TGIF1

The TGIF1 gene provides instructions for making a protein called TG-interacting factor. This protein is important for normal development of the front part of the brain (forebrain). TG-interacting factor is a transcription factor, which means that it regulates the activity of certain genes. This protein turns off genes by attaching (binding) to specific regions of DNA or by interacting with other DNA-binding proteins.

TG-interacting factor regulates signaling pathways that are important for embryonic development. This protein blocks the signals of the transforming growth factor beta (TGF-β) pathway. This signaling pathway transmits chemical signals from the cell surface to the nucleus, which allows the environment outside the cell to affect how the cell produces other proteins. TG-interacting factor also blocks a molecule called retinoic acid from regulating gene activity. Retinoic acid, a form of vitamin A, binds to a group of transcription factors that regulate a number of genes important for early development. By blocking these signaling pathways, TG-interacting factor ensures that certain genes are turned off at the proper time.

nonsyndromic holoprosencephaly - caused by mutations in the TGIF1 gene

At least 13 mutations in the TGIF1 gene have been found to cause nonsyndromic holoprosencephaly. This condition occurs when the brain fails to divide into two halves (hemispheres) during early development. TGIF1 gene mutations are the fourth most common cause of nonsyndromic holoprosencephaly. These mutations disrupt the protein's ability to bind with DNA or interact with other proteins. As a result, TG-interacting factor cannot block the signals of the TGF-β pathway and retinoic acid. If the signals involved in forebrain development are not properly regulated, the brain does not separate into two hemispheres. The signs and symptoms of nonsyndromic holoprosencephaly are caused by abnormal development of the brain and face.