FOXE1
Chr 9ADARforkhead box E1
Also known as: BAMLAZ, FKHL15, FOXE2, HFKH4, HFKL5, NMTC4, TITF2, TTF-2
FOXE1 encodes a forkhead transcription factor that binds gene promoters to regulate thyroid morphogenesis and palate formation through direct targets including MSX1 and TGFB3. Loss-of-function mutations cause Bamforth-Lazarus syndrome (autosomal recessive) and increase susceptibility to nonmedullary thyroid cancer (autosomal dominant). The syndrome results from disrupted thyroid development and palatal morphogenesis due to impaired transcriptional regulation of key developmental genes.
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
Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.
The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
151 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 1 | 3 | 28 | 0 | 32 |
Likely Pathogenic | 0 | 2 | 4 | 0 | 6 |
VUS | 1 | 71 | 3 | 0 | 75 |
Likely Benign | 0 | 2 | 2 | 10 | 14 |
Benign | 0 | 4 | 12 | 7 | 23 |
Conflicting | — | 1 | |||
| Total | 2 | 82 | 49 | 17 | 151 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
FOXE1 · 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