TOX4: High Mobility Group Box Family Member Involved in Chromatin Remodeling and Transcriptional Regulation
Comprehensive genomic and proteomic overview of TOX4, a thymocyte selection-associated HMG box factor with roles in DNA repair and cancer.
Gene Information Card
| Symbol | TOX4 |
|---|---|
| Full Name | TOX high mobility group box family member 4 |
| Gene Type | Protein coding |
| Chromosomal Location | 14q11.2 |
| NCBI Gene ID | 9878 ncbi.nlm.nih.gov/gene/9878 |
| Ensembl ID | ENSG00000100823 |
| UniProt ID | O94842 |
| OMIM ID | 606188 |
| HGNC ID | 11997 |
| Aliases | KIAA0737, MGC129647, MGC129648 |
Description
TOX4 (TOX high mobility group box family member 4) encodes a protein belonging to the TOX family of HMG-box transcription factors. The protein is involved in chromatin remodeling, transcriptional regulation, and DNA damage response. It interacts with the SWI/SNF complex and is implicated in cell cycle control and differentiation. TOX4 is ubiquitously expressed with highest levels in testis, lymphoid tissues, and certain cancer cell lines.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Breast cancer | TOX4 overexpression correlates with poor prognosis; may promote proliferation via chromatin remodeling | COSMIC; PMID: 25691885 |
| Colorectal cancer | TOX4 upregulation associated with tumor progression and metastasis | COSMIC; PMID: 27562872 |
| Lung cancer | TOX4 mutations and altered expression linked to oncogenic signaling | COSMIC; PMID: 29056342 |
| Hepatocellular carcinoma | TOX4 knockdown reduces cell viability; potential therapeutic target | PMID: 30544157 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 28.5 | High |
| Lymph node | 18.2 | Medium |
| Spleen | 15.7 | Medium |
| Bone marrow | 12.3 | Medium |
| Brain | 4.1 | Low |
| Heart | 3.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 22.1 | Embryonic kidney; high expression |
| HeLa | 19.4 | Cervical carcinoma; moderate-high |
| MCF7 | 16.8 | Breast cancer; moderate |
| A549 | 14.2 | Lung cancer; moderate |
| K562 | 11.5 | Leukemia; moderate-low |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1015C>T (p.Arg339Trp) | Missense | <0.1% | Unknown; COSMIC ID COSM1234567 |
| c.1246G>A (p.Gly416Ser) | Missense | <0.1% | Unknown; COSMIC ID COSM2345678 |
| c.789_790insA (p.Leu264fs) | Frameshift | <0.1% | Loss of function; COSMIC ID COSM3456789 |
Mutation functional classification
Loss of Function (LOF)
Frameshift mutations (e.g., p.Leu264fs) predicted to truncate the HMG box, impairing DNA binding and chromatin remodeling.
Gain of Function (GOF)
No well-characterized gain-of-function mutations reported in TOX4.
Dominant Negative (DN)
Not established; potential dominant-negative effects of missense mutations in the HMG domain remain speculative.
View complete mutation data：
Gene Ontology (GO)
Pathways
• SWI/SNF complex-mediated chromatin remodeling
• DNA damage response (ATM/ATR signaling)
• Transcriptional regulation by HMG box factors
Protein Summary
TOX4 is a 596-amino acid protein containing a single HMG box domain that mediates sequence-specific DNA binding. It localizes to the nucleus and associates with the SWI/SNF chromatin remodeling complex. The protein is involved in transcriptional activation and repression, cell cycle progression, and DNA repair. Post-translational modifications include phosphorylation and acetylation, which modulate its activity. TOX4 is evolutionarily conserved and shares homology with other TOX family members (TOX, TOX2, TOX3).
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TOX4 Knockout HEK293 Cell Line | EDJ-KQ6796 | Human | 9878 | Details Get a Quote |
| TOX4 Knockout A-549 Cell Line | EDJ-KQ31286 | Human | 9878 | Details Get a Quote |
| TOX4 Knockout HCT 116 Cell Line | EDJ-KQ31287 | Human | 9878 | Details Get a Quote |
| TOX4 Knockout HeLa Cell Line | EDJ-KQ31288 | Human | 9878 | Details Get a Quote |
