generalized junctional epidermolysis bullosa non-Herlitz type

Summary

generalized junctional epidermolysis bullosa non-Herlitz type (MONDO:0019307) is a disease with 6 cohort genes. The dominant Reactome pathway is Type I hemidesmosome assembly (5 cohort genes).

At a glance

• Prevalence: Unknown (Worldwide)
• Cohort genes: 6
• Phenotypes (HPO): 14

Clinical features

Signs & symptoms

Clinical features (HPO)

14 HPO clinical features (Orphanet curated; top 14 by frequency):

HPO ID	Term	Frequency
HP:0001000	Abnormality of skin pigmentation	Very frequent (80-99%)
HP:0001056	Milia	Very frequent (80-99%)
HP:0001057	Aplasia cutis congenita	Very frequent (80-99%)
HP:0001075	Atrophic scars	Very frequent (80-99%)
HP:0002231	Sparse body hair	Very frequent (80-99%)
HP:0004552	Scarring alopecia of scalp	Very frequent (80-99%)
HP:0008066	Abnormal blistering of the skin	Very frequent (80-99%)
HP:0200097	Oral mucosal blisters	Very frequent (80-99%)
HP:0001798	Anonychia	Frequent (30-79%)
HP:0001903	Anemia	Frequent (30-79%)
HP:0008404	Nail dystrophy	Frequent (30-79%)
HP:0000982	Palmoplantar keratoderma	Occasional (5-29%)
HP:0001510	Growth delay	Occasional (5-29%)
HP:0006297	Enamel hypoplasia	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	generalized junctional epidermolysis bullosa non-Herlitz type
Mondo ID	MONDO:0019307
Orphanet	79402
DOID	DOID:0060738
SNOMED CT	724225008
UMLS	C0432326
MedGen	609458
GARD	0012922
Is cancer (heuristic)	no

Also known as: generalised atrophic benign epidermolysis bullosa · generalised junctional epidermolysis bullosa, non-Herlitz type · generalized atrophic benign epidermolysis bullosa · generalized junctional epidermolysis bullosa, non-Herlitz type · JEB, generalised intermediate · JEB, generalized intermediate · junctional epidermolysis bullosa generalisata mitis · junctional epidermolysis bullosa, Disentis type · junctional epidermolysis bullosa, generalised intermediate

Data availability: 5 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 › generalized junctional epidermolysis bullosa non-Herlitz type

Related subtypes (1): localized 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: 82 · Orphanet: 18 · 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
LAMA3	Definitive	Autosomal recessive	junctional epidermolysis bullosa	13
LAMA4	Definitive	Autosomal recessive	junctional epidermolysis bullosa	18
LAMB3	Definitive	Autosomal recessive	junctional epidermolysis bullosa, non-Herlitz type	15
LAMC2	Definitive	Autosomal recessive	junctional epidermolysis bullosa	8

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
LAMA3	Orphanet:2407	Laryngo-onycho-cutaneous syndrome
LAMA3	Orphanet:79402	Intermediate generalized junctional epidermolysis bullosa
LAMA3	Orphanet:79404	Severe generalized junctional epidermolysis bullosa
LAMA4	Orphanet:154	Familial isolated dilated cardiomyopathy
LAMB3	Orphanet:100031	Hypoplastic amelogenesis imperfecta
LAMB3	Orphanet:79402	Intermediate generalized junctional epidermolysis bullosa
LAMB3	Orphanet:79404	Severe generalized junctional epidermolysis bullosa
LAMC2	Orphanet:79402	Intermediate generalized junctional epidermolysis bullosa
LAMC2	Orphanet:79404	Severe generalized junctional epidermolysis bullosa

Cohort genes → proteins

6 cohort genes, 6 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	6

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
LAMA3	HGNC:6483	ENSG00000053747	Q16787	Laminin subunit alpha-3	gencc
LAMA4	HGNC:6484	ENSG00000112769	Q16363	Laminin subunit alpha-4	gencc
LAMB3	HGNC:6490	ENSG00000196878	Q13751	Laminin subunit beta-3	gencc
LAMC2	HGNC:6493	ENSG00000058085	Q13753	Laminin subunit gamma-2	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.
LAMA3	Laminin subunit alpha-3	Binding to cells via a high affinity receptor, laminin is thought to mediate the attachment, migration and organization of cells into tissues during embryonic development by interacting with other extracellular matrix components.
LAMA4	Laminin subunit alpha-4	Binding to cells via a high affinity receptor, laminin is thought to mediate the attachment, migration and organization of cells into tissues during embryonic development by interacting with other extracellular matrix components.
LAMB3	Laminin subunit beta-3	Binding to cells via a high affinity receptor, laminin is thought to mediate the attachment, migration and organization of cells into tissues during embryonic development by interacting with other extracellular matrix components.
LAMC2	Laminin subunit gamma-2	Binding to cells via a high affinity receptor, laminin is thought to mediate the attachment, migration and organization of cells into tissues during embryonic development by interacting with other extracellular matrix components.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 5 · Druggable fraction: 0.17

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	4.9×	0.189
Other/Unknown	5	1.5×	0.189

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
LAMA3	Other/Unknown	no		Laminin_IV, EGF, Laminin_G
LAMA4	Other/Unknown	no		EGF, Laminin_G, LE_dom
LAMB3	Other/Unknown	no		EGF, LE_dom, Laminin_N
LAMC2	Other/Unknown	no		Laminin_IV, EGF, LE_dom

Expression context

Cohort genes with no expression data: 0.

6 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)	6
unknown	0

Top tissues across cohort

Tissue	Cohort genes
skin of leg	3
skin of abdomen	2
periodontal ligament	2
zone of skin	1
minor salivary gland	1
tibial nerve	1
right lung	1
lower esophagus	1
lower esophagus muscularis layer	1
nerve	1
cartilage tissue	1
gingival epithelium	1
hair follicle	1
islet of Langerhans	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
LAMA3	239	broad	marker	right lung, skin of leg, skin of abdomen
LAMA4	268	ubiquitous	marker	lower esophagus muscularis layer, lower esophagus, nerve
LAMB3	215	ubiquitous	marker	cartilage tissue, periodontal ligament, gingival epithelium
LAMC2	209	broad	marker	islet of Langerhans, hair follicle, periodontal ligament

Protein interactions among cohort

Intra-cohort edges: 14.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
LAMA4	2,688
ITGB4	2,536
LAMA3	2,195
LAMC2	2,061
COL17A1	1,769
LAMB3	1,697

Intra-cohort edges

A	B	Sources
COL17A1	ITGB4	biogrid_interaction, string_interaction
COL17A1	LAMA3	string_interaction
COL17A1	LAMA4	string_interaction
COL17A1	LAMB3	string_interaction
COL17A1	LAMC2	string_interaction
ITGB4	LAMA3	string_interaction
ITGB4	LAMA4	string_interaction
ITGB4	LAMB3	string_interaction
ITGB4	LAMC2	string_interaction
LAMA3	LAMB3	string_interaction
LAMA3	LAMC2	string_interaction
LAMA4	LAMB3	string_interaction
LAMA4	LAMC2	string_interaction
LAMB3	LAMC2	string_interaction

Structural data

PDB: 2 · AlphaFold-only: 4 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ITGB4	P16144	13
COL17A1	Q9UMD9	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
LAMB3	Q13751	78.55
LAMA4	Q16363	73.75
LAMC2	Q13753	72.89
LAMA3	Q16787

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 27. Enrichment computed across 6 evidence-associated genes (6 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 6 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	5	865.1×	5e-14	COL17A1, ITGB4, LAMA3, LAMB3, LAMC2
Laminin interactions	5	317.2×	7e-12	ITGB4, LAMA3, LAMA4, LAMB3, LAMC2
Assembly of collagen fibrils and other multimeric structures	5	167.0×	1e-10	COL17A1, ITGB4, LAMA3, LAMB3, LAMC2
Non-integrin membrane-ECM interactions	5	128.6×	4e-10	ITGB4, LAMA3, LAMA4, LAMB3, LAMC2
MET promotes cell motility	4	400.7×	4e-10	LAMA3, LAMA4, LAMB3, LAMC2
Attachment of bacteria to epithelial cells	4	331.0×	8e-10	LAMA3, LAMA4, LAMB3, LAMC2
Collagen formation	4	304.5×	1e-09	ITGB4, LAMA3, LAMB3, LAMC2
MET activates PTK2 signaling	4	253.8×	2e-09	LAMA3, LAMA4, LAMB3, LAMC2
Signaling by MET	4	211.5×	4e-09	LAMA3, LAMA4, LAMB3, LAMC2
Formation of the dystrophin-glycoprotein complex (DGC)	4	205.8×	4e-09	LAMA3, LAMA4, LAMB3, LAMC2
Developmental Lineage of Pancreatic Ductal Cells	4	152.3×	1e-08	LAMA3, LAMA4, LAMB3, LAMC2
Extracellular matrix organization	5	52.6×	1e-08	ITGB4, LAMA3, LAMA4, LAMB3, LAMC2
Cell junction organization	4	124.8×	2e-08	ITGB4, LAMA3, LAMB3, LAMC2
Anchoring fibril formation	3	380.7×	7e-08	LAMA3, LAMB3, LAMC2
Cell-Cell communication	4	91.7×	7e-08	ITGB4, LAMA3, LAMB3, LAMC2
Signaling by Receptor Tyrosine Kinases	4	34.5×	3e-06	LAMA3, LAMA4, LAMB3, LAMC2
Degradation of the extracellular matrix	3	58.9×	2e-05	LAMA3, LAMB3, LAMC2
ECM proteoglycans	2	50.1×	1e-03	LAMA3, LAMA4
Signal Transduction	4	6.8×	0.002	LAMA3, LAMA4, LAMB3, LAMC2
Syndecan interactions	1	70.5×	0.019	ITGB4
Differentiation of Keratinocytes in Interfollicular Epidermis in Mammalian Skin	1	46.4×	0.027	ITGB4
Collagen chain trimerization	1	43.3×	0.028	COL17A1
Developmental Cell Lineages	1	37.3×	0.031	ITGB4
Collagen degradation	1	29.3×	0.037	COL17A1
Collagen biosynthesis and modifying enzymes	1	28.4×	0.037	COL17A1
Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell	1	14.5×	0.069	COL17A1
Developmental Biology	1	2.4×	0.350	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 6 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	3	1203.7×	2e-08	COL17A1, ITGB4, LAMA3
epidermis development	4	140.4×	9e-08	COL17A1, LAMA3, LAMB3, LAMC2
cell adhesion	4	25.0×	6e-05	ITGB4, LAMA4, LAMB3, LAMC2
endodermal cell differentiation	2	165.2×	4e-04	LAMA3, LAMB3
regulation of embryonic development	2	110.1×	6e-04	LAMA3, LAMA4
regulation of cell adhesion	2	102.1×	6e-04	LAMA3, LAMA4
cell-matrix adhesion	2	54.5×	0.002	COL17A1, ITGB4
regulation of cell migration	2	52.5×	0.002	LAMA3, LAMA4
peripheral nervous system myelin formation	1	936.2×	0.003	ITGB4
cell-cell adhesion	2	33.8×	0.004	ITGB4, LAMA3
nail development	1	401.2×	0.005	ITGB4
trophoblast cell migration	1	401.2×	0.005	ITGB4
mesodermal cell differentiation	1	255.3×	0.008	ITGB4
skin morphogenesis	1	234.1×	0.008	ITGB4
cell adhesion mediated by integrin	1	112.3×	0.014	ITGB4
filopodium assembly	1	108.0×	0.014	ITGB4
brown fat cell differentiation	1	72.0×	0.020	LAMB3
cell motility	1	66.9×	0.021	ITGB4
negative regulation of cold-induced thermogenesis	1	57.3×	0.023	LAMA4
response to wounding	1	37.0×	0.033	ITGB4
integrin-mediated signaling pathway	1	26.8×	0.044	ITGB4
autophagy	1	18.4×	0.061	ITGB4
positive regulation of cell migration	1	10.3×	0.098	LAMC2
cell migration	1	10.2×	0.098	ITGB4
positive regulation of cell population proliferation	1	5.6×	0.166	LAMC2

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 6

Druggability breadth: 5 of 6 evidence-associated genes (83%) 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
LAMA3	0	0
LAMA4	0	0
LAMB3	0	0
LAMC2	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: 6; 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	5	COL17A1, LAMA3, LAMA4, LAMB3, LAMC2

Undrugged target profiles

6 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	—
LAMA3	0	—
LAMA4	0	—
LAMB3	0	—
LAMC2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.