Epidermis-specific type I keratin that plays a key role in skin. Acts as a regulator of innate immunity in response to skin barrier breach: required for some inflammatory checkpoint for the skin barrier maintenance

Pachyonychia congenita 1

An autosomal dominant ectodermal dysplasia characterized by hypertrophic nail dystrophy resulting in onchyogryposis (thickening and increase in curvature of the nail), palmoplantar keratoderma, follicular hyperkeratosis, and oral leukokeratosis. Hyperhidrosis of the hands and feet is usually present.

Component of intercellular desmosome junctions (PubMed:34368962). Involved in the interaction of plaque proteins and intermediate filaments mediating cell-cell adhesion (PubMed:19717567)

Cell membraneCell junction, desmosomeCytoplasmNucleus

Palmoplantar keratoderma 1, striate, focal, or diffuse

A dermatological disorder characterized by thickening of the skin on the palms and soles, and longitudinal hyperkeratotic lesions on the palms, running the length of each finger.

Epidermis-specific type I keratin involved in wound healing. Involved in the activation of follicular keratinocytes after wounding, while it does not play a major role in keratinocyte proliferation or migration. Participates in the regulation of epithelial migration by inhibiting the activity of SRC during wound repair

Pachyonychia congenita 3

An autosomal dominant genodermatosis characterized by hypertrophic nail dystrophy, painful and highly debilitating plantar keratoderma, oral leukokeratosis, and a variety of epidermal cysts.

Transcription factor playing an important role in primary neurulation and in epithelial development (PubMed:25152456, PubMed:29309642). Binds directly to the consensus DNA sequence 5'-AACCGGTT-3' acting as an activator and repressor on distinct target genes (By similarity). During embryogenesis, plays unique and cooperative roles with GRHL3 in establishing distinct zones of primary neurulation. Essential for closure 3 (rostral end of the forebrain), functions cooperatively with GRHL3 in closure

NucleusMembrane

Deafness, autosomal dominant, 28

A form of non-syndromic sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. DFNA28 is characterized by mild to moderate hearing loss across most frequencies that progresses to severe loss in the higher frequencies by the fifth decade.

Non-selective calcium permeant cation channel (PubMed:12077604, PubMed:12077606, PubMed:26818531, PubMed:37648856, PubMed:38691614). It is activated by innocuous (warm) temperatures and shows an increased response at noxious temperatures greater than 39 degrees Celsius (PubMed:12077604, PubMed:12077606). Activation exhibits an outward rectification (PubMed:12077604). The channel pore can dilate to provide permeability to larger cations (PubMed:37648856). May associate with TRPV1 and may modulate

Cell membraneCytoplasmLysosome

Olmsted syndrome 1

An autosomal dominant, rare congenital disorder characterized by bilateral mutilating palmoplantar keratoderma and periorificial keratotic plaques with severe itching at all lesions. Diffuse alopecia, constriction of digits, and onychodystrophy have also been reported. Infections and squamous cell carcinomas can arise on the keratotic areas. The digital constriction may progress to autoamputation of fingers and toes.

Involved in transcription regulation by sequestering in the cytoplasm nuclear receptor coactivators such as NCOA1, NCOA2 and NCOA3 (PubMed:17476305). Involved in regulation of caspase-independent apoptosis by sequestering the proapoptotic factor AIFM1 in mitochondria (PubMed:22371500). Pro-apoptotic stimuli can induce its proteasomal degradation allowing the translocation of AIFM1 to the nucleus to induce apoptosis (PubMed:22371500). Involved in the negative control of vitamin D receptor signali

CytoplasmMitochondrion

Palmoplantar keratoderma and woolly hair

A disorder characterized by abnormal thickening of the skin on the palms and soles, in association with woolly scalp hair. Affected individuals manifest a variable degree of striate palmoplantar keratoderma, generally more severe on the soles. Leukonychia is more pronounced on the fingernails than toenails. Scalp hair, body hair, eyebrows, and eyelashes are sparse. The fifth toes show variable degrees of pseudoainhum, ranging from external rotation to a deep sulcus at the digitoplantar fold, accompanied by a bulbous appearance of the distal toe.

Transaminase involved in tyrosine breakdown. Converts tyrosine to p-hydroxyphenylpyruvate. Can catalyze the reverse reaction, using glutamic acid, with 2-oxoglutarate as cosubstrate (in vitro). Has much lower affinity and transaminase activity towards phenylalanine

Tyrosinemia 2

An inborn error of metabolism characterized by elevations of tyrosine in the blood and urine, and oculocutaneous manifestations. Typical features include palmoplantar keratosis, painful corneal ulcers, and intellectual disability.

Regulates ADAM17 protease, a sheddase of the epidermal growth factor (EGF) receptor ligands and TNF, thereby plays a role in sleep, cell survival, proliferation, migration and inflammation. Does not exhibit any protease activity on its own

Endoplasmic reticulum membraneCell membrane

Tylosis with esophageal cancer

An autosomal dominant syndrome characterized by focal non-epidermolytic palmoplantar keratoderma, oral leukokeratosis, and a high lifetime risk of developing esophageal squamous cell carcinoma.

A component of desmosome cell-cell junctions which are required for positive regulation of cellular adhesion (PubMed:25733715). Critical for cell-cell adhesion in early stage blastocysts and progression through proamniotic cavity formation (By similarity). Not required for preimplantation morphogenic process in blastocysts (By similarity). Required for keratin filament anchoring at the desmosome junction and subsequent organization of the keratin intermediate filament network within the cytoplas

Cell projection, axonCell junction, desmosomeCell membraneCytoplasmNucleus

Keratoderma, palmoplantar, striate 2

A dermatological disorder characterized by thickening of the skin on the palms (linear pattern) and the soles (island-like pattern) and flexor aspect of the fingers. Abnormalities of the nails, the teeth and the hair are rarely present.

Pachyonychia congenita 4

An autosomal dominant genodermatosis characterized by hypertrophic nail dystrophy, painful and highly debilitating plantar keratoderma, oral leukokeratosis, and a variety of epidermal cysts.

Type I keratin involved in the formation and maintenance of various skin appendages, specifically in determining shape and orientation of hair (By similarity). Required for the correct growth of hair follicles, in particular for the persistence of the anagen (growth) state (By similarity). Modulates the function of TNF in the specific context of hair cycling. Regulates protein synthesis and epithelial cell growth through binding to the adapter protein SFN and by stimulating Akt/mTOR pathway (By

Cytoplasm

Pachyonychia congenita 2

An autosomal dominant ectodermal dysplasia characterized by hypertrophic nail dystrophy resulting in onchyogryposis (thickening and increase in curvature of the nail), palmoplantar keratoderma and hyperhidrosis, follicular hyperkeratosis, multiple epidermal cysts, absent/sparse eyebrow and body hair, and by the presence of natal teeth.

May regulate the activity of kinases such as PKC and SRC via binding to integrin beta-1 (ITB1) and the receptor of activated protein C kinase 1 (RACK1). In complex with C1QBP is a high affinity receptor for kininogen-1/HMWK

Cell membraneCytoplasm

Epidermolytic hyperkeratosis 1

A skin disorder characterized by widespread blistering and an ichthyotic erythroderma at birth that persist into adulthood. Histologically there is a diffuse epidermolytic degeneration in the lower spinous layer of the epidermis. Within a few weeks from birth, erythroderma and blister formation diminish and hyperkeratoses develop. EHK1 inheritance is autosomal dominant or autosomal recessive.