TBR1
Chr 2ADT-box brain transcription factor 1
Also known as: AUTS5, IDDAS, TBR-1, TES-56
TBR1 encodes a T-box transcription factor that regulates neuronal migration and axonal projection in the cerebral cortex, hippocampus, amygdala, and olfactory bulb. Loss-of-function mutations cause autosomal dominant intellectual developmental disorder with autism and speech delay. The gene is highly intolerant to loss-of-function variants, indicating haploinsufficiency as the mechanism of pathogenicity.
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly LoF-intolerant (top ~10% of genes)
Highly missense-constrained (top ~0.1%)
This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to loss-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
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
TBR1 · 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
Online Study of People Who Have Genetic Changes and Features of Autism: Simons Searchlight
RECRUITINGA Pilot, Multicentre, Controlled, Open-label Study Evaluating 24 Months of Lithium Carbonate Treatment in Patients With TBR1-related Neurocognitive Disorder
RECRUITINGExternal Resources
Links to major genomics databases and tools