TSG101: Tumor Susceptibility 101 Gene and Its Role in Cancer and Cellular Trafficking
Comprehensive biomedical overview of TSG101, including genomic data, expression, mutations, and clinical significance.
Gene Information Card
| Symbol | TSG101 |
|---|---|
| Full Name | Tumor Susceptibility 101 |
| Gene Type | Protein coding |
| Chromosomal Location | 11p15.1 |
| NCBI Gene ID | 7251 ncbi.nlm.nih.gov/gene/7251 |
| Ensembl ID | ENSG00000074319 |
| UniProt ID | Q99816 |
| OMIM ID | 601387 |
| HGNC ID | 12371 |
| Aliases | TSG10, VPS23, ESCRT-I subunit |
Description
TSG101 (Tumor Susceptibility 101) encodes a protein that is a core component of the endosomal sorting complexes required for transport (ESCRT-I) machinery. It plays a critical role in multivesicular body (MVB) biogenesis, ubiquitin-dependent protein sorting, and cytokinesis. TSG101 also functions in transcriptional regulation and cell cycle control. Loss or dysregulation of TSG101 is implicated in tumorigenesis, particularly in breast and prostate cancers, as well as in viral budding and neurodegenerative disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Breast cancer | TSG101 frameshift mutations and reduced expression lead to genomic instability and altered cell proliferation. | PMID: 10557339; COSMIC |
| Prostate cancer | TSG101 overexpression and aberrant splicing contribute to tumor progression and metastasis. | PMID: 12007233; COSMIC |
| Endometrial cancer | TSG101 mutations and copy number alterations are recurrent in endometrial tumors. | COSMIC; TCGA |
| Colorectal cancer | TSG101 downregulation correlates with poor prognosis and increased invasiveness. | PMID: 19029980 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 18.5 | High |
| Lymph node | 12.3 | Medium |
| Breast | 8.7 | Medium |
| Prostate | 7.2 | Medium |
| Brain | 4.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| MCF7 (breast cancer) | 15.2 | High expression |
| PC3 (prostate cancer) | 11.8 | Moderate expression |
| HeLa (cervical cancer) | 9.5 | Moderate expression |
| HEK293 (embryonic kidney) | 7.3 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1?) | Missense | <0.1% | Loss of start codon; likely loss of function |
| c.209_210insA (p.Gln70fs) | Frameshift insertion | 0.2% | Truncation; loss of ESCRT-I function |
| c.532C>T (p.Arg178Trp) | Missense | 0.1% | Altered protein stability; uncertain significance |
Mutation functional classification
Loss of Function (LOF)
Frameshift and nonsense mutations in TSG101 lead to truncated proteins that disrupt ESCRT-I complex assembly and MVB sorting, promoting tumorigenesis.
Gain of Function (GOF)
No well-established gain-of-function mutations reported; overexpression in some cancers may confer proliferative advantage.
Dominant Negative (DN)
Certain missense mutations (e.g., in the UEV domain) can interfere with wild-type TSG101 function, acting in a dominant-negative manner.
View complete mutation data：
Gene Ontology (GO)
| • endosome (GO:0005768) | • ESCRT I complex (GO:0000813) |
| • protein transport (GO:0015031) | • autophagy (GO:0006914) |
| • cell proliferation (GO:0008283) | • nucleus (GO:0005634) |
Pathways
• ESCRT-mediated multivesicular body sorting (Reactome: R-HSA-917729)
• Endosomal sorting complex required for transport (ESCRT) (KEGG: hsa04144)
• Autophagy (KEGG: hsa04140)
Protein Summary
The TSG101 protein (Q99816) is a 380-amino acid component of the ESCRT-I complex. It contains an N-terminal ubiquitin E2 variant (UEV) domain that binds ubiquitinated cargo, a proline-rich region, and a C-terminal steadiness box. TSG101 is essential for sorting ubiquitinated membrane proteins into intraluminal vesicles of multivesicular bodies, thereby regulating receptor downregulation, cytokinesis, and viral budding. Its structure and interactions are critical for maintaining cellular homeostasis.
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