Striate palmoplantar keratoderma

Summary

Striate palmoplantar keratoderma (MONDO:0018865) is a disease with 3 cohort genes.

At a glance

• Cohort genes: 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:0000982	Palmoplantar keratoderma	Very frequent (80-99%)
HP:0001595	Abnormality of the hair	Frequent (30-79%)
HP:0001597	Abnormality of the nail	Frequent (30-79%)

Identifiers

Disease identifiers

Field	Value
Canonical name	striate palmoplantar keratoderma
Mondo ID	MONDO:0018865
Orphanet	50942
DOID	DOID:0081105
ICD-11	1171134598
SNOMED CT	764958008
UMLS	C4707237
MedGen	1631598
GARD	0015016
Is cancer (heuristic)	no

Also known as: keratosis palmoplantaris striata · keratosis palmoplantaris striata et areata · keratosis palmoplantaris varians of Wachters

Data availability: 3 GenCC gene-disease records.

Disease family

An umbrella term covering 2 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › integumentary system disorder › skin disorder › keratosis › palmoplantar keratosis › hereditary palmoplantar keratoderma › focal palmoplantar keratoderma › striate palmoplantar keratoderma

Related subtypes (11): hereditary painful callosities, palmoplantar keratoderma-esophageal carcinoma syndrome, focal palmoplantar and gingival keratoderma, tyrosinemia type II, hypotrichosis-osteolysis-periodontitis-palmoplantar keratoderma syndrome, palmoplantar keratoderma, nonepidermolytic, focal 1, nail and teeth abnormalities-marginal palmoplantar keratoderma-oral hyperpigmentation syndrome, wooly hair-palmoplantar keratoderma syndrome, isolated focal non-epidermolytic palmoplantar keratoderma, pachyonychia congenita, focal palmoplantar keratoderma with joint keratoses

Subtypes (2): keratosis palmoplantaris striata 3, keratosis palmoplantaris striata 2

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

No tiered GWAS variants or ClinVar records for this disease.

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 56 · Orphanet: 23 · 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
DSG1	Definitive	Autosomal dominant	palmoplantar keratoderma i, striate, focal, or diffuse	12
DSP	Definitive	Autosomal dominant	arrhythmogenic cardiomyopathy with wooly hair and keratoderma	26
KRT1	Strong	Autosomal dominant	diffuse nonepidermolytic palmoplantar keratoderma	18

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
DSP	Orphanet:154	Familial isolated dilated cardiomyopathy
DSP	Orphanet:158687	Lethal acantholytic erosive disorder
DSP	Orphanet:2032	Idiopathic pulmonary fibrosis
DSP	Orphanet:293165	Skin fragility-woolly hair-palmoplantar keratoderma syndrome
DSP	Orphanet:293888	Inherited isolated arrhythmogenic cardiomyopathy, dominant-left variant
DSP	Orphanet:293899	Inherited isolated arrhythmogenic ventricular dysplasia, biventricular variant
DSP	Orphanet:293910	Inherited isolated arrhythmogenic cardiomyopathy, dominant-right variant
DSP	Orphanet:369992	Severe dermatitis-multiple allergies-metabolic wasting syndrome
DSP	Orphanet:476096	Erythrokeratodermia-cardiomyopathy syndrome
DSP	Orphanet:50942	Striate palmoplantar keratoderma
DSP	Orphanet:65282	Carvajal syndrome
KRT1	Orphanet:2199	Epidermolytic palmoplantar keratoderma
KRT1	Orphanet:281139	Annular epidermolytic ichthyosis
KRT1	Orphanet:281190	Congenital reticular ichthyosiform erythroderma
KRT1	Orphanet:312	Autosomal dominant epidermolytic ichthyosis
KRT1	Orphanet:50942	Striate palmoplantar keratoderma
KRT1	Orphanet:530838	KRT1-related diffuse nonepidermolytic keratoderma
KRT1	Orphanet:538574	Palmoplantar keratoderma-hereditary motor and sensory neuropathy syndrome
KRT1	Orphanet:79503	Ichthyosis hystrix of Curth-Macklin

Cohort genes → proteins

3 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
DSG1	HGNC:3048	ENSG00000134760	Q02413	Desmoglein-1	gencc
DSP	HGNC:3052	ENSG00000096696	P15924	Desmoplakin	gencc
KRT1	HGNC:6412	ENSG00000167768	P04264	Keratin, type II cytoskeletal 1	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
DSG1	Desmoglein-1	Component of intercellular desmosome junctions.
DSP	Desmoplakin	A component of desmosome cell-cell junctions which are required for positive regulation of cellular adhesion.
KRT1	Keratin, type II cytoskeletal 1	May regulate the activity of kinases such as PKC and SRC via binding to integrin beta-1 (ITB1) and the receptor of activated protein C kinase 1 (RACK1).

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 2 · 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
Scaffold/PPI	1	5.8×	0.327
Other/Unknown	2	1.2×	0.587

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
DSG1	Other/Unknown	no		Cadherin_Y-type_LIR, Cadherin-like_dom, Desmosomal_cadherin
DSP	Scaffold/PPI	no		Plectin_repeat, SH3_domain, Spectrin/alpha-actinin
KRT1	Other/Unknown	no		Keratin_II, IF_conserved, Keratin_2_head

Expression context

Cohort genes with no expression data: 0.

3 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)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
skin of hip	3
upper leg skin	3
upper arm skin	1
hair follicle	1
mammalian vulva	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
DSG1	152	tissue_specific	marker	upper arm skin, upper leg skin, skin of hip
DSP	253	ubiquitous	marker	skin of hip, upper leg skin, hair follicle
KRT1	177	tissue_specific	marker	mammalian vulva, upper leg skin, skin of hip

Protein interactions among cohort

Intra-cohort edges: 3.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
DSP	2,897
KRT1	2,716
DSG1	1,643

Intra-cohort edges

A	B	Sources
DSG1	DSP	intact, string_interaction
DSG1	KRT1	string_interaction
DSP	KRT1	biogrid_interaction, string_interaction

Structural data

PDB: 2 · AlphaFold-only: 1 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
DSP	P15924	4
KRT1	P04264	3

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
DSG1	Q02413	62.93

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 14. Enrichment computed across 3 evidence-associated genes (3 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 3 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	2	692.1×	2e-05	DSG1, DSP
Formation of the cornified envelope	3	87.8×	2e-05	DSG1, DSP, KRT1
Keratinization	3	55.7×	3e-05	DSG1, DSP, KRT1
RND3 GTPase cycle	2	173.0×	2e-04	DSG1, DSP
Neutrophil degranulation	3	23.1×	2e-04	DSG1, DSP, KRT1
Regulation of FXIIa and plasma kallikrein activity	1	380.7×	0.006	KRT1
Differentiation of Keratinocytes in Interfollicular Epidermis in Mammalian Skin	1	92.8×	0.018	KRT1
RND1 GTPase cycle	1	88.5×	0.018	DSP
RND2 GTPase cycle	1	86.5×	0.018	DSG1
Developmental Cell Lineages	1	74.6×	0.019	KRT1
FXIIa activates plasma kallikrein-kinin system	1	57.7×	0.022	KRT1
Innate Immune System	1	8.5×	0.132	KRT1
Developmental Biology	1	4.8×	0.208	KRT1
Immune System	1	4.3×	0.214	KRT1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
intermediate filament organization	2	160.5×	0.002	DSP, KRT1
cell-cell adhesion	2	67.7×	0.004	DSG1, DSP
ventricular compact myocardium morphogenesis	1	802.5×	0.007	DSP
bundle of His cell-Purkinje myocyte adhesion involved in cell communication	1	802.5×	0.007	DSP
desmosome organization	1	702.2×	0.007	DSP
protein localization to cell-cell junction	1	624.1×	0.007	DSP
complement activation, lectin pathway	1	561.7×	0.007	KRT1
peptide cross-linking	1	468.1×	0.007	DSP
regulation of ventricular cardiac muscle cell action potential	1	468.1×	0.007	DSP
epithelial cell-cell adhesion	1	401.2×	0.007	DSP
protein heterotetramerization	1	351.1×	0.007	KRT1
cornification	1	351.1×	0.007	KRT1
intermediate filament cytoskeleton organization	1	312.1×	0.007	DSP
maternal process involved in female pregnancy	1	312.1×	0.007	DSG1
fibrinolysis	1	280.9×	0.007	KRT1
adherens junction organization	1	170.2×	0.010	DSP
response to progesterone	1	165.2×	0.010	DSG1
calcium-dependent cell-cell adhesion	1	160.5×	0.010	DSG1
establishment of skin barrier	1	151.8×	0.010	KRT1
cell-cell junction assembly	1	147.8×	0.010	DSG1
skin development	1	147.8×	0.010	DSP
regulation of angiogenesis	1	140.4×	0.010	KRT1
regulation of heart rate by cardiac conduction	1	124.8×	0.011	DSP
keratinocyte differentiation	1	82.6×	0.016	DSP
keratinization	1	78.0×	0.016	KRT1
wound healing	1	75.9×	0.016	DSP
epidermis development	1	70.2×	0.016	DSP
homophilic cell-cell adhesion	1	46.8×	0.023	DSG1
negative regulation of inflammatory response	1	45.7×	0.023	KRT1
response to oxidative stress	1	43.5×	0.024	KRT1

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 1 · Undrugged: 2

Druggability breadth: 2 of 3 evidence-associated genes (67%) 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
DSP	0	0
KRT1	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
DSP	2	Binding:2

Pharmacogenomics

Cohort genes with a PharmGKB record: 3; 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	2	DSP, KRT1

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
DSP	2	DSG1
KRT1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.