Tuberous sclerosis syndrome: genes and variants
Tuberous sclerosis syndrome is linked to 2 analyzed proteins (TSC1 and TSC2). 4 DNA variants are known to cause it; 745 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 Tuberous sclerosis syndrome
TSC1: Hamartin
Together with TSC2, it restrains RHEB and mTORC1 signaling, preventing inappropriate cell growth when nutrients or growth signals are limited. Loss-of-function variants cause tuberous sclerosis complex with hamartomas and tumors in the brain, kidney, skin, heart, lungs, and other organs.
2 disease-causing and 435 uncertain variants in TSC1 are linked to Tuberous sclerosis syndrome.
TSC2: Tuberin
Together with TSC1, it inactivates RHEB and restrains mTORC1 when growth conditions are unfavorable. Loss-of-function variants cause tuberous sclerosis complex with hamartomas and tumors affecting the brain, kidneys, skin, heart, lungs, and other organs.
2 disease-causing and 310 uncertain variants in TSC2 are linked to Tuberous sclerosis syndrome.
Known disease-causing variants in Tuberous sclerosis syndrome
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| TSC1 M224R | 224 | Disease-causing (★★) | |
| TSC1 K121M | 121 | Disease-causing (★★) | |
| TSC2 G300V | 300 | Required for interaction with TSC1 | Disease-causing (★) |
| TSC2 Y598N | 598 | Disease-causing (★) |
Same protein, different disease
- Tuberous sclerosis is also caused by TSC1 variants; they fall mostly in different places as the Tuberous sclerosis syndrome variants (18 disease-causing).
- Tuberous sclerosis is also caused by TSC2 variants; they fall mostly in different places as the Tuberous sclerosis syndrome variants (57 disease-causing).
- Ovarian cancer is also caused by TSC2 variants; they fall mostly in different places as the Tuberous sclerosis syndrome variants (4 disease-causing).
Diseases related to Tuberous sclerosis syndrome
- Tuberous sclerosis, also linked to TSC1 and TSC2
- Ovarian cancer, also linked to TSC1 and TSC2
- Isolated focal cortical dysplasia type II, also linked to TSC1 and TSC2
- Lymphangiomyomatosis, also linked to TSC1 and TSC2
- Familial adenomatous polyposis, also linked to TSC2
- Malignant tumor of urinary bladder, also linked to TSC1
- Hepatocellular carcinoma, also linked to TSC2
Frequently asked questions
Which genes are linked to Tuberous sclerosis syndrome?
In CATVariant, Tuberous sclerosis syndrome is linked to 2 analyzed proteins: TSC1 (Hamartin) and TSC2 (Tuberin).
How many genetic variants are linked to Tuberous sclerosis syndrome?
778 variants: 4 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 745 are of uncertain significance or have conflicting reports.
Which uncertain variants in Tuberous sclerosis 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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