epidermolysis bullosa simplex 5A, Ogna type

Summary

epidermolysis bullosa simplex 5A, Ogna type (MONDO:0007555) is a disease caused by PLEC (GenCC Strong), with 4 cohort genes.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: PLEC (GenCC Strong)
• Cohort genes: 4
• ClinVar variants: 5,734
• Phenotypes (HPO): 12

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		6	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

12 HPO clinical features (Orphanet curated; top 12 by frequency):

HPO ID	Term	Frequency
HP:0000982	Palmoplantar keratoderma	Frequent (30-79%)
HP:0001030	Fragile skin	Frequent (30-79%)
HP:0001034	Hypermelanotic macule	Frequent (30-79%)
HP:0007446	Palmoplantar blistering	Frequent (30-79%)
HP:0008066	Abnormal blistering of the skin	Frequent (30-79%)
HP:0020073	Hypopigmented macule	Frequent (30-79%)
HP:0031045	Acral blistering	Frequent (30-79%)
HP:0200041	Skin erosion	Frequent (30-79%)
HP:0000164	Abnormality of the dentition	Occasional (5-29%)
HP:0000478	Abnormality of the eye	Excluded (0%)
HP:0001627	Abnormal heart morphology	Excluded (0%)
HP:0002012	Abnormality of the abdominal organs	Excluded (0%)

Identifiers

Disease identifiers

Field	Value
Canonical name	epidermolysis bullosa simplex 5A, Ogna type
Mondo ID	MONDO:0007555
MeSH	C535962
OMIM	131950
Orphanet	79401
DOID	DOID:0060736
SNOMED CT	398071000
UMLS	C0432317
MedGen	98488
GARD	0002148
Is cancer (heuristic)	no

Also known as: EBSOG · epidermolysis bullosa simplex 5A, Ogna type · epidermolysis bullosa simplex, Ogna type

Data availability: 5,734 ClinVar variants · 4 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 5A, Ogna type

Related subtypes (19): epidermolysis bullosa simplex 1A, generalized severe, epidermolysis bullosa simplex 1C, localized, epidermolysis bullosa simplex 1B, generalized intermediate, 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 3, localized or generalized intermediate, with BP230 deficiency, 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:

301 uncertain significance, 221 likely benign, 34 benign, 22 conflicting classifications of pathogenicity, 13 benign/likely benign, 6 pathogenic, 3 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1069886	NM_201384.3(PLEC):c.12418C>T (p.Arg4140Ter)	PLEC	Pathogenic	criteria provided, single submitter
1071954	NM_201384.3(PLEC):c.7336G>T (p.Glu2446Ter)	PLEC	Pathogenic	criteria provided, single submitter
1073588	NM_201384.3(PLEC):c.13106C>A (p.Ser4369Ter)	PLEC	Pathogenic	criteria provided, single submitter
1074096	NM_201384.3(PLEC):c.6510del (p.His2170fs)	PLEC	Pathogenic	criteria provided, single submitter
1251951	NM_201378.4(PLEC):c.66C>G (p.Tyr22Ter)	PLEC	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1251952	NM_201384.3(PLEC):c.8149C>T (p.Gln2717Ter)	PLEC	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1320041	NM_201384.3(PLEC):c.6970C>T (p.Arg2324Ter)	PLEC	Pathogenic	criteria provided, multiple submitters, no conflicts
1323468	NM_201384.3(PLEC):c.1465_1471del (p.Asn489fs)	PLEC	Pathogenic	criteria provided, multiple submitters, no conflicts
1324937	NM_201384.3(PLEC):c.4468C>T (p.Arg1490Ter)	PLEC	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1001872	NM_201384.3(PLEC):c.7634G>A (p.Arg2545Gln)	PLEC	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1003332	NM_201384.3(PLEC):c.6427G>A (p.Glu2143Lys)	PLEC	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1004138	NM_201384.3(PLEC):c.9317G>A (p.Arg3106Lys)	PLEC	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1006392	NM_201384.3(PLEC):c.8140G>A (p.Ala2714Thr)	PLEC	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1007882	NM_201384.3(PLEC):c.5555C>T (p.Ala1852Val)	PLEC	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1038192	NM_201384.3(PLEC):c.13529G>T (p.Gly4510Val)	PLEC	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1044930	NM_201384.3(PLEC):c.8492G>A (p.Arg2831Gln)	PLEC	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1048028	NM_201384.3(PLEC):c.3850C>T (p.Leu1284Phe)	PLEC	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1058015	NM_201384.3(PLEC):c.9295G>A (p.Glu3099Lys)	PLEC	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1123939	NM_201384.3(PLEC):c.9840C>T (p.Thr3280=)	PLEC	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1124265	NM_201378.4(PLEC):c.70+2T>C	PLEC	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1141659	NM_201384.3(PLEC):c.5191C>T (p.Leu1731=)	PLEC	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1151961	NM_201384.3(PLEC):c.5241G>A (p.Thr1747=)	PLEC	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1174478	NM_201384.3(PLEC):c.8531C>T (p.Ala2844Val)	PLEC	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1194821	NM_201384.3(PLEC):c.7703G>A (p.Arg2568His)	PLEC	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1195336	NM_201384.3(PLEC):c.5920C>G (p.Gln1974Glu)	PLEC	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1215529	NM_201384.3(PLEC):c.5795C>T (p.Ala1932Val)	PLEC	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1216951	NM_201384.3(PLEC):c.3784G>A (p.Gly1262Ser)	PLEC	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
129930	NM_201384.3(PLEC):c.12615C>T (p.Ile4205=)	PLEC	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
129932	NM_000445.5(PLEC):c.133G>A (p.Gly45Ser)	PLEC	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1307332	NM_201384.3(PLEC):c.2613-12C>G	PLEC	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 18 · Orphanet: 5 · 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
PLEC	Strong	Autosomal dominant	epidermolysis bullosa simplex 5A, Ogna type	18

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
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

4 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	4

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
PLEC	HGNC:9069	ENSG00000178209	Q15149	Plectin	gencc,clinvar
ADCK5	HGNC:21738	ENSG00000173137	Q3MIX3	Uncharacterized aarF domain-containing protein kinase 5	clinvar
MIR661	HGNC:32917	ENSG00000207574		microRNA 661	clinvar
CATSPERQ	HGNC:44155	ENSG00000261587	Q2WGJ8	Cation channel sperm-associated auxiliary subunit theta	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PLEC	Plectin	Interlinks intermediate filaments with microtubules and microfilaments and anchors intermediate filaments to desmosomes or hemidesmosomes.
ADCK5	Uncharacterized aarF domain-containing protein kinase 5	The function of this protein is not yet clear.
CATSPERQ	Cation channel sperm-associated auxiliary subunit theta	Auxiliary component of the CatSper complex, a complex involved in sperm cell hyperactivation.

Protein-family classification

Druggable: 1 · Difficult: 1 · Unknown: 2 · Druggable fraction: 0.25

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
Kinase	1	6.9×	0.318
Scaffold/PPI	1	4.3×	0.318
Other/Unknown	2	0.9×	0.769

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
PLEC	Scaffold/PPI	no		Plectin_repeat, SH3_domain, Actinin_actin-bd_CS
ADCK5	Kinase	yes		ABC1_dom, Kinase-like_dom_sf, ADCK1_dom
MIR661	Other/Unknown	no
CATSPERQ	Other/Unknown	no		TMEM249

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)	4
unknown	0

Top tissues across cohort

Tissue	Cohort genes
hindlimb stylopod muscle	1
sural nerve	1
tibial nerve	1
duodenum	1
mucosa of transverse colon	1
right hemisphere of cerebellum	1
adrenal tissue	1
blood	1
vermiform appendix	1
left testis	1
male germ line stem cell (sensu Vertebrata) in testis	1
right testis	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PLEC	283	ubiquitous	marker	sural nerve, hindlimb stylopod muscle, tibial nerve
ADCK5	136	ubiquitous	marker	mucosa of transverse colon, duodenum, right hemisphere of cerebellum
MIR661	89		yes	adrenal tissue, vermiform appendix, blood
CATSPERQ	123	tissue_specific	yes	right testis, left testis, male germ line stem cell (sensu Vertebrata) in testis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PLEC	3,529
ADCK5	978
CATSPERQ	100
MIR661	0

Structural data

PDB: 1 · AlphaFold-only: 2 · No structure: 1

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PLEC	Q15149	14

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ADCK5	Q3MIX3	82.08
CATSPERQ	Q2WGJ8	79.42

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. Enrichment computed across 4 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×	0.002	PLEC
Caspase-mediated cleavage of cytoskeletal proteins	1	951.7×	0.002	PLEC
Assembly of collagen fibrils and other multimeric structures	1	200.3×	0.005	PLEC

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
protein-containing complex organization	1	16852.0×	9e-04	PLEC
actomyosin contractile ring assembly actin filament organization	1	16852.0×	9e-04	PLEC
skeletal myofibril assembly	1	8426.0×	0.001	PLEC
leukocyte migration involved in immune response	1	5617.3×	0.001	PLEC
cellular response to hydrostatic pressure	1	5617.3×	0.001	PLEC
tight junction organization	1	3370.4×	0.002	PLEC
hemidesmosome assembly	1	2407.4×	0.002	PLEC
keratinocyte development	1	1532.0×	0.002	PLEC
peripheral nervous system myelin maintenance	1	1532.0×	0.002	PLEC
cellular response to fluid shear stress	1	1296.3×	0.002	PLEC
T cell chemotaxis	1	1123.5×	0.002	PLEC
regulation of vascular permeability	1	1123.5×	0.002	PLEC
intermediate filament cytoskeleton organization	1	936.2×	0.002	PLEC
fibroblast migration	1	842.6×	0.002	PLEC
respiratory electron transport chain	1	842.6×	0.002	PLEC
myoblast differentiation	1	842.6×	0.002	PLEC
transmission of nerve impulse	1	648.1×	0.003	PLEC
cardiac muscle cell development	1	624.1×	0.003	PLEC
nucleus organization	1	561.7×	0.003	PLEC
skeletal muscle fiber development	1	543.6×	0.003	PLEC
adherens junction organization	1	510.7×	0.003	PLEC
response to food	1	495.6×	0.003	PLEC
establishment of skin barrier	1	455.5×	0.003	PLEC
sarcomere organization	1	383.0×	0.003	PLEC
intermediate filament organization	1	240.7×	0.005	PLEC
wound healing	1	227.7×	0.005	PLEC
cellular response to mechanical stimulus	1	216.1×	0.005	PLEC
cell morphogenesis	1	157.5×	0.007	PLEC
mitochondrion organization	1	151.8×	0.007	PLEC
multicellular organism growth	1	137.0×	0.008	PLEC

Therapeutics

Drug target analysis

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

Druggability breadth: 2 of 4 evidence-associated genes (50%) 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
ADCK5	NERATINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
ADCK5	2	4
PLEC	0	0
MIR661	0	0
CATSPERQ	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
NERATINIB	4	ADCK5
LINSITINIB	3	ADCK5

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
PLEC	12	Binding:12
ADCK5	2	Binding:2

Pharmacogenomics

Cohort genes with a PharmGKB record: 4; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

2 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)
NERATINIB	4	ADCK5
LINSITINIB	3	ADCK5

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	ADCK5
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	3	PLEC, MIR661, CATSPERQ

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
PLEC	12	—
MIR661	0	—
CATSPERQ	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.