Palmoplantar keratosis

Summary

Palmoplantar keratosis (MONDO:0006590) is a disease caused by KRT1 (GenCC Strong), with 2 cohort genes and 3 clinical trials. Top therapeutic interventions include erlotinib and tapinarof.

At a glance

• Causal gene: KRT1 (GenCC Strong)
• Cohort genes: 2
• Clinical trials: 3

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	palmoplantar keratosis
Mondo ID	MONDO:0006590
EFO	EFO:1000745
DOID	DOID:3390
NCIT	C34748
SNOMED CT	706885006
UMLS	C0022596
MedGen	44017
Is cancer (heuristic)	no

Also known as: keratoderma, palmoplantar · palmoplantar keratoderma

Data availability: 2 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

Related subtypes (8): keratosis follicularis spinulosa decalvans, acquired keratosis, cholesteatoma, porokeratosis, hereditary papulotranslucent acrokeratoderma, acrokeratosis verruciformis, seborrheic keratosis, trichostasis spinulosa

Subtypes (2): hereditary palmoplantar keratoderma, aquagenic palmoplantar keratoderma

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: 26 · Orphanet: 9 · 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
KRT1	Strong	Autosomal dominant	diffuse nonepidermolytic palmoplantar keratoderma	18
SLURP1	Supportive	Autosomal recessive	hereditary palmoplantar keratoderma, Gamborg-Nielsen type	8

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SLURP1	Orphanet:87503	Mal de Meleda
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

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SLURP1	HGNC:18746	ENSG00000126233	P55000	Secreted Ly-6/uPAR-related protein 1	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)
SLURP1	Secreted Ly-6/uPAR-related protein 1	Has an antitumor activity.
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: 0 · 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
Other/Unknown	2	1.8×	0.312

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SLURP1	Other/Unknown	no		LY6_UPA_recep-like, Snake_toxin-like_sf, Ly-6/neurotoxin-like_GPI-ap
KRT1	Other/Unknown	no		Keratin_II, IF_conserved, Keratin_2_head

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
esophagus mucosa	1
lower esophagus mucosa	1
skin of leg	1
mammalian vulva	1
skin of hip	1
upper leg skin	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SLURP1	155	tissue_specific	marker	lower esophagus mucosa, skin of leg, esophagus mucosa
KRT1	177	tissue_specific	marker	mammalian vulva, upper leg skin, skin of hip

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
KRT1	2,716
SLURP1	749

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
KRT1	P04264	3
SLURP1	P55000	2

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 10. Enrichment computed across 2 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
Regulation of FXIIa and plasma kallikrein activity	1	1142.0×	0.009	KRT1
Differentiation of Keratinocytes in Interfollicular Epidermis in Mammalian Skin	1	278.5×	0.014	KRT1
Developmental Cell Lineages	1	223.9×	0.014	KRT1
FXIIa activates plasma kallikrein-kinin system	1	173.0×	0.014	KRT1
Formation of the cornified envelope	1	87.8×	0.023	KRT1
Keratinization	1	55.7×	0.030	KRT1
Innate Immune System	1	25.5×	0.054	KRT1
Neutrophil degranulation	1	23.1×	0.054	KRT1
Developmental Biology	1	14.5×	0.077	KRT1
Immune System	1	13.0×	0.077	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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
urokinase plasminogen activator signaling pathway	1	2106.5×	0.006	SLURP1
cell activation	1	842.6×	0.006	SLURP1
complement activation, lectin pathway	1	842.6×	0.006	KRT1
neuromuscular process controlling posture	1	526.6×	0.006	SLURP1
protein heterotetramerization	1	526.6×	0.006	KRT1
cornification	1	526.6×	0.006	KRT1
fibrinolysis	1	421.3×	0.006	KRT1
negative regulation of keratinocyte proliferation	1	351.1×	0.006	SLURP1
establishment of skin barrier	1	227.7×	0.009	KRT1
regulation of angiogenesis	1	210.7×	0.009	KRT1
intermediate filament organization	1	120.4×	0.013	KRT1
keratinization	1	117.0×	0.013	KRT1
locomotory behavior	1	89.6×	0.015	SLURP1
negative regulation of inflammatory response	1	68.5×	0.018	KRT1
response to oxidative stress	1	65.3×	0.018	KRT1
negative regulation of cell migration	1	55.8×	0.020	SLURP1
negative regulation of cell population proliferation	1	21.1×	0.050	SLURP1
cell adhesion	1	18.7×	0.053	SLURP1

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 2 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
SLURP1	0	0
KRT1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

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	2	SLURP1, 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)
SLURP1	0	—
KRT1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 3.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE1/PHASE2	1
PHASE2	1
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT06545695	PHASE1/PHASE2	NOT_YET_RECRUITING	Epidermal Growth Factor Receptor Inhibition for Keratinopathies
NCT06561321	PHASE2	RECRUITING	Study to Evaluate the Safety and Efficacy of Tapinarof in Adults With Palmoplantar Keratoderma
NCT05954416	Not specified	RECRUITING	FARD (RaDiCo Cohort) (RaDiCo-FARD)

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
ERLOTINIB	4	1
TAPINAROF	4	1