TWIST1
Chr 7ADtwist family bHLH transcription factor 1
Also known as: ACS3, BPES2, BPES3, CRS, CRS1, CSO, SCS, SWCOS
The protein is a basic helix-loop-helix transcription factor that binds to DNA E box sequences and regulates transcription of genes controlling cranial suture closure, neural tube closure, and limb development. Mutations cause autosomal dominant craniosynostosis syndromes including Saethre-Chotzen syndrome, Robinow-Sorauf syndrome, and Sweeney-Cox syndrome, typically presenting with premature skull suture fusion, ptosis, and hypertelorism. The pathogenic mechanism involves haploinsufficiency leading to disrupted transcriptional regulation of developmental genes.
Limited evidence — not for standalone diagnostic reporting
3 total gene-disease associations curated
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function, dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to loss-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
TWIST1 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
Network Of Clinical Research Studies On Craniosynostosis, Skull Malformations With Premature Fusion Of Skull Bones
ACTIVE NOT RECRUITINGASO Treatment for Syndromic Craniosynostoses
NOT YET RECRUITINGRole of BMP Pathway in MDS Progression
NOT YET RECRUITINGThe Effect of Monoallelic Variants in the ALPL Gene on the Natural Course of Hypophosphatasia in Russia
RECRUITINGGROWing Up With Rare GENEtic Syndromes
RECRUITINGPathogenetic Basis of Aortopathy and Aortic Valve Disease
ACTIVE NOT RECRUITINGFunctionalized Bioink Delivering Biomolecules for the Treatment of Craniofacial Diseases
ACTIVE NOT RECRUITINGNirogacestat in Patients With Kaposi Sarcoma
NOT YET RECRUITINGExternal Resources
Links to major genomics databases and tools