Junctional epidermolysis bullosa

disease

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Also known as EBJepidermolysis bullosa atrophicansepidermolysis bullosa, junctionalJEB

Summary

Junctional epidermolysis bullosa (MONDO:0017612) is a disease (an umbrella term covering 15 Mondo subtypes) caused by variants in LAMA3, LAMB3, and LAMC2, with 8 cohort genes and 15 clinical trials. The dominant Reactome pathway is Type I hemidesmosome assembly (6 cohort genes). Top therapeutic interventions include gentamicin, birch triterpenes, and diacerein.

At a glance

Prevalence: <1 / 1 000 000 (Sweden) [Orphanet-validated]
Causal genes: LAMA3 (GenCC Definitive), LAMB3 (GenCC Definitive), LAMC2 (GenCC Definitive)
Umbrella term: 15 Mondo subtypes
Cohort genes: 8
ClinVar variants: 381
Clinical trials: 15

Clinical features

Epidemiology

Prevalence records

13 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Annual incidence	1-9 / 1 000 000	0.93	Netherlands	Validated
Point prevalence	<1 / 1 000 000	0.08	Sweden	Validated
Point prevalence	<1 / 1 000 000	0.07	Ireland	Validated
Point prevalence	<1 / 1 000 000	0.02	Finland	Validated
Point prevalence	<1 / 1 000 000	0.07	Australia	Validated
Point prevalence	<1 / 1 000 000	0.02	Japan	Validated
Point prevalence	<1 / 1 000 000	0.04	United States	Validated
Point prevalence	<1 / 1 000 000	0.07	South Africa	Validated
Point prevalence	1-9 / 1 000 000	0.21	Netherlands	Validated
Prevalence at birth	1-9 / 1 000 000	0.38	Italy	Validated
Prevalence at birth	1-9 / 1 000 000	0.22	United States	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Not yet validated
Point prevalence	<1 / 1 000 000		Europe	Not yet validated

Identifiers

Disease identifiers

Field	Value
Canonical name	junctional epidermolysis bullosa
Mondo ID	MONDO:0017612
MeSH	D016109
OMIM	226650
Orphanet	305
DOID	DOID:3209
ICD-11	1501260457
NCIT	C90598
SNOMED CT	79855003
UMLS	C0079301
MedGen	86898
GARD	0002152
Is cancer (heuristic)	no

Also known as: EBJ · epidermolysis bullosa atrophicans · epidermolysis bullosa, junctional · JEB · junctional epidermolysis bullosa

Data availability: 381 ClinVar variants · 3 GenCC gene-disease records · 12 cell lines.

Disease family

An umbrella term covering 15 Mondo subtypes.

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

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

381 retrieved; paginated sample, class counts are floors:

139 uncertain significance, 70 conflicting classifications of pathogenicity, 59 benign, 39 pathogenic, 26 pathogenic/likely pathogenic, 18 benign/likely benign, 16 likely pathogenic, 14 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1047963	NM_000494.4(COL17A1):c.1571_1572dup (p.Gln525fs)	COL17A1	Pathogenic	criteria provided, single submitter
1047964	NM_000494.4(COL17A1):c.2576dup (p.Gly860fs)	COL17A1	Pathogenic	criteria provided, single submitter
1047966	NM_000494.4(COL17A1):c.3766+1G>A	COL17A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1047967	NM_000494.4(COL17A1):c.3827dup (p.Gly1277fs)	COL17A1	Pathogenic	criteria provided, single submitter
1047993	NM_000494.4(COL17A1):c.3828_3829insC (p.Gly1277fs)	COL17A1	Pathogenic	criteria provided, single submitter
1047994	NM_000494.4(COL17A1):c.4156+1G>A	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
379785	NM_000494.4(COL17A1):c.332-1G>A	COL17A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
427173	NM_000494.4(COL17A1):c.25C>T (p.Arg9Ter)	COL17A1	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
973530	NM_000494.4(COL17A1):c.3539dup (p.Gly1181fs)	COL17A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
14742	NM_000213.5(ITGB4):c.3841C>T (p.Arg1281Trp)	GALK1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1047995	NM_000210.4(ITGA6):c.1286C>A (p.Ser429Ter)	ITGA6	Pathogenic	criteria provided, single submitter
14743	NM_000213.5(ITGB4):c.3674G>A (p.Arg1225His)	ITGB4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1047960	NM_198129.4(LAMA3):c.6319-1G>T	LAMA3	Pathogenic	criteria provided, single submitter
1047961	NM_198129.4(LAMA3):c.6348_6352delinsCTGGCAAGA (p.Glu2117fs)	LAMA3	Pathogenic	criteria provided, single submitter
1047962	NM_198129.4(LAMA3):c.9856G>T (p.Ala3286Ser)	LAMA3	Pathogenic	criteria provided, single submitter
1069385	NM_198129.4(LAMA3):c.5546del (p.Gly1849fs)	LAMA3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1321416	NM_198129.4(LAMA3):c.7204C>T (p.Arg2402Ter)	LAMA3	Pathogenic	criteria provided, multiple submitters, no conflicts
1369957	NM_198129.4(LAMA3):c.8755A>T (p.Lys2919Ter)	LAMA3	Pathogenic	criteria provided, multiple submitters, no conflicts
1878281	NM_000227.6(LAMA3):c.69del (p.Gln24fs)	LAMA3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2726163	NM_198129.4(LAMA3):c.9642G>T (p.Lys3214Asn)	LAMA3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
370076	NM_198129.4(LAMA3):c.8203C>T (p.Arg2735Ter)	LAMA3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
4081715	NM_198129.4(LAMA3):c.9858del (p.Asn3287fs)	LAMA3	Pathogenic	criteria provided, single submitter
555742	NM_198129.4(LAMA3):c.6232_6233del (p.Gln2077_Ser2078insTer)	LAMA3	Pathogenic	criteria provided, multiple submitters, no conflicts
556752	NM_198129.4(LAMA3):c.6567del (p.Glu2190fs)	LAMA3	Pathogenic	criteria provided, multiple submitters, no conflicts
1047957	NM_000228.3(LAMB3):c.323T>C (p.Leu108Pro)	LAMB3	Pathogenic	criteria provided, single submitter
1047958	NM_000228.3(LAMB3):c.1634del (p.Gly545fs)	LAMB3	Pathogenic	criteria provided, single submitter
1047959	NM_000228.3(LAMB3):c.2047del (p.Glu683fs)	LAMB3	Pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 54 · Orphanet: 20 · 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
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
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
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
GALK1	Orphanet:79237	Galactokinase deficiency
ITGA6	Orphanet:79403	Junctional epidermolysis bullosa with pyloric atresia
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

8 cohort genes, 8 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	8

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
LAMA3	HGNC:6483	ENSG00000053747	Q16787	Laminin subunit alpha-3	gencc,clinvar
LAMA4	HGNC:6484	ENSG00000112769	Q16363	Laminin subunit alpha-4	gencc,clinvar
LAMB3	HGNC:6490	ENSG00000196878	Q13751	Laminin subunit beta-3	gencc,clinvar
LAMC2	HGNC:6493	ENSG00000058085	Q13753	Laminin subunit gamma-2	gencc,clinvar
COL17A1	HGNC:2194	ENSG00000065618	Q9UMD9	Collagen alpha-1(XVII) chain	clinvar
GALK1	HGNC:4118	ENSG00000108479	P51570	Galactokinase	clinvar
ITGA6	HGNC:6142	ENSG00000091409	P23229	Integrin alpha-6	clinvar
ITGB4	HGNC:6158	ENSG00000132470	P16144	Integrin beta-4	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
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.
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.
GALK1	Galactokinase	Catalyzes the transfer of a phosphate from ATP to alpha-D-galactose and participates in the first committed step in the catabolism of galactose.
ITGA6	Integrin alpha-6	Integrin alpha-6/beta-1 (ITGA6:ITGB1) is a receptor for laminin on platelets.
ITGB4	Integrin beta-4	Integrin alpha-6/beta-4 is a receptor for laminin.

Protein-family classification

Druggable: 3 · Difficult: 0 · Unknown: 5 · Druggable fraction: 0.38

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	2	7.3×	0.086
Kinase	1	3.5×	0.382
Other/Unknown	5	1.1×	0.496

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
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
COL17A1	Other/Unknown	no		Collagen, Collagen_superfamily
GALK1	Kinase	yes	2.7.1.6	Galactokinase, GHMP_knse_ATP-bd_CS, GHMP_kinase_N_dom
ITGA6	Antibody/Immunoglobulin	yes		Integrin_alpha, FG-GAP, Int_alpha_beta-p
ITGB4	Antibody/Immunoglobulin	yes		EGF, Integrin_bsu_VWA, Calx_beta

Expression context

Cohort genes with no expression data: 0.

8 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)	8
unknown	0

Top tissues across cohort

Tissue	Cohort genes
skin of leg	3
skin of abdomen	2
periodontal ligament	2
tibial nerve	2
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
zone of skin	1
apex of heart	1
monocyte	1
right lobe of liver	1
dorsal root ganglion	1
sural nerve	1
minor salivary gland	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
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
COL17A1	182	broad	marker	skin of abdomen, skin of leg, zone of skin
GALK1	174	ubiquitous	marker	right lobe of liver, apex of heart, monocyte
ITGA6	297	ubiquitous	marker	tibial nerve, sural nerve, dorsal root ganglion
ITGB4	267	broad	marker	tibial nerve, minor salivary gland, skin of leg

Protein interactions among cohort

Intra-cohort edges: 20.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ITGA6	3,130
LAMA4	2,688
ITGB4	2,536
GALK1	2,244
LAMA3	2,195
LAMC2	2,061
COL17A1	1,769
LAMB3	1,697

Intra-cohort edges

A	B	Sources
COL17A1	ITGA6	string_interaction
COL17A1	ITGB4	biogrid_interaction, string_interaction
COL17A1	LAMA3	string_interaction
COL17A1	LAMA4	string_interaction
COL17A1	LAMB3	string_interaction
COL17A1	LAMC2	string_interaction
ITGA6	ITGB4	intact, string_interaction
ITGA6	LAMA3	string_interaction
ITGA6	LAMA4	string_interaction
ITGA6	LAMB3	string_interaction
ITGA6	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: 4 · AlphaFold-only: 4 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
GALK1	P51570	20
ITGB4	P16144	13
ITGA6	P23229	2
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: 37. Enrichment computed across 8 evidence-associated genes (8 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 8 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	6	778.6×	2e-16	LAMA3, LAMB3, LAMC2, COL17A1, ITGA6, ITGB4
Laminin interactions	6	285.5×	1e-13	LAMA3, LAMA4, LAMB3, LAMC2, ITGA6, ITGB4
Assembly of collagen fibrils and other multimeric structures	6	150.3×	4e-12	LAMA3, LAMB3, LAMC2, COL17A1, ITGA6, ITGB4
Collagen formation	5	285.5×	1e-11	LAMA3, LAMB3, LAMC2, ITGA6, ITGB4
Non-integrin membrane-ECM interactions	6	115.7×	1e-11	LAMA3, LAMA4, LAMB3, LAMC2, ITGA6, ITGB4
Cell junction organization	5	117.0×	1e-09	LAMA3, LAMB3, LAMC2, ITGA6, ITGB4
MET promotes cell motility	4	300.5×	2e-09	LAMA3, LAMA4, LAMB3, LAMC2
Extracellular matrix organization	6	47.3×	2e-09	LAMA3, LAMA4, LAMB3, LAMC2, ITGA6, ITGB4
Attachment of bacteria to epithelial cells	4	248.3×	4e-09	LAMA3, LAMA4, LAMB3, LAMC2
Cell-Cell communication	5	86.0×	4e-09	LAMA3, LAMB3, LAMC2, ITGA6, ITGB4
MET activates PTK2 signaling	4	190.3×	9e-09	LAMA3, LAMA4, LAMB3, LAMC2
Signaling by MET	4	158.6×	2e-08	LAMA3, LAMA4, LAMB3, LAMC2
Formation of the dystrophin-glycoprotein complex (DGC)	4	154.3×	2e-08	LAMA3, LAMA4, LAMB3, LAMC2
Developmental Lineage of Pancreatic Ductal Cells	4	114.2×	6e-08	LAMA3, LAMA4, LAMB3, LAMC2
Anchoring fibril formation	3	285.5×	3e-07	LAMA3, LAMB3, LAMC2
Signaling by Receptor Tyrosine Kinases	4	25.8×	2e-05	LAMA3, LAMA4, LAMB3, LAMC2
Degradation of the extracellular matrix	3	44.1×	7e-05	LAMA3, LAMB3, LAMC2
Syndecan interactions	2	105.7×	3e-04	ITGA6, ITGB4
Differentiation of Keratinocytes in Interfollicular Epidermis in Mammalian Skin	2	69.6×	7e-04	ITGA6, ITGB4
Developmental Cell Lineages	2	56.0×	1e-03	ITGA6, ITGB4
Defective GALK1 causes GALCT2	1	1427.5×	0.001	GALK1
ECM proteoglycans	2	37.6×	0.002	LAMA3, LAMA4
Galactose catabolism	1	203.9×	0.008	GALK1
Signal Transduction	4	5.1×	0.008	LAMA3, LAMA4, LAMB3, LAMC2
Developmental Lineage of Mammary Stem Cells	1	95.2×	0.015	ITGA6
Developmental Lineage of Mammary Gland Alveolar Cells	1	79.3×	0.018	ITGA6
Developmental Lineage of Mammary Gland Myoepithelial Cells	1	68.0×	0.020	ITGA6
Developmental Lineage of Mammary Gland Luminal Epithelial Cells	1	57.1×	0.023	ITGA6
Basigin interactions	1	54.9×	0.023	ITGA6
Collagen chain trimerization	1	32.4×	0.038	COL17A1

GO biological processes by enrichment

GO term	Cohort genes	Fold	FDR	Sample cohort genes
hemidesmosome assembly	3	902.8×	9e-08	LAMA3, COL17A1, ITGB4
epidermis development	4	105.3×	6e-07	LAMA3, LAMB3, LAMC2, COL17A1
nail development	2	601.9×	5e-05	ITGA6, ITGB4
skin morphogenesis	2	351.1×	1e-04	ITGA6, ITGB4
cell-matrix adhesion	3	61.4×	1e-04	COL17A1, ITGA6, ITGB4
cell adhesion	4	18.7×	2e-04	LAMA4, LAMB3, LAMC2, ITGB4
cell-cell adhesion	3	38.1×	3e-04	LAMA3, ITGA6, ITGB4
endodermal cell differentiation	2	123.9×	5e-04	LAMA3, LAMB3
regulation of embryonic development	2	82.6×	0.001	LAMA3, LAMA4
regulation of cell adhesion	2	76.6×	0.001	LAMA3, LAMA4
galactitol metabolic process	1	2106.5×	0.002	GALK1
glycolytic process from galactose	1	2106.5×	0.002	GALK1
integrin-mediated signaling pathway	2	40.1×	0.003	ITGA6, ITGB4
regulation of cell migration	2	39.4×	0.003	LAMA3, LAMA4
peripheral nervous system myelin formation	1	702.2×	0.004	ITGB4
ectodermal cell differentiation	1	526.6×	0.005	ITGA6
beta-D-galactose catabolic process via UDP-galactose, Leloir pathway	1	421.3×	0.005	GALK1
cell-substrate junction assembly	1	351.1×	0.006	ITGA6
trophoblast cell migration	1	300.9×	0.007	ITGB4
galactose metabolic process	1	263.3×	0.007	GALK1
mesodermal cell differentiation	1	191.5×	0.009	ITGB4
positive regulation of cell migration	2	15.4×	0.012	LAMC2, ITGA6
cell-substrate adhesion	1	95.8×	0.017	ITGA6
cell adhesion mediated by integrin	1	84.3×	0.019	ITGB4
filopodium assembly	1	81.0×	0.019	ITGB4
leukocyte migration	1	78.0×	0.019	ITGA6
brown fat cell differentiation	1	54.0×	0.026	LAMB3
negative regulation of extrinsic apoptotic signaling pathway	1	52.7×	0.026	ITGA6
cell motility	1	50.1×	0.026	ITGB4
negative regulation of cold-induced thermogenesis	1	43.0×	0.029	LAMA4

Therapeutics

Drugs indicated or in trials for this disease

1 approved drug — disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Status
Birch Triterpenes	Approved (phase 4)

1 drug in clinical trials for this disease (phase 2–3, investigational): efficacy not established — a trial record, not an indication.

Drug	Highest phase
Timbetasin Acetate	Phase 2

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 7

Druggability breadth: 7 of 8 evidence-associated genes (88%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
GALK1	PYRANTEL PAMOATE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
GALK1	6	4
LAMA3	0	0
LAMA4	0	0
LAMB3	0	0
LAMC2	0	0
COL17A1	0	0
ITGA6	0	0
ITGB4	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
PYRANTEL PAMOATE	4	GALK1
HEXACHLOROPHENE	4	GALK1
QUERCETIN	3	GALK1
GOSSYPOL	3	GALK1
STREPTONIGRIN	2	GALK1
LUTEOLIN	2	GALK1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
GALK1	19	Binding:15, Functional:4
ITGA6	3	Binding:3
ITGB4	2	Binding:2

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
GALK1	2.7.1.6	galactokinase

Pharmacogenomics

Cohort genes with a PharmGKB record: 8; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

6 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.

Compound	Max phase	Cohort target (bioactivity)
PYRANTEL PAMOATE	4	GALK1
HEXACHLOROPHENE	4	GALK1
QUERCETIN	3	GALK1
GOSSYPOL	3	GALK1
STREPTONIGRIN	2	GALK1
LUTEOLIN	2	GALK1

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	GALK1
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	2	ITGA6, ITGB4
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	5	LAMA3, LAMA4, LAMB3, LAMC2, COL17A1

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
LAMA3	0	—
LAMA4	0	—
LAMB3	0	—
LAMC2	0	—
COL17A1	0	—
ITGA6	3	—
ITGB4	2	—

Clinical trials & evidence

Clinical trials

Clinical trials: 15.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	5
PHASE1/PHASE2	3
PHASE2	3
PHASE3	2
PHASE1	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT06917690	PHASE3	RECRUITING	A Study to Learn About the Safety and Efficacy of the Drug Oleogel-S10 in Japanese Patients With Epidermolysis Bullosa
NCT00587223	PHASE3	TERMINATED	Safety and Efficacy of Apligraf in Nonhealing Wounds of Subjects With Junctional or Dystrophic Epidermolysis Bullosa (EB)
NCT03526159	PHASE1/PHASE2	RECRUITING	Gentamicin for Junctional Epidermolysis Bullosa
NCT06594393	PHASE2	RECRUITING	A Phase 2 Study of TCP-25 Gel in Patients With Epidermolysis Bullosa, STEP-study
NCT03490331	PHASE1/PHASE2	TERMINATED	Clinical Trial to Assess Safety and Efficacy of Autologous Cultured Epidermal Grafts Containing Epidermal Stem Cells Genetically Modified in Patients With JEB (HOLOGENE17)
NCT03578029	PHASE2	TERMINATED	Evaluation of the Safety and Efficacy Study of RGN-137 Topical Gel for Junctional and Dystrophic Epidermolysis Bullosa
NCT04140786	PHASE1/PHASE2	UNKNOWN	Optimizing IV Gentamicin in JEB
NCT04908215	PHASE2	COMPLETED	INM-755 (Cannabinol) Cream for Treatment of Epidermolysis Bullosa
NCT06713434	PHASE1	ACTIVE_NOT_RECRUITING	Pilot Study of ELK-003 Eye Drops for Treating Ocular Manifestations of Epidermolysis Bullosa
NCT03472287	PHASE1	COMPLETED	To Evaluate the Pharmacokinetic of Diacerein and Rhein After Maximum Use in Patients With Epidermolysis Bullosa (EB)
NCT06423573	Not specified	RECRUITING	A Study to Assess the Incidence of Skin Cancers in Patients With Epidermolysis Bullosa Receiving Filsuvez
NCT03269474	Not specified	UNKNOWN	Computational Drug Repurposing for All EBS Cases
NCT04727268	Not specified	UNKNOWN	Genotype-phenotype Correlation in Junctional Epidermolysis Bullosa
NCT05033574	Not specified	UNKNOWN	The State of Sexual Development in Children With Inherited Epidermolysis Bullosa
NCT06007235	Not specified	UNKNOWN	CACIPLIQ20 in Wound Healing in Subjects With Epidermolysis Bullosa

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
GENTAMICIN	4	3
BIRCH TRITERPENES	4	1
DIACEREIN	3	1
TIMBETASIN ACETATE	3	1
GENTAMICIN C1A	0	3
VEHICLE	0	2
CHEMBL195892	0	1
CHEMBL3039597	0	1
GENTAMICIN C2	0	1

Cohort genes: LAMA3, LAMA4, LAMB3, LAMC2, COL17A1, GALK1, ITGA6, ITGB4
Drugs: Gentamicin, Birch Triterpenes, Diacerein, Timbetasin Acetate