Epidermal disease

Summary

Epidermal disease (MONDO:0019268) is a disease (an umbrella term covering 25 Mondo subtypes) with 2 cohort genes.

At a glance

• Umbrella term: 25 Mondo subtypes
• Cohort genes: 2
• ClinVar variants: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	epidermal disease
Mondo ID	MONDO:0019268
Orphanet	79353
UMLS	C5681492
MedGen	1842776
Anatomy (UBERON)	UBERON:0001003
Is cancer (heuristic)	no

Also known as: epidermal disease · rare epidermal disease

Data availability: 1 ClinVar variant · 1 GenCC gene-disease record.

Disease family

An umbrella term covering 25 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › integumentary system disorder › skin disorder › epidermal disease

Related subtypes (71): dermatitis, cutaneous mucinosis, skin neoplasm, pyoderma, chronic ulcer of skin, systemic sclerosis, sunburn, severe cutaneous adverse reaction, paronychia, Achenbach syndrome, erythema multiforme, erythematosquamous dermatosis, exanthem, facial dermatosis, hand dermatosis, keratosis, leg dermatosis, lichen disease, lipodystrophy, mongolian spot, reactive cutaneous fibrous lesion, rosacea, scalp dermatosis, sebaceous gland disorder, skin atrophy, skin sarcoidosis, sweat gland disorder, vesiculobullous skin disease, hyperglobulinemic purpura, ainhum, cheilitis glandularis, erythema palmare hereditarium, multiple benign circumferential skin creases on limbs, actinic prurigo, congenital lethal erythroderma, Parana hard-skin syndrome, Bazex-Dupre-Christol syndrome, nephrogenic systemic fibrosis, erosive pustular dermatosis of the scalp, pseudoxanthoma elasticum-like papillary dermal elastolysis, toxic dermatosis, oral erosive lichen, chronic actinic dermatitis, Jessner lymphocytic infiltration of the skin, acquired kinky hair syndrome, primary cutaneous plasmacytosis, cutaneous pseudolymphoma, corticosteroid-sensitive aseptic abscess syndrome, interstitial granulomatous dermatitis with arthritis, skin pigmentation disorder, skin vascular disease, Wells syndrome, solar urticaria, pellagra, hereditary epidermal appendage anomaly, keratosis pilaris, dermis disorder, aquagenic pruritus, Boudhina Yedes Khiari syndrome, non-neoplastic nevus, cutaneous sclerosis, pityriasis rotunda, hematohidrosis, skin disorder caused by infection, livedoid vasculopathy, prurigo nodularis, granuloma faciale, sclerema neonatorum, hereditary skin disorder, hand-foot syndrome, Nicolau syndrome

Subtypes (25): porokeratosis, Darier disease, absence of fingerprints-congenital milia syndrome, hyperkeratosis lenticularis perstans, keratolytic winter erythema, Hailey-Hailey disease, VPS13A-related neurodegenerative disease, acanthosis nigricans-insulin resistance-muscle cramps-acral enlargement syndrome, keratosis linearis-ichthyosis congenita-sclerosing keratoderma syndrome, seborrhea-like dermatitis with psoriasiform elements, psoriasis 14, pustular, palmoplantar pustulosis, hereditary poikiloderma, congenital erosive and vesicular dermatosis, neonatal inflammatory skin and bowel disease, 13q12.3 microdeletion syndrome, zinc-responsive necrolytic acral erythema, keratosis pilaris atrophicans, ichthyosis, erythrokeratoderma, hereditary palmoplantar keratoderma, inherited epidermolysis bullosa, punctate acrokeratoderma freckle-like pigmentation, aquagenic palmoplantar keratoderma, phrynoderma

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

1 retrieved; paginated sample, class counts are floors:

1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
88660	NM_001942.4(DSG1):c.430A>T (p.Arg144Ter)	DSG1	Pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 2 · Orphanet: 4 · 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
KLF4	Moderate	Autosomal dominant	epidermal disease	2

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
DSG1	Orphanet:369992	Severe dermatitis-multiple allergies-metabolic wasting syndrome
DSG1	Orphanet:369999	Diffuse palmoplantar keratoderma with painful fissures
DSG1	Orphanet:370002	Focal palmoplantar keratoderma with joint keratoses
DSG1	Orphanet:50942	Striate palmoplantar keratoderma

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
KLF4	HGNC:6348	ENSG00000136826	O43474	Krueppel-like factor 4	gencc
DSG1	HGNC:3048	ENSG00000134760	Q02413	Desmoglein-1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
KLF4	Krueppel-like factor 4	Transcription factor; can act both as activator and as repressor.
DSG1	Desmoglein-1	Component of intercellular desmosome junctions.

Protein-family classification

Druggable: 0 · Difficult: 1 · 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
Transcription factor	1	4.1×	0.455
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
KLF4	Transcription factor	no		Znf_C2H2_type, Znf_C2H2_sf
DSG1	Other/Unknown	no		Cadherin_Y-type_LIR, Cadherin-like_dom, Desmosomal_cadherin

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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
skin of hip	2
upper leg skin	2
penis	1
upper arm skin	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
KLF4	290	ubiquitous	marker	upper leg skin, skin of hip, penis
DSG1	152	tissue_specific	marker	upper arm skin, upper leg skin, skin of hip

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
DSG1	1,643
KLF4	316

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
KLF4	O43474	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
DSG1	Q02413	62.93

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 19. Enrichment computed across 2 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Apoptotic cleavage of cell adhesion proteins	1	519.1×	0.014	DSG1
Positive Regulation of CDH1 Gene Transcription	1	475.8×	0.014	KLF4
FOXO-mediated transcription of cell cycle genes	1	335.9×	0.014	KLF4
Synthesis, secretion, and deacylation of Ghrelin	1	300.5×	0.014	KLF4
Transcriptional regulation of pluripotent stem cells	1	271.9×	0.014	KLF4
FOXO-mediated transcription	1	167.9×	0.016	KLF4
Peptide hormone metabolism	1	135.9×	0.016	KLF4
RND3 GTPase cycle	1	129.8×	0.016	DSG1
RND2 GTPase cycle	1	129.8×	0.016	DSG1
Adipogenesis	1	78.2×	0.024	KLF4
Transcriptional regulation of white adipocyte differentiation	1	64.9×	0.027	KLF4
Formation of the cornified envelope	1	43.9×	0.036	DSG1
Keratinization	1	27.9×	0.052	DSG1
Neutrophil degranulation	1	11.5×	0.110	DSG1
RNA Polymerase II Transcription	1	11.3×	0.110	KLF4
Gene expression (Transcription)	1	8.9×	0.129	KLF4
Generic Transcription Pathway	1	7.5×	0.141	KLF4
Developmental Biology	1	7.2×	0.141	KLF4
Metabolism of proteins	1	6.2×	0.155	KLF4

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
negative regulation of leukocyte adhesion to arterial endothelial cell	1	8426.0×	0.004	KLF4
negative regulation of muscle hyperplasia	1	4213.0×	0.004	KLF4
mesodermal cell fate determination	1	2808.7×	0.004	KLF4
post-embryonic camera-type eye development	1	2106.5×	0.004	KLF4
regulation of blastocyst development	1	2106.5×	0.004	KLF4
negative regulation of chemokine (C-X-C motif) ligand 2 production	1	2106.5×	0.004	KLF4
post-embryonic hemopoiesis	1	1404.3×	0.004	KLF4
positive regulation of hemoglobin biosynthetic process	1	1404.3×	0.004	KLF4
epidermis morphogenesis	1	1404.3×	0.004	KLF4
negative regulation of response to cytokine stimulus	1	1404.3×	0.004	KLF4
regulation of axon regeneration	1	1203.7×	0.004	KLF4
cellular response to laminar fluid shear stress	1	1053.2×	0.005	KLF4
negative regulation of heterotypic cell-cell adhesion	1	936.2×	0.005	KLF4
epidermal cell differentiation	1	842.6×	0.005	KLF4
cellular response to endothelin	1	702.2×	0.005	KLF4
defense response to tumor cell	1	648.1×	0.005	KLF4
negative regulation of interleukin-8 production	1	495.6×	0.006	KLF4
positive regulation of protein metabolic process	1	495.6×	0.006	KLF4
negative regulation of cell migration involved in sprouting angiogenesis	1	495.6×	0.006	KLF4
maternal process involved in female pregnancy	1	468.1×	0.006	DSG1
positive regulation of sprouting angiogenesis	1	337.0×	0.008	KLF4
negative regulation of smooth muscle cell proliferation	1	312.1×	0.008	KLF4
positive regulation of telomere maintenance	1	255.3×	0.009	KLF4
response to progesterone	1	247.8×	0.009	DSG1
calcium-dependent cell-cell adhesion	1	240.7×	0.009	DSG1
positive regulation of nitric oxide biosynthetic process	1	227.7×	0.009	KLF4
establishment of skin barrier	1	227.7×	0.009	KLF4
cell-cell junction assembly	1	221.7×	0.009	DSG1
regulation of cell differentiation	1	216.1×	0.009	KLF4
stem cell population maintenance	1	210.7×	0.009	KLF4

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 2 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
DSG1	1	2
KLF4	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
MOLIBRESIB	2	DSG1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
DSG1	8	Binding:8

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

1 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)
MOLIBRESIB	2	DSG1

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	1	DSG1
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	KLF4

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)
KLF4	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.