TWIST1 Gene: Structure, Function, and Clinical Significance
A master regulator of mesodermal development implicated in craniosynostosis and cancer
Gene Information Card
| Symbol | TWIST1 |
|---|---|
| Full Name | twist family bHLH transcription factor 1 |
| Gene Type | protein coding |
| Chromosomal Location | 7p21.1 |
| NCBI Gene ID | 7291 ncbi.nlm.nih.gov/gene/7291 |
| Ensembl ID | ENSG00000122691 |
| UniProt ID | Q15672 |
| OMIM ID | 601622 |
| HGNC ID | 12428 |
| Aliases | BPES2, CRS, CSO, SCS, TWIST, bHLHa38 |
Description
TWIST1 encodes a basic helix-loop-helix (bHLH) transcription factor that plays a critical role in embryonic development, particularly in mesodermal and neural crest cell differentiation. It regulates gene expression by binding to E-box sequences as a homodimer or heterodimer with other bHLH proteins. TWIST1 is essential for limb and craniofacial development, and its dysregulation is linked to Saethre-Chotzen syndrome and various cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Saethre-Chotzen syndrome | Loss-of-function mutations (including haploinsufficiency) disrupt TWIST1's role in osteoblast differentiation, leading to premature fusion of cranial sutures. | ClinVar, OMIM |
| Breast cancer | TWIST1 overexpression promotes epithelial-mesenchymal transition (EMT), enhancing metastasis and invasion. | COSMIC, PubMed |
| Gastric cancer | TWIST1 upregulation correlates with poor prognosis and increased metastatic potential via EMT induction. | COSMIC, PubMed |
| Melanoma | TWIST1 expression is associated with tumor progression and resistance to apoptosis. | COSMIC, PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Placenta | 11.3 | Medium |
| Bone marrow | 8.9 | Low |
| Lung | 5.2 | Low |
| Spleen | 4.1 | Low |
| Other tissues | Low or not detected | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| MCF7 (breast cancer) | 12.5 | TWIST1 expression linked to EMT |
| A549 (lung cancer) | 8.3 | Moderate expression |
| HeLa (cervical cancer) | 6.7 | Low expression |
| K562 (leukemia) | 3.2 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| p.Arg118Cys | Missense | Rare | Impairs DNA binding and transcriptional activity; associated with Saethre-Chotzen syndrome |
| p.Arg121Gly | Missense | Rare | Disrupts bHLH domain, affecting dimerization; pathogenic |
| c.372delC | Frameshift | Rare | Premature truncation; loss of function |
| Whole gene deletion | Copy number loss | Rare | Haploinsufficiency; causes Saethre-Chotzen syndrome |
Mutation functional classification
Loss of Function (LOF)
Most TWIST1 mutations in Saethre-Chotzen syndrome are loss-of-function, often due to haploinsufficiency or dominant-negative effects that reduce transcriptional activity.
Gain of Function (GOF)
In cancer, TWIST1 overexpression can act as a gain-of-function, promoting EMT and metastasis.
Dominant Negative (DN)
Some missense mutations in the bHLH domain produce dominant-negative proteins that interfere with wild-type TWIST1 function.
View complete mutation data：
Gene Ontology (GO)
| • DNA binding transcription factor activity | • RNA polymerase II cis-regulatory region sequence-specific DNA binding |
| • protein dimerization activity | • regulation of transcription by RNA polymerase II |
| • mesoderm development | • skeletal system development |
| • negative regulation of cell differentiation | • epithelial to mesenchymal transition |
Pathways
• Epithelial to mesenchymal transition (EMT)
• Osteoblast differentiation
• p53 signaling pathway
• TGF-beta signaling pathway
Protein Summary
TWIST1 is a 202-amino acid protein containing a basic helix-loop-helix (bHLH) domain that mediates DNA binding and dimerization. It functions as a transcription factor, regulating genes involved in mesodermal and neural crest development. TWIST1 can homodimerize or heterodimerize with E12/E47 proteins, and its activity is modulated by phosphorylation. It plays a dual role in development and cancer, where it promotes EMT and metastasis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TWIST1 Knockout HEK293 Cell Line | EDJ-KQ1102 | Human | 7291 | Details Get a Quote |
| TWIST1 Knockout HeLa Cell Line | EDJ-KQ18930 | Human | 7291 | Details Get a Quote |
| TWIST1 Knockout HCT 116 Cell Line | EDJ-KQ20279 | Human | 7291 | Details Get a Quote |
| TWIST1 Knockout A-549 Cell Line | EDJ-KQ63198 | Human | 7291 | Details Get a Quote |
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