Irido-corneo-trabecular dysgenesis: genes and variants

Genes linked to Irido-corneo-trabecular dysgenesis

• PAX6: Paired box protein Pax-6

  It orchestrates developmental gene programs in the eye, forebrain, and pancreatic endocrine system. Haploinsufficiency most classically causes aniridia and can also produce broader ocular, endocrine, and neurodevelopmental abnormalities.

  40 disease-causing and 93 uncertain variants in PAX6 are linked to Irido-corneo-trabecular dysgenesis.

Weakly linked (only a few uncertain records): FAT1.

Where Irido-corneo-trabecular dysgenesis variants cluster

• PAX6 Paired (positions 4–130): 28 of 40 disease-causing changes, 2.3× more than its size predicts.

Known disease-causing variants in Irido-corneo-trabecular dysgenesis

Uncertain variants in Irido-corneo-trabecular dysgenesis that look disease-causing

Which prediction tools work for Irido-corneo-trabecular dysgenesis

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)
• MetaLR: 99 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• SIFT: 88 out of 100
• PolyPhen-2: 84 out of 100 (learned from overlapping clinical labels, so this is optimistic)

Same protein, different disease

• Aniridia is also caused by PAX6 variants; they fall partly in the same places as the Irido-corneo-trabecular dysgenesis variants (60 disease-causing).
• Coloboma, ocular, autosomal dominant is also caused by PAX6 variants; they fall in the same places as the Irido-corneo-trabecular dysgenesis variants (5 disease-causing).

Diseases related to Irido-corneo-trabecular dysgenesis

• Aniridia, also linked to PAX6
• Coloboma, ocular, autosomal dominant, also linked to PAX6
• Foveal hypoplasia 1, also linked to PAX6
• Coloboma of optic nerve, also linked to PAX6

Frequently asked questions

Which genes are linked to Irido-corneo-trabecular dysgenesis?

In CATVariant, Irido-corneo-trabecular dysgenesis is linked to 1 analyzed protein: PAX6 (Paired box protein Pax-6).

How many genetic variants are linked to Irido-corneo-trabecular dysgenesis?

139 variants: 40 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 94 are of uncertain significance or have conflicting reports.

Which uncertain variants in Irido-corneo-trabecular dysgenesis look disease-causing?

3 uncertain variants reach the likely-pathogenic range of the ACMG/AMP points scale on computable evidence, for example PAX6 G13D, PAX6 G51E and PAX6 R125S. These are leads for expert review, not diagnoses.

Which variant effect predictor works best for Irido-corneo-trabecular dysgenesis?

Among tools not trained on clinical labels, SIFT separates this disease's known disease-causing variants from harmless ones best (AUROC 0.88, based on 29 disease-causing and 123 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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