TGIF1

Chr 18AD

TGFB induced factor homeobox 1

Also known as: HPE4, TGIF

NCBI Gene: 7050 ENSG00000177426 UniProt: Q15583 OMIM: 602630

TGIF1 encodes a homeodomain transcription factor that represses retinoid X receptor signaling and SMAD2-mediated transcription, playing a critical role in forebrain development and ventral midline formation. Mutations cause holoprosencephaly type 4, a structural brain malformation affecting midline forebrain development, with autosomal dominant inheritance. The gene is not highly constrained against loss-of-function variants, consistent with its role in a dominant developmental disorder.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

The protein encoded by this gene is a member of the three-amino acid loop extension (TALE) superclass of atypical homeodomains. TALE homeobox proteins are highly conserved transcription regulators. This particular homeodomain binds to a previously characterized retinoid X receptor responsive element from the cellular retinol-binding protein II promoter. In addition to its role in inhibiting 9-cis-retinoic acid-dependent RXR alpha transcription activation of the retinoic acid responsive element, the protein is an active transcriptional co-repressor of SMAD2 and may participate in the transmission of nuclear signals during development and in the adult. Mutations in this gene are associated with holoprosencephaly type 4, which is a structural anomaly of the brain. Alternative splicing has been observed at this locus and multiple splice variants encoding distinct isoforms are described. [provided by RefSeq, Jul 2013]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Holoprosencephaly 4MIM #142946

Clinical highlights

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.91

LOEUF

LOF

Mechanism· G2P

📖

GeneReview available — TGIF1