Punctate palmoplantar keratoderma type 2

Summary

Punctate palmoplantar keratoderma type 2 (MONDO:0008292) is a disease with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 1
• ClinVar variants: 1

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		13	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	punctate palmoplantar keratoderma type 2
Mondo ID	MONDO:0008292
OMIM	175860
Orphanet	79502
DOID	DOID:0080213
SNOMED CT	765096001
UMLS	C1867982
MedGen	356886
GARD	0004439
Is cancer (heuristic)	no

Also known as: keratoderma palmoplantar, punctate type 2 · palmoplantar keratoderma, punctate type II · PPKP2 · PPPP · punctate palmoplantar hyperkeratosis type 2 · type 2 punctate PPK

Data availability: 1 ClinVar variant.

Disease family

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 2

Related subtypes (3): punctate palmoplantar keratoderma type III, focal acral hyperkeratosis, punctate palmoplantar keratoderma type 1

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

1 retrieved; paginated sample, class counts are floors:

1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
17677	NM_007294.4(BRCA1):c.5266dup (p.Gln1756fs)	BRCA1	Pathogenic	reviewed by expert panel

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 9 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
BRCA1	Orphanet:1331	Familial prostate cancer
BRCA1	Orphanet:1333	Familial pancreatic carcinoma
BRCA1	Orphanet:145	Hereditary breast and/or ovarian cancer syndrome
BRCA1	Orphanet:168829	Primary peritoneal carcinoma
BRCA1	Orphanet:227535	Hereditary breast cancer
BRCA1	Orphanet:667662	Breast implant-associated anaplastic large cell lymphoma
BRCA1	Orphanet:694963	Inflammatory breast cancer
BRCA1	Orphanet:70567	Cholangiocarcinoma
BRCA1	Orphanet:84	Fanconi anemia

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
BRCA1	HGNC:1100	ENSG00000012048	P38398	Breast cancer type 1 susceptibility protein	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
BRCA1	Breast cancer type 1 susceptibility protein	E3 ubiquitin-protein ligase that specifically mediates the formation of ‘Lys-6’-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 0 · 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
Transcription factor	1	8.3×	0.121

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
BRCA1	Transcription factor	no	2.3.2.27	BRCT_dom, Znf_RING, BRCA1

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)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
male germ line stem cell (sensu Vertebrata) in testis	1
primordial germ cell in gonad	1
ventricular zone	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
BRCA1	208	ubiquitous	marker	ventricular zone, male germ line stem cell (sensu Vertebrata) in testis, primordial germ cell in gonad

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
BRCA1	9,064

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
BRCA1	P38398	33

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 59. Enrichment computed across 1 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
Defective DNA double strand break response due to BRCA1 loss of function	1	5710.0×	0.005	BRCA1
Defective DNA double strand break response due to BARD1 loss of function	1	5710.0×	0.005	BRCA1
Regulation of MITF-M-dependent genes involved in DNA replication, damage repair and senescence	1	1631.4×	0.009	BRCA1
Defective homologous recombination repair (HRR) due to PALB2 loss of function	1	951.7×	0.009	BRCA1
Diseases of DNA Double-Strand Break Repair	1	815.7×	0.009	BRCA1
Defective homologous recombination repair (HRR) due to BRCA2 loss of function	1	815.7×	0.009	BRCA1
Resolution of D-Loop Structures	1	634.4×	0.009	BRCA1
Diseases of DNA repair	1	571.0×	0.009	BRCA1
DNA Double Strand Break Response	1	475.8×	0.009	BRCA1
Impaired BRCA2 binding to PALB2	1	456.8×	0.009	BRCA1
Defective homologous recombination repair (HRR) due to BRCA1 loss of function	1	423.0×	0.009	BRCA1
Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA1 binding function	1	423.0×	0.009	BRCA1
Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA2/RAD51/RAD51C binding function	1	423.0×	0.009	BRCA1
Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA)	1	393.8×	0.009	BRCA1
Homologous DNA Pairing and Strand Exchange	1	380.7×	0.009	BRCA1
Homology Directed Repair	1	308.6×	0.009	BRCA1
HDR through Homologous Recombination (HRR) or Single Strand Annealing (SSA)	1	308.6×	0.009	BRCA1
Impaired BRCA2 binding to RAD51	1	308.6×	0.009	BRCA1
Metalloprotease DUBs	1	300.5×	0.009	BRCA1
Resolution of D-loop Structures through Holliday Junction Intermediates	1	300.5×	0.009	BRCA1
HDR through Single Strand Annealing (SSA)	1	292.8×	0.009	BRCA1
Transcriptional Regulation by E2F6	1	292.8×	0.009	BRCA1
Meiosis	1	285.5×	0.009	BRCA1
Presynaptic phase of homologous DNA pairing and strand exchange	1	271.9×	0.009	BRCA1
DNA Double-Strand Break Repair	1	248.3×	0.010	BRCA1
Reproduction	1	190.3×	0.011	BRCA1
HDR through Homologous Recombination (HRR)	1	190.3×	0.011	BRCA1
TP53 Regulates Transcription of DNA Repair Genes	1	181.3×	0.011	BRCA1
MITF-M-dependent gene expression	1	181.3×	0.011	BRCA1
SUMO E3 ligases SUMOylate target proteins	1	178.4×	0.011	BRCA1

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
cellular response to indole-3-methanol	1	3370.4×	0.004	BRCA1
chordate embryonic development	1	2808.7×	0.004	BRCA1
negative regulation of centriole replication	1	2407.4×	0.004	BRCA1
DNA strand resection involved in replication fork processing	1	2106.5×	0.004	BRCA1
DNA damage tolerance	1	1685.2×	0.004	BRCA1
homologous recombination	1	1404.3×	0.004	BRCA1
negative regulation of intracellular estrogen receptor signaling pathway	1	1123.5×	0.004	BRCA1
regulation of DNA damage checkpoint	1	1123.5×	0.004	BRCA1
negative regulation of gene expression via chromosomal CpG island methylation	1	1053.2×	0.004	BRCA1
protein K6-linked ubiquitination	1	991.3×	0.004	BRCA1
random inactivation of X chromosome	1	936.2×	0.004	BRCA1
negative regulation of reactive oxygen species metabolic process	1	936.2×	0.004	BRCA1
negative regulation of fatty acid biosynthetic process	1	887.0×	0.004	BRCA1
mitotic G2/M transition checkpoint	1	802.5×	0.004	BRCA1
negative regulation of extrinsic apoptotic signaling pathway via death domain receptors	1	581.1×	0.005	BRCA1
positive regulation of vascular endothelial growth factor production	1	495.6×	0.005	BRCA1
mitotic G2 DNA damage checkpoint signaling	1	443.5×	0.005	BRCA1
response to ionizing radiation	1	411.0×	0.005	BRCA1
cellular response to ionizing radiation	1	411.0×	0.005	BRCA1
positive regulation of DNA repair	1	358.6×	0.006	BRCA1
fatty acid biosynthetic process	1	351.1×	0.006	BRCA1
centrosome cycle	1	337.0×	0.006	BRCA1
intrinsic apoptotic signaling pathway in response to DNA damage	1	324.1×	0.006	BRCA1
negative regulation of cell cycle	1	290.6×	0.006	BRCA1
regulation of DNA repair	1	276.3×	0.006	BRCA1
protein autoubiquitination	1	234.1×	0.007	BRCA1
double-strand break repair	1	203.0×	0.008	BRCA1
chromosome segregation	1	173.7×	0.009	BRCA1
cellular response to tumor necrosis factor	1	163.6×	0.009	BRCA1
double-strand break repair via homologous recombination	1	156.0×	0.009	BRCA1

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
BRCA1	RIBOFLAVIN

Top cohort targets by molecule count

Symbol	Molecules	Max phase
BRCA1	12	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
RIBOFLAVIN	4	BRCA1
DAUNORUBICIN HYDROCHLORIDE	4	BRCA1
TOPOTECAN HYDROCHLORIDE	4	BRCA1
DAUNORUBICIN	4	BRCA1
DOXORUBICIN HYDROCHLORIDE	4	BRCA1
MESALAMINE	4	BRCA1
DIPYRIDAMOLE	4	BRCA1
CURCUMIN	3	BRCA1
SURAMIN	3	BRCA1
SURAMIN HEXASODIUM	3	BRCA1
SODIUM TANSHINONE IIA SULFONATE	2	BRCA1
HOMIDIUM BROMIDE	2	BRCA1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
BRCA1	13	Binding:9, Functional:4

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
BRCA1	2.3.2.27	RING-type E3 ubiquitin transferase

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

12 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)
RIBOFLAVIN	4	BRCA1
DAUNORUBICIN HYDROCHLORIDE	4	BRCA1
TOPOTECAN HYDROCHLORIDE	4	BRCA1
DAUNORUBICIN	4	BRCA1
DOXORUBICIN HYDROCHLORIDE	4	BRCA1
MESALAMINE	4	BRCA1
DIPYRIDAMOLE	4	BRCA1
CURCUMIN	3	BRCA1
SURAMIN	3	BRCA1
SURAMIN HEXASODIUM	3	BRCA1
SODIUM TANSHINONE IIA SULFONATE	2	BRCA1
HOMIDIUM BROMIDE	2	BRCA1

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	BRCA1
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	0

Undrugged target profiles

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

Clinical trials & evidence

Clinical trials

Clinical trials: 0.