TSC2
Chr 16ADTSC complex subunit 2
Also known as: LAM, PPP1R160, TSC4
TSC2 encodes tuberin, which with hamartin (TSC1) holds mTOR signalling in check; losing one copy causes tuberous sclerosis complex, and a second hit in a tissue grows the hamartomas. TSC affects about 1 in 5,800 to 1 in 13,500 births; two thirds of cases are de novo. TSC2 variants are the more common cause, more often de novo, and on average more severe than TSC1.
Ten to fifteen percent of people who meet the clinical criteria have no variant on standard testing; in up to 58% of them the variant is mosaic, found with deep sequencing or in affected tissue, and in up to 40% it is intronic. A deletion that takes TSC2 and the neighbouring PKD1 adds early polycystic kidney disease, with a real risk of kidney failure.
Vigabatrin is the first-line treatment for infantile spasms in TSC; everolimus and cannabidiol are approved for TSC-associated seizures, and everolimus is first line for growing kidney angiomyolipomas.
Primary Disease Associations & Inheritance
Clinical highlights
- Definitive · tuberous sclerosis 2 · AD · Ambry Genetics
- Strong · lymphangioleiomyomatosis · AD · Genomics England PanelApp
- Supportive · tuberous sclerosis complex · AD · Orphanet
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Among the most LoF-intolerant genes (~top 3%)
Tolerant to missense variation
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
TSC2 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools