Epidermolysis bullosa, junctional 4, intermediate

Summary

Epidermolysis bullosa, junctional 4, intermediate (MONDO:0030750) is a disease caused by COL17A1 (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: COL17A1 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 58

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	epidermolysis bullosa, junctional 4, intermediate
Mondo ID	MONDO:0030750
OMIM	619787
UMLS	C2608084
MedGen	382015
GARD	0025633
Is cancer (heuristic)	no

Also known as: epidermolysis bullosa, generalised atrophic benign · epidermolysis bullosa, generalized atrophic benign · epidermolysis bullosa, junctional 4, intermediate · epidermolysis bullosa, junctional 4, non-herlitz IIA · epidermolysis bullosa, junctional, localisata variant · JEB4

Data availability: 58 ClinVar variants · 2 GenCC gene-disease records.

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 › epidermolysis bullosa, junctional 4, intermediate

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, late-onset junctional epidermolysis bullosa, epidermolysis bullosa, junctional 2A, intermediate, epidermolysis bullosa, junctional 2B, severe, epidermolysis bullosa, junctional 3A, intermediate, epidermolysis bullosa, junctional 3B, severe, 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

58 retrieved; paginated sample, class counts are floors:

20 likely pathogenic, 18 pathogenic, 10 pathogenic/likely pathogenic, 7 uncertain significance, 1 conflicting classifications of pathogenicity, 1 benign/likely benign, 1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1322107	NM_000494.4(COL17A1):c.1939+1G>C	COL17A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1458976	NM_000494.4(COL17A1):c.3766+1G>C	COL17A1	Pathogenic	criteria provided, multiple submitters, no conflicts
1691802	NM_000494.3(COL17A1):c.418_419del	COL17A1	Pathogenic	criteria provided, single submitter
1706597	NM_000494.4(COL17A1):c.3686dup (p.Val1231fs)	COL17A1	Pathogenic	criteria provided, multiple submitters, no conflicts
17645	NM_000494.4(COL17A1):c.3676C>T (p.Arg1226Ter)	COL17A1	Pathogenic	criteria provided, multiple submitters, no conflicts
17646	NM_000494.4(COL17A1):c.4045dup (p.Ala1349fs)	COL17A1	Pathogenic	no assertion criteria provided
17647	NM_000494.4(COL17A1):c.2840_2844del (p.Leu947fs)	COL17A1	Pathogenic	no assertion criteria provided
17648	NM_000494.4(COL17A1):c.3067C>T (p.Gln1023Ter)	COL17A1	Pathogenic	no assertion criteria provided
17649	NM_000494.4(COL17A1):c.1601del (p.Asp534fs)	COL17A1	Pathogenic	no assertion criteria provided
17650	NM_000494.4(COL17A1):c.3908G>A (p.Arg1303Gln)	COL17A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
17652	NM_000494.4(COL17A1):c.2336-1G>T	COL17A1	Pathogenic	no assertion criteria provided
17653	NM_000494.4(COL17A1):c.3899_3900del (p.Ser1300fs)	COL17A1	Pathogenic	no assertion criteria provided
17655	NM_000494.4(COL17A1):c.2861del (p.Gly954fs)	COL17A1	Pathogenic	no assertion criteria provided
17656	NM_000494.4(COL17A1):c.2564T>G (p.Leu855Ter)	COL17A1	Pathogenic	no assertion criteria provided
17657	NM_000494.4(COL17A1):c.1898G>A (p.Gly633Asp)	COL17A1	Pathogenic	no assertion criteria provided
17658	NM_000494.4(COL17A1):c.433C>T (p.Arg145Ter)	COL17A1	Pathogenic	criteria provided, single submitter
2211005	NM_000494.4(COL17A1):c.340del (p.Ser114fs)	COL17A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2634739	NM_000494.4(COL17A1):c.3613_3616del (p.Leu1205fs)	COL17A1	Pathogenic	criteria provided, multiple submitters, no conflicts
2735479	NM_000494.4(COL17A1):c.4156+1G>C	COL17A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
280329	NM_000494.4(COL17A1):c.4050del (p.Ala1351fs)	COL17A1	Pathogenic	criteria provided, multiple submitters, no conflicts
2884031	NM_000494.4(COL17A1):c.3198C>T (p.Ser1066=)	COL17A1	Pathogenic	criteria provided, multiple submitters, no conflicts
2900711	NM_000494.4(COL17A1):c.2551+1G>T	COL17A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
298713	NM_000494.4(COL17A1):c.2407G>T (p.Gly803Ter)	COL17A1	Pathogenic	criteria provided, multiple submitters, no conflicts
419270	NM_000494.4(COL17A1):c.3922del (p.Ser1308fs)	COL17A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
497145	NM_000494.4(COL17A1):c.2228-3_2235delinsTTG	COL17A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
517463	NM_000494.4(COL17A1):c.3821_3829delinsC (p.Gly1274fs)	COL17A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
585309	NM_000494.4(COL17A1):c.214C>T (p.Arg72Ter)	COL17A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
599000	NM_000494.4(COL17A1):c.4145_4148del (p.Glu1382fs)	COL17A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2431850	NM_000494.4(COL17A1):c.1233del (p.Thr412fs)	COL17A1	Likely pathogenic	criteria provided, single submitter
2576976	NM_000494.4(COL17A1):c.44del (p.Thr15fs)	COL17A1	Likely pathogenic	criteria provided, single submitter

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.