Epidermolysis bullosa simplex 7, with nephropathy and deafness

Summary

Epidermolysis bullosa simplex 7, with nephropathy and deafness (MONDO:0012190) is a disease caused by CD151 (GenCC Strong), with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: CD151 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 57

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		3	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	epidermolysis bullosa simplex 7, with nephropathy and deafness
Mondo ID	MONDO:0012190
MeSH	C563798
OMIM	609057
Orphanet	300333
UMLS	C1836823
MedGen	323004
GARD	0017367
Is cancer (heuristic)	no

Also known as: epidermolysis bullosa simplex 7, with nephropathy and deafness · nephrotic syndrome - deafness - pretibial epidermolysis bullosa syndrome · nephrotic syndrome-hearing loss-pretibial epidermolysis bullosa syndrome

Data availability: 57 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 7, with nephropathy and deafness

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 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

57 retrieved; paginated sample, class counts are floors:

38 uncertain significance, 6 conflicting classifications of pathogenicity, 5 likely benign, 4 likely pathogenic, 2 benign/likely benign, 2 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
7380	NM_004357.5(CD151):c.382dup (p.Asp128fs)	CD151	Pathogenic	no assertion criteria provided
982562	NM_004357.5(CD151):c.19A>T (p.Lys7Ter)	CD151	Pathogenic	criteria provided, single submitter
3574085	NM_004357.5(CD151):c.203dup (p.Thr69fs)	CD151	Likely pathogenic	criteria provided, single submitter
3574089	NM_004357.5(CD151):c.276+1G>T	CD151	Likely pathogenic	criteria provided, single submitter
3574091	NM_004357.5(CD151):c.277-2A>C	CD151	Likely pathogenic	criteria provided, single submitter
982563	NM_004357.5(CD151):c.622_630del (p.Cys208_Thr210del)	CD151	Likely pathogenic	criteria provided, single submitter
1028736	NM_004357.5(CD151):c.493C>T (p.Arg165Ter)	CD151	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1625120	NM_004357.5(CD151):c.432C>T (p.Ser144=)	CD151	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1968518	NM_004357.5(CD151):c.477C>T (p.Asn159=)	CD151	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2054181	NM_004357.5(CD151):c.201G>A (p.Ala67=)	CD151	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3393061	NM_004357.5(CD151):c.142dup (p.Tyr48fs)	CD151	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3574096	NM_004357.5(CD151):c.406C>T (p.Gln136Ter)	CD151	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1028737	NM_004357.5(CD151):c.511C>T (p.Arg171Cys)	CD151	Uncertain significance	criteria provided, multiple submitters, no conflicts
1339233	NM_004357.5(CD151):c.633G>C (p.Lys211Asn)	CD151	Uncertain significance	criteria provided, single submitter
1355643	NM_004357.5(CD151):c.328C>G (p.Leu110Val)	CD151	Uncertain significance	criteria provided, multiple submitters, no conflicts
1408948	NM_004357.5(CD151):c.16G>A (p.Glu6Lys)	CD151	Uncertain significance	criteria provided, multiple submitters, no conflicts
1428000	NM_004357.5(CD151):c.241G>A (p.Ala81Thr)	CD151	Uncertain significance	criteria provided, multiple submitters, no conflicts
1431457	NM_004357.5(CD151):c.295A>C (p.Ile99Leu)	CD151	Uncertain significance	criteria provided, multiple submitters, no conflicts
1901915	NM_004357.5(CD151):c.733T>C (p.Tyr245His)	CD151	Uncertain significance	criteria provided, multiple submitters, no conflicts
1943752	NM_004357.5(CD151):c.541C>T (p.Pro181Ser)	CD151	Uncertain significance	criteria provided, multiple submitters, no conflicts
1944435	NM_004357.5(CD151):c.164G>A (p.Gly55Asp)	CD151	Uncertain significance	criteria provided, multiple submitters, no conflicts
2066958	NM_004357.5(CD151):c.352-11C>G	CD151	Uncertain significance	criteria provided, multiple submitters, no conflicts
2103252	NM_004357.5(CD151):c.349C>T (p.Gln117Ter)	CD151	Uncertain significance	criteria provided, multiple submitters, no conflicts
2149834	NM_004357.5(CD151):c.433G>A (p.Ala145Thr)	CD151	Uncertain significance	criteria provided, multiple submitters, no conflicts
2178170	NM_004357.5(CD151):c.702+4A>G	CD151	Uncertain significance	criteria provided, multiple submitters, no conflicts
2244434	NM_004357.5(CD151):c.439G>A (p.Asp147Asn)	CD151	Uncertain significance	criteria provided, multiple submitters, no conflicts
2717855	NM_004357.5(CD151):c.562G>C (p.Val188Leu)	CD151	Uncertain significance	criteria provided, multiple submitters, no conflicts
2883376	NM_004357.5(CD151):c.729C>T (p.Cys243=)	CD151	Uncertain significance	criteria provided, multiple submitters, no conflicts
2975742	NM_004357.5(CD151):c.251A>G (p.Lys84Arg)	CD151	Uncertain significance	criteria provided, multiple submitters, no conflicts
2988288	NM_004357.5(CD151):c.211G>A (p.Val71Ile)	CD151	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · Orphanet: 1 · 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
CD151	Strong	Autosomal recessive	epidermolysis bullosa simplex 7, with nephropathy and deafness	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CD151	Orphanet:300333	Nephrotic syndrome-epidermolysis bullosa-sensorineural deafness syndrome

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
CD151	HGNC:1630	ENSG00000177697	P48509	CD151 antigen	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CD151	CD151 antigen	Structural component of specialized membrane microdomains known as tetraspanin-enriched microdomains (TERMs), which act as platforms for receptor clustering and signaling.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · 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
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CD151	Other/Unknown	no		Tetraspanin_animals, Tetraspanin_EC2_sf, Tetraspanin/Peripherin

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
ascending aorta	1
descending thoracic aorta	1
thoracic aorta	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CD151	276	ubiquitous	marker	descending thoracic aorta, thoracic aorta, ascending aorta

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CD151	1,719

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
CD151	P48509	88.02

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 6. 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×	0.006	CD151
Collagen formation	1	456.8×	0.007	CD151
Assembly of collagen fibrils and other multimeric structures	1	200.3×	0.008	CD151
Cell junction organization	1	187.2×	0.008	CD151
Cell-Cell communication	1	137.6×	0.009	CD151
Extracellular matrix organization	1	63.1×	0.016	CD151

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
wound healing, spreading of cells	1	1123.5×	0.004	CD151
positive regulation of endocytosis	1	802.5×	0.004	CD151
T cell proliferation	1	383.0×	0.005	CD151
positive regulation of cell migration	1	61.7×	0.020	CD151
cell migration	1	61.5×	0.020	CD151
cell adhesion	1	37.5×	0.027	CD151

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
CD151	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	CD151

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)
CD151	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.