KRT14
Chr 17ADARkeratin 14
Also known as: CK14, EBS1, EBS1A, EBS1B, EBS1C, EBS1D, EBS3, EBS4
The protein forms heterotetramer complexes with keratin 5 to create intermediate filaments that comprise the cytoskeleton of epithelial cells, with the nonhelical tail domain promoting filament bundling and mechanical resilience. Mutations cause multiple forms of epidermolysis bullosa simplex (ranging from localized to severe generalized), dermatopathia pigmentosa reticularis, and Naegeli-Franceschetti-Jadassohn syndrome through dominant-negative mechanisms, with inheritance patterns that are typically autosomal dominant but can be autosomal recessive. The pathogenicity results from disrupted keratin filament structure and function, compromising epithelial cell integrity and leading to skin fragility and blistering.
Primary Disease Associations & Inheritance
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative, gain-of-function and loss-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
297 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 9 | 30 | 21 | 0 | 60 |
Likely Pathogenic | 4 | 15 | 5 | 0 | 24 |
VUS | 3 | 80 | 6 | 1 | 90 |
Likely Benign | 0 | 7 | 13 | 26 | 46 |
Benign | 0 | 4 | 6 | 12 | 22 |
Conflicting | — | 2 | |||
| Total | 16 | 136 | 51 | 39 | 244 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
KRT14 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools