TBX3: T-Box Transcription Factor 3
Key regulator of development and cancer, associated with ulnar-mammary syndrome and multiple malignancies.
Gene Information Card
| Symbol | TBX3 |
|---|---|
| Full Name | T-Box Transcription Factor 3 |
| Gene Type | Protein coding |
| Chromosomal Location | 12q24.21 |
| NCBI Gene ID | 6926 ncbi.nlm.nih.gov/gene/6926 |
| Ensembl ID | ENSG00000135111 |
| UniProt ID | O15119 |
| OMIM ID | 601621 |
| HGNC ID | 11602 |
| Aliases | TBX3-ISO, UMS, XHL |
Description
TBX3 encodes a member of the T-box family of transcription factors, characterized by a conserved DNA-binding domain. It acts as a transcriptional repressor, playing critical roles in embryonic development, particularly in limb, heart, and mammary gland formation. TBX3 is also implicated in cancer progression, where it promotes cell proliferation, migration, and invasion. Mutations in TBX3 cause ulnar-mammary syndrome, a developmental disorder affecting limbs, apocrine glands, and genitalia.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Ulnar-mammary syndrome | Loss-of-function mutations in TBX3 disrupt limb and mammary gland development, leading to characteristic malformations. | OMIM #181450 |
| Breast cancer | TBX3 overexpression promotes epithelial-mesenchymal transition and metastasis. | PMID: 23555202 |
| Hepatocellular carcinoma | TBX3 upregulation correlates with poor prognosis and tumor progression. | PMID: 28411376 |
| Melanoma | TBX3 drives invasion and metastasis by repressing E-cadherin. | PMID: 22665077 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Heart | 12.5 | Medium |
| Mammary gland | 8.2 | Low |
| Lung | 6.1 | Low |
| Liver | 4.8 | Low |
| Skeletal muscle | 3.5 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| MCF7 (breast cancer) | 15.3 | High expression |
| HepG2 (liver cancer) | 10.1 | Moderate expression |
| A549 (lung cancer) | 7.4 | Low expression |
| SK-MEL-28 (melanoma) | 18.7 | High expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.907C>T (p.Arg303*) | Nonsense | Rare | Loss of function; truncation of protein |
| c.1012G>A (p.Gly338Arg) | Missense | Rare | Loss of function; impaired DNA binding |
| c.1261C>T (p.Arg421Cys) | Missense | Rare | Loss of function; reduced transcriptional repression |
Mutation functional classification
Loss of Function (LOF)
Most TBX3 mutations in ulnar-mammary syndrome are loss-of-function, leading to haploinsufficiency or dominant-negative effects.
Gain of Function (GOF)
Gain-of-function mutations are not well-documented; overexpression in cancer is often due to epigenetic or transcriptional upregulation.
Dominant Negative (DN)
Some missense mutations may act in a dominant-negative manner by interfering with wild-type TBX3 function.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Developmental Biology (Reactome: R-HSA-1266738)
• Transcriptional regulation by TBX3 (GeneCards)
• Epithelial-to-mesenchymal transition in cancer (KEGG: hsa05205)
Protein Summary
TBX3 is a 743-amino acid transcription factor containing a T-box DNA-binding domain. It functions primarily as a transcriptional repressor by binding to T-box elements in target gene promoters. TBX3 regulates key developmental processes, including limb patterning, cardiac development, and mammary gland formation. In cancer, TBX3 promotes tumor progression by repressing tumor suppressors such as p14ARF and inducing EMT markers. The protein is localized to the nucleus and interacts with other transcription factors and co-repressors.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TBX3 Knockout HEK293 Cell Line | EDJ-KQ5898 | Human | 6926 | Details Get a Quote |
| TBX3 Knockout A-549 Cell Line | EDJ-KQ29403 | Human | 6926 | Details Get a Quote |
| TBX3 Knockout HCT 116 Cell Line | EDJ-KQ29404 | Human | 6926 | Details Get a Quote |
| TBX3 Knockout HeLa Cell Line | EDJ-KQ29405 | Human | 6926 | Details Get a Quote |
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