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AliasesFOXE3, FKHL12, FREAC8, forkhead box E3, AAT11, ASGD2, CTRCT34
External IDsOMIM: 601094 GeneCards: FOXE3
Gene location (Human)
Chromosome 1 (human)
Chr.Chromosome 1 (human)[1]
Chromosome 1 (human)
Genomic location for FOXE3
Genomic location for FOXE3
Band1p33Start47,416,285 bp[1]
End47,418,052 bp[1]
RefSeq (mRNA)



RefSeq (protein)



Location (UCSC)Chr 1: 47.42 – 47.42 Mbn/a
PubMed search[2]n/a
View/Edit Human

Forkhead box protein E3 (FOXE3) also known as forkhead-related transcription factor 8 (FREAC-8) is a protein that in humans is encoded by the FOXE3 gene located on the short arm of chromosome 1.[3]


FOXE3 is a forkhead-box transcription factor which is involved in the proper formation of the ocular lens and is post-natally expressed in the lens epithelium.


Foxe3, also known as Forkhead Box E3, is a transcription factor that is responsible for the formation of the lens placode, a precursor to the lens of the eye, and the lens itself. Foxe3 controls multiple processes during development of the lens including, the expression of Cryaα which controls the solubility of the crystalline protein complex in the developing lens. Reduced solubility can lead to potential cataract formation due to crystallization of the lens. Foxe3 also controls the regulation of Prox1, which is responsible for cell cycle progression. As Foxe3 expression downregulates, Prox1 expression increases causing a reduction in cellular proliferation in the anterior lens. Foxe3 also regulates platelet-derived growth factor receptor-α (Pdgfrα) expression. This is responsible for lens fiber differentiation within the epithelium of certain parts of the lens. There are multiple defects associated with dysfunction of this gene with most being classified under the term anterior segment dysgenesis (ASD). For example, Peters anomaly is a rare disorder obtained during development characterized by adhesions due to malformations of the posterior corneal stroma, the absence of Descemet's membrane and the corneal endothelium, and corneal opacities. This syndrome can be attributed to fetal alcohol syndrome and aneuploidy.[4] Scientists have generated a knockout model for Foxe3 in mice and are testing the effects on the lenses of those animals. So far, it appears that Foxe3 is essential for normal lens development.[5]

Clinical significance[edit]

Mutations in the FOXE3 gene are associated with anterior segment mesenchymal dysgenesis.[6]

Homozygous mutations in this gene have been associated with a number of ocular diseases such as congenital aphakia,[7][8] sclerocornea, microphthalmia, and optic disc coloboma.[9] There have also been reports of heterozygous mutations causing less severe ocular diseases such as anterior segment dysgenesis (sometimes referred to as anterior segment mesenchymal dysgenesis),[6] and Peter's anomaly.[10]

See also[edit]


  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000186790 - Ensembl, May 2017
  2. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  3. ^ "Entrez Gene: forkhead box E3".
  4. ^ Doucette L, Green J, Fernandez B, Johnson G, Parfrey P, Young T (2011). "A novel, non-stop mutation in FOXE3 causes an autosomal dominant form of variable anterior segment dysgenesis including Peters anomaly". European Journal of Human Genetics. 19 (3): 293–299. doi:10.1038/ejhg.2010.210. PMC 3062009. PMID 21150893.
  5. ^ Blixt Å, Landgren H, Johansson BR, Carlsson P (2007). "Foxe3 is required for morphogenesis and differentiation of the anterior segment of the eye and is sensitive to Pax6 gene dosage". Developmental Biology. 302 (1): 218–229. doi:10.1016/j.ydbio.2006.09.021. PMID 17064680.
  6. ^ a b Semina EV, Brownell I, Mintz-Hittner HA, Murray JC, Jamrich M (February 2001). "Mutations in the human forkhead transcription factor FOXE3 associated with anterior segment ocular dysgenesis and cataracts". Hum. Mol. Genet. 10 (3): 231–6. doi:10.1093/hmg/10.3.231. PMID 11159941.
  7. ^ Anjum I, Eiberg H, Baig SM, Tommerup N, Hansen L (2010). "A mutation in the FOXE3 gene causes congenital primary aphakia in an autosomal recessive consanguineous Pakistani family". Mol. Vis. 16: 549–55. PMC 2846847. PMID 20361012.
  8. ^ Valleix S, Niel F, Nedelec B, Algros MP, Schwartz C, Delbosc B, Delpech M, Kantelip B (August 2006). "Homozygous nonsense mutation in the FOXE3 gene as a cause of congenital primary aphakia in humans". Am. J. Hum. Genet. 79 (2): 358–64. doi:10.1086/505654. PMC 1559477. PMID 16826526.
  9. ^ Ali M, Buentello-Volante B, McKibbin M, Rocha-Medina JA, Fernandez-Fuentes N, Koga-Nakamura W, Ashiq A, Khan K, Booth AP, Williams G, Raashid Y, Jafri H, Rice A, Inglehearn CF, Zenteno JC (2010). "Homozygous FOXE3 mutations cause non-syndromic, bilateral, total sclerocornea, aphakia, microphthalmia and optic disc coloboma". Mol. Vis. 16: 1162–8. PMC 2901196. PMID 20664696.
  10. ^ Doucette, Lance; Jane Green; Bridget Fernandez; Gordon J Johnson; Patrick Parfrey; Terry-Lynn Young (2011). "A novel, non-stop mutation in FOXE3 causes an autosomal dominant form of variable anterior segment dysgenesis including Peters anomaly". European Journal of Human Genetics. 19 (3): 293–299. doi:10.1038/ejhg.2010.210. PMC 3062009. PMID 21150893.

Further reading[edit]