Epidermolysis bullosa, junctional 7, with interstitial lung disease and nephrotic syndrome

Summary

Epidermolysis bullosa, junctional 7, with interstitial lung disease and nephrotic syndrome (MONDO:0013881) is a disease caused by ITGA3 (GenCC Definitive), with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: ITGA3 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 181

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		3	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	epidermolysis bullosa, junctional 7, with interstitial lung disease and nephrotic syndrome
Mondo ID	MONDO:0013881
OMIM	614748
Orphanet	306504
UMLS	C4518785
MedGen	1388385
GARD	0017377
Is cancer (heuristic)	no

Also known as: congenital ILNEB syndrome · congenital interstitial lung disease-nephrotic syndrome-epidermolysis bullosa syndrome · congenital NEP syndrome · congenital nephrotic syndrome - interstitial lung disease - epidermolysis bullosa syndrome · congenital nephrotic syndrome-epidermolysis bullosa-pulmonary disease syndrome · ILNEB · interstitial lung disease, nephrotic syndrome, and epidermolysis bullosa, congenital · JEB with respiratory and renal involvement · JEB-RR

Data availability: 181 ClinVar variants · 6 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 7, with interstitial lung disease and nephrotic syndrome

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, 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 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

181 retrieved; paginated sample, class counts are floors:

120 uncertain significance, 19 likely benign, 14 likely pathogenic, 12 conflicting classifications of pathogenicity, 9 benign/likely benign, 4 pathogenic, 2 pathogenic/likely pathogenic, 1 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
209163	NM_002204.4(ITGA3):c.2070+1G>A	ITGA3	Pathogenic	criteria provided, multiple submitters, no conflicts
2127941	NM_002204.4(ITGA3):c.240dup (p.Pro81fs)	ITGA3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
35570	NM_002204.4(ITGA3):c.1173_1174del (p.Pro392fs)	ITGA3	Pathogenic	no assertion criteria provided
35571	NM_002204.4(ITGA3):c.1538-1G>A	ITGA3	Pathogenic	no assertion criteria provided
35572	NM_002204.4(ITGA3):c.1883G>C (p.Arg628Pro)	ITGA3	Pathogenic/Likely pathogenic	no assertion criteria provided
4535843	NM_002204.4(ITGA3):c.2577_2583+13del	ITGA3	Pathogenic	criteria provided, single submitter
208455	NM_002204.4(ITGA3):c.1387C>T (p.Arg463Trp)	ITGA3	Likely pathogenic	criteria provided, single submitter
3067864	NM_002204.4(ITGA3):c.*32-1G>C	ITGA3	Likely pathogenic	criteria provided, single submitter
3358856	NM_002204.4(ITGA3):c.821G>A (p.Arg274Gln)	ITGA3	Likely pathogenic	criteria provided, multiple submitters, no conflicts
3382048	NM_002204.4(ITGA3):c.2685dup (p.Ala896fs)	ITGA3	Likely pathogenic	criteria provided, single submitter
3382049	NM_002204.4(ITGA3):c.1133A>T (p.Asp378Val)	ITGA3	Likely pathogenic	criteria provided, single submitter
3582231	NM_002204.4(ITGA3):c.446G>A (p.Trp149Ter)	ITGA3	Likely pathogenic	criteria provided, single submitter
3582234	NM_002204.4(ITGA3):c.493C>T (p.Arg165Ter)	ITGA3	Likely pathogenic	criteria provided, single submitter
3582237	NM_002204.4(ITGA3):c.665-1G>A	ITGA3	Likely pathogenic	criteria provided, single submitter
3582279	NM_002204.4(ITGA3):c.2261_2264dup (p.Val756fs)	ITGA3	Likely pathogenic	criteria provided, single submitter
3582280	NM_002204.4(ITGA3):c.2299del	ITGA3	Likely pathogenic	criteria provided, single submitter
3582284	NM_002204.4(ITGA3):c.2401-11_2409del	ITGA3	Likely pathogenic	criteria provided, single submitter
3582292	NM_002204.4(ITGA3):c.2641G>T (p.Gly881Ter)	ITGA3	Likely pathogenic	criteria provided, single submitter
817532	NM_002204.4(ITGA3):c.2623C>T (p.Arg875Ter)	ITGA3	Likely pathogenic	criteria provided, multiple submitters, no conflicts
995569	NM_002204.4(ITGA3):c.1621G>C (p.Gly541Arg)	ITGA3	Likely pathogenic	criteria provided, single submitter
2070073	NM_002204.4(ITGA3):c.2512G>A (p.Val838Ile)	ITGA3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
209162	NM_002204.4(ITGA3):c.1973C>G (p.Thr658Arg)	ITGA3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2166988	NM_002204.4(ITGA3):c.867C>T (p.Gly289=)	ITGA3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2189934	NM_002204.4(ITGA3):c.2778C>T (p.Asn926=)	ITGA3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2714631	NM_002204.4(ITGA3):c.1458G>A (p.Thr486=)	ITGA3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2955282	NM_002204.4(ITGA3):c.1825-13G>A	ITGA3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3286713	NM_002204.4(ITGA3):c.2723G>A (p.Arg908His)	ITGA3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3530356	NM_002204.4(ITGA3):c.2767G>A (p.Val923Ile)	ITGA3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3582242	NM_002204.4(ITGA3):c.827G>A (p.Arg276Gln)	ITGA3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
722214	NM_002204.4(ITGA3):c.1200C>T (p.Tyr400=)	ITGA3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · Orphanet: 1 · 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
ITGA3	Definitive	Autosomal recessive	epidermolysis bullosa, junctional 7, with interstitial lung disease and nephrotic syndrome	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ITGA3	Orphanet:306504	Interstitial lung disease-nephrotic syndrome-epidermolysis bullosa syndrome

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
ITGA3	HGNC:6139	ENSG00000005884	P26006	Integrin alpha-3	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ITGA3	Integrin alpha-3	Integrin alpha-3/beta-1 is a receptor for fibronectin, laminin, collagen, epiligrin, thrombospondin and CSPG4.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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
Antibody/Immunoglobulin	1	29.2×	0.034

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ITGA3	Antibody/Immunoglobulin	yes		Integrin_alpha, FG-GAP, Int_alpha_beta-p

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
metanephric glomerulus	1
right coronary artery	1
upper lobe of left lung	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ITGA3	149	ubiquitous	marker	metanephric glomerulus, right coronary artery, upper lobe of left lung

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ITGA3	2,079

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ITGA3	P26006	83.88

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 11. 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
MET promotes cell motility	1	601.0×	0.007	ITGA3
Basigin interactions	1	439.2×	0.007	ITGA3
Laminin interactions	1	380.7×	0.007	ITGA3
MET activates PTK2 signaling	1	380.7×	0.007	ITGA3
Signaling by MET	1	317.2×	0.007	ITGA3
Integrin cell surface interactions	1	134.3×	0.014	ITGA3
Cell surface interactions at the vascular wall	1	95.2×	0.017	ITGA3
Extracellular matrix organization	1	63.1×	0.022	ITGA3
Signaling by Receptor Tyrosine Kinases	1	51.7×	0.024	ITGA3
Hemostasis	1	36.0×	0.031	ITGA3
Signal Transduction	1	10.2×	0.098	ITGA3

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
negative regulation of cell projection organization	1	5617.3×	0.002	ITGA3
response to gonadotropin	1	5617.3×	0.002	ITGA3
renal filtration	1	5617.3×	0.002	ITGA3
nephron development	1	1872.4×	0.003	ITGA3
mesodermal cell differentiation	1	1532.0×	0.003	ITGA3
dendritic spine maintenance	1	1296.3×	0.003	ITGA3
regulation of BMP signaling pathway	1	1203.7×	0.003	ITGA3
maternal process involved in female pregnancy	1	936.2×	0.003	ITGA3
regulation of Wnt signaling pathway	1	887.0×	0.003	ITGA3
regulation of transforming growth factor beta receptor signaling pathway	1	802.5×	0.003	ITGA3
negative regulation of Rho protein signal transduction	1	766.0×	0.003	ITGA3
exploration behavior	1	648.1×	0.004	ITGA3
leukocyte migration	1	624.1×	0.004	ITGA3
synaptic membrane adhesion	1	581.1×	0.004	ITGA3
positive regulation of cell-substrate adhesion	1	495.6×	0.004	ITGA3
skin development	1	443.5×	0.004	ITGA3
positive regulation of epithelial cell migration	1	411.0×	0.004	ITGA3
positive regulation of protein localization to plasma membrane	1	271.8×	0.006	ITGA3
Rho protein signal transduction	1	247.8×	0.006	ITGA3
lung development	1	198.3×	0.007	ITGA3
memory	1	183.2×	0.008	ITGA3
cell-matrix adhesion	1	163.6×	0.008	ITGA3
integrin-mediated signaling pathway	1	160.5×	0.008	ITGA3
positive regulation of neuron projection development	1	137.0×	0.009	ITGA3
neuron migration	1	133.8×	0.009	ITGA3
cell-cell adhesion	1	101.5×	0.011	ITGA3
heart development	1	78.8×	0.014	ITGA3
response to xenobiotic stimulus	1	69.1×	0.015	ITGA3
positive regulation of gene expression	1	38.7×	0.026	ITGA3

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
ITGA3	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
ITGA3	5	Binding:5

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	1	ITGA3
E	Difficult family or no structure, no drug	0

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)
ITGA3	5	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.