TBX6 Gene - T-Box Transcription Factor 6
Key regulator of somite segmentation and vertebral development; mutations linked to congenital scoliosis and spondylocostal dysostosis
Gene Information Card
| Symbol | TBX6 |
|---|---|
| Full Name | T-Box Transcription Factor 6 |
| Gene Type | Protein coding |
| Chromosomal Location | 16p11.2 |
| NCBI Gene ID | 6911 ncbi.nlm.nih.gov/gene/6911 |
| Ensembl ID | ENSG00000149922 |
| UniProt ID | O95947 |
| OMIM ID | 602427 |
| HGNC ID | 11605 |
| Aliases | T-box6, Tbx6 |
Description
TBX6 encodes a member of the T-box family of transcription factors, characterized by a conserved DNA-binding domain. This protein plays a critical role in mesoderm formation and somite segmentation during embryonic development. TBX6 regulates the expression of downstream genes involved in paraxial mesoderm differentiation and vertebral column patterning. Loss-of-function mutations are associated with congenital scoliosis and spondylocostal dysostosis.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Congenital scoliosis (CS) | Haploinsufficiency or hypomorphic alleles of TBX6 disrupt somite boundary formation, leading to vertebral malformations and spinal curvature. | ClinVar, OMIM #122600 |
| Spondylocostal dysostosis (SCD) | Biallelic loss-of-function mutations impair Tbx6-mediated segmentation clock, causing rib fusions and vertebral defects. | OMIM #122600, PMID: 25629078 |
| Klippel-Feil syndrome | TBX6 variants contribute to cervical vertebral fusion through defective somitogenesis. | ClinVar, PMID: 31564436 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Skeletal muscle | 12.5 | Medium |
| Heart | 8.3 | Low |
| Lung | 6.1 | Low |
| Testis | 4.7 | Low |
| Brain | 2.1 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| K562 (leukemia) | 3.2 | Low expression |
| HeLa (cervical carcinoma) | 1.8 | Very low |
| HepG2 (hepatocellular carcinoma) | 2.5 | Low |
| A549 (lung carcinoma) | 4.0 | Low |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1160_1163del (p.Val387Glufs*2) | Frameshift | Rare | Loss of function; associated with congenital scoliosis |
| c.919C>T (p.Arg307*) | Nonsense | Rare | Premature stop; loss of function; spondylocostal dysostosis |
| c.572G>A (p.Arg191His) | Missense | <0.01% | Reduced DNA-binding affinity; hypomorphic allele |
| c.1130C>T (p.Thr377Met) | Missense | <0.01% | Impaired transcriptional activity; congenital scoliosis |
Mutation functional classification
Loss of Function (LOF)
Frameshift and nonsense mutations (e.g., p.Val387Glufs*2, p.Arg307*) lead to truncated or absent protein, causing haploinsufficiency or biallelic loss. Associated with congenital scoliosis and spondylocostal dysostosis.
Gain of Function (GOF)
No gain-of-function mutations have been reported for TBX6.
Dominant Negative (DN)
Missense variants (e.g., p.Arg191His) may act as dominant-negative by competing with wild-type TBX6 for DNA binding, though evidence is limited.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Notch signaling pathway (KEGG hsa04330) - TBX6 is a downstream target of Notch in somitogenesis
• Wnt signaling pathway (KEGG hsa04310) - TBX6 interacts with Wnt3a to regulate paraxial mesoderm
• FGF signaling pathway (Reactome R-HSA-190236) - TBX6 expression is modulated by FGF8
Protein Summary
TBX6 is a 436-amino acid transcription factor containing a T-box DNA-binding domain (residues 56-237). It localizes to the nucleus and binds to the consensus sequence TCACACCT. TBX6 forms homodimers and heterodimers with other T-box proteins (e.g., TBX5). It is essential for somitogenesis: TBX6 activates genes such as Lfng and Mesp2 to establish segmental boundaries. Post-translational modifications include phosphorylation, which modulates its stability and activity.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TBX6 Knockout HEK293 Cell Line | EDJ-KQ3762 | Human | 6911 | Details Get a Quote |
| TBX6 Knockout HeLa Cell Line | EDJ-KQ54619 | Human | 6911 | Details Get a Quote |
| TBX6 Knockout A-549 Cell Line | EDJ-KQ63099 | Human | 6911 | Details Get a Quote |
| TBX6 Knockout HCT 116 Cell Line | EDJ-KQ71573 | Human | 6911 | Details Get a Quote |
