TBX5 Gene: T-Box Transcription Factor 5
Key regulator of cardiac and limb development; mutations cause Holt-Oram syndrome
Gene Information Card
| Symbol | TBX5 |
|---|---|
| Full Name | T-Box Transcription Factor 5 |
| Gene Type | Protein coding |
| Chromosomal Location | 12q24.21 |
| NCBI Gene ID | 6910 ncbi.nlm.nih.gov/gene/6910 |
| Ensembl ID | ENSG00000121091 |
| UniProt ID | Q99593 |
| OMIM ID | 601620 |
| HGNC ID | 11599 |
| Aliases | HOS, T-box5 |
Description
TBX5 encodes a member of the T-box family of transcription factors, characterized by a conserved DNA-binding domain. This protein is essential for embryonic development, particularly of the heart and upper limbs. Mutations in TBX5 cause Holt-Oram syndrome, an autosomal dominant disorder characterized by cardiac septation defects and preaxial radial ray anomalies. TBX5 regulates gene expression by binding to T-box elements in target gene promoters, interacting with other transcription factors such as NKX2-5 and GATA4.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Holt-Oram syndrome | Loss-of-function mutations in TBX5 disrupt cardiac and limb development pathways | OMIM #142900; multiple familial and sporadic cases reported |
| Atrial septal defect | TBX5 haploinsufficiency impairs septation of the atria | ClinVar; functional studies in mouse models |
| Ventricular septal defect | Reduced TBX5 activity alters ventricular morphogenesis | ClinVar; case reports |
| Radial ray anomalies | TBX5 deficiency disrupts limb bud patterning | OMIM; clinical observations |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Heart | 12.5 | High |
| Skeletal muscle | 3.2 | Low |
| Lung | 1.8 | Low |
| Brain | 0.5 | Not detected |
| Liver | 0.3 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Cardiomyocytes (iPS-derived) | 15.0 | High expression; essential for cardiac differentiation |
| HeLa | 0.2 | Very low expression |
| HEK293 | 0.1 | Not expressed |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.373C>T (p.Arg125Trp) | Missense | Rare | Loss of DNA-binding activity; associated with Holt-Oram syndrome |
| c.757delC (p.Leu253Trpfs*19) | Frameshift | Rare | Premature truncation; loss of function |
| c.239G>A (p.Arg80His) | Missense | Rare | Reduced transcriptional activity; Holt-Oram phenotype |
Mutation functional classification
Loss of Function (LOF)
Most TBX5 mutations are loss-of-function, leading to haploinsufficiency and Holt-Oram syndrome.
Gain of Function (GOF)
No gain-of-function mutations have been reported in TBX5.
Dominant Negative (DN)
Some missense mutations (e.g., p.Arg125Trp) may exert dominant-negative effects by interfering with wild-type TBX5 function.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Cardiac progenitor differentiation (Reactome: R-HSA-8943724)
• Transcriptional regulation of pluripotent stem cells (WikiPathways: WP3996)
• Holt-Oram syndrome pathway (NCBI Bookshelf: NBK1116)
Protein Summary
TBX5 is a 518-amino acid transcription factor containing a T-box DNA-binding domain. It localizes to the nucleus and forms complexes with NKX2-5, GATA4, and other cardiac transcription factors to regulate genes involved in heart and limb development. The protein is highly conserved across vertebrates. Structural studies show that the T-box domain recognizes a specific DNA sequence (T-box element). Post-translational modifications include phosphorylation, which modulates its activity.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TBX5 Knockout HEK293 Cell Line | EDJ-KQ5889 | Human | 6910 | Details Get a Quote |
| TBX5 Knockout HeLa Cell Line | EDJ-KQ54618 | Human | 6910 | Details Get a Quote |
| TBX5 Knockout A-549 Cell Line | EDJ-KQ63098 | Human | 6910 | Details Get a Quote |
| TBX5 Knockout HCT 116 Cell Line | EDJ-KQ71572 | Human | 6910 | Details Get a Quote |
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