hereditary palmoplantar keratoderma, Gamborg-Nielsen type

Summary

hereditary palmoplantar keratoderma, Gamborg-Nielsen type (MONDO:0009489) is a disease with 2 cohort genes.

At a glance

• Cohort genes: 2
• ClinVar variants: 2

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	hereditary palmoplantar keratoderma, Gamborg-Nielsen type
Mondo ID	MONDO:0009489
MeSH	C565454
OMIM	244850
Orphanet	86923
SNOMED CT	717228004
GARD	0016767
Is cancer (heuristic)	no

Also known as: hereditary palmoplantar hyperkeratosis, Gamborg-Nielsen type · palmoplantar keratoderma, Norrbotten recessive type · PPK, Gamborg-Nielsen type · PPKNR

Data availability: 2 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › integumentary system disorder › skin disorder › keratosis › palmoplantar keratosis › hereditary palmoplantar keratoderma › diffuse palmoplantar keratoderma › hereditary palmoplantar keratoderma, Gamborg-Nielsen type

Related subtypes (31): autosomal dominant palmoplantar keratoderma and congenital alopecia, dermatopathia pigmentosa reticularis, Clouston syndrome, epidermolytic palmoplantar keratoderma, 1, palmoplantar keratoderma-deafness syndrome, palmoplantar keratoderma-hereditary motor and sensory neuropathy syndrome, keratosis palmaris et plantaris-clinodactyly syndrome, Bart-Pumphrey syndrome, Naegeli-Franceschetti-Jadassohn syndrome, palmoplantar keratoderma-sclerodactyly syndrome, autosomal recessive palmoplantar keratoderma and congenital alopecia, Schöpf-Schulz-Passarge syndrome, Papillon-Lefevre disease, Haim-Munk syndrome, mal de Meleda, odonto-onycho-dermal dysplasia, palmoplantar keratoderma, Bothnian type, diffuse nonepidermolytic palmoplantar keratoderma, loricrin keratoderma, skin fragility-woolly hair-palmoplantar keratoderma syndrome, Curly hair - acral keratoderma - caries syndrome, CEDNIK syndrome, palmoplantar keratoderma-XX sex reversal-predisposition to squamous cell carcinoma syndrome, corneal intraepithelial dyskeratosis-palmoplantar hyperkeratosis-laryngeal dyskeratosis syndrome, hypohidrosis-enamel hypoplasia-palmoplantar keratoderma-intellectual disability syndrome, palmoplantar keratoderma, Nagashima type, erythrokeratodermia variabilis, diffuse palmoplantar keratoderma with painful fissures, KID syndrome, diffuse palmoplantar keratoderma - acrocyanosis syndrome, hearing loss with skin disease

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 likely benign, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
2574604	NM_001382267.1(SERPINA12):c.1051G>T (p.Glu351Ter)	SERPINA12	Pathogenic	no assertion criteria provided
2574603	NM_001382267.1(SERPINA12):c.631C>T (p.Arg211Ter)	SERPINA12	Likely benign	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 9 · 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
SERPINA12	Supportive	Autosomal recessive	hereditary palmoplantar keratoderma, Gamborg-Nielsen type
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

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
SERPINA12	HGNC:18359	ENSG00000165953	Q8IW75	Serpin A12	gencc,clinvar
SLURP1	HGNC:18746	ENSG00000126233	P55000	Secreted Ly-6/uPAR-related protein 1	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SERPINA12	Serpin A12	Adipokine that modulates insulin action by specifically inhibiting its target protease KLK7 in white adipose tissues.
SLURP1	Secreted Ly-6/uPAR-related protein 1	Has an antitumor activity.

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)
SERPINA12	Other/Unknown	no		Serpin_fam, Serpin_dom, Serpin_sf
SLURP1	Other/Unknown	no		LY6_UPA_recep-like, Snake_toxin-like_sf, Ly-6/neurotoxin-like_GPI-ap

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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
skin of leg	2
upper leg skin	1
zone of skin	1
esophagus mucosa	1
lower esophagus mucosa	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SERPINA12	120		yes	skin of leg, upper leg skin, zone of skin
SLURP1	155	tissue_specific	marker	lower esophagus mucosa, skin of leg, esophagus mucosa

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SERPINA12	1,098
SLURP1	749

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SERPINA12	Q8IW75	5
SLURP1	P55000	2

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 2 evidence-associated genes (0 with Reactome annotation).

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×	0.005	SLURP1
negative regulation of lipid biosynthetic process	1	1685.2×	0.005	SERPINA12
regulation of triglyceride metabolic process	1	1053.2×	0.005	SERPINA12
cell activation	1	842.6×	0.005	SLURP1
regulation of cholesterol metabolic process	1	561.7×	0.005	SERPINA12
neuromuscular process controlling posture	1	526.6×	0.005	SLURP1
lipid biosynthetic process	1	495.6×	0.005	SERPINA12
positive regulation of insulin receptor signaling pathway	1	421.3×	0.005	SERPINA12
negative regulation of gluconeogenesis	1	401.2×	0.005	SERPINA12
negative regulation of keratinocyte proliferation	1	351.1×	0.005	SLURP1
gluconeogenesis	1	162.0×	0.010	SERPINA12
phosphatidylinositol 3-kinase/protein kinase B signal transduction	1	105.3×	0.013	SERPINA12
locomotory behavior	1	89.6×	0.015	SLURP1
negative regulation of cell migration	1	55.8×	0.022	SLURP1
positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	1	39.2×	0.029	SERPINA12
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
SERPINA12	0	0
SLURP1	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	SERPINA12, SLURP1

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)
SERPINA12	0	—
SLURP1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.