FOXE1 Gene
Forkhead Box E1: A Key Transcription Factor in Thyroid Development and Cleft Palate
Gene Information Card
| Symbol | FOXE1 |
|---|---|
| Full Name | Forkhead Box E1 |
| Gene Type | Protein coding |
| Chromosomal Location | 9q22.33 |
| NCBI Gene ID | 2304 ncbi.nlm.nih.gov/gene/2304 |
| Ensembl ID | ENSG00000178919 |
| UniProt ID | O00358 |
| OMIM ID | 602617 |
| HGNC ID | 3806 |
| Aliases | TITF2, FKHL15, TTF-2, TTF2 |
Description
FOXE1 (Forkhead Box E1) encodes a transcription factor belonging to the forkhead/winged-helix family. It is essential for thyroid morphogenesis, migration, and function, as well as for palate development. FOXE1 binds to DNA via a forkhead domain and regulates expression of thyroid-specific genes such as thyroglobulin (TG) and thyroid peroxidase (TPO). Mutations in FOXE1 cause Bamforth-Lazarus syndrome, characterized by congenital hypothyroidism due to thyroid agenesis or dysgenesis, cleft palate, and spiky hair. FOXE1 is also implicated in susceptibility to thyroid cancer and orofacial clefts.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Bamforth-Lazarus syndrome (congenital hypothyroidism, cleft palate, spiky hair) | Loss-of-function mutations in FOXE1 disrupt thyroid development and palate fusion, leading to agenesis or dysgenesis of the thyroid gland and cleft palate. | OMIM #241850; ClinVar; multiple case reports |
| Thyroid dysgenesis | FOXE1 mutations impair thyroid gland migration and differentiation, resulting in ectopic or absent thyroid tissue. | OMIM #218700; NCBI GeneReviews |
| Cleft palate (nonsyndromic) | FOXE1 variants alter transcriptional regulation of palatal fusion genes, increasing risk of isolated cleft palate. | GWAS studies; ClinVar |
| Thyroid cancer (papillary) | FOXE1 polymorphisms (e.g., rs965513) are associated with increased risk of papillary thyroid carcinoma. | COSMIC; NCBI PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Thyroid gland | 12.5 | High |
| Salivary gland | 5.2 | Medium |
| Esophagus | 3.8 | Medium |
| Skin | 2.1 | Low |
| Lung | 1.0 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Thyroid follicular epithelial cells | 15.0 | Primary expression site |
| Nthy-ori 3-1 (thyroid cell line) | 8.4 | Model for thyroid function |
| HeLa | 0.5 | Low expression |
| HEK293 | 0.3 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.251C>T (p.Ala84Val) | Missense | Rare | Loss of DNA-binding activity; associated with Bamforth-Lazarus syndrome |
| c.307C>T (p.Arg103Ter) | Nonsense | Rare | Premature truncation; loss of function; thyroid agenesis |
| c.559C>T (p.Arg187Trp) | Missense | Rare | Impaired transcriptional activation; cleft palate phenotype |
| rs965513 (intergenic near FOXE1) | SNP | Common (allele frequency ~0.3) | Risk allele for papillary thyroid carcinoma |
Mutation functional classification
Loss of Function (LOF)
FOXE1 loss-of-function mutations (e.g., p.Ala84Val, p.Arg103Ter) impair DNA binding or protein stability, leading to reduced transcription of thyroid-specific genes, resulting in thyroid dysgenesis and Bamforth-Lazarus syndrome.
Gain of Function (GOF)
No well-characterized gain-of-function mutations reported in FOXE1. Overexpression in thyroid cancer may contribute to tumor progression but is not classified as a mutation-driven gain-of-function.
Dominant Negative (DN)
Dominant-negative effects have not been clearly demonstrated for FOXE1 mutations; the disorder follows autosomal recessive inheritance, suggesting haploinsufficiency or complete loss of function.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Thyroid hormone synthesis (Reactome: R-HSA-209968)
• Developmental biology (Reactome: R-HSA-1266738)
• Transcriptional regulation by FOXE1 (Reactome: R-HSA-9619483)
Protein Summary
FOXE1 (Forkhead Box E1) is a 367-amino acid transcription factor with a conserved forkhead DNA-binding domain. It localizes to the nucleus and binds to DNA sequences containing the core motif 5'-A(A/T)TRTT(G/T)-3'. FOXE1 is critical for thyroid gland development, regulating genes such as TG, TPO, and TSHR. It also plays a role in palate formation and hair follicle development. The protein interacts with other transcription factors (e.g., PAX8, NKX2-1) to coordinate thyroid organogenesis. Post-translational modifications include phosphorylation, which may modulate its activity.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| FOXE1 Knockout HEK293 Cell Line | EDJ-KQ4611 | Human | 2304 | Details Get a Quote |
| FOXE1 Knockout A-549 Cell Line | EDJ-KQ27284 | Human | 2304 | Details Get a Quote |
| FOXE1 Knockout HeLa Cell Line | EDJ-KQ27285 | Human | 2304 | Details Get a Quote |
| FOXE1 Knockout HCT 116 Cell Line | EDJ-KQ70213 | Human | 2304 | Details Get a Quote |
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