Twist-related protein 1

Twist-related protein 1 (TWIST1) also known as class A basic helix–loop–helix protein 38 (bHLHa38) is a basic helix-loop-helix transcription factor that in humans is encoded by the TWIST1 gene.

Function

Basic helix-loop-helix (bHLH) transcription factors have been implicated in cell lineage determination and differentiation. The protein encoded by this gene is a bHLH transcription factor and shares similarity with another bHLH transcription factor, Dermo1 (a.k.a. TWIST2). The strongest expression of this mRNA is in placental tissue; in adults, mesodermally derived tissues express this mRNA preferentially.

Twist1 is thought to regulate osteogenic lineage.

Clinical significance

Mutations in the TWIST1 gene are associated with Saethre–Chotzen syndrome, breast cancer, and Sézary syndrome.

Craniosynostosis

TWIST1 mutations are involved in a number of craniosynostosis presentations. It can present in nonsyndromic forms (isolated scaphocephaly, right unicoronal synostosis, and turricephaly), but also in syndromic forms such as:

Acrocephalosyndactyly type 1 (Apert syndrome) (primary FGFR2)

Beare-Stevenson cutis gyrata syndrome (primary FGFR2)

Crouzon syndrome (primary FGFR2)

Crouzon syndrome-acanthosis nigricans syndrome (primary FGFR3)

Jackson-Weiss syndrome (primary FGFR1 or FGFR2)

Muenke syndrome (primary FGFR3)

Pfeiffer syndrome (primary FGFR1 or FGFR2)

As an oncogene

Twist plays an essential role in cancer metastasis. Over-expression of Twist or methylation of its promoter is common in metastatic carcinomas.