Ichthyosis and erythrokeratoderma: genes and variants

Genes linked to Ichthyosis and erythrokeratoderma

• GJB2: Gap junction beta-2 protein

  Its connexin 26 channels support potassium and metabolite recycling within the cochlea and communication across epithelial gap junctions. Biallelic pathogenic variants are among the most common causes of congenital nonsyndromic hearing loss, while dominant variants can cause syndromic deafness with skin disease.

  2 disease-causing and 0 uncertain variants in GJB2 are linked to Ichthyosis and erythrokeratoderma.

• TGM1: Protein-glutamine gamma-glutamyltransferase K

  It crosslinks structural proteins and lipids during formation of the cornified envelope, creating the mechanically resilient outer skin barrier. Biallelic loss-of-function variants are a major cause of autosomal recessive congenital ichthyosis, particularly lamellar ichthyosis.

  2 disease-causing and 0 uncertain variants in TGM1 are linked to Ichthyosis and erythrokeratoderma.

• KRT10: Keratin, type I cytoskeletal 10

  It forms intermediate filaments with keratin 1 in differentiating epidermal keratinocytes, protecting the upper epidermis from mechanical stress. Dominant pathogenic variants cause epidermolytic ichthyosis, while specific mechanisms can produce ichthyosis with confetti.

  1 disease-causing and 0 uncertain variants in KRT10 are linked to Ichthyosis and erythrokeratoderma.

• KRT16: Keratin, type I cytoskeletal 16

  It is induced in mechanically stressed and repairing epithelia and helps reinforce keratinocyte intermediate filaments. Dominant pathogenic variants can cause pachyonychia congenita and focal palmoplantar keratoderma with painful hyperkeratosis.

  1 disease-causing and 0 uncertain variants in KRT16 are linked to Ichthyosis and erythrokeratoderma.

Known disease-causing variants in Ichthyosis and erythrokeratoderma

Same protein, different disease

• Autosomal recessive nonsyndromic hearing loss 4 is also caused by GJB2 variants; they fall mostly in different places as the Ichthyosis and erythrokeratoderma variants (38 disease-causing).
• Nonsyndromic genetic hearing loss is also caused by GJB2 variants; they fall mostly in different places as the Ichthyosis and erythrokeratoderma variants (28 disease-causing).
• Rare genetic deafness is also caused by GJB2 variants; they fall mostly in different places as the Ichthyosis and erythrokeratoderma variants (25 disease-causing).
• Mutilating keratoderma is also caused by GJB2 variants; they fall mostly in different places as the Ichthyosis and erythrokeratoderma variants (15 disease-causing).
• Ichthyosis, hystrix-like, with hearing loss is also caused by GJB2 variants; they fall mostly in different places as the Ichthyosis and erythrokeratoderma variants (13 disease-causing).
• Autosomal recessive congenital ichthyosis is also caused by TGM1 variants; they fall mostly in different places as the Ichthyosis and erythrokeratoderma variants (64 disease-causing).
• Lamellar ichthyosis is also caused by TGM1 variants; they fall mostly in different places as the Ichthyosis and erythrokeratoderma variants (24 disease-causing).
• Epidermolytic hyperkeratosis 2A, autosomal dominant is also caused by KRT10 variants; they fall mostly in different places as the Ichthyosis and erythrokeratoderma variants (7 disease-causing).
• Pachyonychia congenita is also caused by KRT16 variants; they fall partly in the same places as the Ichthyosis and erythrokeratoderma variants (12 disease-causing).
• Palmoplantar keratoderma, nonepidermolytic, focal 1 is also caused by KRT16 variants; they fall mostly in different places as the Ichthyosis and erythrokeratoderma variants (6 disease-causing).

Diseases related to Ichthyosis and erythrokeratoderma

• Pachyonychia congenita, also linked to KRT10 and KRT16
• Congenital reticular ichthyosiform erythroderma, also linked to KRT10 and TGM1
• Autosomal recessive nonsyndromic hearing loss 4, also linked to GJB2
• Noonan syndrome, also linked to GJB2
• Rare genetic deafness, also linked to GJB2
• Autosomal dominant nonsyndromic hearing loss, also linked to GJB2
• Autosomal recessive congenital ichthyosis, also linked to TGM1
• Nonsyndromic genetic hearing loss, also linked to GJB2
• Lamellar ichthyosis, also linked to TGM1
• Hearing loss, also linked to GJB2
• Monogenic hearing loss, also linked to GJB2
• Mutilating keratoderma, also linked to GJB2

Frequently asked questions

Which genes are linked to Ichthyosis and erythrokeratoderma?

In CATVariant, Ichthyosis and erythrokeratoderma is linked to 4 analyzed proteins: GJB2 (Gap junction beta-2 protein), TGM1 (Protein-glutamine gamma-glutamyltransferase K), KRT10 (Keratin, type I cytoskeletal 10) and KRT16 (Keratin, type I cytoskeletal 16).

How many genetic variants are linked to Ichthyosis and erythrokeratoderma?

6 variants: 6 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 0 are of uncertain significance or have conflicting reports.

Which uncertain variants in Ichthyosis and erythrokeratoderma look disease-causing?

None of the uncertain variants currently reaches the likely-pathogenic range on computable evidence alone.

About this data

Variant–disease links come from ClinVar, Open Targets and UniProt, pooled from the latest public CATVariant analysis of each human protein. Evidence scores use the ACMG/AMP Bayesian points scale with computable criteria only (position among known disease variants, rarity in gnomAD, calibrated predictors, deep mutational scanning); there is no family or patient data, so they prioritise variants for expert review and never classify them.

Download every variant as CSV · Browse all diseases · Methods · About the Center