White sponge nevus 1

Summary

White sponge nevus 1 (MONDO:0008676) is a disease caused by KRT4 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: KRT4 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 83

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	white sponge nevus 1
Mondo ID	MONDO:0008676
OMIM	193900
DOID	DOID:0081287
UMLS	C4011926
MedGen	860363
GARD	0024637
Is cancer (heuristic)	no

Also known as: hereditary mucosal leukokeratosis caused by mutation in KRT4 · KRT4 hereditary mucosal leukokeratosis · white sponge nevus 1 · White sponge Nevus type 1 · WSN1

Data availability: 83 ClinVar variants · 3 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › integumentary system disorder › integumentary system benign neoplasm › benign neoplasm of skin › melanocytic nevus › hereditary mucosal leukokeratosis › white sponge nevus 1

Related subtypes (1): white sponge nevus 2

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

83 retrieved; paginated sample, class counts are floors:

29 benign, 23 uncertain significance, 12 likely benign, 11 conflicting classifications of pathogenicity, 5 benign/likely benign, 3 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
16918	NM_002272.4(KRT4):c.432CAA[2] (p.Asn146del)	KRT4	Pathogenic	no assertion criteria provided
16919	NM_002272.4(KRT4):c.419_420insCAA (p.Gln140delinsHisLys)	KRT4	Pathogenic	no assertion criteria provided
16920	NM_002272.4(KRT4):c.1303G>A (p.Glu435Lys)	KRT4	Pathogenic	no assertion criteria provided
309667	NM_002272.4(KRT4):c.1495G>C (p.Gly499Arg)	KRT4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
309668	NM_002272.4(KRT4):c.1493T>C (p.Phe498Ser)	KRT4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
309672	NM_002272.4(KRT4):c.1259G>A (p.Arg420His)	KRT4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
309682	NM_002272.4(KRT4):c.766G>A (p.Val256Met)	KRT4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
309692	NM_002272.4(KRT4):c.527C>T (p.Thr176Met)	KRT4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
309694	NM_002272.4(KRT4):c.475G>A (p.Glu159Lys)	KRT4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
881186	NM_002272.4(KRT4):c.983C>T (p.Ala328Val)	KRT4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
881235	NM_002272.4(KRT4):c.359C>A (p.Thr120Asn)	KRT4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
881697	NM_002272.4(KRT4):c.193G>A (p.Val65Met)	KRT4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
881698	NM_002272.4(KRT4):c.31G>A (p.Gly11Arg)	KRT4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
883597	NM_002272.4(KRT4):c.361C>A (p.Pro121Thr)	KRT4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
309658	NM_002272.4(KRT4):c.*405G>A	KRT4	Uncertain significance	criteria provided, single submitter
309659	NM_002272.4(KRT4):c.*289G>A	KRT4	Uncertain significance	criteria provided, single submitter
309662	NM_002272.4(KRT4):c.*126C>A	KRT4	Uncertain significance	criteria provided, single submitter
309683	NM_002272.4(KRT4):c.741C>G (p.Asp247Glu)	KRT4	Uncertain significance	criteria provided, multiple submitters, no conflicts
309684	NM_002272.4(KRT4):c.726G>A (p.Val242=)	KRT4	Uncertain significance	criteria provided, single submitter
309686	NM_002272.4(KRT4):c.678-10C>T	KRT4	Uncertain significance	criteria provided, single submitter
309688	NM_002272.4(KRT4):c.677+4C>T	KRT4	Uncertain significance	criteria provided, single submitter
309697	NM_002272.4(KRT4):c.463-9T>C	KRT4	Uncertain significance	criteria provided, single submitter
309698	NM_002272.4(KRT4):c.457G>A (p.Asp153Asn)	KRT4	Uncertain significance	criteria provided, multiple submitters, no conflicts
309700	NM_002272.4(KRT4):c.405G>A (p.Thr135=)	KRT4	Uncertain significance	criteria provided, single submitter
309702	NM_002272.4(KRT4):c.364C>G (p.Leu122Val)	KRT4	Uncertain significance	criteria provided, single submitter
309703	NM_002272.4(KRT4):c.353T>G (p.Leu118Trp)	KRT4	Uncertain significance	criteria provided, single submitter
309711	NM_002272.4(KRT4):c.186C>T (p.Ser62=)	KRT4	Uncertain significance	criteria provided, single submitter
309713	NM_002272.4(KRT4):c.54C>G (p.Gly18=)	KRT4	Uncertain significance	criteria provided, single submitter
309714	NM_002272.4(KRT4):c.25C>G (p.Arg9Gly)	KRT4	Uncertain significance	criteria provided, single submitter
3891527	NM_002272.4(KRT4):c.412C>T (p.Arg138Cys)	KRT4	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · 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
KRT4	Strong	Autosomal dominant	white sponge nevus 1	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
KRT4	Orphanet:171723	White sponge nevus

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
KRT4	HGNC:6441	ENSG00000170477	P19013	Keratin, type II cytoskeletal 4	gencc,clinvar

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)
KRT4	Other/Unknown	no		Keratin_II, IF_conserved, Keratin_2_head

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 mucosa	1
pharyngeal mucosa	1
tongue squamous epithelium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
KRT4	179	tissue_specific	marker	tongue squamous epithelium, pharyngeal mucosa, lower esophagus mucosa

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
KRT4	1,660

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
KRT4	P19013	71.77

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. 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
Formation of the cornified envelope	1	87.8×	0.027	KRT4
Keratinization	1	55.7×	0.027	KRT4
Developmental Biology	1	14.5×	0.069	KRT4

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 epithelial cell proliferation	1	290.6×	0.007	KRT4
intermediate filament organization	1	240.7×	0.007	KRT4
keratinization	1	234.1×	0.007	KRT4
epithelial cell differentiation	1	175.5×	0.007	KRT4
cytoskeleton organization	1	132.7×	0.008	KRT4

Therapeutics

Drug target analysis

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

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

Top cohort targets by molecule count

Symbol	Molecules	Max phase
KRT4	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
KRT4	1	Binding:1

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	KRT4

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)
KRT4	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.