Epidermolysis bullosa simplex 1A, generalized severe: genes and variants

Genes linked to Epidermolysis bullosa simplex 1A, generalized severe

• KRT14: Keratin, type I cytoskeletal 14

  It pairs with keratin 5 to provide mechanical strength to basal epidermal keratinocytes. Dominant-negative variants are a major cause of epidermolysis bullosa simplex, while other variants can cause pigmentation disorders or ectodermal phenotypes.

  6 disease-causing and 1 uncertain variants in KRT14 are linked to Epidermolysis bullosa simplex 1A, generalized severe.

• KRT5: Keratin, type II cytoskeletal 5

  It pairs with keratin 14 to form the primary intermediate-filament scaffold of basal epidermal keratinocytes. Dominant pathogenic variants are a major cause of epidermolysis bullosa simplex, while other alleles can cause pigmentary disorders such as Dowling-Degos disease.

  2 disease-causing and 2 uncertain variants in KRT5 are linked to Epidermolysis bullosa simplex 1A, generalized severe.

• COL7A1: Collagen alpha-1(VII) chain

  It forms anchoring fibrils that secure the epidermal basement membrane to the underlying dermis. Pathogenic variants cause dystrophic epidermolysis bullosa, with skin fragility and scarring ranging from localized disease to severe generalized forms with major complications.

  1 disease-causing and 0 uncertain variants in COL7A1 are linked to Epidermolysis bullosa simplex 1A, generalized severe.

Where Epidermolysis bullosa simplex 1A, generalized severe variants cluster

• KRT14 Coil 1A (positions 115–150): 4 of 6 disease-causing changes, 8.7× more than its size predicts.

Known disease-causing variants in Epidermolysis bullosa simplex 1A, generalized severe

Which prediction tools work for Epidermolysis bullosa simplex 1A, generalized severe

How often each tool ranks a disease-causing variant above a harmless one (AUROC × 100).

• CATVariant: 100 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• AlphaMissense: 100 out of 100
• PolyPhen-2: 92 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• MetaLR: 91 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• SIFT: 87 out of 100

Same protein, different disease

• Dermatopathia pigmentosa reticularis is also caused by KRT14 variants; they fall partly in the same places as the Epidermolysis bullosa simplex 1A, generalized severe variants (8 disease-causing).
• Epidermolysis bullosa simplex, Koebner type is also caused by KRT14 variants; they fall in the same places as the Epidermolysis bullosa simplex 1A, generalized severe variants (7 disease-causing).
• Epidermolysis bullosa simplex is also caused by KRT14 variants; they fall mostly in different places as the Epidermolysis bullosa simplex 1A, generalized severe variants (6 disease-causing).
• Epidermolysis bullosa simplex 1C, localized is also caused by KRT14 variants; they fall mostly in different places as the Epidermolysis bullosa simplex 1A, generalized severe variants (4 disease-causing).
• Epidermolysis bullosa simplex 1D, generalized, intermediate or severe, autosomal recessive is also caused by KRT14 variants; they fall mostly in different places as the Epidermolysis bullosa simplex 1A, generalized severe variants (4 disease-causing).
• Epidermolysis bullosa simplex is also caused by KRT5 variants; they fall mostly in different places as the Epidermolysis bullosa simplex 1A, generalized severe variants (18 disease-causing).
• Epidermolysis bullosa simplex 2B, generalized intermediate is also caused by KRT5 variants; they fall mostly in different places as the Epidermolysis bullosa simplex 1A, generalized severe variants (5 disease-causing).
• Epidermolysis bullosa simplex 1C, localized is also caused by KRT5 variants; they fall mostly in different places as the Epidermolysis bullosa simplex 1A, generalized severe variants (3 disease-causing).
• Epidermolysis bullosa dystrophica is also caused by COL7A1 variants; they fall mostly in different places as the Epidermolysis bullosa simplex 1A, generalized severe variants (64 disease-causing).
• Recessive dystrophic epidermolysis bullosa is also caused by COL7A1 variants; they fall mostly in different places as the Epidermolysis bullosa simplex 1A, generalized severe variants (53 disease-causing).
• Generalized dominant dystrophic epidermolysis bullosa is also caused by COL7A1 variants; they fall mostly in different places as the Epidermolysis bullosa simplex 1A, generalized severe variants (26 disease-causing).
• Nonsyndromic congenital nail disorder 8 is also caused by COL7A1 variants; they fall mostly in different places as the Epidermolysis bullosa simplex 1A, generalized severe variants (15 disease-causing).
• Dominant dystrophic epidermolysis bullosa with absence of skin is also caused by COL7A1 variants; they fall mostly in different places as the Epidermolysis bullosa simplex 1A, generalized severe variants (12 disease-causing).

Diseases related to Epidermolysis bullosa simplex 1A, generalized severe

• Epidermolysis bullosa simplex, also linked to KRT14 and KRT5
• Epidermolysis bullosa simplex, Koebner type, also linked to KRT14 and KRT5
• Epidermolysis bullosa simplex 1C, localized, also linked to KRT14 and KRT5
• Epidermolysis bullosa simplex 1D, generalized, intermediate or severe, autosomal recessive, also linked to KRT14 and KRT5
• Epidermolysis bullosa, also linked to COL7A1 and KRT5
• Epidermolysis bullosa dystrophica, also linked to COL7A1
• Recessive dystrophic epidermolysis bullosa, also linked to COL7A1
• Generalized dominant dystrophic epidermolysis bullosa, also linked to COL7A1
• Nonsyndromic congenital nail disorder 8, also linked to COL7A1
• Dominant dystrophic epidermolysis bullosa with absence of skin, also linked to COL7A1
• Transient bullous dermolysis of the newborn, also linked to COL7A1
• Dermatopathia pigmentosa reticularis, also linked to KRT14

Frequently asked questions

Which genes are linked to Epidermolysis bullosa simplex 1A, generalized severe?

In CATVariant, Epidermolysis bullosa simplex 1A, generalized severe is linked to 3 analyzed proteins: KRT14 (Keratin, type I cytoskeletal 14), KRT5 (Keratin, type II cytoskeletal 5) and COL7A1 (Collagen alpha-1(VII) chain).

How many genetic variants are linked to Epidermolysis bullosa simplex 1A, generalized severe?

36 variants: 9 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 3 are of uncertain significance or have conflicting reports.

Which uncertain variants in Epidermolysis bullosa simplex 1A, generalized severe look disease-causing?

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

Which variant effect predictor works best for Epidermolysis bullosa simplex 1A, generalized severe?

Among tools not trained on clinical labels, AlphaMissense separates this disease's known disease-causing variants from harmless ones best (AUROC 1.00, based on 8 disease-causing and 8 harmless variants).

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.

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