KRT9 Gene (Keratin 9)
Epidermolytic Palmoplantar Keratoderma (EPPK) Associated Gene
Gene Information Card
| Symbol | KRT9 |
|---|---|
| Full Name | Keratin 9 |
| Gene Type | Protein coding |
| Chromosomal Location | 17q21.2 |
| NCBI Gene ID | 3857 ncbi.nlm.nih.gov/gene/3857 |
| Ensembl ID | ENSG00000171403 |
| UniProt ID | P35527 |
| OMIM ID | 607606 |
| HGNC ID | 6449 |
| Aliases | CK-9, keratin-9, cytokeratin-9 |
Description
KRT9 encodes keratin 9, a type I (acidic) intermediate filament protein specifically expressed in the suprabasal layers of palmoplantar epidermis. Keratin 9 forms heteropolymers with keratin 1 (KRT1) to provide mechanical resilience to skin on palms and soles. Mutations in KRT9 cause epidermolytic palmoplantar keratoderma (EPPK), a dominantly inherited disorder characterized by diffuse thickening of the skin on palms and soles with histologic epidermolysis.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Epidermolytic Palmoplantar Keratoderma (EPPK) | Dominant-negative mutations in the helix initiation or termination motifs of keratin 9 disrupt intermediate filament assembly, leading to keratinocyte fragility and hyperkeratosis. | Multiple families and sporadic cases reported; OMIM #144200; ClinVar pathogenic variants. |
| Palmoplantar Keratoderma, Non-Epidermolytic | Rare missense variants may cause milder phenotypes without epidermolysis. | Limited case reports; functional studies pending. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Skin (palmoplantar) | High (nTPM ~2000) | High |
| Skin (non-palmoplantar) | Low (nTPM <10) | Low |
| Esophagus | Not detected | Not detected |
| Oral mucosa | Not detected | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HaCaT (keratinocyte) | ~1500 | Immortalized keratinocyte line; high expression |
| NHEK (normal human epidermal keratinocytes) | ~1200 | Primary keratinocytes; moderate-high expression |
| A431 (epidermoid carcinoma) | ~800 | Vulvar carcinoma line; lower expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.487C>T (p.Arg163Trp) | Missense | ~30% of EPPK cases | Dominant-negative; disrupts helix initiation motif |
| c.488G>A (p.Arg163Gln) | Missense | ~15% of EPPK cases | Dominant-negative; similar effect |
| c.1406T>C (p.Leu469Pro) | Missense | Rare | Dominant-negative; helix termination motif |
| c.1648G>A (p.Glu550Lys) | Missense | Rare | Dominant-negative; rod domain |
Mutation functional classification
Loss of Function (LOF)
Not described; KRT9 null alleles are not reported in human disease.
Gain of Function (GOF)
Not described.
Dominant Negative (DN)
Major mechanism: mutant keratin 9 incorporates into filaments and disrupts assembly, causing keratinocyte fragility and hyperkeratosis.
View complete mutation data：
Gene Ontology (GO)
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 9 is a 623-amino acid type I keratin with a central alpha-helical rod domain flanked by non-helical head and tail domains. It is expressed exclusively in suprabasal keratinocytes of palmoplantar epidermis. The protein dimerizes with keratin 1 to form intermediate filaments that confer mechanical strength. Mutations in the conserved helix boundary motifs cause EPPK via dominant-negative interference.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| KRT9 Knockout HEK293 Cell Line | EDJ-KQ2018 | Human | 3857 | Details Get a Quote |
| KRT9 Knockout HeLa Cell Line | EDJ-KQ22041 | Human | 3857 | Details Get a Quote |
| KRT9 Knockout A-549 Cell Line | EDJ-KQ62234 | Human | 3857 | Details Get a Quote |
| KRT9 Knockout HCT 116 Cell Line | EDJ-KQ70719 | Human | 3857 | Details Get a Quote |
