FOXE3: Forkhead Box E3 Gene in Ocular Development and Disease
Comprehensive genomic, functional, and clinical overview of FOXE3
Gene Information Card
| Symbol | FOXE3 |
|---|---|
| Full Name | Forkhead Box E3 |
| Gene Type | Protein coding |
| Chromosomal Location | 1p33 |
| NCBI Gene ID | 2301 ncbi.nlm.nih.gov/gene/2301 |
| Ensembl ID | ENSG00000186767 |
| UniProt ID | Q13461 |
| OMIM ID | 601094 |
| HGNC ID | 3808 |
| Aliases | FKHL12, FREAC8, FOXE3 |
Description
FOXE3 (Forkhead Box E3) encodes a member of the forkhead family of transcription factors, characterized by a conserved DNA-binding forkhead domain. It is essential for lens and anterior segment development of the eye. FOXE3 regulates gene expression during lens placode formation, lens vesicle closure, and maintenance of lens fiber cell integrity. Mutations in FOXE3 are associated with various ocular disorders including anterior segment dysgenesis, congenital cataracts, microphthalmia, and Peters anomaly.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Anterior segment dysgenesis (ASD) | Loss-of-function mutations disrupt lens and corneal development, leading to malformation of the anterior eye chamber. | ClinVar, OMIM |
| Congenital cataracts | FOXE3 mutations impair lens fiber cell differentiation and transparency, resulting in cataract formation at birth. | ClinVar, OMIM |
| Microphthalmia | Biallelic loss-of-function variants cause reduced eye size due to defective lens induction and growth. | ClinVar, OMIM |
| Peters anomaly | FOXE3 mutations contribute to corneal opacity and iridocorneal adhesions by disrupting anterior segment morphogenesis. | ClinVar, OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lens | 12.5 | High |
| Retina | 4.2 | Medium |
| Cornea | 3.8 | Medium |
| Brain | 0.5 | Low |
| Heart | 0.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| ARPE-19 (retinal pigment epithelium) | 2.1 | Moderate expression |
| HLE-B3 (human lens epithelial) | 15.3 | High expression |
| HeLa | 0.3 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.240C>A (p.Tyr80*) | Nonsense | Rare | Loss of function; truncation of forkhead domain |
| c.289G>A (p.Gly97Arg) | Missense | Rare | Impaired DNA binding; dominant negative effect |
| c.1A>G (p.Met1?) | Start loss | Rare | Loss of function; no protein translation |
| c.730C>T (p.Arg244Trp) | Missense | Rare | Reduced transactivation activity |
Mutation functional classification
Loss of Function (LOF)
Nonsense, frameshift, and start-loss mutations that abolish FOXE3 protein function, leading to recessive ocular disorders.
Gain of Function (GOF)
Not reported for FOXE3.
Dominant Negative (DN)
Missense mutations in the forkhead domain (e.g., p.Gly97Arg) that interfere with wild-type FOXE3 DNA binding and transcriptional activity, causing dominant inheritance.
View complete mutation data：
Gene Ontology (GO)
| • DNA-binding transcription factor activity | • RNA polymerase II cis-regulatory region sequence-specific DNA binding |
| • regulation of transcription by RNA polymerase II | • lens development in camera-type eye |
| • anterior segment morphogenesis | • cell differentiation |
Pathways
• Lens development (Reactome: R-HSA-1474244)
• Transcriptional regulation by FOXE3 (Gene Ontology)
Protein Summary
FOXE3 is a 319-amino acid transcription factor containing a highly conserved forkhead DNA-binding domain. It localizes to the nucleus and regulates target genes involved in lens fiber cell differentiation, cell cycle control, and extracellular matrix remodeling. The protein interacts with other transcription factors such as PAX6 and SOX2 to coordinate eye development. Structural integrity of the forkhead domain is critical for DNA binding; mutations in this region disrupt transcriptional activity and lead to ocular malformations.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| FOXE3 Knockout HEK293 Cell Line | EDJ-KQ3530 | Human | 2301 | Details Get a Quote |
| FOXE3 Knockout HeLa Cell Line | EDJ-KQ53244 | Human | 2301 | Details Get a Quote |
| FOXE3 Knockout A-549 Cell Line | EDJ-KQ61725 | Human | 2301 | Details Get a Quote |
| FOXE3 Knockout HCT 116 Cell Line | EDJ-KQ70210 | Human | 2301 | Details Get a Quote |
