localized junctional epidermolysis bullosa, non-Herlitz type

Summary

localized junctional epidermolysis bullosa, non-Herlitz type (MONDO:0016673) is a disease with 2 cohort genes.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 2
• Phenotypes (HPO): 19

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		20	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

19 HPO clinical features (Orphanet curated; top 19 by frequency):

HPO ID	Term	Frequency
HP:0001030	Fragile skin	Very frequent (80-99%)
HP:0008066	Abnormal blistering of the skin	Very frequent (80-99%)
HP:0002215	Sparse axillary hair	Frequent (30-79%)
HP:0002225	Sparse pubic hair	Frequent (30-79%)
HP:0004529	Atrophic, patchy alopecia	Frequent (30-79%)
HP:0006297	Enamel hypoplasia	Frequent (30-79%)
HP:0008404	Nail dystrophy	Frequent (30-79%)
HP:0009722	Dental enamel pits	Frequent (30-79%)
HP:0011073	Abnormality of dental color	Frequent (30-79%)
HP:0031045	Acral blistering	Frequent (30-79%)
HP:0032156	Skin detachment	Frequent (30-79%)
HP:0001057	Aplasia cutis congenita	Occasional (5-29%)
HP:0001810	Dystrophic toenail	Occasional (5-29%)
HP:0004552	Scarring alopecia of scalp	Occasional (5-29%)
HP:0008391	Dystrophic fingernails	Occasional (5-29%)
HP:0000987	Atypical scarring of skin	Very rare (<1-4%)
HP:0001056	Milia	Very rare (<1-4%)
HP:0003121	Limb joint contracture	Very rare (<1-4%)
HP:0004057	Mitten deformity	Very rare (<1-4%)

Identifiers

Disease identifiers

Field	Value
Canonical name	localized junctional epidermolysis bullosa, non-Herlitz type
Mondo ID	MONDO:0016673
Orphanet	251393
UMLS	C5700116
MedGen	1814511
GARD	0012923
Is cancer (heuristic)	no

Also known as: JEB-nH loc

Data availability: 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 › junctional epidermolysis bullosa, non-Herlitz type › localized junctional epidermolysis bullosa, non-Herlitz type

Related subtypes (1): generalized junctional epidermolysis bullosa non-Herlitz type

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: 28 · 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
COL17A1	Definitive	Autosomal recessive	epidermolysis bullosa, junctional 4, intermediate	14
ITGB4	Definitive	Autosomal recessive	junctional epidermolysis bullosa with pyloric atresia	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
ITGB4	Orphanet:1114	Aplasia cutis congenita
ITGB4	Orphanet:158684	Epidermolysis bullosa simplex with pyloric atresia
ITGB4	Orphanet:251393	Localized junctional epidermolysis bullosa
ITGB4	Orphanet:79402	Intermediate generalized junctional epidermolysis bullosa
ITGB4	Orphanet:79403	Junctional epidermolysis bullosa with pyloric atresia

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
COL17A1	HGNC:2194	ENSG00000065618	Q9UMD9	Collagen alpha-1(XVII) chain	gencc
ITGB4	HGNC:6158	ENSG00000132470	P16144	Integrin beta-4	gencc

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.
ITGB4	Integrin beta-4	Integrin alpha-6/beta-4 is a receptor for laminin.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.5

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	14.6×	0.135
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
COL17A1	Other/Unknown	no		Collagen, Collagen_superfamily
ITGB4	Antibody/Immunoglobulin	yes		EGF, Integrin_bsu_VWA, Calx_beta

Expression context

Cohort genes with no expression data: 0.

2 cohort genes 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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
skin of leg	2
skin of abdomen	1
zone of skin	1
minor salivary gland	1
tibial nerve	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
ITGB4	267	broad	marker	tibial nerve, minor salivary gland, skin of leg

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ITGB4	2,536
COL17A1	1,769

Intra-cohort edges

A	B	Sources
COL17A1	ITGB4	biogrid_interaction, string_interaction

Structural data

PDB: 2 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ITGB4	P16144	13
COL17A1	Q9UMD9	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 16. Enrichment computed across 2 evidence-associated genes (2 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 2 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	2	1038.2×	1e-05	COL17A1, ITGB4
Assembly of collagen fibrils and other multimeric structures	2	200.3×	2e-04	COL17A1, ITGB4
Collagen formation	1	228.4×	0.017	ITGB4
Syndecan interactions	1	211.5×	0.017	ITGB4
Laminin interactions	1	190.3×	0.017	ITGB4
Differentiation of Keratinocytes in Interfollicular Epidermis in Mammalian Skin	1	139.3×	0.017	ITGB4
Collagen chain trimerization	1	129.8×	0.017	COL17A1
Developmental Cell Lineages	1	112.0×	0.017	ITGB4
Cell junction organization	1	93.6×	0.017	ITGB4
Collagen degradation	1	87.8×	0.017	COL17A1
Collagen biosynthesis and modifying enzymes	1	85.2×	0.017	COL17A1
Non-integrin membrane-ECM interactions	1	77.2×	0.017	ITGB4
Cell-Cell communication	1	68.8×	0.018	ITGB4
Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell	1	43.6×	0.026	COL17A1
Extracellular matrix organization	1	31.6×	0.034	ITGB4
Developmental Biology	1	7.2×	0.134	ITGB4

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 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	2	2407.4×	3e-06	COL17A1, ITGB4
cell-matrix adhesion	2	163.6×	3e-04	COL17A1, ITGB4
peripheral nervous system myelin formation	1	2808.7×	0.002	ITGB4
nail development	1	1203.7×	0.003	ITGB4
trophoblast cell migration	1	1203.7×	0.003	ITGB4
mesodermal cell differentiation	1	766.0×	0.003	ITGB4
skin morphogenesis	1	702.2×	0.003	ITGB4
cell adhesion mediated by integrin	1	337.0×	0.006	ITGB4
filopodium assembly	1	324.1×	0.006	ITGB4
cell motility	1	200.6×	0.008	ITGB4
response to wounding	1	110.9×	0.013	ITGB4
epidermis development	1	105.3×	0.013	COL17A1
integrin-mediated signaling pathway	1	80.2×	0.016	ITGB4
autophagy	1	55.1×	0.022	ITGB4
cell-cell adhesion	1	50.8×	0.022	ITGB4
cell migration	1	30.8×	0.034	ITGB4
cell adhesion	1	18.7×	0.053	ITGB4

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 1 of 2 evidence-associated genes (50%) 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
ITGB4	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
ITGB4	2	Binding:2

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; 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	1	ITGB4
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	COL17A1

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
COL17A1	0	—
ITGB4	2	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.