Macrocephaly-intellectual disability-neurodevelopmental disorder-small thorax syndrome: genes and variants

Genes linked to Macrocephaly-intellectual disability-neurodevelopmental disorder-small thorax syndrome

• MTOR: Serine/threonine-protein kinase mTOR

  It integrates nutrient, energy, oxygen, and growth-factor signals to control protein synthesis, autophagy, metabolism, and cell growth. Activating germline or mosaic variants can cause developmental brain overgrowth and epilepsy, while persistent pathway activation is common in cancer.

  13 disease-causing and 53 uncertain variants in MTOR are linked to Macrocephaly-intellectual disability-neurodevelopmental disorder-small thorax syndrome.

Where Macrocephaly-intellectual disability-neurodevelopmental disorder-small thorax syndrome variants cluster

• MTOR FAT (positions 1382–1982): 6 of 13 disease-causing changes, 2.0× more than its size predicts.
• MTOR PI3K/PI4K catalytic (positions 2156–2469): 3 of 13 disease-causing changes, 1.9× more than its size predicts.

Known disease-causing variants in Macrocephaly-intellectual disability-neurodevelopmental disorder-small thorax syndrome

Which prediction tools work for Macrocephaly-intellectual disability-neurodevelopmental disorder-small thorax syndrome

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

• PolyPhen-2: 85 out of 100 (learned from overlapping clinical labels, so this is optimistic)

Same protein, different disease

• Overgrowth syndrome and/or cerebral malformations due to abnormalities in MTOR pathway genes is also caused by MTOR variants; they fall mostly in different places as the Macrocephaly-intellectual disability-neurodevelopmental disorder-small thorax syndrome variants (12 disease-causing).
• Isolated focal cortical dysplasia type II is also caused by MTOR variants; they fall mostly in different places as the Macrocephaly-intellectual disability-neurodevelopmental disorder-small thorax syndrome variants (9 disease-causing).
• CEBALID syndrome is also caused by MTOR variants; they fall mostly in different places as the Macrocephaly-intellectual disability-neurodevelopmental disorder-small thorax syndrome variants (6 disease-causing).

Diseases related to Macrocephaly-intellectual disability-neurodevelopmental disorder-small thorax syndrome

• Overgrowth syndrome and/or cerebral malformations due to abnormalities in MTOR pathway genes, also linked to MTOR
• Isolated focal cortical dysplasia type II, also linked to MTOR
• CEBALID syndrome, also linked to MTOR

Frequently asked questions

Which genes are linked to Macrocephaly-intellectual disability-neurodevelopmental disorder-small thorax syndrome?

In CATVariant, Macrocephaly-intellectual disability-neurodevelopmental disorder-small thorax syndrome is linked to 1 analyzed protein: MTOR (Serine/threonine-protein kinase mTOR).

How many genetic variants are linked to Macrocephaly-intellectual disability-neurodevelopmental disorder-small thorax syndrome?

77 variants: 13 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 53 are of uncertain significance or have conflicting reports.

Which uncertain variants in Macrocephaly-intellectual disability-neurodevelopmental disorder-small thorax syndrome look disease-causing?

None of the uncertain variants currently reaches the likely-pathogenic range on computable evidence alone.

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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