TLE1
Chr 9TLE family member 1, transcriptional corepressor
Also known as: ESG, ESG1, GRG1, TLE-1
The TLE1 protein functions as a transcriptional corepressor that inhibits gene expression by binding to various transcription factors, including those in NF-kappa-B and Wnt signaling pathways. Loss-of-function mutations in TLE1 cause an autosomal dominant neurodevelopmental disorder characterized by intellectual disability, developmental delay, and behavioral abnormalities. The pathogenic mechanism involves haploinsufficiency, where reduced TLE1 protein levels disrupt normal transcriptional regulation during brain development.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly LoF-intolerant (top ~10% of genes)
Moderately missense-constrained (top ~2.5%)
The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).
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
TLE1 · 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
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools