TWIST2: A Key Regulator of Mesenchymal Development and Craniofacial Patterning
Comprehensive genomic and functional analysis of the TWIST2 gene, its role in development, and associated disorders.
Gene Information Card
| Symbol | TWIST2 |
|---|---|
| Full Name | twist family bHLH transcription factor 2 |
| Gene Type | protein-coding |
| Chromosomal Location | 2q37.3 |
| NCBI Gene ID | 117581 ncbi.nlm.nih.gov/gene/117581 |
| Ensembl ID | ENSG00000168811 |
| UniProt ID | Q8WVJ9 |
| OMIM ID | 607556 |
| HGNC ID | 13070 |
| Aliases | bHLHa39, Dermo1, twist2 |
Description
TWIST2 (twist family bHLH transcription factor 2) encodes a basic helix-loop-helix (bHLH) transcription factor that plays a critical role in mesenchymal cell differentiation, craniofacial development, and suppression of osteoblast maturation. It functions as a heterodimer with E12/E47 proteins and represses transcription of target genes. Mutations in TWIST2 are associated with autosomal recessive focal facial dermal dysplasia (Setleis syndrome) and autosomal dominant craniofacial anomalies.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Focal facial dermal dysplasia type 3 (Setleis syndrome) | Loss-of-function mutations in TWIST2 disrupt bHLH-mediated transcriptional repression, leading to abnormal facial development. | OMIM #227260; ClinVar |
| Craniofacial anomalies (unspecified) | Dominant-negative or haploinsufficient TWIST2 variants impair mesenchymal differentiation. | OMIM #607556; PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Skin | 12.5 | Medium |
| Adipose tissue | 8.2 | Low |
| Bone marrow | 6.1 | Low |
| Lung | 4.8 | Low |
| Heart | 3.5 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Fibroblasts | 15.3 | Primary dermal fibroblasts |
| Mesenchymal stem cells | 10.7 | Bone marrow-derived |
| HeLa | 2.1 | Cervical carcinoma |
| A549 | 1.8 | Lung carcinoma |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.186C>G (p.Tyr62*) | Nonsense | Rare | Loss of function; associated with Setleis syndrome |
| c.232C>T (p.Arg78Trp) | Missense | Rare | Dominant-negative effect; craniofacial anomalies |
| c.1A>G (p.Met1?) | Start loss | Rare | Loss of function; Setleis syndrome |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations leading to premature termination or nonsense-mediated decay; associated with autosomal recessive Setleis syndrome.
Gain of Function (GOF)
Not reported for TWIST2.
Dominant Negative (DN)
Missense mutations in the bHLH domain (e.g., p.Arg78Trp) that impair DNA binding or dimerization, causing autosomal dominant craniofacial defects.
View complete mutation data：
Gene Ontology (GO)
Pathways
• TWIST2 in mesenchymal cell differentiation
• bHLH transcription factor network
Protein Summary
TWIST2 is a 160-amino acid bHLH transcription factor that localizes to the nucleus. It contains a basic DNA-binding domain and a helix-loop-helix dimerization domain. TWIST2 forms heterodimers with E12/E47 proteins and represses target gene transcription, including RUNX2, to inhibit osteoblast differentiation. It is essential for proper craniofacial and skin development.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TWIST2 Knockout HEK293 Cell Line | EDJ-KQ2454 | Human | 117581 | Details Get a Quote |
| TWIST2 Knockout A-549 Cell Line | EDJ-KQ22987 | Human | 117581 | Details Get a Quote |
| TWIST2 Knockout HeLa Cell Line | EDJ-KQ21652 | Human | 117581 | Details Get a Quote |
