Junctional epidermolysis bullosa with pyloric atresia

Summary

Junctional epidermolysis bullosa with pyloric atresia (MONDO:0009183) is a disease caused by variants in ITGB4 and ITGA6, with 6 cohort genes. The dominant Reactome pathway is Type I hemidesmosome assembly (3 cohort genes).

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal genes: ITGB4 (GenCC Definitive), ITGA6 (GenCC Strong)
• Cohort genes: 6
• ClinVar variants: 757
• Phenotypes (HPO): 21

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		100	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

21 HPO clinical features (Orphanet curated; top 21 by frequency):

HPO ID	Term	Frequency
HP:0002017	Nausea and vomiting	Very frequent (80-99%)
HP:0003270	Abdominal distention	Very frequent (80-99%)
HP:0004399	Congenital pyloric atresia	Very frequent (80-99%)
HP:0008066	Abnormal blistering of the skin	Very frequent (80-99%)
HP:0011100	Intestinal atresia	Very frequent (80-99%)
HP:0200097	Oral mucosal blisters	Very frequent (80-99%)
HP:0000070	Ureterocele	Frequent (30-79%)
HP:0000075	Renal duplication	Frequent (30-79%)
HP:0000110	Renal dysplasia	Frequent (30-79%)
HP:0000126	Hydronephrosis	Frequent (30-79%)
HP:0000790	Hematuria	Frequent (30-79%)
HP:0001561	Polyhydramnios	Frequent (30-79%)
HP:0001581	Recurrent skin infections	Frequent (30-79%)
HP:0006297	Enamel hypoplasia	Frequent (30-79%)
HP:0010477	Aplasia of the bladder	Frequent (30-79%)
HP:0012227	Urethral stricture	Frequent (30-79%)
HP:0100577	Urinary bladder inflammation	Frequent (30-79%)
HP:0000656	Ectropion	Occasional (5-29%)
HP:0001057	Aplasia cutis congenita	Occasional (5-29%)
HP:0001059	Pterygium	Occasional (5-29%)
HP:0008404	Nail dystrophy	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	junctional epidermolysis bullosa with pyloric atresia
Mondo ID	MONDO:0009183
MeSH	C535377
OMIM	226730
Orphanet	79403
DOID	DOID:0060733
ICD-11	1877890811
UMLS	C5676875
MedGen	1810975
GARD	0009694
Is cancer (heuristic)	no

Also known as: Carmi syndrome · epidermolysis bullosa junctionalis with pyloric atresia · epidermolysis bullosa with pyloric atresia · epidermolysis bullosa, junctional, with pyloric stenosis · JEB-PA · junctional epidermolysis bullosa - pyloric atresia · junctional epidermolysis bullosa with pyloric atresia

Data availability: 757 ClinVar variants · 9 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 with pyloric atresia

Related subtypes (14): late-onset localized junctional epidermolysis bullosa-intellectual disability syndrome, junctional epidermolysis bullosa, non-Herlitz type, junctional epidermolysis bullosa Herlitz type, 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 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

600 retrieved; paginated sample, class counts are floors:

335 uncertain significance, 106 conflicting classifications of pathogenicity, 37 benign/likely benign, 36 benign, 30 pathogenic, 25 likely pathogenic, 17 pathogenic/likely pathogenic, 14 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
14731	NM_000213.5(ITGB4):c.4620del (p.Thr1542fs)	GALK1	Pathogenic	criteria provided, single submitter
14737	NM_000213.5(ITGB4):c.4643G>A (p.Trp1548Ter)	GALK1	Pathogenic	no assertion criteria provided
14739	NM_000213.5(ITGB4):c.3977-19T>A	GALK1	Pathogenic	criteria provided, single submitter
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
3256593	NM_000213.5(ITGB4):c.4505_4508dup (p.Thr1504fs)	GALK1	Pathogenic	criteria provided, single submitter
3256594	NM_000213.5(ITGB4):c.3842G>C (p.Arg1281Pro)	GALK1	Pathogenic	criteria provided, single submitter
1179120	NM_000210.4(ITGA6):c.915del (p.His305fs)	ITGA6	Pathogenic	criteria provided, single submitter
1048031	NM_000213.5(ITGB4):c.472_566+184del	ITGB4	Pathogenic	criteria provided, single submitter
1048032	NM_000213.5(ITGB4):c.701G>T (p.Gly234Val)	ITGB4	Pathogenic	criteria provided, single submitter
1048060	NM_000213.5(ITGB4):c.847C>T (p.Arg283Cys)	ITGB4	Pathogenic	criteria provided, single submitter
1048061	NM_000213.5(ITGB4):c.997T>G (p.Tyr333Asp)	ITGB4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1048062	NM_000213.5(ITGB4):c.1370G>A (p.Cys457Tyr)	ITGB4	Pathogenic	criteria provided, single submitter
1048063	NM_000213.5(ITGB4):c.2012G>C (p.Cys671Ser)	ITGB4	Pathogenic	criteria provided, single submitter
1048064	NM_000213.5(ITGB4):c.2465T>C (p.Leu822Ser)	ITGB4	Pathogenic	criteria provided, single submitter
1048065	NM_000213.5(ITGB4):c.2633+1G>A	ITGB4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1048066	NM_000213.5(ITGB4):c.3040C>T (p.Arg1014Trp)	ITGB4	Pathogenic	criteria provided, single submitter
1048067	NM_000213.5(ITGB4):c.3321_3331del (p.Asp1109fs)	ITGB4	Pathogenic	criteria provided, multiple submitters, no conflicts
1048068	NM_000213.5(ITGB4):c.3707_3725del (p.Thr1236fs)	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
1252046	NM_000213.5(ITGB4):c.3793+1G>C	ITGB4	Pathogenic	criteria provided, single submitter
1292044	NM_000213.5(ITGB4):c.794dup (p.Ala266fs)	ITGB4	Pathogenic	criteria provided, multiple submitters, no conflicts
14730	ITGB4, 1-BP DEL, 1150G	ITGB4	Pathogenic	no assertion criteria provided
14732	NM_000213.5(ITGB4):c.467T>C (p.Leu156Pro)	ITGB4	Pathogenic	no assertion criteria provided
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
14736	NM_000213.5(ITGB4):c.3793+1G>A	ITGB4	Pathogenic	criteria provided, multiple submitters, no conflicts
14738	NM_000213.5(ITGB4):c.112T>C (p.Cys38Arg)	ITGB4	Pathogenic	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 18 · Orphanet: 15 · 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
ITGA6	Strong	Autosomal recessive	junctional epidermolysis bullosa with pyloric atresia	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
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
GALK1	Orphanet:79237	Galactokinase deficiency
MYO6	Orphanet:228012	Progressive sensorineural hearing loss-hypertrophic cardiomyopathy syndrome
MYO6	Orphanet:90635	Rare autosomal dominant non-syndromic sensorineural deafness type DFNA
MYO6	Orphanet:90636	Rare autosomal recessive non-syndromic sensorineural deafness type DFNB
PLEC	Orphanet:1114	Aplasia cutis congenita
PLEC	Orphanet:158684	Epidermolysis bullosa simplex with pyloric atresia
PLEC	Orphanet:254361	Plectin-related limb-girdle muscular dystrophy R17
PLEC	Orphanet:257	Epidermolysis bullosa simplex with muscular dystrophy
PLEC	Orphanet:79401	PLEC-related intermediate epidermolysis bullosa simplex without extracutaneous involvement

Cohort genes → proteins

6 cohort genes, 5 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	6

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
ITGA6	HGNC:6142	ENSG00000091409	P23229	Integrin alpha-6	gencc,clinvar
ITGB4	HGNC:6158	ENSG00000132470	P16144	Integrin beta-4	gencc,clinvar
ITGA6-AS1	HGNC:40308	ENSG00000232788		ITGA6 and PDK1 antisense RNA 1	clinvar
GALK1	HGNC:4118	ENSG00000108479	P51570	Galactokinase	clinvar
MYO6	HGNC:7605	ENSG00000196586	Q9UM54	Unconventional myosin-VI	clinvar
PLEC	HGNC:9069	ENSG00000178209	Q15149	Plectin	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
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.
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.
MYO6	Unconventional myosin-VI	Myosins are actin-based motor molecules with ATPase activity.
PLEC	Plectin	Interlinks intermediate filaments with microtubules and microfilaments and anchors intermediate filaments to desmosomes or hemidesmosomes.

Protein-family classification

Druggable: 3 · Difficult: 2 · Unknown: 1 · Druggable fraction: 0.5

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	9.7×	0.064
Scaffold/PPI	2	5.8×	0.086
Kinase	1	4.6×	0.264
Other/Unknown	1	0.3×	0.993

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ITGA6	Antibody/Immunoglobulin	yes		Integrin_alpha, FG-GAP, Int_alpha_beta-p
ITGB4	Antibody/Immunoglobulin	yes		EGF, Integrin_bsu_VWA, Calx_beta
ITGA6-AS1	Other/Unknown	no
GALK1	Kinase	yes	2.7.1.6	Galactokinase, GHMP_knse_ATP-bd_CS, GHMP_kinase_N_dom
MYO6	Scaffold/PPI	no		Myosin_head_motor_dom-like, SH3_Myosin, Myosin_S1_N
PLEC	Scaffold/PPI	no		Plectin_repeat, SH3_domain, Actinin_actin-bd_CS

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
tibial nerve	3
sural nerve	2
dorsal root ganglion	1
minor salivary gland	1
skin of leg	1
bone marrow cell	1
colonic epithelium	1
male germ line stem cell (sensu Vertebrata) in testis	1
apex of heart	1
monocyte	1
right lobe of liver	1
amniotic fluid	1
corpus callosum	1
medial globus pallidus	1
hindlimb stylopod muscle	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ITGA6	297	ubiquitous	marker	tibial nerve, sural nerve, dorsal root ganglion
ITGB4	267	broad	marker	tibial nerve, minor salivary gland, skin of leg
ITGA6-AS1	130		marker	colonic epithelium, male germ line stem cell (sensu Vertebrata) in testis, bone marrow cell
GALK1	174	ubiquitous	marker	right lobe of liver, apex of heart, monocyte
MYO6	278	ubiquitous	marker	amniotic fluid, medial globus pallidus, corpus callosum
PLEC	283	ubiquitous	marker	sural nerve, hindlimb stylopod muscle, tibial nerve

Protein interactions among cohort

Intra-cohort edges: 3.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PLEC	3,529
ITGA6	3,130
MYO6	2,972
ITGB4	2,536
GALK1	2,244
ITGA6-AS1	0

Intra-cohort edges

A	B	Sources
ITGA6	ITGB4	intact, string_interaction
ITGA6	PLEC	string_interaction
ITGB4	PLEC	intact, string_interaction

Structural data

PDB: 5 · AlphaFold-only: 0 · No structure: 1

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
GALK1	P51570	20
PLEC	Q15149	14
ITGB4	P16144	13
MYO6	Q9UM54	8
ITGA6	P23229	2

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 41. Enrichment computed across 6 evidence-associated genes (5 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 5 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	3	622.9×	3e-07	ITGA6, ITGB4, PLEC
Assembly of collagen fibrils and other multimeric structures	3	120.2×	2e-05	ITGA6, ITGB4, PLEC
Collagen formation	2	182.7×	5e-04	ITGA6, ITGB4
Syndecan interactions	2	169.2×	5e-04	ITGA6, ITGB4
Laminin interactions	2	152.3×	5e-04	ITGA6, ITGB4
Differentiation of Keratinocytes in Interfollicular Epidermis in Mammalian Skin	2	111.4×	9e-04	ITGA6, ITGB4
Developmental Cell Lineages	2	89.6×	0.001	ITGA6, ITGB4
Cell junction organization	2	74.9×	0.001	ITGA6, ITGB4
Defective GALK1 causes GALCT2	1	2284.0×	0.002	GALK1
Non-integrin membrane-ECM interactions	2	61.7×	0.002	ITGA6, ITGB4
Cell-Cell communication	2	55.0×	0.002	ITGA6, ITGB4
Extracellular matrix organization	2	25.2×	0.008	ITGA6, ITGB4
Galactose catabolism	1	326.3×	0.010	GALK1
Gap junction degradation	1	190.3×	0.014	MYO6
Caspase-mediated cleavage of cytoskeletal proteins	1	190.3×	0.014	PLEC
RHOBTB GTPase Cycle	1	163.1×	0.015	MYO6
Glutamate binding, activation of AMPA receptors and synaptic plasticity	1	152.3×	0.015	MYO6
Developmental Lineage of Mammary Stem Cells	1	152.3×	0.015	ITGA6
Developmental Lineage of Mammary Gland Alveolar Cells	1	126.9×	0.017	ITGA6
Trafficking of AMPA receptors	1	108.8×	0.017	MYO6
Developmental Lineage of Mammary Gland Myoepithelial Cells	1	108.8×	0.017	ITGA6
Gap junction trafficking and regulation	1	95.2×	0.017	MYO6
Gap junction trafficking	1	95.2×	0.017	MYO6
RHOBTB2 GTPase cycle	1	95.2×	0.017	MYO6
RHOBTB1 GTPase cycle	1	95.2×	0.017	MYO6
Developmental Lineage of Mammary Gland Luminal Epithelial Cells	1	91.4×	0.017	ITGA6
Basigin interactions	1	87.8×	0.017	ITGA6
RHOU GTPase cycle	1	55.7×	0.026	MYO6
Integrin cell surface interactions	1	26.9×	0.052	ITGA6
Developmental Biology	2	5.8×	0.057	ITGA6, 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 5 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	2	963.0×	5e-05	ITGB4, PLEC
nail development	2	963.0×	5e-05	ITGA6, ITGB4
skin morphogenesis	2	561.7×	1e-04	ITGA6, ITGB4
galactitol metabolic process	1	3370.4×	0.003	GALK1
protein-containing complex organization	1	3370.4×	0.003	PLEC
glycolytic process from galactose	1	3370.4×	0.003	GALK1
actomyosin contractile ring assembly actin filament organization	1	3370.4×	0.003	PLEC
cell-matrix adhesion	2	65.4×	0.003	ITGA6, ITGB4
integrin-mediated signaling pathway	2	64.2×	0.003	ITGA6, ITGB4
skeletal myofibril assembly	1	1685.2×	0.004	PLEC
leukocyte migration involved in immune response	1	1123.5×	0.004	PLEC
peripheral nervous system myelin formation	1	1123.5×	0.004	ITGB4
cellular response to hydrostatic pressure	1	1123.5×	0.004	PLEC
intracellular protein localization	2	41.9×	0.004	MYO6, PLEC
cell-cell adhesion	2	40.6×	0.004	ITGA6, ITGB4
ectodermal cell differentiation	1	842.6×	0.005	ITGA6
beta-D-galactose catabolic process via UDP-galactose, Leloir pathway	1	674.1×	0.006	GALK1
tight junction organization	1	674.1×	0.006	PLEC
cell-substrate junction assembly	1	561.7×	0.006	ITGA6
regulation of secretion	1	561.7×	0.006	MYO6
trophoblast cell migration	1	481.5×	0.007	ITGB4
galactose metabolic process	1	421.3×	0.008	GALK1
keratinocyte development	1	306.4×	0.009	PLEC
peripheral nervous system myelin maintenance	1	306.4×	0.009	PLEC
mesodermal cell differentiation	1	306.4×	0.009	ITGB4
cellular response to fluid shear stress	1	259.3×	0.011	PLEC
inner ear auditory receptor cell differentiation	1	240.7×	0.011	MYO6
T cell chemotaxis	1	224.7×	0.011	PLEC
regulation of vascular permeability	1	224.7×	0.011	PLEC
intermediate filament cytoskeleton organization	1	187.2×	0.013	PLEC

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 5

Druggability breadth: 4 of 6 evidence-associated genes (67%) 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
ITGA6	0	0
ITGB4	0	0
ITGA6-AS1	0	0
MYO6	0	0
PLEC	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
PLEC	12	Binding:12
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: 5; 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	3	ITGA6-AS1, MYO6, PLEC

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
ITGA6	3	—
ITGB4	2	—
ITGA6-AS1	0	—
MYO6	0	—
PLEC	12	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.