TOX3: A Key Regulator in Breast Cancer Susceptibility and Neuronal Development
Comprehensive genomic and functional analysis of the TOX3 gene, its role in calcium-dependent transcription, and implications in cancer and neurological disorders.
Gene Information Card
| Symbol | TOX3 |
|---|---|
| Full Name | TOX high mobility group box family member 3 |
| Gene Type | Protein coding |
| Chromosomal Location | 16q12.1 |
| NCBI Gene ID | 27324 ncbi.nlm.nih.gov/gene/27324 |
| Ensembl ID | ENSG00000103495 |
| UniProt ID | O15405 |
| OMIM ID | 611416 |
| HGNC ID | 11979 |
| Aliases | TNRC9, CAGF9, HMG-box transcription factor TOX3 |
Description
TOX3 (TOX high mobility group box family member 3) encodes a protein containing an HMG-box domain that binds DNA and modulates chromatin structure. It functions as a calcium-dependent transcription factor involved in neuronal development and has been strongly associated with breast cancer susceptibility through genome-wide association studies. The protein interacts with CREB and CBP/p300 to regulate gene expression.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Breast cancer | TOX3 variants (e.g., rs3803662) are associated with increased risk; the protein may influence estrogen receptor signaling and chromatin remodeling. | GWAS (Easton et al., 2007); multiple replication studies |
| Neurodevelopmental disorders | TOX3 is expressed in neurons and regulates calcium-dependent transcription; mutations may affect synaptic plasticity. | Expression studies in mouse models (Dittmer et al., 2011) |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Breast | 8.3 | Low |
| Ovary | 6.1 | Low |
| Testis | 4.7 | Low |
| Lung | 3.2 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| MCF7 (breast cancer) | 15.2 | High expression; estrogen-responsive |
| SK-BR-3 (breast cancer) | 9.8 | Moderate expression |
| SH-SY5Y (neuroblastoma) | 22.1 | High expression; neuronal origin |
| HEK293 (embryonic kidney) | 2.4 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| rs3803662 | SNP (intronic) | Common (MAF ~0.25 in Europeans) | Associated with increased breast cancer risk; may alter TOX3 expression |
| rs4784227 | SNP (intronic) | Common (MAF ~0.30 in Asians) | Linked to breast cancer risk in Asian populations |
| c.1072C>T (p.Arg358Trp) | Missense | Rare | Reported in breast cancer; functional impact unknown |
Mutation functional classification
Loss of Function (LOF)
No confirmed loss-of-function mutations reported in TOX3; knockdown studies in cell lines reduce cell proliferation.
Gain of Function (GOF)
Overexpression of TOX3 in breast cancer cells enhances cell migration and invasion in vitro.
Dominant Negative (DN)
Not described for TOX3.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Calcium signaling pathway (Reactome: R-HSA-4086398)
• CREB phosphorylation through the activation of CaMKII (Reactome: R-HSA-442729)
• Chromatin modifying enzymes (Reactome: R-HSA-3247502)
Protein Summary
The TOX3 protein (UniProt O15405) is a 526-amino acid nuclear protein containing a single HMG-box domain that mediates sequence-specific DNA binding. It acts as a calcium-dependent transcription coactivator by interacting with CREB and CBP/p300, thereby regulating genes involved in neuronal development and breast cancer progression. The protein is highly expressed in brain and breast tissue.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TOX3 Knockout HEK293 Cell Line | EDJ-KQ2231 | Human | 27324 | Details Get a Quote |
| TOX3 Knockout HeLa Cell Line | EDJ-KQ56057 | Human | 27324 | Details Get a Quote |
| TOX3 Knockout A-549 Cell Line | EDJ-KQ64541 | Human | 27324 | Details Get a Quote |
| TOX3 Knockout HCT 116 Cell Line | EDJ-KQ73000 | Human | 27324 | Details Get a Quote |
