Epidermolytic nevus

Summary

Epidermolytic nevus (MONDO:0044656) is a disease with 2 cohort genes.

At a glance

• Prevalence: >1 / 1000 (Worldwide) [Orphanet-validated]
• Cohort genes: 2
• ClinVar variants: 2

Clinical features

Epidemiology

Prevalence records

1 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Prevalence at birth	>1 / 1000	100	Worldwide	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	epidermolytic nevus
Mondo ID	MONDO:0044656
Orphanet	497737
SNOMED CT	400142003
UMLS	C1302848
MedGen	724389
GARD	0022016
Is cancer (heuristic)	no

Also known as: Epidermal nevus with epidermolytic hyperkeratosis · epidermolytic epidermal nevus · epidermolytic verrucous epidermal nevus

Data availability: 2 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by body system or component › integumentary system disorder › skin disorder › epidermal disease › ichthyosis › inherited ichthyosis › keratinopathic ichthyosis › epidermolytic nevus

Related subtypes (4): epidermolytic ichthyosis, ichthyosis hystrix of Curth-Macklin, superficial epidermolytic ichthyosis, congenital reticular ichthyosiform erythroderma

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:

1 pathogenic, 1 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
14576	NM_000421.5(KRT10):c.466C>T (p.Arg156Cys)	KRT10	Pathogenic	criteria provided, multiple submitters, no conflicts
2672093	NM_005343.4(HRAS):c.450+181G>A	HRAS	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 9 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
HRAS	Orphanet:146	Differentiated thyroid carcinoma
HRAS	Orphanet:2612	Linear nevus sebaceus syndrome
HRAS	Orphanet:2874	Phakomatosis pigmentokeratotica
HRAS	Orphanet:3071	Costello syndrome
HRAS	Orphanet:79414	Woolly hair nevus
KRT10	Orphanet:281139	Annular epidermolytic ichthyosis
KRT10	Orphanet:281190	Congenital reticular ichthyosiform erythroderma
KRT10	Orphanet:312	Autosomal dominant epidermolytic ichthyosis
KRT10	Orphanet:512103	Autosomal recessive epidermolytic ichthyosis

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
HRAS	HGNC:5173	ENSG00000174775	P01112	GTPase HRas	clinvar
KRT10	HGNC:6413	ENSG00000186395	P13645	Keratin, type I cytoskeletal 10	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
HRAS	GTPase HRas	Involved in the activation of Ras protein signal transduction.
KRT10	Keratin, type I cytoskeletal 10	Plays a role in the establishment of the epidermal barrier on plantar skin.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.5

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
Enzyme (other)	1	6.0×	0.320
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
HRAS	Enzyme (other)	yes	3.6.5.2	Small_GTPase, Small_GTP-bd, Small_GTPase_Ras-type
KRT10	Other/Unknown	no		Keratin_I, IF_conserved, IF_rod_dom

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 abdomen	1
skin of leg	1
zone of skin	1
mammalian vulva	1
penis	1
upper leg skin	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
HRAS	139	ubiquitous	marker	skin of abdomen, skin of leg, zone of skin
KRT10	299	broad	marker	upper leg skin, penis, mammalian vulva

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
HRAS	8,064
KRT10	2,304

Structural data

PDB: 2 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
HRAS	P01112	246
KRT10	P13645	6

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 73. 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
Signaling by RAS GAP mutants	1	1903.3×	0.007	HRAS
Signaling by RAS GTPase mutants	1	1903.3×	0.007	HRAS
Activation of RAS in B cells	1	1142.0×	0.007	HRAS
RAS signaling downstream of NF1 loss-of-function variants	1	815.7×	0.007	HRAS
Estrogen-stimulated signaling through PRKCZ	1	815.7×	0.007	HRAS
SOS-mediated signalling	1	713.8×	0.007	HRAS
Activated NTRK3 signals through RAS	1	634.4×	0.007	HRAS
EGFR Transactivation by Gastrin	1	571.0×	0.007	HRAS
SHC-related events triggered by IGF1R	1	571.0×	0.007	HRAS
Activated NTRK2 signals through RAS	1	571.0×	0.007	HRAS
MET activates RAS signaling	1	519.1×	0.007	HRAS
Signaling by FGFR4 in disease	1	475.8×	0.007	HRAS
Activated NTRK2 signals through FRS2 and FRS3	1	475.8×	0.007	HRAS
Constitutive Signaling by Overexpressed ERBB2	1	475.8×	0.007	HRAS
p38MAPK events	1	439.2×	0.007	HRAS
Signaling by PDGFRA transmembrane, juxtamembrane and kinase domain mutants	1	439.2×	0.007	HRAS
Signaling by PDGFRA extracellular domain mutants	1	439.2×	0.007	HRAS
PTK6 Regulates RHO GTPases, RAS GTPase and MAP kinases	1	407.9×	0.007	HRAS
GRB2 events in EGFR signaling	1	380.7×	0.007	HRAS
Erythropoietin activates RAS	1	380.7×	0.007	HRAS
Signaling by FLT3 ITD and TKD mutants	1	380.7×	0.007	HRAS
SHC1 events in ERBB4 signaling	1	356.9×	0.007	HRAS
SHC1 events in EGFR signaling	1	356.9×	0.007	HRAS
Constitutive Signaling by EGFRvIII	1	356.9×	0.007	HRAS
Signalling to RAS	1	335.9×	0.007	HRAS
Insulin receptor signalling cascade	1	335.9×	0.007	HRAS
Signaling by ERBB2 ECD mutants	1	335.9×	0.007	HRAS
GRB2 events in ERBB2 signaling	1	317.2×	0.007	HRAS
Tie2 Signaling	1	300.5×	0.007	HRAS
SHC-mediated cascade:FGFR3	1	300.5×	0.007	HRAS

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
positive regulation of miRNA metabolic process	1	2808.7×	0.011	HRAS
positive regulation of epidermis development	1	1685.2×	0.011	KRT10
oncogene-induced cell senescence	1	1203.7×	0.011	HRAS
T-helper 1 type immune response	1	936.2×	0.011	HRAS
Schwann cell development	1	526.6×	0.011	HRAS
protein heterotetramerization	1	526.6×	0.011	KRT10
cornification	1	526.6×	0.011	KRT10
regulation of long-term neuronal synaptic plasticity	1	495.6×	0.011	HRAS
positive regulation of ruffle assembly	1	495.6×	0.011	HRAS
regulation of neurotransmitter receptor localization to postsynaptic specialization membrane	1	443.5×	0.011	HRAS
defense response to protozoan	1	300.9×	0.013	HRAS
cellular response to gamma radiation	1	300.9×	0.013	HRAS
positive regulation of protein targeting to membrane	1	280.9×	0.013	HRAS
positive regulation of wound healing	1	263.3×	0.013	HRAS
adipose tissue development	1	200.6×	0.015	HRAS
fibroblast proliferation	1	195.9×	0.015	HRAS
intrinsic apoptotic signaling pathway	1	179.3×	0.015	HRAS
morphogenesis of an epithelium	1	172.0×	0.015	KRT10
positive regulation of fibroblast proliferation	1	147.8×	0.016	HRAS
cellular senescence	1	147.8×	0.016	HRAS
myelination	1	125.8×	0.017	HRAS
keratinocyte differentiation	1	123.9×	0.017	KRT10
positive regulation of epithelial cell proliferation	1	122.1×	0.017	HRAS
intermediate filament organization	1	120.4×	0.017	KRT10
positive regulation of type II interferon production	1	112.3×	0.017	HRAS
insulin receptor signaling pathway	1	110.9×	0.017	HRAS
Ras protein signal transduction	1	102.8×	0.017	HRAS
animal organ morphogenesis	1	95.8×	0.018	HRAS
neuron apoptotic process	1	92.6×	0.018	HRAS
positive regulation of JNK cascade	1	81.8×	0.019	HRAS

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · 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).

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
HRAS	LONAFARNIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
HRAS	4	4
KRT10	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
LONAFARNIB	4	HRAS
STALLIMYCIN	2	HRAS
L-778123 FREE BASE	1	HRAS
BMS-214662	1	HRAS

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
HRAS	48	Binding:45, Functional:3

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
HRAS	3.6.5.2	small monomeric GTPase

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

4 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)
LONAFARNIB	4	HRAS
STALLIMYCIN	2	HRAS
L-778123 FREE BASE	1	HRAS
BMS-214662	1	HRAS

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	HRAS
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	KRT10

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)
KRT10	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.