TBX18: A Key T-Box Transcription Factor in Cardiac and Urogenital Development
Comprehensive gene card, expression, mutations, and disease associations for TBX18
Gene Information Card
| Symbol | TBX18 |
|---|---|
| Full Name | T-box transcription factor 18 |
| Gene Type | protein-coding |
| Chromosomal Location | 6q14.3 |
| NCBI Gene ID | 9096 ncbi.nlm.nih.gov/gene/9096 |
| Ensembl ID | ENSG00000112337 |
| UniProt ID | O95935 |
| OMIM ID | 604613 |
| HGNC ID | 11595 |
| Aliases | TBX18, T-box 18, T-box transcription factor TBX18 |
Description
TBX18 (T-box transcription factor 18) is a member of the T-box family of transcription factors, characterized by a conserved DNA-binding domain (T-box). It plays critical roles in embryonic development, particularly in the formation of the sinoatrial node (cardiac pacemaker), ureter smooth muscle, and vertebral column. TBX18 regulates cell fate specification and differentiation. Mutations and altered expression are associated with congenital heart defects, ureteropelvic junction obstruction, and certain cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Congenital heart disease (e.g., atrial septal defect, ventricular septal defect) | Loss-of-function mutations impair TBX18 transcriptional activity, disrupting cardiac pacemaker and septal development | ClinVar, OMIM #604613 |
| Ureteropelvic junction obstruction | TBX18 deficiency leads to abnormal smooth muscle differentiation in the ureter, causing obstruction | OMIM #604613, NCBI Gene |
| Vertebral anomalies (e.g., hemivertebrae) | TBX18 is required for somite segmentation and vertebral patterning; mutations disrupt axial skeleton development | OMIM #604613 |
| Cancer (e.g., hepatocellular carcinoma, colorectal cancer) | TBX18 overexpression or epigenetic silencing may alter cell proliferation and differentiation pathways | COSMIC, NCBI Gene |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Heart | 12.5 | Medium |
| Kidney | 8.3 | Low |
| Ureter | 15.1 | Medium |
| Skeletal muscle | 4.2 | Low |
| Liver | 2.1 | Not detected |
| Lung | 6.7 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 9.8 | Embryonic kidney cell line |
| HeLa | 3.4 | Cervical cancer cell line |
| HepG2 | 1.2 | Hepatocellular carcinoma cell line |
| A549 | 5.6 | Lung carcinoma cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.112C>T (p.Arg38Cys) | Missense | Rare | Reduced DNA-binding affinity; loss of function |
| c.421_423del (p.Lys141del) | In-frame deletion | Rare | Impaired protein stability; loss of function |
| c.788G>A (p.Arg263Gln) | Missense | Rare | Altered transcriptional activity; likely loss of function |
| c.1015C>T (p.Arg339Ter) | Nonsense | Rare | Premature truncation; loss of function |
Mutation functional classification
Loss of Function (LOF)
Most reported TBX18 mutations (missense, nonsense, deletions) result in loss of DNA binding or protein stability, leading to haploinsufficiency in cardiac and urogenital development.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported in TBX18.
Dominant Negative (DN)
Some missense mutations (e.g., p.Arg38Cys) may act in a dominant-negative manner by interfering with wild-type TBX18 function, though evidence is limited.
View complete mutation data：
Gene Ontology (GO)
Pathways
• T-box transcription factor pathway (Reactome: R-HSA-5617472)
• Cardiac conduction system development (KEGG: hsa05414)
• Ureteric bud development (KEGG: hsa05200)
Protein Summary
TBX18 encodes a 602-amino acid protein containing a T-box DNA-binding domain. It localizes to the nucleus and regulates transcription of target genes involved in cell fate determination, particularly in the sinoatrial node, ureter smooth muscle, and somites. The protein interacts with other transcription factors (e.g., NKX2-5, GATA4) and co-regulators. Post-translational modifications include phosphorylation, which may modulate activity. Structural studies show the T-box domain binds to a consensus DNA sequence (T-box binding element).
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TBX18 Knockout HEK293 Cell Line | EDJ-KQ5785 | Human | 9096 | Details Get a Quote |
| TBX18 Knockout A-549 Cell Line | EDJ-KQ30539 | Human | 9096 | Details Get a Quote |
| TBX18 Knockout HCT 116 Cell Line | EDJ-KQ30541 | Human | 9096 | Details Get a Quote |
| TBX18 Knockout HeLa Cell Line | EDJ-KQ55084 | Human | 9096 | Details Get a Quote |
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