epidermolysis bullosa, junctional 5A, intermediate

Summary

epidermolysis bullosa, junctional 5A, intermediate (MONDO:0030768) is a disease caused by ITGB4 (GenCC Strong), with 2 cohort genes.

At a glance

• Causal gene: ITGB4 (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 392

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	epidermolysis bullosa, junctional 5A, intermediate
Mondo ID	MONDO:0030768
OMIM	619816
UMLS	C5676956
MedGen	1811851
GARD	0025634
Is cancer (heuristic)	no

Also known as: epidermolysis bullosa, junctional 5A, generalised intermediate · epidermolysis bullosa, junctional 5A, generalized intermediate · epidermolysis bullosa, junctional 5A, intermediate · epidermolysis bullosa, junctional 5A, non-herlitz IIA · JEB5A

Data availability: 392 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 5A, 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 3A, intermediate, epidermolysis bullosa, junctional 3B, severe, epidermolysis bullosa, junctional 4, 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

392 retrieved; paginated sample, class counts are floors:

262 uncertain significance, 61 conflicting classifications of pathogenicity, 19 likely pathogenic, 18 likely benign, 14 pathogenic/likely pathogenic, 10 pathogenic, 6 benign/likely benign, 2 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
14731	NM_000213.5(ITGB4):c.4620del (p.Thr1542fs)	GALK1	Pathogenic	criteria provided, single submitter
14741	NM_000213.5(ITGB4):c.4574_4575del (p.Ala1525fs)	GALK1	Pathogenic	no assertion criteria provided
14742	NM_000213.5(ITGB4):c.3841C>T (p.Arg1281Trp)	GALK1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2872718	NM_000213.5(ITGB4):c.5058_5064del (p.Ala1687fs)	GALK1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2913409	NM_000213.5(ITGB4):c.4355dup (p.Ser1454fs)	GALK1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3002284	NM_000213.5(ITGB4):c.5257C>T (p.Gln1753Ter)	GALK1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
817024	NM_000213.5(ITGB4):c.4635_4636del (p.Arg1545fs)	GALK1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1048061	NM_000213.5(ITGB4):c.997T>G (p.Tyr333Asp)	ITGB4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1048067	NM_000213.5(ITGB4):c.3321_3331del (p.Asp1109fs)	ITGB4	Pathogenic	criteria provided, multiple submitters, no conflicts
1180851	NM_000213.5(ITGB4):c.1135C>T (p.Arg379Ter)	ITGB4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1292044	NM_000213.5(ITGB4):c.794dup (p.Ala266fs)	ITGB4	Pathogenic	criteria provided, multiple submitters, no conflicts
14733	NM_000213.5(ITGB4):c.1660C>T (p.Arg554Ter)	ITGB4	Pathogenic	criteria provided, multiple submitters, no conflicts
14734	NM_000213.5(ITGB4):c.182G>A (p.Cys61Tyr)	ITGB4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
14740	NM_000213.5(ITGB4):c.2792G>A (p.Gly931Asp)	ITGB4	Pathogenic	no assertion criteria provided
1723026	NM_000213.5(ITGB4):c.2254+1G>T	ITGB4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2576774	NM_000213.5(ITGB4):c.884_885del (p.Thr295fs)	ITGB4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2713609	NM_000213.5(ITGB4):c.614del (p.Asn205fs)	ITGB4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2736649	NM_000213.5(ITGB4):c.658del (p.Leu220fs)	ITGB4	Pathogenic	criteria provided, multiple submitters, no conflicts
279814	NM_000213.5(ITGB4):c.600dup (p.Phe201fs)	ITGB4	Pathogenic	criteria provided, multiple submitters, no conflicts
2869842	NM_000213.5(ITGB4):c.1860G>A (p.Ala620=)	ITGB4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2878836	NM_000213.5(ITGB4):c.1614del (p.Glu537_Tyr538insTer)	ITGB4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3582841	NM_000213.5(ITGB4):c.310del (p.Gln104fs)	ITGB4	Pathogenic	criteria provided, single submitter
3582853	NM_000213.5(ITGB4):c.754C>T (p.Arg252Cys)	ITGB4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3582978	NM_000213.5(ITGB4):c.3719G>A (p.Trp1240Ter)	ITGB4	Pathogenic	criteria provided, multiple submitters, no conflicts
2737652	NM_000213.5(ITGB4):c.5053+1G>A	GALK1	Likely pathogenic	criteria provided, multiple submitters, no conflicts
3340498	NM_000213.5(ITGB4):c.5150dup (p.Ala1718fs)	GALK1	Likely pathogenic	criteria provided, single submitter
3582985	NM_000213.5(ITGB4):c.3874C>T (p.Gln1292Ter)	GALK1	Likely pathogenic	criteria provided, single submitter
3582995	NM_000213.5(ITGB4):c.4319-2A>G	GALK1	Likely pathogenic	criteria provided, single submitter
3582998	NM_000213.5(ITGB4):c.4369del (p.Ser1457fs)	GALK1	Likely pathogenic	criteria provided, single submitter
3583013	NM_000213.5(ITGB4):c.4744C>T (p.Gln1582Ter)	GALK1	Likely pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 14 · Orphanet: 6 · 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
ITGB4	Definitive	Autosomal recessive	junctional epidermolysis bullosa with pyloric atresia	14

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
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
GALK1	Orphanet:79237	Galactokinase deficiency

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
ITGB4	HGNC:6158	ENSG00000132470	P16144	Integrin beta-4	gencc,clinvar
GALK1	HGNC:4118	ENSG00000108479	P51570	Galactokinase	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ITGB4	Integrin beta-4	Integrin alpha-6/beta-4 is a receptor for laminin.
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.

Protein-family classification

Druggable: 2 · 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	14.6×	0.071
Kinase	1	13.9×	0.071

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ITGB4	Antibody/Immunoglobulin	yes		EGF, Integrin_bsu_VWA, Calx_beta
GALK1	Kinase	yes	2.7.1.6	Galactokinase, GHMP_knse_ATP-bd_CS, GHMP_kinase_N_dom

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
minor salivary gland	1
skin of leg	1
tibial nerve	1
apex of heart	1
monocyte	1
right lobe of liver	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ITGB4	267	broad	marker	tibial nerve, minor salivary gland, skin of leg
GALK1	174	ubiquitous	marker	right lobe of liver, apex of heart, monocyte

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ITGB4	2,536
GALK1	2,244

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
GALK1	P51570	20
ITGB4	P16144	13

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 14. 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
Defective GALK1 causes GALCT2	1	5710.0×	0.002	GALK1
Galactose catabolism	1	815.7×	0.009	GALK1
Type I hemidesmosome assembly	1	519.1×	0.009	ITGB4
Collagen formation	1	228.4×	0.012	ITGB4
Syndecan interactions	1	211.5×	0.012	ITGB4
Laminin interactions	1	190.3×	0.012	ITGB4
Differentiation of Keratinocytes in Interfollicular Epidermis in Mammalian Skin	1	139.3×	0.014	ITGB4
Developmental Cell Lineages	1	112.0×	0.015	ITGB4
Assembly of collagen fibrils and other multimeric structures	1	100.2×	0.015	ITGB4
Cell junction organization	1	93.6×	0.015	ITGB4
Non-integrin membrane-ECM interactions	1	77.2×	0.016	ITGB4
Cell-Cell communication	1	68.8×	0.017	ITGB4
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
galactitol metabolic process	1	8426.0×	0.001	GALK1
glycolytic process from galactose	1	8426.0×	0.001	GALK1
peripheral nervous system myelin formation	1	2808.7×	0.002	ITGB4
beta-D-galactose catabolic process via UDP-galactose, Leloir pathway	1	1685.2×	0.002	GALK1
hemidesmosome assembly	1	1203.7×	0.002	ITGB4
nail development	1	1203.7×	0.002	ITGB4
trophoblast cell migration	1	1203.7×	0.002	ITGB4
galactose metabolic process	1	1053.2×	0.002	GALK1
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×	0.005	ITGB4
filopodium assembly	1	324.1×	0.005	ITGB4
cell motility	1	200.6×	0.008	ITGB4
response to wounding	1	110.9×	0.013	ITGB4
cell-matrix adhesion	1	81.8×	0.016	ITGB4
integrin-mediated signaling pathway	1	80.2×	0.016	ITGB4
autophagy	1	55.1×	0.021	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): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 1

Druggability breadth: 2 of 2 evidence-associated genes (100%) 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
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
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: 2; 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	1	ITGB4
D	Druggable family + AlphaFold only, no drug	0
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)
ITGB4	2	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.