TCF12: A Basic Helix-Loop-Helix Transcription Factor in Development and Cancer
Comprehensive genomic and clinical resource for TCF12 (HEB, HTF4) – gene function, expression, mutations, and associated diseases.
Gene Information Card
| Symbol | TCF12 |
|---|---|
| Full Name | Transcription factor 12 |
| Gene Type | Protein coding |
| Chromosomal Location | 15q21.3 |
| NCBI Gene ID | 6938 ncbi.nlm.nih.gov/gene/6938 |
| Ensembl ID | ENSG00000140262 |
| UniProt ID | Q99081 |
| OMIM ID | 600480 |
| HGNC ID | 11623 |
| Aliases | HEB, HTF4, TCF-12, bHLHb20, ME2 |
Description
TCF12 (Transcription factor 12) encodes a member of the basic helix-loop-helix (bHLH) family of transcription factors. The protein forms homodimers or heterodimers with other bHLH proteins and binds to E-box sequences (CANNTG) to regulate gene expression. TCF12 is essential for neurogenesis, myogenesis, and T-cell development. Heterozygous loss-of-function mutations cause coronal craniosynostosis, and somatic alterations are implicated in T-cell acute lymphoblastic leukemia (T-ALL) and neuroblastoma.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Coronal craniosynostosis | Heterozygous loss-of-function mutations in TCF12 impair bHLH dimerization and DNA binding, disrupting cranial suture development. | ClinVar, OMIM #600480 |
| T-cell acute lymphoblastic leukemia (T-ALL) | Somatic deletions and mutations (e.g., frameshift, nonsense) lead to loss of TCF12 function, contributing to leukemogenesis. | COSMIC, NCBI PubMed |
| Neuroblastoma | Somatic missense and truncating mutations in TCF12 are recurrent in high-risk neuroblastoma, suggesting a tumor suppressor role. | COSMIC, NCBI PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 28.5 | High |
| Heart | 18.2 | Medium |
| Skeletal muscle | 22.1 | Medium |
| Lung | 12.4 | Medium |
| Liver | 6.8 | Low |
| Kidney | 10.3 | Medium |
| Testis | 15.7 | Medium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 20.1 | Embryonic kidney; high expression |
| K562 | 14.5 | Leukemia; moderate expression |
| SH-SY5Y | 18.9 | Neuroblastoma; high expression |
| HepG2 | 9.2 | Hepatocellular carcinoma; low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1045C>T (p.Arg349*) | Nonsense | <1% in general population; recurrent in T-ALL | Loss of function; truncation of bHLH domain |
| c.1372_1373del (p.Leu458Glufs*12) | Frameshift | <1% in general population; found in craniosynostosis | Loss of function; premature stop |
| c.1060G>A (p.Gly354Arg) | Missense | <0.1% in general population; reported in neuroblastoma | Likely loss of function; disrupts DNA binding |
Mutation functional classification
Loss of Function (LOF)
Most TCF12 mutations in craniosynostosis and T-ALL are loss-of-function (nonsense, frameshift, splice-site), leading to haploinsufficiency or complete loss of protein activity.
Gain of Function (GOF)
No recurrent gain-of-function mutations have been reported for TCF12.
Dominant Negative (DN)
Some missense mutations in the bHLH domain may act as dominant-negative by forming non-functional dimers, but evidence is limited.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Notch signaling pathway (Reactome: R-HSA-157118)
• Transcriptional regulation by bHLH factors (Reactome: R-HSA-9616222)
• Developmental biology (Reactome: R-HSA-1266738)
Protein Summary
TCF12 (HEB) is a 682-amino-acid bHLH transcription factor that localizes to the nucleus. It contains a basic DNA-binding domain and a helix-loop-helix dimerization domain. TCF12 heterodimerizes with E2A (TCF3) or other bHLH proteins to activate or repress target genes involved in neurogenesis, myogenesis, and T-cell development. The protein is widely expressed, with highest levels in brain and muscle. Pathogenic variants predominantly cause loss of function, leading to developmental disorders and cancer.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TCF12 Knockout HEK293 Cell Line | EDJ-KQ2699 | Human | 6938 | Details Get a Quote |
| TCF12 Knockout A-549 Cell Line | EDJ-KQ23534 | Human | 6938 | Details Get a Quote |
| TCF12 Knockout HCT 116 Cell Line | EDC08350 | Human | 6938 | Details Get a Quote |
| TCF12 Knockout HeLa Cell Line | EDJ-KQ23536 | Human | 6938 | Details Get a Quote |
