intermediate, epidermolysis bullosa, junctional 3B, severe, epidermolysis bullosa, junctional 4, intermediate, epidermolysis bullosa, junctional 5A, intermediate, epidermolysis bullosa, junctional 6, with pyloric atresia

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

1 retrieved; paginated sample, class counts are floors:

1 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
877147	NM_000494.4(COL17A1):c.3739C>T (p.Arg1247Trp)	COL17A1	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 14 · Orphanet: 4 · 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
COL17A1	Definitive	Autosomal recessive	epidermolysis bullosa, junctional 4, intermediate	14

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
COL17A1	Orphanet:251393	Localized junctional epidermolysis bullosa
COL17A1	Orphanet:293381	Epithelial recurrent erosion dystrophy
COL17A1	Orphanet:79402	Intermediate generalized junctional epidermolysis bullosa
COL17A1	Orphanet:79406	Late-onset junctional epidermolysis bullosa

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
COL17A1	HGNC:2194	ENSG00000065618	Q9UMD9	Collagen alpha-1(XVII) chain	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
COL17A1	Collagen alpha-1(XVII) chain	May play a role in the integrity of hemidesmosome and the attachment of basal keratinocytes to the underlying basement membrane.

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)
COL17A1	Other/Unknown	no		Collagen, Collagen_superfamily

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
zone of skin	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
COL17A1	182	broad	marker	skin of abdomen, skin of leg, zone of skin

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
COL17A1	1,769

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
COL17A1	Q9UMD9	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 6. 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
Type I hemidesmosome assembly	1	1038.2×	0.006	COL17A1
Collagen chain trimerization	1	259.6×	0.007	COL17A1
Assembly of collagen fibrils and other multimeric structures	1	200.3×	0.007	COL17A1
Collagen degradation	1	175.7×	0.007	COL17A1
Collagen biosynthesis and modifying enzymes	1	170.4×	0.007	COL17A1
Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell	1	87.2×	0.011	COL17A1

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
hemidesmosome assembly	1	2407.4×	0.001	COL17A1
epidermis development	1	210.7×	0.006	COL17A1
cell-matrix adhesion	1	163.6×	0.006	COL17A1

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
COL17A1	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	0
E	Difficult family or no structure, no drug	1	COL17A1

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)
COL17A1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.