TSC1 Gene (Tuberous Sclerosis 1): Structure, Function, and Clinical Significance
A comprehensive biomedical overview of the TSC1 gene, its protein product hamartin, associated diseases, expression patterns, and mutational landscape.
Gene Information Card
| Symbol | TSC1 |
|---|---|
| Full Name | TSC complex subunit 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 9q34.13 |
| NCBI Gene ID | 7248 ncbi.nlm.nih.gov/gene/7248 |
| Ensembl ID | ENSG00000165699 |
| UniProt ID | Q92574 |
| OMIM ID | 605284 |
| HGNC ID | 11830 |
| Aliases | KIAA0243, LAM, TSC |
Description
The TSC1 gene encodes hamartin, a protein that forms a complex with tuberin (encoded by TSC2) to regulate cell growth and proliferation via the mTOR signaling pathway. Mutations in TSC1 cause tuberous sclerosis complex, a multisystem disorder characterized by benign tumors in the brain, kidneys, skin, and other organs. TSC1 also plays roles in vesicular trafficking, ciliogenesis, and regulation of the Wnt and AMPK pathways.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Tuberous sclerosis complex (TSC) | Loss-of-function mutations in TSC1 lead to hyperactivation of mTORC1, promoting uncontrolled cell growth and tumor formation. | ClinVar, OMIM |
| Lymphangioleiomyomatosis (LAM) | Somatic or germline TSC1 mutations cause abnormal proliferation of smooth muscle-like cells in the lungs. | OMIM, COSMIC |
| Focal cortical dysplasia (FCD) | Somatic mutations in TSC1 are associated with malformations of cortical development, leading to epilepsy. | ClinVar, literature |
| Renal cell carcinoma | Loss of TSC1 function contributes to renal tumorigenesis through mTOR pathway activation. | COSMIC, ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 10.2 | Medium |
| Kidney | 8.5 | Medium |
| Lung | 7.9 | Medium |
| Heart | 6.8 | Low |
| Liver | 5.4 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 12.3 | Embryonic kidney cells; high expression |
| HeLa | 9.8 | Cervical carcinoma; moderate expression |
| A549 | 7.5 | Lung carcinoma; moderate expression |
| MCF7 | 6.2 | Breast carcinoma; low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1909C>T (p.Arg637Ter) | Nonsense | ~5% of TSC1 mutations | Truncated protein, loss of function |
| c.2074C>T (p.Arg692Ter) | Nonsense | ~3% of TSC1 mutations | Truncated protein, loss of function |
| c.1550_1551del (p.Glu517ValfsTer2) | Frameshift | ~2% of TSC1 mutations | Frameshift leading to premature stop codon |
| c.733C>T (p.Arg245Ter) | Nonsense | ~1% of TSC1 mutations | Truncated protein, loss of function |
Mutation functional classification
Loss of Function (LOF)
Most TSC1 mutations are loss-of-function, leading to reduced hamartin protein levels or impaired complex formation with TSC2, resulting in mTORC1 hyperactivation.
Gain of Function (GOF)
No gain-of-function mutations have been reported for TSC1; it acts as a tumor suppressor.
Dominant Negative (DN)
Some missense mutations may exert dominant-negative effects by disrupting the TSC1-TSC2 complex, but evidence is limited.
View complete mutation data：
Gene Ontology (GO)
| • protein binding | • GTPase activator activity |
| • signal transduction | • negative regulation of cell growth |
| • regulation of mTOR signaling | • vesicle-mediated transport |
| • cilium assembly |
Pathways
• mTOR signaling pathway
• AMPK signaling
• Wnt signaling pathway
• PI3K-Akt signaling pathway
• Autophagy regulation
Protein Summary
Hamartin (TSC1) is a 130 kDa protein that interacts with tuberin (TSC2) to form a tumor suppressor complex. This complex acts as a GTPase-activating protein (GAP) for Rheb, inhibiting mTORC1 signaling. Hamartin also stabilizes TSC2 and is involved in cellular processes such as vesicular trafficking, cell adhesion, and ciliogenesis. Mutations in TSC1 lead to loss of this regulatory function, causing uncontrolled cell growth and tumor development.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TSC1 Knockout HEK293 Cell Line | EDJ-KQ17911 | Human | 7248 | Details Get a Quote |
| TSC1 Knockout HCT 116 Cell Line | EDJ-KQ18155 | Human | 7248 | Details Get a Quote |
| TSC1 Knockout A-549 Cell Line | EDJ-KQ19693 | Human | 7248 | Details Get a Quote |
| TSC1 Knockout HeLa Cell Line | EDJ-KQ19694 | Human | 7248 | Details Get a Quote |
| Tsc1 Knockout MC3T3-E1 Cell Line | EDJ-KZ65 | Mouse | 64930 | Details Get a Quote |
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