Punctate palmoplantar keratoderma type 1

Summary

Punctate palmoplantar keratoderma type 1 (MONDO:0019332) is a disease with 2 cohort genes and 2 clinical trials.

At a glance

• Prevalence: 1-9 / 100 000 (Europe) [Orphanet-validated]
• Cohort genes: 2
• Phenotypes (HPO): 25
• Clinical trials: 2

Clinical features

Epidemiology

Prevalence records

4 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		437	Worldwide	Validated
Point prevalence	1-9 / 100 000	2.22	Europe	Validated
Point prevalence	1-9 / 100 000	1.17	Croatia	Validated
Point prevalence	1-9 / 100 000	3.3	Slovenia	Validated

Signs & symptoms

Clinical features (HPO)

25 HPO clinical features (Orphanet curated; top 25 by frequency):

HPO ID	Term	Frequency
HP:0000972	Palmoplantar hyperkeratosis	Very frequent (80-99%)
HP:0000982	Palmoplantar keratoderma	Very frequent (80-99%)
HP:0011124	Abnormality of epidermal morphology	Very frequent (80-99%)
HP:0045059	Hyperkeratotic papule	Very frequent (80-99%)
HP:0025092	Epidermal acanthosis	Frequent (30-79%)
HP:0025114	Hypergranulosis	Frequent (30-79%)
HP:0040162	Orthokeratosis	Frequent (30-79%)
HP:0002861	Melanoma	Occasional (5-29%)
HP:0003002	Breast carcinoma	Occasional (5-29%)
HP:0012500	Verrucous papule	Occasional (5-29%)
HP:0012531	Pain	Occasional (5-29%)
HP:0100751	Esophageal neoplasm	Occasional (5-29%)
HP:0002671	Basal cell carcinoma	Very rare (<1-4%)
HP:0002860	Squamous cell carcinoma	Very rare (<1-4%)
HP:0005584	Renal cell carcinoma	Very rare (<1-4%)
HP:0006725	Pancreatic adenocarcinoma	Very rare (<1-4%)
HP:0008404	Nail dystrophy	Very rare (<1-4%)
HP:0010622	Neoplasm of the skeletal system	Very rare (<1-4%)
HP:0012125	Prostate cancer	Very rare (<1-4%)
HP:0012126	Stomach cancer	Very rare (<1-4%)
HP:0012189	Hodgkin lymphoma	Very rare (<1-4%)
HP:0030692	Brain neoplasm	Very rare (<1-4%)
HP:0040274	Adenocarcinoma of the small intestine	Very rare (<1-4%)
HP:0040276	Adenocarcinoma of the colon	Very rare (<1-4%)
HP:0100526	Neoplasm of the lung	Very rare (<1-4%)

Identifiers

Disease identifiers

Field	Value
Canonical name	punctate palmoplantar keratoderma type 1
Mondo ID	MONDO:0019332
Orphanet	79501
SNOMED CT	717184007
UMLS	C1835662
MedGen	372099
GARD	0003103
Is cancer (heuristic)	no

Also known as: Brauer-Buschke-Fischer syndrome · Buschke-Fischer-Brauer syndrome · keratoderma, palmoplantar punctate type 1 · keratodermia palmoplantaris papulosa, Buschke-Fischer-Brauer type · PPKP1 · punctate palmoplantar keratoderma type I · type I punctate 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 › hereditary palmoplantar keratoderma › punctate palmoplantar keratoderma › punctate palmoplantar keratoderma type 1

Related subtypes (3): punctate palmoplantar keratoderma type III, punctate palmoplantar keratoderma type 2, focal acral hyperkeratosis

Subtypes (2): palmoplantar keratoderma, punctate type 1A, palmoplantar keratoderma, punctate type ib

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: 9 · Orphanet: 2 · 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
AAGAB	Definitive	Autosomal dominant	palmoplantar keratoderma, punctate type 1A	7
COL14A1	Supportive	Autosomal dominant	punctate palmoplantar keratoderma type 1	2

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
COL14A1	Orphanet:79501	Punctate palmoplantar keratoderma type 1
AAGAB	Orphanet:79501	Punctate palmoplantar keratoderma type 1

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
COL14A1	HGNC:2191	ENSG00000187955	Q05707	Collagen alpha-1(XIV) chain	gencc
AAGAB	HGNC:25662	ENSG00000103591	Q6PD74	Alpha- and gamma-adaptin-binding protein p34	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
COL14A1	Collagen alpha-1(XIV) chain	Plays an adhesive role by integrating collagen bundles.
AAGAB	Alpha- and gamma-adaptin-binding protein p34	May be involved in endocytic recycling of growth factor receptors such as EGFR.

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
Antibody/Immunoglobulin	1	14.6×	0.135
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
COL14A1	Antibody/Immunoglobulin	yes		VWF_A, FN3_dom, Collagen
AAGAB	Other/Unknown	no		Alpha/Gamma-adaptin-bd_p34

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
descending thoracic aorta	1
popliteal artery	1
right coronary artery	1
islet of Langerhans	1
mucosa of transverse colon	1
rectum	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
COL14A1	245	broad	marker	descending thoracic aorta, right coronary artery, popliteal artery
AAGAB	282	ubiquitous	marker	islet of Langerhans, rectum, mucosa of transverse colon

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
COL14A1	1,991
AAGAB	931

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
AAGAB	Q6PD74	3

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
COL14A1	Q05707	74.06

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 4. 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
Collagen chain trimerization	1	259.6×	0.006	COL14A1
Assembly of collagen fibrils and other multimeric structures	1	200.3×	0.006	COL14A1
Collagen degradation	1	175.7×	0.006	COL14A1
Collagen biosynthesis and modifying enzymes	1	170.4×	0.006	COL14A1

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
regulation of cell growth involved in cardiac muscle cell development	1	8426.0×	8e-04	COL14A1
ventricular cardiac muscle tissue development	1	1053.2×	0.003	COL14A1
homeostasis of number of cells within a tissue	1	221.7×	0.011	COL14A1
collagen fibril organization	1	112.3×	0.016	COL14A1
extracellular matrix organization	1	61.1×	0.023	COL14A1
cell-cell adhesion	1	50.8×	0.023	COL14A1
protein transport	1	21.9×	0.045	AAGAB

Therapeutics

Drug target analysis

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

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
COL14A1	0	0
AAGAB	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
COL14A1	1	Binding:1

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	1	COL14A1
E	Difficult family or no structure, no drug	1	AAGAB

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)
COL14A1	1	—
AAGAB	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 2.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE1	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05435638	PHASE1	COMPLETED	Study Designed to Evaluate Safety and Efficacy of 1% Topical Formulation of KM-001 on Type 1 Punctate Palmoplantar Keratoderma or Pachyonychia Congenita Diseases
NCT05956314	PHASE1	COMPLETED	Assessment of KM-001 - Safety, Tolerability, and Efficacy in Patients With PPPK1 or PC