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 ClinVar pathogenic / likely pathogenic and 1 uncertain variants in KRT14 have source records linked to Epidermolysis bullosa simplex 1A, generalized severe. Association strength is not clinical gene validity.

• 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 ClinVar pathogenic / likely pathogenic and 2 uncertain variants in KRT5 have source records linked to Epidermolysis bullosa simplex 1A, generalized severe. Association strength is not clinical gene validity.

• 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 ClinVar pathogenic / likely pathogenic and 0 uncertain variants in COL7A1 have source records linked to Epidermolysis bullosa simplex 1A, generalized severe. Association strength is not clinical gene validity.

Where Epidermolysis bullosa simplex 1A, generalized severe variants cluster

• KRT14 Coil 1A (positions 115–150): 4 of 6 ClinVar pathogenic / likely pathogenic variants, 8.7× more than its size predicts.

ClinVar pathogenic and likely pathogenic variants linked to Epidermolysis bullosa simplex 1A, generalized severe

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

Observed separation of ClinVar pathogenic / likely pathogenic from benign / likely benign variants (AUROC × 100). This benchmark is not a clinical recommendation.

• 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 also has ClinVar records linked to KRT14 variants; they fall partly in the same places as the Epidermolysis bullosa simplex 1A, generalized severe variants (8 pathogenic / likely pathogenic).
• Generalized epidermolysis bullosa simplex, non-Dowling-Meara type also has ClinVar records linked to KRT14 variants; they fall in the same places as the Epidermolysis bullosa simplex 1A, generalized severe variants (7 pathogenic / likely pathogenic).
• Epidermolysis bullosa simplex also has ClinVar records linked to KRT14 variants; they fall mostly in different places as the Epidermolysis bullosa simplex 1A, generalized severe variants (6 pathogenic / likely pathogenic).
• KRT14-related epidermolysis bullosa simplex also has ClinVar records linked to KRT14 variants; they fall mostly in different places as the Epidermolysis bullosa simplex 1A, generalized severe variants (4 pathogenic / likely pathogenic).
• Localized epidermolysis bullosa simplex also has ClinVar records linked to KRT14 variants; they fall mostly in different places as the Epidermolysis bullosa simplex 1A, generalized severe variants (4 pathogenic / likely pathogenic).
• Epidermolysis bullosa simplex also has ClinVar records linked to KRT5 variants; they fall mostly in different places as the Epidermolysis bullosa simplex 1A, generalized severe variants (18 pathogenic / likely pathogenic).
• Epidermolysis bullosa simplex 2B, generalized intermediate also has ClinVar records linked to KRT5 variants; they fall mostly in different places as the Epidermolysis bullosa simplex 1A, generalized severe variants (5 pathogenic / likely pathogenic).
• Localized epidermolysis bullosa simplex also has ClinVar records linked to KRT5 variants; they fall mostly in different places as the Epidermolysis bullosa simplex 1A, generalized severe variants (3 pathogenic / likely pathogenic).
• Dystrophic epidermolysis bullosa also has ClinVar records linked to COL7A1 variants; they fall mostly in different places as the Epidermolysis bullosa simplex 1A, generalized severe variants (64 pathogenic / likely pathogenic).
• Recessive dystrophic epidermolysis bullosa also has ClinVar records linked to COL7A1 variants; they fall mostly in different places as the Epidermolysis bullosa simplex 1A, generalized severe variants (53 pathogenic / likely pathogenic).
• Generalized dominant dystrophic epidermolysis bullosa also has ClinVar records linked to COL7A1 variants; they fall mostly in different places as the Epidermolysis bullosa simplex 1A, generalized severe variants (26 pathogenic / likely pathogenic).
• Nonsyndromic congenital nail disorder 8 also has ClinVar records linked to COL7A1 variants; they fall mostly in different places as the Epidermolysis bullosa simplex 1A, generalized severe variants (15 pathogenic / likely pathogenic).
• Dominant dystrophic epidermolysis bullosa with absence of skin also has ClinVar records linked to COL7A1 variants; they fall mostly in different places as the Epidermolysis bullosa simplex 1A, generalized severe variants (12 pathogenic / likely pathogenic).

Diseases related to Epidermolysis bullosa simplex 1A, generalized severe

• Epidermolysis bullosa simplex, also linked to KRT14 and KRT5
• Generalized epidermolysis bullosa simplex, non-Dowling-Meara type, also linked to KRT14 and KRT5
• Localized epidermolysis bullosa simplex, also linked to KRT14 and KRT5
• KRT14-related epidermolysis bullosa simplex, also linked to KRT14 and KRT5
• Epidermolysis bullosa, also linked to COL7A1 and KRT5
• Dystrophic epidermolysis bullosa, 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 have records linked to Epidermolysis bullosa simplex 1A, generalized severe?

This view contains 3 analyzed proteins: KRT14, KRT5, COL7A1. Links come from clinical records and association databases. They do not imply that every listed gene is a validated cause, and missing genes may not yet be analyzed.

What do the clinical classifications mean?

Linked records include 9 pathogenic or likely pathogenic variants, 3 variants of uncertain significance and 0 with conflicting classifications. Labels summarize source records; multi-condition records may not make a separate assertion for this disease. Check the original record and review status.

Does the evidence score change a VUS classification?

No. 0 VUS or conflicting variants reach the likely-pathogenic points range on the computable criteria available here. This is a research prioritization signal, not a clinical classification. Patient, family and other required evidence may be missing.

Can I download the variant evidence?

Download the CSV for all 36 variants in the selected disease scope, including clinical labels, review status, evidence criteria, predictor scores, functional measurements and population frequency where available.

About this data

Variant–disease links come from ClinVar, Open Targets and UniProt, pooled from eligible public CATVariant analyses 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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