Epidermolysis bullosa, junctional 6, with pyloric atresia

Summary

Epidermolysis bullosa, junctional 6, with pyloric atresia (MONDO:0859233) is a disease with 2 cohort genes.

At a glance

• Cohort genes: 2
• ClinVar variants: 151

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	epidermolysis bullosa, junctional 6, with pyloric atresia
Mondo ID	MONDO:0859233
OMIM	619817
UMLS	C5676957
MedGen	1803348
GARD	0026673
Is cancer (heuristic)	no

Data availability: 151 ClinVar variants.

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 6, 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, 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 5A, intermediate

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

151 retrieved; paginated sample, class counts are floors:

111 uncertain significance, 9 conflicting classifications of pathogenicity, 7 likely pathogenic, 7 likely benign, 5 benign/likely benign, 4 pathogenic, 4 pathogenic/likely pathogenic, 4 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
14745	NM_000210.4(ITGA6):c.809del (p.Ser270fs)	ITGA6	Pathogenic	no assertion criteria provided
1526407	NM_000210.4(ITGA6):c.388-5T>G	ITGA6	Pathogenic	no assertion criteria provided
1526408	NM_000210.4(ITGA6):c.387G>T (p.Val129=)	ITGA6	Pathogenic	no assertion criteria provided
1526409	NM_000210.4(ITGA6):c.2506-1G>C	ITGA6	Pathogenic	no assertion criteria provided
2822039	NM_000210.4(ITGA6):c.611dup (p.Phe205fs)	ITGA6	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
632334	NM_000210.4(ITGA6):c.2926C>T (p.Arg976Ter)	ITGA6	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
870820	NM_000210.4(ITGA6):c.442C>T (p.Arg148Ter)	ITGA6	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2980098	NM_000210.4(ITGA6):c.1224dup (p.Ile409fs)	PDK1-AS1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1526406	NM_000210.4(ITGA6):c.140C>T (p.Ser47Leu)	ITGA6	Likely pathogenic	criteria provided, single submitter
3584970	NM_000210.4(ITGA6):c.241_254dup (p.Ser85fs)	ITGA6	Likely pathogenic	criteria provided, single submitter
3584973	NM_000210.4(ITGA6):c.271dup (p.Arg91fs)	ITGA6	Likely pathogenic	criteria provided, single submitter
3585009	NM_000210.4(ITGA6):c.1737del (p.Ile580fs)	ITGA6	Likely pathogenic	criteria provided, single submitter
3585011	NM_000210.4(ITGA6):c.1786C>T (p.Arg596Ter)	ITGA6	Likely pathogenic	criteria provided, single submitter
3585017	NM_000210.4(ITGA6):c.1933C>T (p.Arg645Ter)	ITGA6	Likely pathogenic	criteria provided, single submitter
3585047	NM_000210.4(ITGA6):c.3044G>A (p.Trp1015Ter)	ITGA6	Likely pathogenic	criteria provided, single submitter
2192545	NM_000210.4(ITGA6):c.1752C>T (p.Ala584=)	ITGA6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
225394	NM_000210.4(ITGA6):c.*142dup	ITGA6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2791425	NM_000210.4(ITGA6):c.1270-11G>T	ITGA6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3003680	NM_000210.4(ITGA6):c.1932C>T (p.Thr644=)	ITGA6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3004965	NM_000210.4(ITGA6):c.2292C>T (p.Thr764=)	ITGA6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
332384	NM_000210.4(ITGA6):c.2861C>T (p.Ser954Leu)	ITGA6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
623184	NM_000210.4(ITGA6):c.3167del (p.Lys1056fs)	ITGA6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
332376	NM_000210.4(ITGA6):c.2651A>G (p.Gln884Arg)	PDK1-AS1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
894199	NM_000210.4(ITGA6):c.1850T>C (p.Ile617Thr)	PDK1-AS1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1907145	NM_000210.4(ITGA6):c.2981G>A (p.Gly994Asp)	ITGA6	Uncertain significance	criteria provided, multiple submitters, no conflicts
1939749	NM_000210.4(ITGA6):c.2785A>G (p.Ser929Gly)	ITGA6	Uncertain significance	criteria provided, multiple submitters, no conflicts
1946220	NM_000210.4(ITGA6):c.2215C>A (p.Leu739Ile)	ITGA6	Uncertain significance	criteria provided, multiple submitters, no conflicts
2063163	NM_000210.4(ITGA6):c.1450C>T (p.Arg484Cys)	ITGA6	Uncertain significance	criteria provided, multiple submitters, no conflicts
2200802	NM_000210.4(ITGA6):c.55C>T (p.Arg19Trp)	ITGA6	Uncertain significance	criteria provided, multiple submitters, no conflicts
2211975	NM_000210.4(ITGA6):c.2705G>A (p.Arg902Gln)	ITGA6	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ITGA6	Orphanet:79403	Junctional epidermolysis bullosa with pyloric atresia

Cohort genes → proteins

2 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
ITGA6-AS1	HGNC:40308	ENSG00000232788		ITGA6 and PDK1 antisense RNA 1	clinvar
ITGA6	HGNC:6142	ENSG00000091409	P23229	Integrin alpha-6	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.

Protein-family classification

Druggable: 1 · Difficult: 0 · 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	1	14.6×	0.135
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ITGA6-AS1	Other/Unknown	no
ITGA6	Antibody/Immunoglobulin	yes		Integrin_alpha, FG-GAP, Int_alpha_beta-p

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
bone marrow cell	1
colonic epithelium	1
male germ line stem cell (sensu Vertebrata) in testis	1
dorsal root ganglion	1
sural nerve	1
tibial nerve	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ITGA6-AS1	130		marker	colonic epithelium, male germ line stem cell (sensu Vertebrata) in testis, bone marrow cell
ITGA6	297	ubiquitous	marker	tibial nerve, sural nerve, dorsal root ganglion

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ITGA6	3,130
ITGA6-AS1	0

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ITGA6	P23229	2

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 20. Enrichment computed across 2 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	ITGA6
Developmental Lineage of Mammary Stem Cells	1	761.3×	0.006	ITGA6
Developmental Lineage of Mammary Gland Alveolar Cells	1	634.4×	0.006	ITGA6
Developmental Lineage of Mammary Gland Myoepithelial Cells	1	543.8×	0.006	ITGA6
Collagen formation	1	456.8×	0.006	ITGA6
Developmental Lineage of Mammary Gland Luminal Epithelial Cells	1	456.8×	0.006	ITGA6
Basigin interactions	1	439.2×	0.006	ITGA6
Syndecan interactions	1	423.0×	0.006	ITGA6
Laminin interactions	1	380.7×	0.006	ITGA6
Differentiation of Keratinocytes in Interfollicular Epidermis in Mammalian Skin	1	278.5×	0.007	ITGA6
Developmental Cell Lineages	1	223.9×	0.008	ITGA6
Assembly of collagen fibrils and other multimeric structures	1	200.3×	0.008	ITGA6
Cell junction organization	1	187.2×	0.008	ITGA6
Non-integrin membrane-ECM interactions	1	154.3×	0.009	ITGA6
Cell-Cell communication	1	137.6×	0.009	ITGA6
Integrin cell surface interactions	1	134.3×	0.009	ITGA6
Cell surface interactions at the vascular wall	1	95.2×	0.012	ITGA6
Extracellular matrix organization	1	63.1×	0.018	ITGA6
Hemostasis	1	36.0×	0.029	ITGA6
Developmental Biology	1	14.5×	0.069	ITGA6

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
ectodermal cell differentiation	1	4213.0×	0.002	ITGA6
cell-substrate junction assembly	1	2808.7×	0.002	ITGA6
nail development	1	2407.4×	0.002	ITGA6
skin morphogenesis	1	1404.3×	0.003	ITGA6
cell-substrate adhesion	1	766.0×	0.004	ITGA6
leukocyte migration	1	624.1×	0.004	ITGA6
negative regulation of extrinsic apoptotic signaling pathway	1	421.3×	0.005	ITGA6
positive regulation of GTPase activity	1	276.3×	0.007	ITGA6
cell-matrix adhesion	1	163.6×	0.009	ITGA6
integrin-mediated signaling pathway	1	160.5×	0.009	ITGA6
positive regulation of neuron projection development	1	137.0×	0.010	ITGA6
cell-cell adhesion	1	101.5×	0.012	ITGA6
positive regulation of cell migration	1	61.7×	0.019	ITGA6
positive regulation of apoptotic process	1	56.7×	0.019	ITGA6
positive regulation of transcription by RNA polymerase II	1	14.9×	0.067	ITGA6

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 1 of 2 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
ITGA6-AS1	0	0
ITGA6	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
ITGA6	3	Binding:3

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	1	ITGA6
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	ITGA6-AS1

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
ITGA6-AS1	0	—
ITGA6	3	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.