Erythrokeratodermia variabilis et progressiva 7

disease

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Also known as EKVP7

Summary

Erythrokeratodermia variabilis et progressiva 7 (MONDO:0030941) is a disease caused by PERP (GenCC Strong), with 1 cohort gene.

At a glance

Causal gene: PERP (GenCC Strong)
Cohort genes: 1
ClinVar variants: 2

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	erythrokeratodermia variabilis et progressiva 7
Mondo ID	MONDO:0030941
OMIM	619209
UMLS	C5543106
MedGen	1780408
GARD	0018674
Is cancer (heuristic)	no

Also known as: EKVP7 · erythrokeratodermia variabilis et progressiva 7

Data availability: 2 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 › keratosis › palmoplantar keratosis › hereditary palmoplantar keratoderma › diffuse palmoplantar keratoderma › erythrokeratodermia variabilis › erythrokeratodermia variabilis et progressiva 7

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

2 retrieved; paginated sample, class counts are floors:

2 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
997851	NM_022121.5(PERP):c.112del (p.Ser38fs)	PERP	Pathogenic	criteria provided, single submitter
997853	NM_022121.5(PERP):c.466G>A (p.Gly156Arg)	PERP	Pathogenic	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 9 · 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
PERP	Strong	Autosomal recessive	erythrokeratodermia variabilis et progressiva 7	9

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
PERP	Orphanet:659	Mutilating palmoplantar keratoderma with periorificial keratotic plaques

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
PERP	HGNC:17637	ENSG00000112378	Q96FX8	p53 apoptosis effector related to PMP-22	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PERP	p53 apoptosis effector related to PMP-22	Component of intercellular desmosome junctions.

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
Transcription factor	1	8.3×	0.121

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
PERP	Transcription factor	no		PMP22/EMP/MP20/Claudin, P53_induced

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
penis	1
pharyngeal mucosa	1
upper leg skin	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PERP	277	ubiquitous	marker	penis, upper leg skin, pharyngeal mucosa

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PERP	1,228

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
PERP	Q96FX8	82.59

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 2. 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
TP53 regulates transcription of several additional cell death genes whose specific roles in p53-dependent apoptosis remain uncertain	1	761.3×	0.003	PERP
Formation of the cornified envelope	1	87.8×	0.011	PERP

GO biological processes by enrichment

GO term	Cohort genes	Fold	FDR	Sample cohort genes
mammary gland duct morphogenesis	1	2407.4×	0.002	PERP
desmosome organization	1	2106.5×	0.002	PERP
positive regulation of T cell apoptotic process	1	2106.5×	0.002	PERP
amelogenesis	1	1404.3×	0.002	PERP
positive regulation of proteolysis	1	802.5×	0.002	PERP
positive regulation of neutrophil chemotaxis	1	648.1×	0.002	PERP
heterotypic cell-cell adhesion	1	581.1×	0.002	PERP
intrinsic apoptotic signaling pathway by p53 class mediator	1	581.1×	0.002	PERP
tissue homeostasis	1	561.7×	0.002	PERP
Notch signaling pathway	1	141.6×	0.008	PERP
cell-cell adhesion	1	101.5×	0.010	PERP

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
PERP	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	PERP

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)
PERP	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.

Cohort genes: PERP