Wooly hair-palmoplantar keratoderma syndrome

Summary

Wooly hair-palmoplantar keratoderma syndrome (MONDO:0014492) is a disease with 1 cohort gene.

At a glance

• Prevalence: (Worldwide) [Orphanet-validated]
• Cohort genes: 1
• ClinVar variants: 10

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		8	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Not yet validated

Identifiers

Disease identifiers

Field	Value
Canonical name	wooly hair-palmoplantar keratoderma syndrome
Mondo ID	MONDO:0014492
OMIM	616099
Orphanet	420686
DOID	DOID:0070554
SNOMED CT	764108000
UMLS	C4015202
MedGen	863639
GARD	0017697
Is cancer (heuristic)	no

Also known as: keratoderma with woolly hair type IV · keratoderma with wooly hair type IV · KWWH type IV · palmoplantar keratoderma and woolly hair · palmoplantar keratoderma and wooly hair · PPKWH · woolly hair-palmoplantar hyperkeratosis syndrome · wooly hair-palmoplantar hyperkeratosis syndrome

Data availability: 10 ClinVar variants · 4 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 › focal palmoplantar keratoderma › wooly hair-palmoplantar keratoderma syndrome

Related subtypes (11): hereditary painful callosities, palmoplantar keratoderma-esophageal carcinoma syndrome, focal palmoplantar and gingival keratoderma, tyrosinemia type II, hypotrichosis-osteolysis-periodontitis-palmoplantar keratoderma syndrome, palmoplantar keratoderma, nonepidermolytic, focal 1, nail and teeth abnormalities-marginal palmoplantar keratoderma-oral hyperpigmentation syndrome, isolated focal non-epidermolytic palmoplantar keratoderma, pachyonychia congenita, focal palmoplantar keratoderma with joint keratoses, striate 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

ClinVar germline variants

10 retrieved; paginated sample, class counts are floors:

5 uncertain significance, 2 benign/likely benign, 1 conflicting classifications of pathogenicity, 1 pathogenic, 1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
158088	NM_001136191.3(KANK2):c.2009C>T (p.Ala670Val)	KANK2	Pathogenic	no assertion criteria provided
1510116	NM_001136191.3(KANK2):c.1138C>T (p.Arg380Cys)	KANK2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1356217	NM_001136191.3(KANK2):c.1369C>T (p.Pro457Ser)	KANK2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1394568	NM_001136191.3(KANK2):c.2543C>T (p.Ser848Leu)	KANK2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1432926	NM_001136191.3(KANK2):c.1504G>A (p.Val502Met)	KANK2	Uncertain significance	criteria provided, multiple submitters, no conflicts
3583402	NM_001136191.3(KANK2):c.2282G>A (p.Cys761Tyr)	KANK2	Uncertain significance	criteria provided, single submitter
3583403	NM_001136191.3(KANK2):c.749T>G (p.Leu250Arg)	KANK2	Uncertain significance	criteria provided, single submitter
1317914	NM_001136191.3(KANK2):c.2502+15G>A	KANK2	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
715318	NM_001136191.3(KANK2):c.1038C>T (p.Ala346=)	KANK2	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
774524	NM_001136191.3(KANK2):c.10G>A (p.Val4Ile)	KANK2	Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · 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
KANK2	Supportive	Autosomal recessive	wooly hair-palmoplantar keratoderma syndrome	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
KANK2	Orphanet:420686	Woolly hair-palmoplantar keratoderma syndrome
KANK2	Orphanet:656	Hereditary steroid-resistant nephrotic syndrome

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
KANK2	HGNC:29300	ENSG00000197256	Q63ZY3	KN motif and ankyrin repeat domain-containing protein 2	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
KANK2	KN motif and ankyrin repeat domain-containing protein 2	Involved in transcription regulation by sequestering in the cytoplasm nuclear receptor coactivators such as NCOA1, NCOA2 and NCOA3.

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
Scaffold/PPI	1	17.3×	0.058

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
KANK2	Scaffold/PPI	no		Ankyrin_rpt, KN_motif, Ankyrin_rpt-contain_sf

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
lower esophagus muscularis layer	1
mucosa of stomach	1
saphenous vein	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
KANK2	276	ubiquitous	marker	saphenous vein, mucosa of stomach, lower esophagus muscularis layer

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
KANK2	2,918

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
KANK2	Q63ZY3	3

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
negative regulation of vitamin D receptor signaling pathway	1	8426.0×	7e-04	KANK2
kidney epithelium development	1	8426.0×	7e-04	KANK2
podocyte cell migration	1	2407.4×	0.002	KANK2
negative regulation of intracellular estrogen receptor signaling pathway	1	1123.5×	0.002	KANK2
negative regulation of actin filament polymerization	1	936.2×	0.002	KANK2
negative regulation of programmed cell death	1	732.7×	0.003	KANK2
regulation of Rho protein signal transduction	1	510.7×	0.003	KANK2
negative regulation of G1/S transition of mitotic cell cycle	1	358.6×	0.004	KANK2
negative regulation of cell population proliferation	1	42.1×	0.029	KANK2
apoptotic process	1	28.7×	0.038	KANK2
negative regulation of transcription by RNA polymerase II	1	17.7×	0.056	KANK2

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
KANK2	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	KANK2

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)
KANK2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.