Hereditary mucosal leukokeratosis

Summary

Hereditary mucosal leukokeratosis (MONDO:0015748) is a disease with 2 cohort genes.

At a glance

• Cohort genes: 2

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	hereditary mucosal leukokeratosis
Mondo ID	MONDO:0015748
MeSH	D053529
OMIM	193900
Orphanet	171723
DOID	DOID:0050448
NCIT	C84760
SNOMED CT	389203001
UMLS	C1721005
MedGen	328433
GARD	0008501
Is cancer (heuristic)	no

Also known as: hereditary mucosal leukokeratosis · white sponge nevus · White sponge nevus of Cannon · white sponge nevus of Cannon

Data availability: 2 GenCC gene-disease records.

Disease family

An umbrella term covering 2 Mondo subtypes.

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

Related subtypes (27): conjunctival nevus, blue nevus, halo nevus, intradermal nevus, pigmented spindle cell nevus, nevus, epidermal, neurocutaneous melanocytosis, neutrophil actin dysfunction, CHILD syndrome, Becker nevus syndrome, CLOVES syndrome, nevus comedonicus syndrome, segmental outgrowth-lipomatosis-arteriovenous malformation-epidermal nevus syndrome, congenital panfollicular nevus, porokeratotic eccrine ostial and dermal duct nevus, linear verrucous nevus syndrome, nevus of Ota, nevus of Ito, phakomatosis pigmentokeratotica, PENS syndrome, Angora hair nevus, didymosis aplasticosebacea, scalp syndrome, Nevada syndrome, palpebral nevus, large congenital melanocytic nevus, benign melanocytic skin nevus

Subtypes (2): white sponge nevus 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

No tiered GWAS variants or ClinVar records for this disease.

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 8 · 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
KRT13	Supportive	Autosomal dominant	hereditary mucosal leukokeratosis	4
KRT4	Supportive	Autosomal dominant	hereditary mucosal leukokeratosis	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
KRT13	Orphanet:171723	White sponge nevus
KRT4	Orphanet:171723	White sponge nevus

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
KRT13	HGNC:6415	ENSG00000171401	P13646	Keratin, type I cytoskeletal 13	gencc
KRT4	HGNC:6441	ENSG00000170477	P19013	Keratin, type II cytoskeletal 4	gencc

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: 2 · 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	2	1.8×	0.312

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
KRT13	Other/Unknown	no		Keratin_I, IF_conserved, IF_rod_dom
KRT4	Other/Unknown	no		Keratin_II, IF_conserved, Keratin_2_head

Expression context

Cohort genes with no expression data: 0.

2 cohort genes 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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
lower esophagus mucosa	2
esophagus squamous epithelium	1
oral cavity	1
pharyngeal mucosa	1
tongue squamous epithelium	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
KRT4	179	tissue_specific	marker	tongue squamous epithelium, pharyngeal mucosa, lower esophagus mucosa

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
KRT13	1,789
KRT4	1,660

Intra-cohort edges

A	B	Sources
KRT13	KRT4	intact, string_interaction

Structural data

PDB: 0 · AlphaFold-only: 2 · No structure: 0

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
KRT13	P13646	75.47
KRT4	P19013	71.77

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. Enrichment computed across 2 evidence-associated genes (2 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 2 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	2	87.8×	4e-04	KRT13, KRT4
Keratinization	2	55.7×	5e-04	KRT13, KRT4
Developmental Biology	2	14.5×	0.005	KRT13, 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
intermediate filament organization	2	240.7×	1e-04	KRT13, KRT4
epithelial cell differentiation	2	175.5×	1e-04	KRT13, KRT4
cytoskeleton organization	2	132.7×	1e-04	KRT13, KRT4
regulation of translation in response to stress	1	2808.7×	6e-04	KRT13
morphogenesis of an epithelium	1	172.0×	0.008	KRT13
negative regulation of epithelial cell proliferation	1	145.3×	0.008	KRT4
keratinization	1	117.0×	0.009	KRT4

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 1 of 2 evidence-associated genes (50%) 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
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: 2; 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	2	KRT13, KRT4

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
KRT13	0	—
KRT4	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.