Junctional epidermolysis bullosa: genes and variants

Genes linked to Junctional epidermolysis bullosa

• LAMB3: Laminin subunit beta-3

  It contributes the beta3 chain of laminin-332, an essential ligand for hemidesmosomal adhesion at the epidermal basement membrane. Biallelic loss-of-function variants cause junctional epidermolysis bullosa, and selected variants can also cause amelogenesis imperfecta.

  4 disease-causing and 63 uncertain variants in LAMB3 are linked to Junctional epidermolysis bullosa.

• LAMA3: Laminin subunit alpha-3

  It contributes to laminin-332 in epithelial basement membranes, where it supports stable attachment of basal keratinocytes to underlying matrix. Biallelic pathogenic variants can cause junctional epidermolysis bullosa, while some variants cause amelogenesis imperfecta or milder skin disease.

  2 disease-causing and 5 uncertain variants in LAMA3 are linked to Junctional epidermolysis bullosa.

• ITGB4: Integrin beta-4

  It pairs with alpha6 integrin in hemidesmosomes to anchor epithelial cells to laminin-rich basement membranes. Biallelic loss-of-function variants can cause junctional epidermolysis bullosa with pyloric atresia and severe epithelial fragility.

  2 disease-causing and 0 uncertain variants in ITGB4 are linked to Junctional epidermolysis bullosa.

• LAMC2: Laminin subunit gamma-2

  It contributes the gamma2 chain of laminin-332 and helps anchor epithelial cells to basement membrane through integrin and dystroglycan interactions. Biallelic pathogenic variants cause junctional epidermolysis bullosa with skin and mucosal fragility.

  1 disease-causing and 31 uncertain variants in LAMC2 are linked to Junctional epidermolysis bullosa.

• COL17A1: Collagen alpha-1(XVII) chain

  It anchors basal keratinocytes to the basement membrane through hemidesmosomes and is essential for stable epidermal adhesion. Biallelic loss-of-function variants cause junctional epidermolysis bullosa, while autoantibodies against the protein cause bullous pemphigoid.

  0 disease-causing and 1 uncertain variants in COL17A1 are linked to Junctional epidermolysis bullosa.

Weakly linked (only a few uncertain records): ITGA6.

Known disease-causing variants in Junctional epidermolysis bullosa

Which prediction tools work for Junctional epidermolysis bullosa

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

• CATVariant: 90 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• PolyPhen-2: 84 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• SIFT: 82 out of 100

Same protein, different disease

• Junctional epidermolysis bullosa with pyloric atresia is also caused by ITGB4 variants; they fall mostly in different places as the Junctional epidermolysis bullosa variants (13 disease-causing).
• Epidermolysis bullosa, junctional 5A, intermediate is also caused by ITGB4 variants; they fall mostly in different places as the Junctional epidermolysis bullosa variants (5 disease-causing).

Diseases related to Junctional epidermolysis bullosa

• Junctional epidermolysis bullosa, non-Herlitz type, also linked to COL17A1, ITGB4, LAMA3, LAMB3 and 1 more
• Junctional epidermolysis bullosa gravis of Herlitz, also linked to LAMA3, LAMB3 and LAMC2
• Amelogenesis imperfecta, also linked to COL17A1 and LAMB3
• Epidermolysis bullosa, junctional 4, intermediate, also linked to COL17A1 and LAMA3
• Junctional epidermolysis bullosa with pyloric atresia, also linked to ITGB4
• Fetal anomalies with a likely genetic cause, also linked to ITGB4
• Epidermolysis bullosa, junctional 5A, intermediate, also linked to ITGB4
• Epithelial recurrent erosion dystrophy, also linked to COL17A1

Frequently asked questions

Which genes are linked to Junctional epidermolysis bullosa?

In CATVariant, Junctional epidermolysis bullosa is linked to 5 analyzed proteins: LAMB3 (Laminin subunit beta-3), LAMA3 (Laminin subunit alpha-3), ITGB4 (Integrin beta-4), LAMC2 (Laminin subunit gamma-2) and COL17A1 (Collagen alpha-1(XVII) chain).

How many genetic variants are linked to Junctional epidermolysis bullosa?

160 variants: 9 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 100 are of uncertain significance or have conflicting reports.

Which uncertain variants in Junctional epidermolysis bullosa 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 Junctional epidermolysis bullosa?

Among tools not trained on clinical labels, SIFT separates this disease's known disease-causing variants from harmless ones best (AUROC 0.82, based on 9 disease-causing and 209 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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