TCF12
Chr 15ADARtranscription factor 12
Also known as: CRS3, HEB, HH26, HTF4, HsT17266, TCF-12, bHLHb20, p64
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.
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
Mild missense constraint
The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
TCF12 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
External Resources
Links to major genomics databases and tools