Keratolytic winter erythema

Summary

Keratolytic winter erythema (MONDO:0007854) is a disease caused by CTSB (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: CTSB (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 3
• Phenotypes (HPO): 3

Clinical features

Signs & symptoms

Clinical features (HPO)

3 HPO clinical features (Orphanet curated; top 3 by frequency):

HPO ID	Term	Frequency
HP:0010783	Erythema	Very frequent (80-99%)
HP:0000975	Hyperhidrosis	Occasional (5-29%)
HP:0200039	Pustule	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	keratolytic winter erythema
Mondo ID	MONDO:0007854
MeSH	C536155
OMIM	148370
Orphanet	50943
ICD-11	1491245207
SNOMED CT	239064000
UMLS	C0406756
MedGen	98359
GARD	0008275
NORD	1286
Is cancer (heuristic)	no

Also known as: Erythrokeratolysis hiemalis · Erythrokeratolysis hiemalis ichthyosis · keratolytic winter erythema · KWE · Oudtshoorn disease · Oudtshoorn skin

Data availability: 3 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 › epidermal disease › keratolytic winter erythema

Related subtypes (24): porokeratosis, Darier disease, absence of fingerprints-congenital milia syndrome, hyperkeratosis lenticularis perstans, 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

3 retrieved; paginated sample, class counts are floors:

2 benign, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
1425868	NM_001908.5(CTSB):c.127-11CT[2]	CTSB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1098730	NM_001908.5(CTSB):c.157A>G (p.Ser53Gly)	CTSB	Benign	criteria provided, multiple submitters, no conflicts
1166852	NM_001908.5(CTSB):c.533-11C>G	CTSB	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · 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
CTSB	Strong	Autosomal dominant	keratolytic winter erythema	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CTSB	Orphanet:50943	Keratolytic winter erythema

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
CTSB	HGNC:2527	ENSG00000164733	P07858	Cathepsin B	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CTSB	Cathepsin B	Thiol protease which is believed to participate in intracellular degradation and turnover of proteins.

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
Protease	1	36.6×	0.027

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CTSB	Protease	yes	3.4.22.1	Pept_cys_AS, Peptidase_C1A_C, Propeptide_C1A

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
left lobe of thyroid gland	1
right lobe of thyroid gland	1
stromal cell of endometrium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CTSB	161	ubiquitous	marker	stromal cell of endometrium, right lobe of thyroid gland, left lobe of thyroid gland

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CTSB	4,922

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CTSB	P07858	21

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 14. 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
Trafficking and processing of endosomal TLR	1	815.7×	0.010	CTSB
SRC activates STAT3 in a quantitative manner, through Cadherin-11 (CDH11), RAC1 and gp130 (IL6ST)	1	496.5×	0.010	CTSB
Collagen formation	1	456.8×	0.010	CTSB
Assembly of collagen fibrils and other multimeric structures	1	200.3×	0.013	CTSB
Degradation of CDH1	1	196.9×	0.013	CTSB
Collagen degradation	1	175.7×	0.013	CTSB
Toll-like Receptor Cascades	1	124.1×	0.015	CTSB
Degradation of the extracellular matrix	1	117.7×	0.015	CTSB
MHC class II antigen presentation	1	89.2×	0.017	CTSB
Extracellular matrix organization	1	63.1×	0.022	CTSB
Adaptive Immune System	1	29.8×	0.043	CTSB
Innate Immune System	1	25.5×	0.046	CTSB
Neutrophil degranulation	1	23.1×	0.047	CTSB
Immune System	1	13.0×	0.077	CTSB

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
cellular response to thyroid hormone stimulus	1	1532.0×	0.004	CTSB
thyroid hormone generation	1	991.3×	0.004	CTSB
decidualization	1	674.1×	0.004	CTSB
obsolete proteolysis involved in protein catabolic process	1	526.6×	0.004	CTSB
symbiont entry into host cell	1	401.2×	0.004	CTSB
collagen catabolic process	1	391.9×	0.004	CTSB
epithelial cell differentiation	1	175.5×	0.007	CTSB
regulation of apoptotic process	1	83.4×	0.013	CTSB
proteolysis	1	34.2×	0.029	CTSB

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) 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
CTSB	NITROXOLINE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CTSB	13	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
NITROXOLINE	4	CTSB
BOCEPREVIR	4	CTSB
TELAPREVIR	4	CTSB
CARFILZOMIB	4	CTSB
FALDAPREVIR	3	CTSB
ODANACATIB	3	CTSB
RELACATIB	2	CTSB
PEPSTATIN	2	CTSB
ALLICIN	2	CTSB
BALICATIB	2	CTSB
ATUZAGINSTAT	2	CTSB
ALOXISTATIN	2	CTSB
K-777	2	CTSB

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
CTSB	610	Binding:577, ADMET:25, Toxicity:5, Functional:3

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
CTSB	3.4.22.1	cathepsin B

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
CTSB	610

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

13 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)
NITROXOLINE	4	CTSB
BOCEPREVIR	4	CTSB
TELAPREVIR	4	CTSB
CARFILZOMIB	4	CTSB
FALDAPREVIR	3	CTSB
ODANACATIB	3	CTSB
RELACATIB	2	CTSB
PEPSTATIN	2	CTSB
ALLICIN	2	CTSB
BALICATIB	2	CTSB
ATUZAGINSTAT	2	CTSB
ALOXISTATIN	2	CTSB
K-777	2	CTSB

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	CTSB
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	0

Undrugged target profiles

0 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Clinical trials & evidence

Clinical trials

Clinical trials: 0.