Alt. symbols: WHN | RONU | FKHL20

Approved name: forkhead box N1
Alt. names: winged-helix nude, Rowett nude

Location: 17q11.2: 28506243 - 28538900 (+)
Gene type: protein_coding, 3 transcripts.

Scores: LoFtool: 0.059200 | pLI: 0.96949755 | LOEUF: 0.349

HGNC: 12765

NCBI: 8456, RefSeq: NG_007260.1

Ensembl: ENSG00000109101.8

LRG_61 | Status: public

OMIM: 600838

Expression | ProteinAtlas

FOXN1 is a transcription factor that plays a crucial role in the development and function of the thymus, but also for the normal development of the skin, hair and nails. Therefore, FOXN1 regulates the expression of genes involved in thymus development and T cell maturation and selection, but also in the formation of hair follicles and the growth of fingernails and toenails. FOXN1 regulates the differentiation of thymic epithelial cells, ensuring their proper function in supporting T cell maturation. It helps create a specialized microenvironment within the thymus, where T cells can undergo positive and negative selection. This process ensures that T cells with functional and non-self-reactive receptors are allowed to mature and survive, while those with dysfunctional or self-reactive receptors are eliminated. FOXN1's own expression is differentially regulated during organogenesis. It forms multimolecular nuclear aggregates with other molecules, and it uses its C-terminal sequence to regulate the diffusion velocity within these aggregates and to modulate the binding to proximal gene regulatory regions to exert its transcriptional activity (PMID:34860543).

Biallelic or monoallelic mutations in the FOXN1 gene can lead to an overlapping spectrum of phenotypes that can include T-cell lymphopenia, severe combined immunodeficiency due to thymic aplasia, nail dystrophy and alopecia (nude phenotype). Lack or dysfunction of FOXN1 protein prevents the formation of the thymus and thereby impairs T cell development, maturation and function. As a result, people with complete FOXN1 deficiency develop recurrent serious infections starting early in life. Loss of the FOXN1 protein also prevents the formation of hair follicles, leading to alopecia, and to malformations of the fingernails and toenails (nail dystrophy). Abnormalities of the central nervous system have also been reported in a few patients; however, it is not yet known whether CNS abnormalities are a common feature of this condition and how a lack of FOXN1 might contribute to this phenotype. C-terminus mutations seem to alter FOXN1's capacity to form multimolecular nuclear aggregates and to modulate binding to proximal gene regulatory regions. This type of transcriptionally inactive mutants act in a dominant negative manner over the WT-FOXN1 causing athymia and severe lymphopenia in heterozygotes (PMID:34860543). [Load More]