TSC2 Gene (Tuberin): Function, Mutations, and Associated Diseases
A comprehensive biomedical overview of the TSC2 gene, its protein product tuberin, related disorders, expression patterns, and mutation landscape.
Gene Information Card
| Symbol | TSC2 |
|---|---|
| Full Name | TSC complex subunit 2 |
| Gene Type | protein-coding |
| Chromosomal Location | 16p13.3 |
| NCBI Gene ID | 7249 ncbi.nlm.nih.gov/gene/7249 |
| Ensembl ID | ENSG00000103197 |
| UniProt ID | P49815 |
| OMIM ID | 191092 |
| HGNC ID | 12363 |
| Aliases | TSC4, LAM, PPP1R160 |
Description
The TSC2 gene encodes tuberin, a large protein that functions as a GTPase-activating protein (GAP) for the small GTPase Rheb. Tuberin forms a complex with hamartin (encoded by TSC1) to inhibit mTORC1 signaling, thereby regulating cell growth, proliferation, and autophagy. Loss-of-function mutations in TSC2 lead to tuberous sclerosis complex (TSC), characterized by benign tumors in multiple organs. TSC2 is also implicated in lymphangioleiomyomatosis (LAM) and various cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Tuberous sclerosis complex (TSC) | Loss-of-function mutations in TSC2 lead to constitutive activation of mTORC1 due to loss of Rheb GAP activity, causing uncontrolled cell growth and hamartoma formation. | ClinVar, OMIM |
| Lymphangioleiomyomatosis (LAM) | Somatic or germline TSC2 mutations cause abnormal proliferation of smooth muscle-like cells in the lungs, driven by mTORC1 hyperactivation. | ClinVar, OMIM |
| Renal cell carcinoma | TSC2 mutations (often somatic) contribute to tumorigenesis via mTORC1 activation and metabolic reprogramming. | COSMIC, ClinVar |
| Focal cortical dysplasia (type IIb) | Somatic TSC2 mutations in brain tissue lead to mTORC1 hyperactivation, causing abnormal neuronal migration and cortical malformations. | ClinVar, PubMed (via OMIM) |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 10.2 | Medium |
| Lung | 8.5 | Medium |
| Kidney | 12.3 | High |
| Heart | 7.1 | Low |
| Liver | 6.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 15.4 | High expression; commonly used for functional studies |
| HeLa | 9.8 | Moderate expression |
| A549 (lung carcinoma) | 7.2 | Low expression; relevant for LAM studies |
| MCF7 (breast cancer) | 6.5 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1378C>T (p.Arg460Ter) | Nonsense | ~2% in TSC patients | Truncated protein, loss of GAP domain function |
| c.1513C>T (p.Arg505Ter) | Nonsense | ~1.5% in TSC patients | Premature stop, loss of function |
| c.1831_1832del (p.Leu611fs) | Frameshift | ~1% in TSC patients | Frameshift leading to truncated protein |
| c.2095C>T (p.Arg699Trp) | Missense | ~0.5% in TSC patients | Disrupts GAP domain, reduced Rheb GAP activity |
| c.5238_5242del (p.Glu1747fs) | Frameshift | Somatic in LAM | Loss of function, mTORC1 activation |
Mutation functional classification
Loss of Function (LOF)
Most TSC2 mutations are loss-of-function, leading to reduced or absent tuberin activity, resulting in mTORC1 hyperactivation.
Gain of Function (GOF)
No gain-of-function mutations have been reported for TSC2; all pathogenic variants are loss-of-function.
Dominant Negative (DN)
Some missense mutations may exert a dominant-negative effect by disrupting the TSC1-TSC2 complex, but this is not well established.
View complete mutation data：
Gene Ontology (GO)
| • GTPase activator activity | • Protein binding |
| • Signal transduction | • Negative regulation of TOR signaling |
| • Regulation of cell growth | • Autophagy |
Pathways
• mTOR signaling pathway
• AMPK signaling pathway
• PI3K-Akt signaling pathway
• Autophagy pathway
Protein Summary
Tuberin (TSC2) is a 1807-amino-acid protein with a C-terminal GTPase-activating protein (GAP) domain that specifically acts on Rheb. It forms a heterodimer with hamartin (TSC1) to integrate signals from PI3K/Akt, AMPK, and ERK pathways. The TSC1-TSC2 complex converts Rheb-GTP to Rheb-GDP, thereby inhibiting mTORC1. Loss of tuberin function leads to uncontrolled cell growth and tumorigenesis. Tuberin also plays roles in vesicular trafficking, cytoskeletal organization, and transcriptional regulation.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TSC22D1 Knockout HEK293 Cell Line | EDJ-KQ5700 | Human | 8848 | Details Get a Quote |
| TSC22D2 Knockout HEK293 Cell Line | EDJ-KQ6761 | Human | 9819 | Details Get a Quote |
| TSC2 Knockout HEK293 Cell Line | EDJ-KQ17912 | Human | 7249 | Details Get a Quote |
| TSC2 Knockout HCT 116 Cell Line | EDJ-KQ18154 | Human | 7249 | Details Get a Quote |
| TSC22D2 Knockout HCT 116 Cell Line | EDJ-KQ31195 | Human | 9819 | Details Get a Quote |
| TSC22D2 Knockout HeLa Cell Line | EDJ-KQ31196 | Human | 9819 | Details Get a Quote |
| TSC2 Knockout A-549 Cell Line | EDJ-KQ19695 | Human | 7249 | Details Get a Quote |
| TSC2 Knockout HeLa Cell Line | EDJ-KQ19696 | Human | 7249 | Details Get a Quote |
| TSC22D1 Knockout A-549 Cell Line | EDJ-KQ30394 | Human | 8848 | Details Get a Quote |
| TSC22D1 Knockout HCT 116 Cell Line | EDJ-KQ30396 | Human | 8848 | Details Get a Quote |
| TSC22D1 Knockout HeLa Cell Line | EDJ-KQ30397 | Human | 8848 | Details Get a Quote |
| Tsc2 Knockout NIH 3T3 Cell Line | EDJ-KZ66 | Mouse | 22084 | Details Get a Quote |
| Tsc2 Knockout RAW 264.7 Cell Line | EDJ-KZ67 | Mouse | 22084 | Details Get a Quote |
| TSC2 Knockout U-87MG ATCC Cell Line | EDJ-KZ68 | Human | 7249 | Details Get a Quote |
| TSC22D3 Knockout HEK293 Cell Line | EDJ-KQ50244 | Human | 1831 | Details Get a Quote |
Displaying Records 1 To 15 Of 25 Records
