FOXN1

FOXN1
Identifiers
Aliases	FOXN1, FKHL20, RONU, WHN, forkhead box N1, TIDAND, TLIND
External IDs	OMIM: 600838; MGI: 102949; HomoloGene: 2664; GeneCards: FOXN1; OMA:FOXN1 - orthologs
Gene location (Human) Chr. Chromosome 17 (human) Band 17q11.2 Start 28,506,243 bp End 28,538,900 bp
Gene location (Mouse) Chr. Chromosome 11 (mouse) Band 11 B5|11 46.74 cM Start 78,248,403 bp End 78,277,384 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in gingival epithelium skin of thigh skin of abdomen human penis skin of hip vulva nipple oral cavity mucosa of pharynx vagina Top expressed in hair outer root sheath of hair follicle cortex of hair lip filiform papilla thymus skin of back skin of abdomen morula embryo More reference expression data BioGPS More reference expression data
Gene ontology Molecular function sequence-specific DNA binding DNA binding DNA-binding transcription factor activity DNA-binding transcription activator activity, RNA polymerase II-specific DNA-binding transcription factor activity, RNA polymerase II-specific Cellular component nucleus Biological process hair follicle development defense response nail development regulation of transcription, DNA-templated blood vessel morphogenesis thymus epithelium morphogenesis thymus development regulation of transcription by RNA polymerase II lymphocyte homeostasis positive regulation of hair follicle development epithelial cell proliferation transcription by RNA polymerase II transcription, DNA-templated regulation of positive thymic T cell selection keratinocyte differentiation lymphoid lineage cell migration into thymus T cell homeostasis multicellular organism development regulation of T cell differentiation in thymus epidermis development animal organ morphogenesis regulation of gene expression cell population proliferation T cell lineage commitment positive regulation of epithelial cell differentiation cell differentiation positive regulation of transcription by RNA polymerase II hemopoiesis Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 8456 15218 Ensembl ENSG00000109101 ENSMUSG00000002057 UniProt O15353 Q61575 RefSeq (mRNA) NM_003593 NM_001369369 NM_001277290 NM_008238 RefSeq (protein) NP_003584 NP_001356298 NP_001264219 NP_032264 Location (UCSC) Chr 17: 28.51 – 28.54 Mb Chr 11: 78.25 – 78.28 Mb PubMed search
Wikidata
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Forkhead box protein N1 is a protein that in humans is encoded by the FOXN1 gene.

Function

Mutations in the winged-helix transcription factor gene at the nude locus in mice and rats produce the pleiotropic phenotype of hairlessness and athymia, resulting in a severely compromised immune system. This gene is orthologous to the mouse and rat genes and encodes a similar DNA-binding transcription factor that is thought to regulate keratin gene expression. A mutation in this gene has been correlated with T-cell immunodeficiency, the skin disorder congenital alopecia, and nail dystrophy. Alternative splicing in the 5' UTR of this gene has been observed. In the chick embryo, the FOXN1 gene is expressed in the developing thymus, claws and feathers. The expression of FOXN1 in feathers and claws indicates that it may regulate feather outgrowth. In feathers and claws, FOXN1 can potentially regulate expression of keratins similar to mammalian orthologs. In thymic epithelial cells, FOXN1 has been shown to bind to and regulate genes involved in T-cell maturation and antigen presentation.

Medical significance

Pathogenic mutations in the FOXN1 gene are associated congenital athymia, an ultra-rare disorder where the thymus fails to develop. This leads to severe immunodeficiency, with symptoms similar to severe combined immunodeficiency. The condition can be fatal if not diagnosed quickly, so screening is commonly provided for newborns in countries like the US.

Further reading

• Zhang Z, Burnley P, Coder B, Su DM (2012). "Insights on FoxN1 biological significance and usages of the "nude" mouse in studies of T-lymphopoiesis". International Journal of Biological Sciences. 8 (8): 1156–67. doi:10.7150/ijbs.5033. PMC 3477685. PMID 23091413.
• Mecklenburg L, Tychsen B, Paus R (Nov 2005). "Learning from nudity: lessons from the nude phenotype". Experimental Dermatology. 14 (11): 797–810. doi:10.1111/j.1600-0625.2005.00362.x. PMID 16232301. S2CID 27700105.
• Nehls M, Pfeifer D, Schorpp M, Hedrich H, Boehm T (Nov 1994). "New member of the winged-helix protein family disrupted in mouse and rat nude mutations". Nature. 372 (6501): 103–7. Bibcode:1994Natur.372..103N. doi:10.1038/372103a0. PMID 7969402. S2CID 2656526.
• Frank J, Pignata C, Panteleyev AA, Prowse DM, Baden H, Weiner L, Gaetaniello L, Ahmad W, Pozzi N, Cserhalmi-Friedman PB, Aita VM, Uyttendaele H, Gordon D, Ott J, Brissette JL, Christiano AM (Apr 1999). "Exposing the human nude phenotype". Nature. 398 (6727): 473–4. Bibcode:1999Natur.398..473F. doi:10.1038/18997. hdl:2299/16173. PMID 10206641. S2CID 107413.
• Gattenlöhner S, Müller-Hermelink HK, Marx A (1999). "Transcription of the nude gene (WHN) in human normal organs and mediastinal and pulmonary tumors". Pathology, Research and Practice. 195 (8): 571–4. doi:10.1016/s0344-0338(99)80007-7. PMID 10483588.
• Schlake T, Schorpp M, Maul-Pavicic A, Malashenko AM, Boehm T (Apr 2000). "Forkhead/winged-helix transcription factor Whn regulates hair keratin gene expression: molecular analysis of the nude skin phenotype". Developmental Dynamics. 217 (4): 368–76. doi:10.1002/(SICI)1097-0177(200004)217:4<368::AID-DVDY4>3.0.CO;2-Z. PMID 10767081.
• Adriani M, Martinez-Mir A, Fusco F, Busiello R, Frank J, Telese S, Matrecano E, Ursini MV, Christiano AM, Pignata C (May 2004). "Ancestral founder mutation of the nude (FOXN1) gene in congenital severe combined immunodeficiency associated with alopecia in southern Italy population". Annals of Human Genetics. 68 (Pt 3): 265–8. doi:10.1046/j.1529-8817.2004.00091.x. PMID 15180707. S2CID 20067101.
• Janes SM, Ofstad TA, Campbell DH, Watt FM, Prowse DM (Aug 2004). "Transient activation of FOXN1 in keratinocytes induces a transcriptional programme that promotes terminal differentiation: contrasting roles of FOXN1 and Akt" (PDF). Journal of Cell Science. 117 (Pt 18): 4157–68. doi:10.1242/jcs.01302. PMID 15316080. S2CID 9153395.
• Nonaka D, Henley JD, Chiriboga L, Yee H (Jul 2007). "Diagnostic utility of thymic epithelial markers CD205 (DEC205) and Foxn1 in thymic epithelial neoplasms". The American Journal of Surgical Pathology. 31 (7): 1038–44. doi:10.1097/PAS.0b013e31802b4917. PMID 17592270. S2CID 30502411.
• Weiner L, Han R, Scicchitano BM, Li J, Hasegawa K, Grossi M, Lee D, Brissette JL (Sep 2007). "Dedicated epithelial recipient cells determine pigmentation patterns". Cell. 130 (5): 932–42. doi:10.1016/j.cell.2007.07.024. PMID 17803914. S2CID 14622851.