FOXN1 Gene
Forkhead Box N1: Master Regulator of Thymic Epithelial Cell Development and T-Cell Lymphopoiesis
Gene Information Card
| Symbol | FOXN1 |
|---|---|
| Full Name | Forkhead Box N1 |
| Gene Type | Protein coding |
| Chromosomal Location | 17q11.2 |
| NCBI Gene ID | 8456 ncbi.nlm.nih.gov/gene/8456 |
| Ensembl ID | ENSG00000109101 |
| UniProt ID | O15353 |
| OMIM ID | 600838 |
| HGNC ID | 12765 |
| Aliases | WHN, RONU, FKHL20, nude |
Description
FOXN1 (Forkhead Box N1) encodes a transcription factor essential for the development and function of thymic epithelial cells (TECs). It regulates the expression of genes critical for T-cell maturation and selection. Loss-of-function mutations cause severe combined immunodeficiency (SCID) with congenital alopecia and nail dystrophy (T-cell immunodeficiency, congenital alopecia, and nail dystrophy; TIDAND). FOXN1 is also a key marker for thymic epithelial progenitor cells.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| T-cell immunodeficiency, congenital alopecia, and nail dystrophy (TIDAND) | Loss-of-function mutations in FOXN1 impair thymic epithelial cell development, leading to absent or hypoplastic thymus, defective T-cell lymphopoiesis, and severe combined immunodeficiency. | OMIM #601705; ClinVar |
| Severe combined immunodeficiency (SCID) | Biallelic FOXN1 mutations cause a SCID phenotype with absent T cells, normal B cells, and natural killer cells (T-B+NK+ SCID). | OMIM #601705; PubMed: 10391211 |
| Alopecia universalis congenita | FOXN1 deficiency disrupts hair follicle development, resulting in congenital total hair loss. | OMIM #601705; PubMed: 10391211 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Thymus | 12.5 | High |
| Skin | 0.8 | Low |
| Lung | 0.3 | Not detected |
| Spleen | 0.1 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Thymic epithelial cells (TECs) | 15.2 | Highest expression in medullary and cortical TECs |
| Keratinocytes | 1.1 | Low expression |
| HEK 293 | 0.0 | Not detected |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.792C>A (p.Tyr264*) | Nonsense | Rare | Loss of function; truncated protein |
| c.1034_1035del (p.Arg345Profs*49) | Frameshift | Rare | Loss of function; premature termination |
| c.1183C>T (p.Arg395*) | Nonsense | Rare | Loss of function; truncated protein |
Mutation functional classification
Loss of Function (LOF)
Most FOXN1 disease-associated mutations are loss-of-function (nonsense, frameshift, splice-site), leading to absent or non-functional protein, resulting in thymic aplasia and SCID.
Gain of Function (GOF)
No gain-of-function mutations reported in FOXN1.
Dominant Negative (DN)
No dominant-negative mutations reported; FOXN1 acts as a monomer and haploinsufficiency is not disease-causing.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Thymic epithelial cell development (Reactome: R-HSA-8866423)
• T-cell receptor signaling (Reactome: R-HSA-202403)
Protein Summary
FOXN1 is a 648-amino acid transcription factor containing a forkhead DNA-binding domain. It localizes to the nucleus and binds to forkhead response elements in target gene promoters. FOXN1 is critical for the differentiation and maintenance of thymic epithelial cells, which provide the microenvironment for T-cell development. It also regulates genes involved in hair follicle morphogenesis. The protein is highly conserved across vertebrates.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| FOXN1 Knockout HEK293 Cell Line | EDJ-KQ3024 | Human | 8456 | Details Get a Quote |
| FOXN1 Knockout HeLa Cell Line | EDJ-KQ54912 | Human | 8456 | Details Get a Quote |
| FOXN1 Knockout A-549 Cell Line | EDJ-KQ63398 | Human | 8456 | Details Get a Quote |
| FOXN1 Knockout HCT 116 Cell Line | EDJ-KQ71865 | Human | 8456 | Details Get a Quote |
