epidermolysis bullosa simplex 3, localized or generalized intermediate, with BP230 deficiency

Summary

epidermolysis bullosa simplex 3, localized or generalized intermediate, with BP230 deficiency (MONDO:0014180) is a disease caused by DST (GenCC Strong), with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: DST (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 3,387

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		2	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	epidermolysis bullosa simplex 3, localized or generalized intermediate, with BP230 deficiency
Mondo ID	MONDO:0014180
OMIM	615425
Orphanet	412181
UMLS	C3809470
MedGen	815800
GARD	0017690
Is cancer (heuristic)	no

Also known as: DST-related epidermolysis bullosa simplex · EBS-AR BP230 · EBSB2 · epidermolysis bullosa simplex 3, localised or generalised intermediate, with bp230 deficiency · epidermolysis bullosa simplex 3, localized or generalized intermediate, with bp230 deficiency · epidermolysis bullosa simplex due to BP230 deficiency · epidermolysis bullosa simplex, autosomal recessive 2 · epidermolysis bullosa simplex, autosomal recessive type 2

Data availability: 3,387 ClinVar variants · 5 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 › epidermolysis bullosa simplex › epidermolysis bullosa simplex 3, localized or generalized intermediate, with BP230 deficiency

Related subtypes (19): epidermolysis bullosa simplex 1A, generalized severe, epidermolysis bullosa simplex 1C, localized, epidermolysis bullosa simplex 1B, generalized intermediate, epidermolysis bullosa simplex 5A, Ogna type, epidermolysis bullosa simplex 2F, with mottled pigmentation, epidermolysis bullosa simplex 5B, with muscular dystrophy, epidermolysis bullosa simplex 1D, generalized, intermediate or severe, autosomal recessive, epidermolysis bullosa simplex 7, with nephropathy and deafness, epidermolysis bullosa simplex 2E, with migratory circinate erythema, epidermolysis bullosa simplex 5C, with pyloric atresia, epidermolysis bullosa simplex 4, localized or generalized intermediate, autosomal recessive, epidermolysis bullosa simplex with nail dystrophy, epidermolysis bullosa simplex 6, generalized, with scarring and hair loss, suprabasal epidermolysis bullosa simplex, epidermolysis bullosa simplex with anodontia/hypodontia, epidermolysis bullosa simplex 2A, generalized severe, epidermolysis bullosa simplex 2B, generalized intermediate, epidermolysis bullosa simplex 2C, localized, epidermolysis bullosa simplex 2d, generalized, intermediate or severe, autosomal recessive

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:

313 likely benign, 269 uncertain significance, 5 conflicting classifications of pathogenicity, 4 pathogenic, 4 benign, 2 likely pathogenic, 2 benign/likely benign, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1069200	NM_001723.7(DST):c.4534C>T (p.Arg1512Ter)	DST	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1072927	NM_001374736.1(DST):c.4083_4086dup (p.Val1363Ter)	DST	Pathogenic	criteria provided, single submitter
1073401	NM_001374736.1(DST):c.16780C>T (p.Arg5594Ter)	DST	Pathogenic	criteria provided, single submitter
1074277	NM_001723.7(DST):c.4477del (p.Ala1493fs)	DST	Pathogenic	criteria provided, single submitter
1074760	NM_001374736.1(DST):c.3015C>A (p.Cys1005Ter)	DST	Pathogenic	criteria provided, single submitter
1067146	NM_001374736.1(DST):c.21048-1G>T	DST	Likely pathogenic	criteria provided, single submitter
1068243	NM_001374736.1(DST):c.20757+1G>A	DST	Likely pathogenic	criteria provided, single submitter
1013292	NM_001374736.1(DST):c.21538A>G (p.Met7180Val)	DST	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1089487	NM_001374736.1(DST):c.22195C>T (p.Arg7399Cys)	DST	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1091095	NM_001374736.1(DST):c.14441-7_14441-6del	DST	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1100057	NM_001374736.1(DST):c.11679T>C (p.Tyr3893=)	DST	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1132123	NM_001374736.1(DST):c.3585T>C (p.Asn1195=)	DST	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1000054	NM_001723.7(DST):c.11G>C (p.Ser4Thr)	DST	Uncertain significance	criteria provided, single submitter
1000055	NM_001374736.1(DST):c.21659G>A (p.Arg7220Gln)	DST	Uncertain significance	criteria provided, single submitter
1000158	NM_001374736.1(DST):c.14418G>C (p.Trp4806Cys)	DST	Uncertain significance	criteria provided, single submitter
1000373	NM_001723.7(DST):c.4351A>G (p.Lys1451Glu)	DST	Uncertain significance	criteria provided, single submitter
1000475	NM_001723.7(DST):c.7552C>T (p.Arg2518Ter)	DST	Uncertain significance	criteria provided, multiple submitters, no conflicts
1000845	NM_001374736.1(DST):c.18917T>C (p.Met6306Thr)	DST	Uncertain significance	criteria provided, single submitter
1001170	NM_001374736.1(DST):c.4306A>G (p.Lys1436Glu)	DST	Uncertain significance	criteria provided, single submitter
1001341	NM_001374736.1(DST):c.17783C>T (p.Ala5928Val)	DST	Uncertain significance	criteria provided, multiple submitters, no conflicts
1001539	NM_001374736.1(DST):c.17922+3A>G	DST	Uncertain significance	criteria provided, single submitter
1001642	NM_001723.7(DST):c.6887A>T (p.Asn2296Ile)	DST	Uncertain significance	criteria provided, single submitter
1001772	NM_001374736.1(DST):c.17593C>T (p.Arg5865Trp)	DST	Uncertain significance	criteria provided, single submitter
1001899	NM_001374736.1(DST):c.15898G>A (p.Asp5300Asn)	DST	Uncertain significance	criteria provided, multiple submitters, no conflicts
1001976	NM_001374736.1(DST):c.4876A>T (p.Thr1626Ser)	DST	Uncertain significance	criteria provided, multiple submitters, no conflicts
1002331	NM_001374736.1(DST):c.17443C>A (p.Leu5815Ile)	DST	Uncertain significance	criteria provided, multiple submitters, no conflicts
1002591	NM_001723.7(DST):c.4613A>G (p.His1538Arg)	DST	Uncertain significance	criteria provided, single submitter
1002603	NM_001374736.1(DST):c.3838A>G (p.Ile1280Val)	DST	Uncertain significance	criteria provided, multiple submitters, no conflicts
1002647	NM_001723.7(DST):c.7219A>G (p.Ile2407Val)	DST	Uncertain significance	criteria provided, multiple submitters, no conflicts
1002797	NM_001374736.1(DST):c.14297T>C (p.Val4766Ala)	DST	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 10 · 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
DST	Strong	Autosomal recessive	epidermolysis bullosa simplex 3, localized or generalized intermediate, with BP230 deficiency	10

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
DST	Orphanet:314381	Hereditary sensory and autonomic neuropathy type 6
DST	Orphanet:412181	Epidermolysis bullosa simplex due to BP230 deficiency

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
DST	HGNC:1090	ENSG00000151914	Q03001	Dystonin	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
DST	Dystonin	Cytoskeletal linker protein.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 0 · 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
Scaffold/PPI	1	17.3×	0.058

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
DST	Scaffold/PPI	no		Plectin_repeat, SH3_domain, Actinin_actin-bd_CS

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
calcaneal tendon	1
corpus callosum	1
medial globus pallidus	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
DST	305	ubiquitous	marker	corpus callosum, calcaneal tendon, medial globus pallidus

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
DST	2,009

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
DST	Q03001	2

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 7. 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×	0.004	DST
RHOV GTPase cycle	1	285.5×	0.004	DST
RHOU GTPase cycle	1	278.5×	0.004	DST
RND1 GTPase cycle	1	265.6×	0.004	DST
RND3 GTPase cycle	1	259.6×	0.004	DST
RND2 GTPase cycle	1	259.6×	0.004	DST
Assembly of collagen fibrils and other multimeric structures	1	200.3×	0.005	DST

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
maintenance of cell polarity	1	2407.4×	0.002	DST
hemidesmosome assembly	1	2407.4×	0.002	DST
retrograde axonal transport	1	1532.0×	0.002	DST
intermediate filament cytoskeleton organization	1	936.2×	0.003	DST
cell motility	1	401.2×	0.005	DST
wound healing	1	227.7×	0.007	DST
response to wounding	1	221.7×	0.007	DST
integrin-mediated signaling pathway	1	160.5×	0.009	DST
cytoskeleton organization	1	132.7×	0.009	DST
microtubule cytoskeleton organization	1	121.2×	0.009	DST
cell adhesion	1	37.5×	0.027	DST

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
DST	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	DST

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)
DST	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.