FOXE1 explained

Forkhead box protein E1 is a protein that in humans is encoded by the FOXE1 gene.^{[1] [2] [3]}

Location

The FOXE1 gene is located on the long (q) arm of chromosome 9 at position 22^[4]

Function

This intronless gene belongs to the forkhead family of transcription factors, which is characterized by a distinct forkhead domain. This gene functions as a thyroid transcription factor which likely plays a crucial role in thyroid morphogenesis.

Clinical significance

Mutations in this gene cause Bamforth-Lazarus syndrome^[5] and are associated with congenital hypothyroidism and cleft palate with thyroid dysgenesis. The map localization of this gene suggests it may also be a candidate gene for squamous cell epithelioma and hereditary sensory neuropathy type I.

The region surrounding the FOXE1 gene has shown association in the pathogenesis of cleft lip and palate with genome-wide levels of significance in linkage analysis studies with additional fine-mapping and replication.^[5]

Tissue localization

FOXE1 is expressed transiently in the developing thyroid and the anterior pituitary gland.^[6]

Avian FOXE1 is also expressed in developing feathers.^[7]

See also

• FOX proteins

Further reading

• Wiese S, Emmerich D, Schröder B . The novel human HNF-3/fork head-like 5 gene: chromosomal localization and expression pattern. . DNA Cell Biol. . 16 . 2 . 165–71 . 1997 . 9052737 . 10.1089/dna.1997.16.165 . 20745762 . etal.
• Zannini M, Avantaggiato V, Biffali E . TTF-2, a new forkhead protein, shows a temporal expression in the developing thyroid which is consistent with a role in controlling the onset of differentiation. . EMBO J. . 16 . 11 . 3185–97 . 1997 . 9214635 . 10.1093/emboj/16.11.3185 . 1169936 . etal.
• Macchia PE, Mattei MG, Lapi P . Cloning, chromosomal localization and identification of polymorphisms in the human thyroid transcription factor 2 gene (TITF2). . Biochimie . 81 . 5 . 433–40 . 1999 . 10403172 . 10.1016/S0300-9084(99)80092-3 . etal.
• Wang JC, Waltner-Law M, Yamada K . Transducin-like enhancer of split proteins, the human homologs of Drosophila groucho, interact with hepatic nuclear factor 3beta. . J. Biol. Chem. . 275 . 24 . 18418–23 . 2000 . 10748198 . 10.1074/jbc.M910211199 . etal. free .
• Sequeira MJ, Morgan JM, Fuhrer D . Thyroid transcription factor-2 gene expression in benign and malignant thyroid lesions. . Thyroid . 11 . 11 . 995–1001 . 2002 . 11762722 . 10.1089/105072501753271662 . etal.
• Castanet M, Park SM, Smith A . A novel loss-of-function mutation in TTF-2 is associated with congenital hypothyroidism, thyroid agenesis and cleft palate. . Hum. Mol. Genet. . 11 . 17 . 2051–9 . 2003 . 12165566 . 10.1093/hmg/11.17.2051 . etal. free .
• Sequeira M, Al-Khafaji F, Park S . Production and application of polyclonal antibody to human thyroid transcription factor 2 reveals thyroid transcription factor 2 protein expression in adult thyroid and hair follicles and prepubertal testis. . Thyroid . 13 . 10 . 927–32 . 2004 . 14611701 . 10.1089/105072503322511328 . etal.
• Romanelli MG, Tato' L, Lorenzi P, Morandi C . Nuclear localization domains in human thyroid transcription factor 2. . Biochim. Biophys. Acta . 1643 . 1–3 . 55–64 . 2004 . 14654228 . 10.1016/j.bbamcr.2003.09.002.
• Eichberger T, Regl G, Ikram MS . FOXE1, a new transcriptional target of GLI2 is expressed in human epidermis and basal cell carcinoma. . J. Invest. Dermatol. . 122 . 5 . 1180–7 . 2004 . 15140221 . 10.1111/j.0022-202X.2004.22505.x . etal. free .
• Tonacchera M, Banco M, Lapi P . Genetic analysis of TTF-2 gene in children with congenital hypothyroidism and cleft palate, congenital hypothyroidism, or isolated cleft palate. . Thyroid . 14 . 8 . 584–8 . 2005 . 15320969 . 10.1089/1050725041692864 . etal.
• Brancaccio A, Minichiello A, Grachtchouk M . Requirement of the forkhead gene Foxe1, a target of sonic hedgehog signaling, in hair follicle morphogenesis. . Hum. Mol. Genet. . 13 . 21 . 2595–606 . 2005 . 15367491 . 10.1093/hmg/ddh292 . etal. free .
• Watkins WJ, Harris SE, Craven MJ . An investigation into FOXE1 polyalanine tract length in premature ovarian failure. . Mol. Hum. Reprod. . 12 . 3 . 145–9 . 2006 . 16481406 . 10.1093/molehr/gal017 . etal.
• Baris I, Arisoy AE, Smith A . A novel missense mutation in human TTF-2 (FKHL15) gene associated with congenital hypothyroidism but not athyreosis. . J. Clin. Endocrinol. Metab. . 91 . 10 . 4183–7 . 2006 . 16882747 . 10.1210/jc.2006-0405 . etal. free .

Notes and References

1. Chadwick BP, Obermayr F, Frischauf AM . FKHL15, a new human member of the forkhead gene family located on chromosome 9q22 . Genomics . 41 . 3 . 390–6 . Jul 1997 . 9169137 . 10.1006/geno.1997.4692 .
2. Clifton-Bligh RJ, Wentworth JM, Heinz P, Crisp MS, John R, Lazarus JH, Ludgate M, Chatterjee VK . Mutation of the gene encoding human TTF-2 associated with thyroid agenesis, cleft palate and choanal atresia . Nat Genet . 19 . 4 . 399–401 . Sep 1998 . 9697705 . 10.1038/1294 . 20334877 .
3. Web site: Entrez Gene: FOXE1 forkhead box E1 (thyroid transcription factor 2).
4. http://ghr.nlm.nih.gov/dynamicImages/chromomap/FOXE1.jpeg FOXE1
5. Dixon MJ, Marazita ML, Beaty TH, Murray JC . Cleft lip and palate: understanding genetic and environmental influences . Nat. Rev. Genet. . 12 . 3 . 167–78 . March 2011 . 21331089 . 3086810 . 10.1038/nrg2933 .
6. Zannini M, Avantaggiato V, Biffali E . TTF-2, a new forkhead protein, shows a temporal expression in the developing thyroid which is consistent with a role in controlling the onset of differentiation. EMBO J.. 16. 11. 3185–97. June 1997. 9214635. 1169936. 10.1093/emboj/16.11.3185. etal.
7. Yaklichkin SY, Darnell DK, Pier MV . Accelerated evolution of 3'avian FOXE1 genes, and thyroid and feather specific expression of chicken FoxE1.. BMC Evol. Biol. . 11. 302. 3185–97. Oct 2011. 21999483. 3207924. 10.1186/1471-2148-11-302. 2011BMCEE..11..302Y. etal. free.