Lamellar ichthyosis: genes and variants

Genes linked to Lamellar ichthyosis

• 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.

  24 disease-causing and 0 uncertain variants in TGM1 are linked to Lamellar ichthyosis.

Known disease-causing variants in Lamellar ichthyosis

Which prediction tools work for Lamellar ichthyosis

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

• REVEL: 99 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• CATVariant: 96 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• MetaLR: 96 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• SIFT: 91 out of 100
• CADD: 90 out of 100
• PolyPhen-2: 90 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• phyloP: 71 out of 100

Same protein, different disease

• Autosomal recessive congenital ichthyosis is also caused by TGM1 variants; they fall partly in the same places as the Lamellar ichthyosis variants (64 disease-causing).

Diseases related to Lamellar ichthyosis

• Autosomal recessive congenital ichthyosis, also linked to TGM1
• Ichthyosis and erythrokeratoderma, also linked to TGM1
• Treacher Collins syndrome 2, also linked to TGM1
• Congenital reticular ichthyosiform erythroderma, also linked to TGM1

Frequently asked questions

Which genes are linked to Lamellar ichthyosis?

In CATVariant, Lamellar ichthyosis is linked to 1 analyzed protein: TGM1 (Protein-glutamine gamma-glutamyltransferase K).

How many genetic variants are linked to Lamellar ichthyosis?

30 variants: 24 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 Lamellar ichthyosis 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 Lamellar ichthyosis?

Among tools not trained on clinical labels, SIFT separates this disease's known disease-causing variants from harmless ones best (AUROC 0.91, based on 24 disease-causing and 18 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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