epidermolysis bullosa, junctional 3A, intermediate

Summary

epidermolysis bullosa, junctional 3A, intermediate (MONDO:0030748) is a disease caused by LAMC2 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: LAMC2 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 47

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	epidermolysis bullosa, junctional 3A, intermediate
Mondo ID	MONDO:0030748
OMIM	619785
UMLS	C5676938
MedGen	1812940
GARD	0025631
Is cancer (heuristic)	no

Also known as: epidermolysis bullosa, junctional 3A, generalised intermediate · epidermolysis bullosa, junctional 3A, generalized intermediate · epidermolysis bullosa, junctional 3A, intermediate · epidermolysis bullosa, junctional 3A, non-herlitz IIA · JEB3A

Data availability: 47 ClinVar variants · 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 › epidermolysis bullosa, junctional 3A, 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 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

47 retrieved; paginated sample, class counts are floors:

22 likely pathogenic, 8 pathogenic, 7 pathogenic/likely pathogenic, 5 uncertain significance, 4 conflicting classifications of pathogenicity, 1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1048072	NM_005562.3(LAMC2):c.2074C>T (p.Gln692Ter)	LAMC2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1177256	NM_005562.3(LAMC2):c.1045C>T (p.Arg349Ter)	LAMC2	Pathogenic	criteria provided, multiple submitters, no conflicts
14556	NM_005562.3(LAMC2):c.1065C>G (p.Tyr355Ter)	LAMC2	Pathogenic	criteria provided, multiple submitters, no conflicts
14559	NM_005562.3(LAMC2):c.733C>T (p.Arg245Ter)	LAMC2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
14560	NM_005562.3(LAMC2):c.405-1G>A	LAMC2	Pathogenic	criteria provided, single submitter
14561	NM_005562.3(LAMC2):c.3394dup (p.Thr1132fs)	LAMC2	Pathogenic	no assertion criteria provided
188791	NM_005562.3(LAMC2):c.667C>T (p.Arg223Ter)	LAMC2	Pathogenic	criteria provided, multiple submitters, no conflicts
2697774	NM_005562.3(LAMC2):c.1924G>T (p.Gly642Ter)	LAMC2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
370838	NM_005562.3(LAMC2):c.134_137del (p.Arg45fs)	LAMC2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
371316	NM_005562.3(LAMC2):c.2006_2012del (p.Ile669fs)	LAMC2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
371541	NM_005562.3(LAMC2):c.146_150dup (p.Phe51fs)	LAMC2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
550635	NM_005562.3(LAMC2):c.1782_1783del (p.Lys594fs)	LAMC2	Pathogenic	criteria provided, multiple submitters, no conflicts
556962	NM_005562.3(LAMC2):c.2755-2A>G	LAMC2	Pathogenic	criteria provided, single submitter
591594	NM_005562.3(LAMC2):c.3328+1G>A	LAMC2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
841746	NM_005562.3(LAMC2):c.1711C>T (p.Arg571Ter)	LAMC2	Pathogenic	criteria provided, single submitter
1066955	NM_005562.3(LAMC2):c.1715-2A>G	LAMC2	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1067977	NM_005562.3(LAMC2):c.640+1G>A	LAMC2	Likely pathogenic	criteria provided, multiple submitters, no conflicts
3370435	NM_005562.3(LAMC2):c.1857+1G>A	LAMC2	Likely pathogenic	no assertion criteria provided
3370436	NM_005562.3(LAMC2):c.1882C>T (p.Gln628Ter)	LAMC2	Likely pathogenic	no assertion criteria provided
3574538	NM_005562.3(LAMC2):c.284del (p.Arg95fs)	LAMC2	Likely pathogenic	criteria provided, single submitter
3574553	NM_005562.3(LAMC2):c.1700dup (p.Asp568fs)	LAMC2	Likely pathogenic	criteria provided, single submitter
3574561	NM_005562.3(LAMC2):c.1705A>T (p.Lys569Ter)	LAMC2	Likely pathogenic	criteria provided, single submitter
3574569	NM_005562.3(LAMC2):c.1779C>A (p.Cys593Ter)	LAMC2	Likely pathogenic	criteria provided, single submitter
3574583	NM_005562.3(LAMC2):c.2137C>T (p.Gln713Ter)	LAMC2	Likely pathogenic	criteria provided, single submitter
3574587	NM_005562.3(LAMC2):c.2208_2209delinsA (p.Leu737fs)	LAMC2	Likely pathogenic	criteria provided, single submitter
3574593	NM_005562.3(LAMC2):c.2220+1_2220+2del	LAMC2	Likely pathogenic	criteria provided, single submitter
3574600	NM_005562.3(LAMC2):c.2281del (p.Ala761fs)	LAMC2	Likely pathogenic	criteria provided, single submitter
3574606	NM_005562.3(LAMC2):c.2418_2426delinsG (p.Ser807fs)	LAMC2	Likely pathogenic	criteria provided, single submitter
3574612	NM_005562.3(LAMC2):c.2497_2500del (p.Glu833fs)	LAMC2	Likely pathogenic	criteria provided, single submitter
3574619	NM_005562.3(LAMC2):c.2571del (p.Leu858fs)	LAMC2	Likely pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 8 · Orphanet: 2 · 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
LAMC2	Definitive	Autosomal recessive	junctional epidermolysis bullosa	8

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
LAMC2	Orphanet:79402	Intermediate generalized junctional epidermolysis bullosa
LAMC2	Orphanet:79404	Severe generalized 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
LAMC2	HGNC:6493	ENSG00000058085	Q13753	Laminin subunit gamma-2	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
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: 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)
LAMC2	Other/Unknown	no		Laminin_IV, EGF, LE_dom

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
hair follicle	1
islet of Langerhans	1
periodontal ligament	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
LAMC2	209	broad	marker	islet of Langerhans, hair follicle, periodontal ligament

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
LAMC2	2,061

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
LAMC2	Q13753	72.89

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 18. 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	LAMC2
Anchoring fibril formation	1	761.3×	0.006	LAMC2
MET promotes cell motility	1	601.0×	0.006	LAMC2
Attachment of bacteria to epithelial cells	1	496.5×	0.006	LAMC2
Collagen formation	1	456.8×	0.006	LAMC2
Laminin interactions	1	380.7×	0.006	LAMC2
MET activates PTK2 signaling	1	380.7×	0.006	LAMC2
Signaling by MET	1	317.2×	0.006	LAMC2
Formation of the dystrophin-glycoprotein complex (DGC)	1	308.6×	0.006	LAMC2
Developmental Lineage of Pancreatic Ductal Cells	1	228.4×	0.008	LAMC2
Assembly of collagen fibrils and other multimeric structures	1	200.3×	0.008	LAMC2
Cell junction organization	1	187.2×	0.008	LAMC2
Non-integrin membrane-ECM interactions	1	154.3×	0.009	LAMC2
Cell-Cell communication	1	137.6×	0.009	LAMC2
Degradation of the extracellular matrix	1	117.7×	0.010	LAMC2
Extracellular matrix organization	1	63.1×	0.018	LAMC2
Signaling by Receptor Tyrosine Kinases	1	51.7×	0.020	LAMC2
Signal Transduction	1	10.2×	0.098	LAMC2

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
epidermis development	1	210.7×	0.019	LAMC2
positive regulation of cell migration	1	61.7×	0.030	LAMC2
cell adhesion	1	37.5×	0.030	LAMC2
positive regulation of cell population proliferation	1	33.6×	0.030	LAMC2

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
LAMC2	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	LAMC2

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)
LAMC2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.