palmoplantar keratoderma, Nagashima type

Summary

palmoplantar keratoderma, Nagashima type (MONDO:0014272) is a disease caused by SERPINB7 (GenCC Definitive), with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: SERPINB7 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 8
• Phenotypes (HPO): 2

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		40	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

2 HPO clinical features (Orphanet curated; top 2 by frequency):

HPO ID	Term	Frequency
HP:0000975	Hyperhidrosis	Very frequent (80-99%)
HP:0000982	Palmoplantar keratoderma	Very frequent (80-99%)

Identifiers

Disease identifiers

Field	Value
Canonical name	palmoplantar keratoderma, Nagashima type
Mondo ID	MONDO:0014272
OMIM	615598
Orphanet	140966
DOID	DOID:0070555
SNOMED CT	722205008
UMLS	C3810072
MedGen	816402
GARD	0016967
Is cancer (heuristic)	no

Also known as: palmoplantar hyperkeratosis, Nagashima type · palmoplantar keratoderma, Nagashima type · PPK, Nagashima type · PPKN

Data availability: 8 ClinVar variants · 5 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 › palmoplantar keratoderma, Nagashima 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, hereditary palmoplantar keratoderma, Gamborg-Nielsen type, 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, 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

8 retrieved; paginated sample, class counts are floors:

6 pathogenic, 1 benign, 1 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
102446	NM_003784.4(SERPINB7):c.796C>T (p.Arg266Ter)	SERPINB7	Pathogenic	criteria provided, multiple submitters, no conflicts
102447	NM_003784.4(SERPINB7):c.218_219delinsTAAACTTTACCT (p.Gln73fs)	SERPINB7	Pathogenic	criteria provided, single submitter
102448	NM_003784.4(SERPINB7):c.455-1G>A	SERPINB7	Pathogenic	no assertion criteria provided
1323576	NM_003784.4(SERPINB7):c.157C>T (p.Gln53Ter)	SERPINB7	Pathogenic	criteria provided, multiple submitters, no conflicts
1333198	NM_003784.4(SERPINB7):c.650_653del (p.Ser217fs)	SERPINB7	Pathogenic	criteria provided, multiple submitters, no conflicts
157566	NM_003784.4(SERPINB7):c.522dup (p.Val175fs)	SERPINB7	Pathogenic	criteria provided, multiple submitters, no conflicts
3583391	NM_003784.4(SERPINB7):c.716T>C (p.Val239Ala)	SERPINB7	Uncertain significance	criteria provided, single submitter
1225792	NM_003784.4(SERPINB7):c.797G>A (p.Arg266Gln)	SERPINB7	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · 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
SERPINB7	Definitive	Autosomal recessive	palmoplantar keratoderma, Nagashima type	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SERPINB7	Orphanet:140966	Palmoplantar keratoderma, Nagashima type

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
SERPINB7	HGNC:13902	ENSG00000166396	O75635	Serpin B7	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SERPINB7	Serpin B7	Might function as an inhibitor of Lys-specific proteases.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · 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	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SERPINB7	Other/Unknown	no		Serpin_fam, Serpin_CS, Serpin_dom

Expression context

Cohort genes with no expression data: 0.

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
penis	1
skin of leg	1
upper arm skin	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SERPINB7	139	broad	yes	upper arm skin, skin of leg, penis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SERPINB7	1,172

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
SERPINB7	O75635	89.91

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 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 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
positive regulation of platelet-derived growth factor production	1	8426.0×	5e-04	SERPINB7
positive regulation of transforming growth factor beta1 production	1	2808.7×	5e-04	SERPINB7
positive regulation of glomerular mesangial cell proliferation	1	2808.7×	5e-04	SERPINB7
positive regulation of collagen biosynthetic process	1	648.1×	0.002	SERPINB7

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 1 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
SERPINB7	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

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	1	SERPINB7

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
SERPINB7	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.