White sponge nevus 2

Summary

White sponge nevus 2 (MONDO:0014346) is a disease caused by KRT13 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: KRT13 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 59

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	white sponge nevus 2
Mondo ID	MONDO:0014346
OMIM	615785
DOID	DOID:0081288
UMLS	C4014321
MedGen	862758
GARD	0016012
Is cancer (heuristic)	no

Also known as: white sponge nevus 2 · White sponge Nevus type 2 · WSN2

Data availability: 59 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 2

Related subtypes (1): white sponge nevus 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

59 retrieved; paginated sample, class counts are floors:

32 benign, 16 uncertain significance, 5 likely benign, 4 conflicting classifications of pathogenicity, 2 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
14629	NM_153490.3(KRT13):c.356T>C (p.Leu119Pro)	KRT13	Pathogenic	no assertion criteria provided
66751	NM_153490.3(KRT13):c.332T>C (p.Leu111Pro)	KRT13	Pathogenic	no assertion criteria provided
323078	NM_153490.3(KRT13):c.1217G>T (p.Arg406Leu)	KRT13	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
323086	NM_153490.3(KRT13):c.844G>A (p.Glu282Lys)	KRT13	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
323089	NM_153490.3(KRT13):c.766G>A (p.Gly256Ser)	KRT13	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
323098	NM_153490.3(KRT13):c.509C>G (p.Thr170Ser)	KRT13	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
323069	NM_153490.3(KRT13):c.*228C>G	KRT13	Uncertain significance	criteria provided, single submitter
323072	NM_153490.3(KRT13):c.*85C>T	KRT13	Uncertain significance	criteria provided, single submitter
323073	NM_153490.3(KRT13):c.*74A>C	KRT13	Uncertain significance	criteria provided, single submitter
323082	NM_153490.3(KRT13):c.991C>T (p.Leu331=)	KRT13	Uncertain significance	criteria provided, single submitter
323091	NM_153490.3(KRT13):c.759G>C (p.Gln253His)	KRT13	Uncertain significance	criteria provided, single submitter
323099	NM_153490.3(KRT13):c.496-9A>G	KRT13	Uncertain significance	criteria provided, single submitter
323105	NM_153490.3(KRT13):c.337G>A (p.Asp113Asn)	KRT13	Uncertain significance	criteria provided, single submitter
889141	NM_153490.3(KRT13):c.*162T>C	KRT13	Uncertain significance	criteria provided, single submitter
889142	NM_153490.3(KRT13):c.*19C>T	KRT13	Uncertain significance	criteria provided, single submitter
889144	NM_153490.3(KRT13):c.1350C>T (p.Arg450=)	KRT13	Uncertain significance	criteria provided, single submitter
889145	NM_153490.3(KRT13):c.1295C>G (p.Ser432Cys)	KRT13	Uncertain significance	criteria provided, single submitter
889825	NM_153490.3(KRT13):c.1220G>A (p.Ser407Asn)	KRT13	Uncertain significance	criteria provided, multiple submitters, no conflicts
889891	NM_153490.3(KRT13):c.523C>G (p.Arg175Gly)	KRT13	Uncertain significance	criteria provided, single submitter
891625	NM_153490.3(KRT13):c.853G>A (p.Ala285Thr)	KRT13	Uncertain significance	criteria provided, single submitter
891626	NM_153490.3(KRT13):c.823G>A (p.Ala275Thr)	KRT13	Uncertain significance	criteria provided, single submitter
892506	NM_153490.3(KRT13):c.*175G>A	KRT13	Uncertain significance	criteria provided, single submitter
1300083	NM_153490.3(KRT13):c.892A>G (p.Thr298Ala)	KRT13	Benign	criteria provided, multiple submitters, no conflicts
1300084	NM_153490.3(KRT13):c.114C>T (p.Ser38=)	KRT13	Benign	criteria provided, multiple submitters, no conflicts
323070	NM_153490.3(KRT13):c.*171G>T	KRT13	Benign	criteria provided, multiple submitters, no conflicts
323071	NM_153490.3(KRT13):c.*170C>T	KRT13	Benign	criteria provided, multiple submitters, no conflicts
323074	NM_153490.3(KRT13):c.1352G>A (p.Arg451His)	KRT13	Benign	criteria provided, single submitter
323075	NM_153490.3(KRT13):c.1286G>A (p.Arg429His)	KRT13	Benign	criteria provided, multiple submitters, no conflicts
323076	NM_153490.3(KRT13):c.1276G>A (p.Val426Ile)	KRT13	Benign	criteria provided, single submitter
323077	NM_153490.3(KRT13):c.1227C>T (p.Leu409=)	KRT13	Benign	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
KRT13	Strong	Autosomal dominant	white sponge nevus 2	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
KRT13	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
KRT13	HGNC:6415	ENSG00000171401	P13646	Keratin, type I cytoskeletal 13	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
KRT13	Keratin, type I cytoskeletal 13	Type 1 keratin.

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)
KRT13	Other/Unknown	no		Keratin_I, IF_conserved, IF_rod_dom

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
esophagus squamous epithelium	1
lower esophagus mucosa	1
oral cavity	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
KRT13	189	broad	marker	lower esophagus mucosa, esophagus squamous epithelium, oral cavity

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
KRT13	1,789

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
KRT13	P13646	75.47

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	KRT13
Keratinization	1	55.7×	0.027	KRT13
Developmental Biology	1	14.5×	0.069	KRT13

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
regulation of translation in response to stress	1	5617.3×	9e-04	KRT13
morphogenesis of an epithelium	1	343.9×	0.007	KRT13
intermediate filament organization	1	240.7×	0.007	KRT13
epithelial cell differentiation	1	175.5×	0.007	KRT13
cytoskeleton organization	1	132.7×	0.008	KRT13

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
KRT13	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	KRT13

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)
KRT13	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.