Keratin, type II cytoskeletal 6A (KRT6A) (KRT6A)

Keratin, type II cytoskeletal 6A (KRT6A) is a structural protein that forms intermediate filaments, providing mechanical stability to epithelial cells, particularly in the palms, soles, and hair follicles [UniProt P02538]. Unlike many other keratins, KRT6A is rapidly induced in keratinocytes following wounding or stress, playing a critical role in cell migration and the inflammatory response during tissue repair [Zhang et al., 2019]. Mutations in KRT6A are a primary cause of Pachyonychia Congenita (PC), a rare autosomal dominant disorder characterized by severe palmoplantar keratoderma and nail dystrophy [Smith et al., 2005]. In the context of oncology, KRT6A is frequently overexpressed in squamous cell carcinomas and is used as a diagnostic biomarker to distinguish lung squamous cell carcinoma from adenocarcinoma [Zhang et al., 2019]. Because PC is caused by dominant-negative mutations, therapeutic efforts have pioneered the use of allele-specific small interfering RNAs (siRNAs) to selectively silence the mutant allele while sparing the wild-type, aiming to restore skin integrity [Leachman et al., 2010]. Additionally, mTOR inhibitors like sirolimus have been investigated for their ability to downregulate KRT6A expression and alleviate symptoms in PC patients [Hickerson et al., 2009].

Other names

K6ACK6ACytokeratin 6AKRT6Type II keratin Kb6KRT6BKRT6C

Allele-specific RNA interference (siRNA) targeting mutant mRNA to prevent translation of dominant-negative proteins [Leachman et al., 2010]; mTOR inhibition to downregulate keratin synthesis [Hickerson et al., 2009].