TCF12

Chr 15

transcription factor 12

Also known as: CRS3, HEB, HH26, HTF4, HsT17266, TCF-12, bHLHb20, p64

NCBI Gene: 6938 ENSG00000140262 UniProt: Q99081

The protein is a basic helix-loop-helix transcription factor that recognizes E-box DNA sequences and regulates lineage-specific gene expression through heterodimerization with other bHLH proteins. Loss-of-function mutations cause craniosynostosis 3 and hypogonadotropic hypogonadism with or without anosmia through both autosomal dominant and autosomal recessive inheritance patterns. The protein is expressed in multiple tissues including skeletal muscle, thymus, and immune cells where it controls developmental gene expression programs.

GeneReviews ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

The protein encoded by this gene is a member of the basic helix-loop-helix (bHLH) E-protein family that recognizes the consensus binding site (E-box) CANNTG. This encoded protein is expressed in many tissues, among them skeletal muscle, thymus, B- and T-cells, and may participate in regulating lineage-specific gene expression through the formation of heterodimers with other bHLH E-proteins. Several alternatively spliced transcript variants of this gene have been described, but the full-length nature of some of these variants has not been determined. [provided by RefSeq, Jul 2008]

GeneReviews ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtCraniosynostosis 3

UniProtHypogonadotropic hypogonadism 26 with or without anosmia

Clinical highlights

Gene-disease validity (ClinGen)

TCF12-related craniosynostosis · ADDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

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P/LP missense

0.37

LOEUF

LOF

Mechanism· G2P

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GeneReview available — TCF12