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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 15 days ago
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KRT6C
keratin 6C
Chromosome 12 Β· 12q13.13
NCBI Gene: 286887Ensembl: ENSG00000170465.10HGNC: HGNC:20406UniProt: P48668
55PubMed Papers
21Diseases
0Drugs
3Pathogenic Variants
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
protein bindingintermediate filament cytoskeleton organizationextracellular exosomeintermediate filament organizationNon-epidermolytic palmoplantar keratodermaAutosomal dominant focal non-epidermolytic palmoplantar keratoderma with plantar blisteringpalmoplantar keratoderma, nonepidermolytic, focal or diffusefocal palmoplantar keratoderma
✦AI Summary

KRT6C is a type II keratin protein that functions as a structural component of the intermediate filament cytoskeleton, particularly in epidermal and epithelial tissues 1. It forms heterodimeric pairs with type I keratins, notably with KRT9 in palmoplantar epidermis, to organize and stabilize the cytoskeleton and regulate keratinization processes 1. KRT6C is expressed in multiple epithelial tissues including the nail bed, palmoplantar epidermis, oral mucosa, hair follicles, sweat glands, and esophageal epithelium 23. Mutations in KRT6C cause pachyonychia congenita (PC-K6c), a milder form of pachyonychia congenita characterized by nail dystrophy and palmoplantar keratoderma 14. KRT6C mutations also increase susceptibility to dental caries through disruption of enamel rod sheaths and altered keratin filament assembly in ameloblasts 2. In esophageal squamous cell carcinoma, KRT6C+ epithelial cells occupy an intermediate differentiation state during cancer progression 3. Notably, elevated KRT6C expression in lung adenocarcinoma is associated with poor prognosis and accelerates cancer cell proliferation, migration, and invasion by modulating epithelial-mesenchymal transition 5. KRT6C also appears as a candidate biomarker in melanoma classification, helping distinguish benign from malignant melanocytic neoplasms 6.

Sources cited
1
KRT6C is a heterodimer partner for KRT9 in palmoplantar epidermis; participates in cytoskeleton organization and keratinization; mutations cause PC-K6c
PMID: 37467889
2
KRT6C mutations cause pachyonychia congenita; genetic classification and phenotype-genotype correlations in 815-patient cohort
PMID: 31823354
3
KRT6C is expressed in multiple epithelial tissues; KRT6C mutations increase tooth decay susceptibility; keratins incorporated into tooth enamel
PMID: 29357356
4
KRT6C+ epithelial cells represent intermediate differentiation state in esophageal squamous cell carcinoma progression
PMID: 39391485
5
High KRT6C expression in lung adenocarcinoma associated with poor prognosis; KRT6C promotes proliferation, migration, invasion via EMT modulation
PMID: 31768767
6
KRT6C identified as part of 23-gene transcriptomic biomarker for distinguishing benign from malignant melanocytic neoplasms
PMID: 41042798
Disease Associationsβ“˜21
Non-epidermolytic palmoplantar keratodermaOpen Targets
0.62Moderate
Autosomal dominant focal non-epidermolytic palmoplantar keratoderma with plantar blisteringOpen Targets
0.55Moderate
palmoplantar keratoderma, nonepidermolytic, focal or diffuseOpen Targets
0.54Moderate
focal palmoplantar keratodermaOpen Targets
0.42Moderate
Palmoplantar keratodermaOpen Targets
0.37Weak
Nail dystrophyOpen Targets
0.37Weak
genetic disorderOpen Targets
0.19Weak
metabolic syndromeOpen Targets
0.07Suggestive
actinic keratosisOpen Targets
0.07Suggestive
sebaceous of Jadassohn nevusOpen Targets
0.07Suggestive
squamous cell carcinomaOpen Targets
0.06Suggestive
psoriasisOpen Targets
0.06Suggestive
non-small cell lung carcinomaOpen Targets
0.05Suggestive
palmoplantar keratoderma-esophageal carcinoma syndromeOpen Targets
0.05Suggestive
skin diseaseOpen Targets
0.05Suggestive
pachyonychia congenitaOpen Targets
0.04Suggestive
nail and teeth abnormalities-marginal palmoplantar keratoderma-oral hyperpigmentation syndromeOpen Targets
0.04Suggestive
van der Woude syndromeOpen Targets
0.04Suggestive
cleft palate with or without ankyloglossia, X-linkedOpen Targets
0.04Suggestive
visceral myopathy 2Open Targets
0.04Suggestive
Palmoplantar keratoderma, non-epidermolytic, focal or diffuseUniProt
Pathogenic Variants3
NM_173086.5(KRT6C):c.1414G>A (p.Glu472Lys)Pathogenic
Palmoplantar keratoderma, nonepidermolytic, focal or diffuse|not provided
β˜…β˜…β˜†β˜†2024β†’ Residue 472
NM_173086.5(KRT6C):c.510CAA[2] (p.Asn172del)Pathogenic
not provided|Focal palmoplantar keratoderma
β˜…β˜†β˜†β˜†2022β†’ Residue 172
NM_173086.5(KRT6C):c.1384_1410del (p.Ile462_Glu470del)Pathogenic
not provided|Focal palmoplantar keratoderma
β˜†β˜†β˜†β˜†2010β†’ Residue 462
View on ClinVar β†—
Related Genes
KRT74Shared pathway100%KRT3Shared pathway75%KRT5Protein interaction72%KRT6AProtein interaction72%KRT77Shared pathway67%KRT79Shared pathway67%
Tissue Expression6 tissues
Liver
100%
Ovary
60%
Lung
20%
Brain
0%
Heart
0%
Bone Marrow
0%
Gene Interaction Network
Click a node to explore
KRT6CKRT74KRT3KRT5KRT6AKRT77KRT79
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted Β· UniProt P48668
View on AlphaFold β†—
Constraintβ“˜
LOEUFβ“˜
1.34LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF1.05 [0.83–1.34]
RankingsWhere KRT6C stands among ~20K protein-coding genes
  • #8,212of 20,598
    Most Researched55
  • #4,050of 5,498
    Most Pathogenic Variants3
  • #14,030of 17,882
    Most Constrained (LOEUF)1.34
Genes detectedKRT6C
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Towards a transcriptomic biomarker for the classification of melanocytic neoplasms.
PMID: 41042798
PLoS Genet Β· 2025
1.00
2
Landscape of epithelial cell subpopulations in the human esophageal squamous cell carcinoma microenvironment.
PMID: 39391485
Heliyon Β· 2024
0.90
3
Proteomic profiling reveals KRT6C as a probable hereterodimer partner for KRT9: New insights into re-classifying epidermolytic palmoplantar keratoderma (EPPK) and a milder form of pachyonychia congenita (PC-K6c) as a group of genetic cutaneous disorders.
PMID: 37467889
J Proteomics Β· 2023
0.80
4
Proteomic profiling of Pachyonychia congenita plantar callus.
PMID: 28648685
J Proteomics Β· 2017
0.70
5
Revisiting pachyonychia congenita: a case-cohort study of 815 patients.
PMID: 31823354
Br J Dermatol Β· 2020
0.60