KRT4 Gene - Keratin 4
Key structural protein in epithelial tissues, associated with white sponge nevus and oral/esophageal disorders
Gene Information Card
| Symbol | KRT4 |
|---|---|
| Full Name | Keratin 4 |
| Gene Type | Protein coding |
| Chromosomal Location | 12q13.13 |
| NCBI Gene ID | 3851 ncbi.nlm.nih.gov/gene/3851 |
| Ensembl ID | ENSG00000170477 |
| UniProt ID | P19013 |
| OMIM ID | 123940 |
| HGNC ID | 6441 |
| Aliases | CK4, K4, cytokeratin 4, keratin, type II cytoskeletal 4 |
Description
KRT4 encodes keratin 4, a type II intermediate filament protein expressed in differentiated suprabasal cells of stratified squamous epithelia, particularly in the oral mucosa, esophagus, and cornea. It forms heteropolymers with type I keratins (e.g., KRT13) to maintain epithelial integrity. Mutations in KRT4 cause white sponge nevus (WSN), an autosomal dominant disorder characterized by white, spongy plaques in the oral mucosa. Altered expression is also reported in esophageal squamous cell carcinoma.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| White Sponge Nevus (WSN) | Dominant-negative mutations in the helix initiation or termination motifs disrupt keratin filament assembly, leading to epithelial fragility and mucosal thickening. | OMIM #193900; ClinVar; PMID: 10581026 |
| Oral Squamous Cell Carcinoma | Downregulation or aberrant expression of KRT4 is associated with loss of epithelial differentiation and tumor progression. | PMID: 23429703; COSMIC |
| Esophageal Squamous Cell Carcinoma | Reduced KRT4 expression correlates with poor differentiation and worse prognosis. | PMID: 25636527 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Oral mucosa | 98.7 | High |
| Esophagus | 85.3 | High |
| Cornea | 72.1 | High |
| Skin | 5.2 | Low |
| Lung | 2.1 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HaCaT (keratinocyte) | 120.5 | High expression; used as positive control |
| SCC-25 (oral squamous) | 45.3 | Reduced compared to normal keratinocytes |
| A549 (lung carcinoma) | 1.2 | Minimal expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.416T>C (p.Leu139Pro) | Missense | Rare | Dominant-negative; disrupts helix initiation motif; causes WSN |
| c.467G>A (p.Gly156Asp) | Missense | Rare | Dominant-negative; associated with WSN |
| c.1435C>T (p.Arg479Cys) | Missense | Rare | Likely pathogenic; reported in WSN |
| c.1249G>A (p.Glu417Lys) | Missense | Rare | Uncertain significance; COSMIC ID COSM1425672 |
Mutation functional classification
Loss of Function (LOF)
Not established; no homozygous loss-of-function reported in humans.
Gain of Function (GOF)
Not described.
Dominant Negative (DN)
Primary mechanism for WSN; mutant keratin 4 interferes with filament polymerization, causing cytoskeletal collapse.
View complete mutation data：
Gene Ontology (GO)
| • structural molecule activity (GO:0005198) | • intermediate filament (GO:0005882) |
| • keratin filament (GO:0045095) | • epithelial cell differentiation (GO:0030855) |
| • epidermis development (GO:0008544) |
Pathways
• Intermediate filament organization (Reactome: R-HSA-6809371)
• Keratinization (Reactome: R-HSA-6805567)
• Formation of the cornified envelope (Reactome: R-HSA-6809374)
Protein Summary
Keratin 4 (UniProt P19013) is a 526-amino acid type II intermediate filament protein with a central alpha-helical rod domain flanked by non-helical head and tail domains. It heteropolymerizes with keratin 13 to form intermediate filaments in suprabasal stratified epithelia. The protein provides mechanical resilience and maintains tissue integrity. Mutations in the rod domain cause filament aggregation and lead to white sponge nevus.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| KRT4 Knockout HEK293 Cell Line | EDJ-KQ5085 | Human | 3851 | Details Get a Quote |
| KRT40 Knockout HEK293 Cell Line | EDJ-KQ8739 | Human | 125115 | Details Get a Quote |
| KRT4 Knockout A-549 Cell Line | EDJ-KQ28024 | Human | 3851 | Details Get a Quote |
| KRT4 Knockout HeLa Cell Line | EDJ-KQ53755 | Human | 3851 | Details Get a Quote |
| KRT40 Knockout HeLa Cell Line | EDJ-KQ58151 | Human | 125115 | Details Get a Quote |
| KRT40 Knockout A-549 Cell Line | EDJ-KQ66634 | Human | 125115 | Details Get a Quote |
| KRT4 Knockout HCT 116 Cell Line | EDJ-KQ70716 | Human | 3851 | Details Get a Quote |
| KRT40 Knockout HCT 116 Cell Line | EDJ-KQ75055 | Human | 125115 | Details Get a Quote |
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