epidermolytic hyperkeratosis 2A, autosomal dominant
disease diseaseOn this page
Summary
epidermolytic hyperkeratosis 2A, autosomal dominant (MONDO:0700248) is a disease caused by KRT10 (GenCC Strong), with 2 cohort genes.
At a glance
- Causal gene: KRT10 (GenCC Strong)
- Cohort genes: 2
- ClinVar variants: 15
Clinical features
No curated clinical features (Orphanet) for this disease.
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | epidermolytic hyperkeratosis 2A, autosomal dominant |
| Mondo ID | MONDO:0700248 |
| OMIM | 620150 |
| DOID | DOID:0061223 |
| UMLS | C5882671 |
| MedGen | 1846123 |
| GARD | 0026396 |
| Is cancer (heuristic) | no |
Data availability: 15 ClinVar variants · 2 GenCC gene-disease records.
Disease family
Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › autosomal genetic disease › autosomal dominant disease › autosomal dominant epidermolytic ichthyosis › epidermolytic hyperkeratosis 2A, autosomal dominant
Related subtypes (1): annular epidermolytic ichthyosis
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
15 retrieved; paginated sample, class counts are floors:
8 pathogenic, 4 uncertain significance, 1 likely pathogenic, 1 pathogenic/likely pathogenic, 1 conflicting classifications of pathogenicity
| ClinVar | Variant (HGVS) | Gene | Classification | Review |
|---|---|---|---|---|
| 14569 | NM_000421.5(KRT10):c.482T>C (p.Leu161Ser) | KRT10 | Pathogenic | no assertion criteria provided |
| 14572 | NM_000421.5(KRT10):c.478T>G (p.Tyr160Asp) | KRT10 | Pathogenic | no assertion criteria provided |
| 14575 | NM_000421.5(KRT10):c.1325T>A (p.Leu442Gln) | KRT10 | Pathogenic | no assertion criteria provided |
| 14576 | NM_000421.5(KRT10):c.466C>T (p.Arg156Cys) | KRT10 | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 14577 | NM_000421.5(KRT10):c.449T>G (p.Met150Arg) | KRT10 | Pathogenic | no assertion criteria provided |
| 14579 | NM_000421.5(KRT10):c.449T>C (p.Met150Thr) | KRT10 | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 3377268 | NM_000421.5(KRT10):c.1307T>C (p.Leu436Pro) | KRT10 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 14571 | NM_000421.5(KRT10):c.460A>C (p.Asn154His) | KRT10-AS1 | Pathogenic | no assertion criteria provided |
| 14573 | NM_000421.5(KRT10):c.467G>A (p.Arg156His) | KRT10-AS1 | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 2431374 | NM_000421.5(KRT10):c.1374-1G>A | KRT10 | Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 808260 | NM_000421.5(KRT10):c.1639_1653dup (p.543GGGSS[3]) | KRT10 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 3891517 | NM_000421.5(KRT10):c.1676G>T (p.Gly559Val) | KRT10 | Uncertain significance | criteria provided, single submitter |
| 3891518 | NM_000421.5(KRT10):c.1650_1667dup (p.Gly556_Tyr557insSerSerSerGlyGlyGly) | KRT10 | Uncertain significance | criteria provided, single submitter |
| 3891519 | NM_000421.5(KRT10):c.1460_1461insGTTC (p.His487fs) | KRT10 | Uncertain significance | criteria provided, single submitter |
| 66176 | NM_000421.5(KRT10):c.467G>T (p.Arg156Leu) | KRT10 | Uncertain significance | criteria provided, single submitter |
Genes & proteins
Mendelian disease overlap and somatic drivers
GenCC: 15 · Orphanet: 4 · 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 |
|---|---|---|---|---|
| KRT10 | Definitive | Autosomal dominant | annular epidermolytic ichthyosis | 15 |
Orphanet rare-disease linkage (cohort genes)
| Gene | Orphanet ID | Rare disease |
|---|---|---|
| KRT10 | Orphanet:281139 | Annular epidermolytic ichthyosis |
| KRT10 | Orphanet:281190 | Congenital reticular ichthyosiform erythroderma |
| KRT10 | Orphanet:312 | Autosomal dominant epidermolytic ichthyosis |
| KRT10 | Orphanet:512103 | Autosomal recessive epidermolytic ichthyosis |
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 |
|---|---|---|---|---|---|
| KRT10 | HGNC:6413 | ENSG00000186395 | P13645 | Keratin, type I cytoskeletal 10 | gencc,clinvar |
| KRT10-AS1 | HGNC:28305 | ENSG00000167920 | Q8N816 | Uncharacterized protein KRT10-AS1 | clinvar |
Cohort function summary
Lead sentence per gene, UniProt-curated.
| Symbol | Protein name | Function (lead sentence) |
|---|---|---|
| KRT10 | Keratin, type I cytoskeletal 10 | Plays a role in the establishment of the epidermal barrier on plantar skin. |
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) |
|---|---|---|---|---|
| KRT10 | Other/Unknown | no | Keratin_I, IF_conserved, IF_rod_dom | |
| KRT10-AS1 | Other/Unknown | no |
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 |
|---|---|
| mammalian vulva | 1 |
| penis | 1 |
| upper leg skin | 1 |
| left testis | 1 |
| pancreatic ductal cell | 1 |
| right testis | 1 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|---|---|---|---|
| KRT10 | 299 | broad | marker | upper leg skin, penis, mammalian vulva |
| KRT10-AS1 | 234 | ubiquitous | marker | left testis, right testis, pancreatic ductal cell |
Protein interactions among cohort
Intra-cohort edges: 0.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|---|
| KRT10 | 2,304 |
| KRT10-AS1 | 2 |
Structural data
PDB: 1 · AlphaFold-only: 1 · No structure: 0
Cohort genes with PDB structures (top 30)
| Symbol | UniProt | PDB entries |
|---|---|---|
| KRT10 | P13645 | 6 |
AlphaFold-only cohort genes (top 30 by pLDDT)
| Symbol | UniProt | pLDDT |
|---|---|---|
| KRT10-AS1 | Q8N816 | 46.64 |
Function
Pathway analysis
Distinct Reactome pathways touched by cohort: 5. Enrichment computed across 2 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 |
|---|---|---|---|---|
| Differentiation of Keratinocytes in Interfollicular Epidermis in Mammalian Skin | 1 | 278.5× | 0.011 | KRT10 |
| Developmental Cell Lineages | 1 | 223.9× | 0.011 | KRT10 |
| Formation of the cornified envelope | 1 | 87.8× | 0.019 | KRT10 |
| Keratinization | 1 | 55.7× | 0.022 | KRT10 |
| Developmental Biology | 1 | 14.5× | 0.069 | KRT10 |
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 |
|---|---|---|---|---|
| positive regulation of epidermis development | 1 | 3370.4× | 0.002 | KRT10 |
| protein heterotetramerization | 1 | 1053.2× | 0.002 | KRT10 |
| cornification | 1 | 1053.2× | 0.002 | KRT10 |
| morphogenesis of an epithelium | 1 | 343.9× | 0.004 | KRT10 |
| keratinocyte differentiation | 1 | 247.8× | 0.004 | KRT10 |
| intermediate filament organization | 1 | 240.7× | 0.004 | KRT10 |
Therapeutics
Drug target analysis
Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2
Druggability breadth: 0 of 2 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 |
|---|---|---|
| KRT10 | 0 | 0 |
| KRT10-AS1 | 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 | 2 | KRT10, KRT10-AS1 |
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) |
|---|---|---|
| KRT10 | 0 | — |
| KRT10-AS1 | 0 | — |
Clinical trials & evidence
Clinical trials
Clinical trials: 0.