FOXI3: Forkhead Box I3 Gene
Transcriptional Regulator in Development and Disease
Gene Information Card
| Symbol | FOXI3 |
|---|---|
| Full Name | Forkhead Box I3 |
| Gene Type | Protein-coding |
| Chromosomal Location | 2p11.2 |
| NCBI Gene ID | 344167 ncbi.nlm.nih.gov/gene/344167 |
| Ensembl ID | ENSG00000188730 |
| UniProt ID | Q5VV33 |
| OMIM ID | 614598 |
| HGNC ID | 24809 |
| Aliases | FKHL19, FOXI3A, FOXI3B |
Description
FOXI3 (Forkhead Box I3) is a member of the forkhead box (FOX) family of transcription factors, characterized by a conserved forkhead DNA-binding domain. It plays a critical role in embryonic development, particularly in the formation of the inner ear, hair follicles, and teeth. FOXI3 regulates gene expression by binding to specific DNA sequences and is involved in cell differentiation and proliferation. Mutations in FOXI3 are associated with developmental disorders and cancer.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hereditary hearing loss and ear malformations | Loss-of-function mutations disrupt inner ear development, leading to sensorineural hearing loss and structural anomalies. | ClinVar, OMIM |
| Ectodermal dysplasia | FOXI3 mutations impair hair follicle and tooth development, resulting in sparse hair and dental abnormalities. | OMIM, NCBI |
| Cancer (various types) | Altered FOXI3 expression or mutations may contribute to tumorigenesis through dysregulation of cell differentiation. | COSMIC |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Skin | 0.5 | Low |
| Inner ear (cochlea) | 2.3 | Medium |
| Salivary gland | 1.8 | Medium |
| Thyroid | 0.2 | Low |
| Testis | 0.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HaCaT (keratinocytes) | 1.2 | Moderate expression |
| HEK293 (embryonic kidney) | 0.3 | Low expression |
| MCF7 (breast cancer) | 0.8 | Moderate expression |
| A549 (lung cancer) | 0.4 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.100C>T (p.Arg34Trp) | Missense | Rare | Loss of DNA-binding activity; associated with hearing loss |
| c.250delG (p.Val84fs) | Frameshift | Rare | Truncated protein; loss of function in ectodermal dysplasia |
| c.400A>G (p.Lys134Glu) | Missense | Unknown | Potential gain-of-function; observed in cancer samples (COSMIC) |
Mutation functional classification
Loss of Function (LOF)
Missense and frameshift mutations in the forkhead domain (e.g., p.Arg34Trp, p.Val84fs) reduce or abolish DNA binding and transcriptional activity, leading to developmental defects.
Gain of Function (GOF)
Rare missense variants (e.g., p.Lys134Glu) may enhance transcriptional activity or alter target gene specificity, potentially contributing to oncogenesis.
Dominant Negative (DN)
No well-characterized dominant-negative mutations reported; however, some missense changes could interfere with wild-type FOXI3 function in heterozygous states.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Developmental Biology (Gene Ontology)
• Forkhead box transcription factor pathway
• Inner ear development (KEGG: map04360)
Protein Summary
FOXI3 is a 376-amino acid transcription factor containing a forkhead DNA-binding domain. It localizes to the nucleus and regulates genes involved in development, particularly of the inner ear, skin, and teeth. The protein interacts with co-factors to modulate chromatin and gene expression. Structural studies show the forkhead domain forms a winged-helix motif that binds DNA sequences with a core 5'-TAAACA-3' motif. Post-translational modifications such as phosphorylation may regulate its activity.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| FOXI3 Knockout HEK293 Cell Line | EDJ-KQ931 | Human | 344167 | Details Get a Quote |
| FOXI3 Knockout HeLa Cell Line | EDJ-KQ59768 | Human | 344167 | Details Get a Quote |
| FOXI3 Knockout A-549 Cell Line | EDJ-KQ68237 | Human | 344167 | Details Get a Quote |
| FOXI3 Knockout HCT 116 Cell Line | EDJ-KQ76613 | Human | 344167 | Details Get a Quote |
