Autosomal recessive congenital ichthyosis: genes and variants

Genes linked to Autosomal recessive congenital 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.

  64 disease-causing and 91 uncertain variants in TGM1 are linked to Autosomal recessive congenital ichthyosis.

Weakly linked (only a few uncertain records): BACH2, FLG and MEFV.

Known disease-causing variants in Autosomal recessive congenital ichthyosis

Showing 60 of 64.

Which prediction tools work for Autosomal recessive congenital ichthyosis

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

• MutPred2: 100 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• MetaLR: 100 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• REVEL: 99 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• CATVariant: 98 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• AlphaMissense: 94 out of 100
• SIFT: 94 out of 100
• CADD: 90 out of 100
• PolyPhen-2: 87 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• phyloP: 76 out of 100

Diseases related to Autosomal recessive congenital ichthyosis

• Lamellar 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 Autosomal recessive congenital ichthyosis?

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

How many genetic variants are linked to Autosomal recessive congenital ichthyosis?

207 variants: 64 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 93 are of uncertain significance or have conflicting reports.

Which uncertain variants in Autosomal recessive congenital 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 Autosomal recessive congenital ichthyosis?

Among tools not trained on clinical labels, AlphaMissense separates this disease's known disease-causing variants from harmless ones best (AUROC 0.94, based on 16 disease-causing and 278 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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