KRT14 Gene: Keratin 14 – Structure, Function, and Clinical Significance
A comprehensive guide to the KRT14 gene, its associated diseases, expression patterns, and mutation landscape, based on authoritative genomic databases.
Gene Information Card
| Symbol | KRT14 |
|---|---|
| Full Name | Keratin 14 |
| Gene Type | Protein coding |
| Chromosomal Location | 17q21.2 |
| NCBI Gene ID | 3861 ncbi.nlm.nih.gov/gene/3861 |
| Ensembl ID | ENSG00000186847 |
| UniProt ID | P02533 |
| OMIM ID | 148066 |
| HGNC ID | 6416 |
| Aliases | CK14, EBS4, K14, NFJ |
Description
The KRT14 gene encodes keratin 14, a type I intermediate filament protein that pairs with keratin 5 (KRT5) to form the cytoskeleton of basal epithelial cells, particularly in the epidermis. Keratin 14 is essential for maintaining the structural integrity of keratinocytes, providing mechanical resilience to the skin. Mutations in KRT14 are primarily associated with epidermolysis bullosa simplex (EBS), a group of skin fragility disorders characterized by blistering of the skin and mucous membranes. The gene is also implicated in certain cancers and other skin conditions.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Epidermolysis bullosa simplex (EBS) | Mutations in KRT14 disrupt the keratin filament network, leading to cytolysis of basal keratinocytes upon minor trauma, causing blister formation. | ClinVar, OMIM |
| Keratoderma, palmoplantar, non-epidermolytic | Specific KRT14 mutations can cause focal or diffuse thickening of the palms and soles due to abnormal keratin filament assembly. | ClinVar, OMIM |
| Dermatopathia pigmentosa reticularis | Rare mutations in KRT14 have been linked to this ectodermal dysplasia, affecting skin pigmentation and hair/nail development. | OMIM |
| Breast cancer | Altered KRT14 expression is observed in basal-like breast cancer subtypes, contributing to tumor aggressiveness and epithelial-mesenchymal transition. | COSMIC, NCBI |
| Oral squamous cell carcinoma | KRT14 overexpression is associated with poor differentiation and invasive potential in oral cancers. | COSMIC, NCBI |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Skin | High (nTPM ~ 2000) | High |
| Esophagus | Moderate (nTPM ~ 500) | Medium |
| Cervix | Moderate (nTPM ~ 400) | Medium |
| Breast | Low (nTPM ~ 50) | Low |
| Lung | Low (nTPM ~ 30) | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HaCaT (keratinocyte) | High | Immortalized keratinocyte line; strong KRT14 expression |
| A431 (epidermoid carcinoma) | High | Derived from skin; high KRT14 levels |
| MCF7 (breast cancer) | Low | Luminal subtype; low KRT14 expression |
| MDA-MB-231 (breast cancer) | Moderate | Basal-like subtype; elevated KRT14 |
| HeLa (cervical cancer) | Low | Low KRT14 expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.526A>G (p.Asn176Asp) | Missense | Rare | Disrupts keratin filament assembly; associated with EBS |
| c.1159C>T (p.Arg387Cys) | Missense | Rare | Causes EBS; affects rod domain stability |
| c.374G>A (p.Arg125His) | Missense | Rare | Hotspot mutation; severe EBS phenotype |
| c.IVS1+1G>A | Splice site | Rare | Aberrant splicing; leads to truncated protein and EBS |
| c.2T>C (p.Met1Thr) | Start codon loss | Rare | Loss of translation initiation; severe EBS |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations (e.g., start codon loss, frameshift) lead to haploinsufficiency or absence of keratin 14, causing severe skin fragility and blistering due to compromised cytoskeletal integrity.
Gain of Function (GOF)
Gain-of-function mutations are rare for KRT14; some missense mutations may produce abnormal protein aggregates that disrupt filament dynamics, but this is not a classic mechanism.
Dominant Negative (DN)
Most EBS-associated KRT14 mutations are dominant-negative: the mutant protein incorporates into keratin filaments, disrupting the normal assembly and leading to filament collapse and cell fragility.
View complete mutation data：
Gene Ontology (GO)
| • structural constituent of cytoskeleton | • intermediate filament binding |
| • protein heterodimerization activity | • structural molecule activity |
| • cytoskeleton organization | • epidermis development |
| • cell differentiation | • response to wound healing |
Pathways
• Intermediate filament organization
• Keratinization
• Formation of the cornified envelope
• Developmental biology (epidermal differentiation)
Protein Summary
Keratin 14 is a 472-amino-acid type I keratin with a central alpha-helical rod domain flanked by non-helical head and tail domains. It forms obligate heterodimers with keratin 5, assembling into 10-nm intermediate filaments that provide mechanical support to basal keratinocytes. The protein is highly expressed in the basal layer of stratified epithelia, including skin, oral mucosa, and esophagus. Post-translational modifications such as phosphorylation regulate filament dynamics during cell division and differentiation. Mutations in KRT14 compromise filament integrity, leading to skin blistering disorders. Additionally, KRT14 expression is a marker for basal-like breast cancer and correlates with epithelial-mesenchymal transition.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| KRT14 Knockout HEK293 Cell Line | EDJ-KQ50411 | Human | 3861 | Details Get a Quote |
| KRT14 Knockout HeLa Cell Line | EDJ-KQ53759 | Human | 3861 | Details Get a Quote |
| KRT14 Knockout A-549 Cell Line | EDJ-KQ62237 | Human | 3861 | Details Get a Quote |
| KRT14 Knockout HCT 116 Cell Line | EDJ-KQ70721 | Human | 3861 | Details Get a Quote |
Displaying Records 1 To 4 Of 4 Records
