Pretibial dystrophic epidermolysis bullosa

Summary

Pretibial dystrophic epidermolysis bullosa (MONDO:0007552) is a disease caused by COL7A1 (GenCC Strong), with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: COL7A1 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 245
• Phenotypes (HPO): 35

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		40	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

35 HPO clinical features (Orphanet curated; top 35 by frequency):

HPO ID	Term	Frequency
HP:0008066	Abnormal blistering of the skin	Very frequent (80-99%)
HP:0011355	Localized skin lesion	Very frequent (80-99%)
HP:0012221	Pretibial blistering	Very frequent (80-99%)
HP:0000987	Atypical scarring of skin	Frequent (30-79%)
HP:0000989	Pruritus	Frequent (30-79%)
HP:0001030	Fragile skin	Frequent (30-79%)
HP:0001056	Milia	Frequent (30-79%)
HP:0001075	Atrophic scars	Frequent (30-79%)
HP:0001231	Abnormal fingernail morphology	Frequent (30-79%)
HP:0001798	Anonychia	Frequent (30-79%)
HP:0007446	Palmoplantar blistering	Frequent (30-79%)
HP:0008388	Abnormal toenail morphology	Frequent (30-79%)
HP:0008404	Nail dystrophy	Frequent (30-79%)
HP:0010562	Keloids	Frequent (30-79%)
HP:0000478	Abnormality of the eye	Occasional (5-29%)
HP:0000670	Carious teeth	Occasional (5-29%)
HP:0001792	Small nail	Occasional (5-29%)
HP:0004057	Mitten deformity	Occasional (5-29%)
HP:0030350	Erythematous papule	Occasional (5-29%)
HP:0045059	Hyperkeratotic papule	Occasional (5-29%)
HP:0200037	Skin vesicle	Occasional (5-29%)
HP:0200041	Skin erosion	Occasional (5-29%)
HP:0200097	Oral mucosal blisters	Occasional (5-29%)
HP:0000079	Abnormality of the urinary system	Excluded (0%)
HP:0000982	Palmoplantar keratoderma	Excluded (0%)
HP:0001510	Growth delay	Excluded (0%)
HP:0001903	Anemia	Excluded (0%)
HP:0001965	Abnormality of the scalp	Excluded (0%)
HP:0002671	Basal cell carcinoma	Excluded (0%)
HP:0002860	Squamous cell carcinoma	Excluded (0%)
HP:0004386	Gastrointestinal inflammation	Excluded (0%)
HP:0006297	Enamel hypoplasia	Excluded (0%)
HP:0012056	Cutaneous melanoma	Excluded (0%)
HP:0012252	Abnormal respiratory system morphology	Excluded (0%)
HP:0031464	Genital blistering	Excluded (0%)

Identifiers

Disease identifiers

Field	Value
Canonical name	pretibial dystrophic epidermolysis bullosa
Mondo ID	MONDO:0007552
MeSH	C535494
OMIM	131850
Orphanet	79410
DOID	DOID:0080988
SNOMED CT	67653003
UMLS	C0432321
MedGen	98154
GARD	0002155
Is cancer (heuristic)	no

Also known as: DEB-Pt · pretibial DEB · pretibial epidermolysis bullosa

Data availability: 245 ClinVar variants · 3 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 dystrophica › pretibial dystrophic epidermolysis bullosa

Related subtypes (11): transient bullous dermolysis of the newborn, generalized dominant dystrophic epidermolysis bullosa, epidermolysis bullosa dystrophica Neurotrophica, recessive dystrophic epidermolysis bullosa, dystrophic epidermolysis bullosa pruriginosa, acral dystrophic epidermolysis bullosa, dystrophic epidermolysis bullosa, nails only, centripetalis recessive dystrophic epidermolysis bullosa, recessive dystrophic epidermolysis bullosa-generalized other, localized dystrophic epidermolysis bullosa, epidermolysis bullosa dystrophica with subcorneal cleavage

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

245 retrieved; paginated sample, class counts are floors:

60 likely pathogenic, 57 pathogenic/likely pathogenic, 55 pathogenic, 48 conflicting classifications of pathogenicity, 16 uncertain significance, 5 benign/likely benign, 4 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1032188	NM_000094.4(COL7A1):c.8304+1G>A	COL7A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1047934	NM_000094.4(COL7A1):c.58_70del (p.Arg20fs)	COL7A1	Pathogenic	criteria provided, multiple submitters, no conflicts
1047951	NM_000094.4(COL7A1):c.8209G>C (p.Gly2737Arg)	COL7A1	Pathogenic	criteria provided, multiple submitters, no conflicts
1048003	NM_000094.4(COL7A1):c.3130C>T (p.Gln1044Ter)	COL7A1	Pathogenic	criteria provided, multiple submitters, no conflicts
1048010	NM_000094.4(COL7A1):c.4012G>A (p.Gly1338Arg)	COL7A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1048045	NM_000094.4(COL7A1):c.7270C>T (p.Arg2424Trp)	COL7A1	Pathogenic	criteria provided, multiple submitters, no conflicts
1048050	NM_000094.4(COL7A1):c.7474C>T (p.Arg2492Ter)	COL7A1	Pathogenic	criteria provided, multiple submitters, no conflicts
1048054	NM_000094.4(COL7A1):c.7738C>T (p.Arg2580Cys)	COL7A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1066186	NM_000094.4(COL7A1):c.8020G>C (p.Gly2674Arg)	COL7A1	Pathogenic	criteria provided, multiple submitters, no conflicts
1070885	NM_000094.4(COL7A1):c.565C>T (p.Gln189Ter)	COL7A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1072343	NM_000094.4(COL7A1):c.3830del (p.Pro1277fs)	COL7A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1073113	NM_000094.4(COL7A1):c.4965C>T (p.Gly1655=)	COL7A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1074416	NM_000094.4(COL7A1):c.8263del (p.Ala2755fs)	COL7A1	Pathogenic	criteria provided, multiple submitters, no conflicts
1074690	NM_000094.4(COL7A1):c.6501+1G>C	COL7A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1075255	NM_000094.4(COL7A1):c.1837C>T (p.Arg613Ter)	COL7A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1212890	NM_000094.4(COL7A1):c.6235G>A (p.Gly2079Arg)	COL7A1	Pathogenic	criteria provided, multiple submitters, no conflicts
1324153	NM_000094.4(COL7A1):c.6023G>A (p.Arg2008His)	COL7A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1363259	NM_000094.4(COL7A1):c.189del (p.Leu64fs)	COL7A1	Pathogenic	criteria provided, multiple submitters, no conflicts
1393079	NM_000094.4(COL7A1):c.8219G>C (p.Gly2740Ala)	COL7A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1402177	NM_000094.4(COL7A1):c.3636del (p.Phe1213fs)	COL7A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1404275	NM_000094.4(COL7A1):c.6395G>A (p.Gly2132Asp)	COL7A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1404283	NM_000094.4(COL7A1):c.5108G>A (p.Gly1703Glu)	COL7A1	Pathogenic	criteria provided, multiple submitters, no conflicts
1409788	NM_000094.4(COL7A1):c.3850G>A (p.Gly1284Ser)	COL7A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1443361	NM_000094.4(COL7A1):c.2785C>T (p.Gln929Ter)	COL7A1	Pathogenic	criteria provided, multiple submitters, no conflicts
1453658	NM_000094.4(COL7A1):c.3832_3833del	COL7A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1458606	NM_000094.4(COL7A1):c.5532+5G>A	COL7A1	Pathogenic	criteria provided, multiple submitters, no conflicts
1459712	NM_000094.4(COL7A1):c.5107G>T (p.Gly1703Ter)	COL7A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1492815	NM_000094.4(COL7A1):c.5304_5307+1del	COL7A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1526043	NM_000094.4(COL7A1):c.5560G>A (p.Gly1854Arg)	COL7A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1676611	NM_000094.4(COL7A1):c.7104+3A>T	COL7A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 26 · Orphanet: 9 · 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
COL7A1	Definitive	Autosomal recessive	recessive dystrophic epidermolysis bullosa	26

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
COL7A1	Orphanet:158673	Localized dystrophic epidermolysis bullosa, acral form
COL7A1	Orphanet:158676	Localized dystrophic epidermolysis bullosa, nails only
COL7A1	Orphanet:231568	Autosomal dominant generalized dystrophic epidermolysis bullosa
COL7A1	Orphanet:79408	Autosomal recessive generalized dystrophic epidermolysis bullosa, severe form
COL7A1	Orphanet:79409	Recessive dystrophic epidermolysis bullosa inversa
COL7A1	Orphanet:79410	Localized dystrophic epidermolysis bullosa, pretibial form
COL7A1	Orphanet:79411	Self-improving dystrophic epidermolysis bullosa
COL7A1	Orphanet:89842	Autosomal recessive generalized dystrophic epidermolysis bullosa, intermediate form
COL7A1	Orphanet:89843	Dystrophic epidermolysis bullosa pruriginosa

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
COL7A1	HGNC:2214	ENSG00000114270	Q02388	Collagen alpha-1(VII) chain	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
COL7A1	Collagen alpha-1(VII) chain	Stratified squamous epithelial basement membrane protein that forms anchoring fibrils which may contribute to epithelial basement membrane organization and adherence by interacting with extracellular matrix (ECM) proteins such as type IV c…

Protein-family classification

Druggable: 1 · 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	29.2×	0.034

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
COL7A1	Antibody/Immunoglobulin	yes		VWF_A, Kunitz_BPTI, FN3_dom

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
skin of abdomen	1
skin of leg	1
stromal cell of endometrium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
COL7A1	267	ubiquitous	marker	stromal cell of endometrium, skin of abdomen, skin of leg

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
COL7A1	1,767

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
COL7A1	Q02388

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 10. 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
Anchoring fibril formation	1	761.3×	0.007	COL7A1
Fibronectin matrix formation	1	571.0×	0.007	COL7A1
Laminin interactions	1	380.7×	0.007	COL7A1
Cargo concentration in the ER	1	335.9×	0.007	COL7A1
Collagen chain trimerization	1	259.6×	0.007	COL7A1
Assembly of collagen fibrils and other multimeric structures	1	200.3×	0.007	COL7A1
Collagen degradation	1	175.7×	0.007	COL7A1
Collagen biosynthesis and modifying enzymes	1	170.4×	0.007	COL7A1
COPII-mediated vesicle transport	1	163.1×	0.007	COL7A1
Integrin cell surface interactions	1	134.3×	0.007	COL7A1

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
endodermal cell differentiation	1	495.6×	0.006	COL7A1
epidermis development	1	210.7×	0.007	COL7A1
cell adhesion	1	37.5×	0.027	COL7A1

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
COL7A1	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	1	COL7A1
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)
COL7A1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.