Skip Navigation
Genetics Home Reference: your guide to understanding genetic conditions
http://ghr.nlm.nih.gov/     A service of the U.S. National Library of Medicine®

TWIST1

Reviewed February 2008

What is the official name of the TWIST1 gene?

The official name of this gene is “twist basic helix-loop-helix transcription factor 1.”

TWIST1 is the gene's official symbol. The TWIST1 gene is also known by other names, listed below.

What is the normal function of the TWIST1 gene?

The TWIST1 gene provides instructions for making a protein that plays an important role in early development. This protein is a transcription factor, which means that it attaches (binds) to specific regions of DNA and controls the activity of particular genes. Specifically, the TWIST1 protein is part of a large protein family called basic helix-loop-helix (bHLH) transcription factors. Each of these proteins includes a region called the bHLH domain, which determines the protein's 3-dimensional shape and enables it to target particular sequences of DNA. The bHLH family of transcription factors helps regulate the development of many organs and tissues before birth.

During embryonic development, the TWIST1 protein is essential for the formation of cells that give rise to bone, muscle, and other tissues in the head and face. The TWIST1 protein also plays a role in the early development of the limbs. Researchers believe that the TWIST1 protein regulates several genes that are known to be key players in bone formation, including the FGFR2 and RUNX2 genes.

Does the TWIST1 gene share characteristics with other genes?

The TWIST1 gene belongs to a family of genes called bHLH (basic helix-loop-helix).

A gene family is a group of genes that share important characteristics. Classifying individual genes into families helps researchers describe how genes are related to each other. For more information, see What are gene families? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genefamilies) in the Handbook.

How are changes in the TWIST1 gene related to health conditions?

Saethre-Chotzen syndrome - caused by mutations in the TWIST1 gene

More than 80 mutations in the TWIST1 gene have been identified in people with Saethre-Chotzen syndrome. Some of these mutations change single protein building blocks (amino acids) in the TWIST1 protein, while others delete or insert genetic material in the gene. In some cases, this condition is caused by chromosomal abnormalities (translocations or deletions) involving the region of chromosome 7 that contains the TWIST1 gene.

TWIST1 mutations prevent one copy of the gene in each cell from producing any functional protein. A shortage of functional TWIST1 protein affects the development and maturation of cells in the skull, face, and limbs. These abnormalities underlie the signs and symptoms of Saethre-Chotzen syndrome, although it is unclear exactly how a shortage of the TWIST1 protein causes specific features such as the premature fusion of certain skull bones.

other disorders - caused by mutations in the TWIST1 gene

TWIST1 mutations have also been found in several people with isolated craniosynostosis, which is a premature fusion of certain skull bones that occurs without the other signs and symptoms of Saethre-Chotzen syndrome. These mutations occur near the end of the gene in a region known as the TWIST box domain. This domain enables the TWIST1 protein to bind to and regulate a gene called RUNX2, which is a critical regulator of bone formation. Researchers believe that mutations in the TWIST box domain prevent the TWIST1 protein from effectively controlling the activity of the RUNX2 gene, which disrupts the normal pattern of bone formation in the skull and leads to craniosynostosis.

Where is the TWIST1 gene located?

Cytogenetic Location: 7p21.2

Molecular Location on chromosome 7: base pairs 19,155,090 to 19,157,294

The TWIST1 gene is located on the short (p) arm of chromosome 7 at position 21.2.

The TWIST1 gene is located on the short (p) arm of chromosome 7 at position 21.2.

More precisely, the TWIST1 gene is located from base pair 19,155,090 to base pair 19,157,294 on chromosome 7.

See How do geneticists indicate the location of a gene? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genelocation) in the Handbook.

Where can I find additional information about TWIST1?

You and your healthcare professional may find the following resources about TWIST1 helpful.

  • Educational resources - Information pages
    Johns Hopkins Center for Craniofacial Development and Disorders: Disorders of the Skull Vault (http://www.hopkinsmedicine.org/neurology_neurosurgery/specialty_areas/pediatric_neurosurgery/conditions/craniosynostosis/)
  • Gene Reviews - Clinical summary (http://www.ncbi.nlm.nih.gov/books/NBK1189/)

  • Genetic Testing Registry - Repository of genetic test information

    • GTR: Genetic tests for TWIST1 (http://www.ncbi.nlm.nih.gov/gtr/tests/?term=7291%5Bgeneid%5D)

You may also be interested in these resources, which are designed for genetics professionals and researchers.

  • PubMed - Recent literature (http://www.ncbi.nlm.nih.gov/pubmed?term=((TWIST1%5BTIAB%5D)%20OR%20(TWIST%20AND%20craniosynostosis%5BTIAB%5D))%20AND%20((Genes%5BMH%5D)%20OR%20(Genetic%20Phenomena%5BMH%5D))%20AND%20english%5Bla%5D%20AND%20human%5Bmh%5D%20AND%20%22last%201800%20days%22%5Bdp%5D)
  • OMIM - Genetic disorder catalog (http://omim.org/entry/601622)

  • Research Resources - Tools for researchers

    • Atlas of Genetics and Cytogenetics in Oncology and Haematology (http://atlasgeneticsoncology.org/Genes/GC_TWIST1.html)
    • Entrez Gene (http://www.ncbi.nlm.nih.gov/gene/7291)
    • GeneCards (http://www.genecards.org/cgi-bin/carddisp.pl?id_type=entrezgene&id=7291)
    • HUGO Gene Nomenclature Committee (http://www.genenames.org/data/hgnc_data.php?hgnc_id=12428)

What other names do people use for the TWIST1 gene or gene products?

  • acrocephalosyndactyly 3
  • ACS3
  • B-HLH DNA binding protein
  • H-twist
  • SCS
  • Transcription factor TWIST
  • TWIST
  • Twist Homolog
  • twist homolog 1 (acrocephalosyndactyly 3; Saethre-Chotzen syndrome) (Drosophila)
  • twist homolog 1 (Drosophila)
  • TWST1_HUMAN

See How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What glossary definitions help with understanding TWIST1?

acids ; bone formation ; cell ; chromosome ; coronal ; craniosynostosis ; DNA ; domain ; embryonic ; gene ; mesoderm ; neural crest ; osteoblast ; protein ; syndrome ; transcription ; transcription factor

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

  • Cai J, Goodman BK, Patel AS, Mulliken JB, Van Maldergem L, Hoganson GE, Paznekas WA, Ben-Neriah Z, Sheffer R, Cunningham ML, Daentl DL, Jabs EW. Increased risk for developmental delay in Saethre-Chotzen syndrome is associated with TWIST deletions: an improved strategy for TWIST mutation screening. Hum Genet. 2003 Dec;114(1):68-76. Epub 2003 Sep 25. (http://www.ncbi.nlm.nih.gov/pubmed/14513358?dopt=Abstract)
  • Cai J, Jabs EW. A twisted hand: bHLH protein phosphorylation and dimerization regulate limb development. Bioessays. 2005 Nov;27(11):1102-6. (http://www.ncbi.nlm.nih.gov/pubmed/16237669?dopt=Abstract)
  • Chun K, Teebi AS, Jung JH, Kennedy S, Laframboise R, Meschino WS, Nakabayashi K, Scherer SW, Ray PN, Teshima I. Genetic analysis of patients with the Saethre-Chotzen phenotype. Am J Med Genet. 2002 Jun 15;110(2):136-43. (http://www.ncbi.nlm.nih.gov/pubmed/12116251?dopt=Abstract)
  • de Heer IM, de Klein A, van den Ouweland AM, Vermeij-Keers C, Wouters CH, Vaandrager JM, Hovius SE, Hoogeboom JM. Clinical and genetic analysis of patients with Saethre-Chotzen syndrome. Plast Reconstr Surg. 2005 Jun;115(7):1894-902; discussion 1903-5. (http://www.ncbi.nlm.nih.gov/pubmed/15923834?dopt=Abstract)
  • Entrez Gene (http://www.ncbi.nlm.nih.gov/gene/7291)
  • Gripp KW, Zackai EH, Stolle CA. Mutations in the human TWIST gene. Hum Mutat. 2000;15(2):150-5. Review. Erratum in: Hum Mutat 2000;15(5):479. (http://www.ncbi.nlm.nih.gov/pubmed/10649491?dopt=Abstract)
  • Guenou H, Kaabeche K, Mée SL, Marie PJ. A role for fibroblast growth factor receptor-2 in the altered osteoblast phenotype induced by Twist haploinsufficiency in the Saethre-Chotzen syndrome. Hum Mol Genet. 2005 Jun 1;14(11):1429-39. Epub 2005 Apr 13. (http://www.ncbi.nlm.nih.gov/pubmed/15829502?dopt=Abstract)
  • Kress W, Schropp C, Lieb G, Petersen B, Büsse-Ratzka M, Kunz J, Reinhart E, Schäfer WD, Sold J, Hoppe F, Pahnke J, Trusen A, Sörensen N, Krauss J, Collmann H. Saethre-Chotzen syndrome caused by TWIST 1 gene mutations: functional differentiation from Muenke coronal synostosis syndrome. Eur J Hum Genet. 2006 Jan;14(1):39-48. (http://www.ncbi.nlm.nih.gov/pubmed/16251895?dopt=Abstract)
  • Seto ML, Hing AV, Chang J, Hu M, Kapp-Simon KA, Patel PK, Burton BK, Kane AA, Smyth MD, Hopper R, Ellenbogen RG, Stevenson K, Speltz ML, Cunningham ML. Isolated sagittal and coronal craniosynostosis associated with TWIST box mutations. Am J Med Genet A. 2007 Apr 1;143(7):678-86. (http://www.ncbi.nlm.nih.gov/pubmed/17343269?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: February 2008
Published: May 20, 2013