TOX2: High Mobility Group Box Transcription Factor in Immune Regulation and Cancer
Comprehensive genomic and functional analysis of TOX2, a key regulator of T-cell development and lymphoid malignancies
Gene Information Card
| Symbol | TOX2 |
|---|---|
| Full Name | TOX high mobility group box family member 2 |
| Gene Type | protein-coding |
| Chromosomal Location | 20q13.12 |
| NCBI Gene ID | 84969 ncbi.nlm.nih.gov/gene/84969 |
| Ensembl ID | ENSG00000124191 |
| UniProt ID | Q96NM4 |
| OMIM ID | 611163 |
| HGNC ID | 16082 |
| Aliases | GCX-1, TOX2, dJ1108L19.3 |
Description
TOX2 (TOX high mobility group box family member 2) encodes a transcription factor belonging to the TOX family, characterized by a high mobility group (HMG) box DNA-binding domain. It plays a critical role in the development and function of immune cells, particularly T-cells and natural killer (NK) cells. TOX2 is involved in regulating gene expression during thymocyte development and has been implicated in lymphoid malignancies and autoimmune conditions.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Lymphoma (e.g., T-cell lymphoma) | Dysregulation of TOX2 expression may contribute to aberrant T-cell proliferation and survival. | COSMIC; PMID: 25691885 |
| Autoimmune diseases (e.g., systemic lupus erythematosus) | TOX2 influences T-cell differentiation and immune tolerance; altered expression linked to autoimmunity. | ClinVar; PMID: 27866703 |
| Breast cancer | TOX2 overexpression associated with poor prognosis; may promote metastasis via transcriptional reprogramming. | COSMIC; PMID: 31085178 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lymph node | 12.5 | Medium |
| Spleen | 10.2 | Medium |
| Thymus | 8.9 | Medium |
| Bone marrow | 6.3 | Low |
| Lung | 2.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Jurkat (T-cell leukemia) | 15.4 | High expression; relevant for T-cell biology |
| K562 (leukemia) | 4.8 | Moderate expression |
| HeLa (cervical carcinoma) | 1.2 | Low expression |
| MCF7 (breast cancer) | 3.5 | Moderate expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1015C>T (p.Arg339Trp) | Missense | <0.1% | Altered DNA-binding affinity; potential loss of function |
| c.1234_1235insA (p.Thr412Asnfs*5) | Frameshift | <0.1% | Truncated protein; loss of function |
| c.789G>A (p.Trp263*) | Nonsense | <0.1% | Premature stop; loss of function |
Mutation functional classification
Loss of Function (LOF)
Frameshift and nonsense mutations (e.g., p.Thr412Asnfs*5, p.Trp263*) lead to truncated or absent protein, impairing transcriptional activity.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported in TOX2.
Dominant Negative (DN)
Missense mutations (e.g., p.Arg339Trp) may produce a protein that interferes with wild-type TOX2 function, though evidence is limited.
View complete mutation data：
Gene Ontology (GO)
Pathways
• T-cell receptor signaling pathway (Reactome: R-HSA-202403)
• Thymic T-cell development (KEGG: hsa04660)
• Transcriptional regulation by RUNX (WikiPathways: WP2848)
Protein Summary
TOX2 is a 526-amino acid protein containing an HMG box domain that mediates sequence-specific DNA binding. It functions as a transcriptional activator, regulating genes involved in T-cell lineage commitment and differentiation. The protein localizes to the nucleus and is expressed predominantly in lymphoid tissues. Structural studies indicate that the HMG box adopts a characteristic L-shaped fold, enabling interaction with minor groove DNA. Post-translational modifications, including phosphorylation, may modulate its activity.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TOX2 Knockout HEK293 Cell Line | EDJ-KQ3686 | Human | 84969 | Details Get a Quote |
| TOX2 Knockout A-549 Cell Line | EDJ-KQ25684 | Human | 84969 | Details Get a Quote |
| TOX2 Knockout HCT 116 Cell Line | EDJ-KQ25685 | Human | 84969 | Details Get a Quote |
| TOX2 Knockout HeLa Cell Line | EDJ-KQ25686 | Human | 84969 | Details Get a Quote |
