Severe intellectual disability-progressive spastic diplegia syndrome: genes and variants
Severe intellectual disability-progressive spastic diplegia syndrome is linked to 1 analyzed protein (CTNNB1). 5 DNA variants are known to cause it; 13 more are uncertain, and 0 of those already look disease-causing on computable evidence.
Last updated 2026-09-30. Research information, not medical advice.
Genes linked to Severe intellectual disability-progressive spastic diplegia syndrome
CTNNB1: Catenin beta-1
It links cadherins to the cytoskeleton at adherens junctions and, when stabilized by Wnt signaling, enters the nucleus to regulate transcription. Activating somatic variants drive many cancers, while germline loss-of-function variants cause CTNNB1 neurodevelopmental disorder.
5 disease-causing and 13 uncertain variants in CTNNB1 are linked to Severe intellectual disability-progressive spastic diplegia syndrome.
Known disease-causing variants in Severe intellectual disability-progressive spastic diplegia syndrome
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| CTNNB1 S348F | 348 | ARM 5 | Disease-causing (★) |
| CTNNB1 L424R | 424 | ARM 7 | Disease-causing (★) |
| CTNNB1 G575R | 575 | Disease-causing (★) | |
| CTNNB1 E692D | 692 | Disease-causing (★) | |
| CTNNB1 G216R | 216 | ARM 2 | Disease-causing |
Same protein, different disease
- Pilomatrixoma is also caused by CTNNB1 variants; they fall mostly in different places as the Severe intellectual disability-progressive spastic diplegia syndrome variants (8 disease-causing).
- Medulloblastoma is also caused by CTNNB1 variants; they fall mostly in different places as the Severe intellectual disability-progressive spastic diplegia syndrome variants (4 disease-causing).
Diseases related to Severe intellectual disability-progressive spastic diplegia syndrome
- Ovarian cancer, also linked to CTNNB1
- Colorectal cancer, also linked to CTNNB1
- Malignant tumor of urinary bladder, also linked to CTNNB1
- Ovarian neoplasm, also linked to CTNNB1
- Carcinoma of colon, also linked to CTNNB1
- Pilomatrixoma, also linked to CTNNB1
- Hepatocellular carcinoma, also linked to CTNNB1
- Medulloblastoma, also linked to CTNNB1
- Desmoid disease, hereditary, also linked to CTNNB1
- Autosomal dominant polycystic liver disease, also linked to CTNNB1
- Familial exudative vitreoretinopathy, also linked to CTNNB1
- Hepatoblastoma, also linked to CTNNB1
Frequently asked questions
Which genes are linked to Severe intellectual disability-progressive spastic diplegia syndrome?
In CATVariant, Severe intellectual disability-progressive spastic diplegia syndrome is linked to 1 analyzed protein: CTNNB1 (Catenin beta-1).
How many genetic variants are linked to Severe intellectual disability-progressive spastic diplegia syndrome?
44 variants: 5 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 13 are of uncertain significance or have conflicting reports.
Which uncertain variants in Severe intellectual disability-progressive spastic diplegia 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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