FOXE3

Protein-coding gene in the species Homo sapiens
FOXE3
Identifiers
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]
RNA expression pattern
Bgee
HumanMouse (ortholog)
Top expressed in
  • tibial nerve

  • putamen

  • cerebellar cortex

  • cerebellar hemisphere

  • kidney

  • kidney

  • sensory nervous system

  • face

  • sensory organ

  • caudate nucleus
    n/a
More reference expression data
BioGPS
n/a
Gene ontology
Molecular function
  • DNA binding
  • sequence-specific DNA binding
  • DNA-binding transcription factor activity
  • DNA-binding transcription factor activity, RNA polymerase II-specific
Cellular component
  • transcription regulator complex
  • nucleus
Biological process
  • positive regulation of lens epithelial cell proliferation
  • regulation of transcription, DNA-templated
  • negative regulation of lens fiber cell differentiation
  • cell development
  • positive regulation of epithelial cell proliferation
  • iris morphogenesis
  • cornea development in camera-type eye
  • negative regulation of apoptotic process
  • ciliary body morphogenesis
  • transcription by RNA polymerase II
  • transcription, DNA-templated
  • trabecular meshwork development
  • camera-type eye development
  • regulation of transcription by RNA polymerase II
  • eye development
  • lens development in camera-type eye
  • mRNA transcription by RNA polymerase II
  • anatomical structure morphogenesis
  • cell differentiation
Sources:Amigo / QuickGO
Orthologs
SpeciesHumanMouse
Entrez

2301

n/a

Ensembl

ENSG00000186790

n/a

UniProt

Q13461

n/a

RefSeq (mRNA)

NM_012186

n/a

RefSeq (protein)

NP_036318

n/a

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

Function

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.

Development

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

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

References

  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

  • Iseri SU, Osborne RJ, Farrall M, et al. (2009). "Seeing clearly: the dominant and recessive nature of FOXE3 in eye developmental anomalies". Hum. Mutat. 30 (10): 1378–86. doi:10.1002/humu.21079. PMID 19708017. S2CID 13387656.
  • Brémond-Gignac D, Bitoun P, Reis LM, et al. (2010). "Identification of dominant FOXE3 and PAX6 mutations in patients with congenital cataract and aniridia". Mol. Vis. 16: 1705–11. PMC 2927439. PMID 20806047.
  • Perosa F, Vicenti C, Racanelli V, et al. (2010). "The immunodominant epitope of centromere-associated protein A displays homology with the transcription factor forkhead box E3 (FOXE3)". Clin. Immunol. 137 (1): 60–73. doi:10.1016/j.clim.2010.06.008. PMID 20630806.
  • Valleix S, Niel F, Nedelec B, et al. (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.
  • Blixt A, Mahlapuu M, Aitola M, et al. (2000). "A forkhead gene, FoxE3, is essential for lens epithelial proliferation and closure of the lens vesicle". Genes Dev. 14 (2): 245–54. doi:10.1101/gad.14.2.245. PMC 316354. PMID 10652278.
  • Reis LM, Tyler RC, Schneider A, et al. (2010). "FOXE3 plays a significant role in autosomal recessive microphthalmia". Am. J. Med. Genet. A. 152A (3): 582–90. doi:10.1002/ajmg.a.33257. PMC 2998041. PMID 20140963.
  • Larsson C, Hellqvist M, Pierrou S, et al. (1995). "Chromosomal localization of six human forkhead genes, freac-1 (FKHL5), -3 (FKHL7), -4 (FKHL8), -5 (FKHL9), -6 (FKHL10), and -8 (FKHL12)". Genomics. 30 (3): 464–9. doi:10.1006/geno.1995.1266. PMID 8825632.
  • v
  • t
  • e
(1) Basic domains
(1.1) Basic leucine zipper (bZIP)
(1.2) Basic helix-loop-helix (bHLH)
Group A
Group B
Group C
bHLH-PAS
Group D
Group E
Group F
bHLH-COE
(1.3) bHLH-ZIP
(1.4) NF-1
(1.5) RF-X
(1.6) Basic helix-span-helix (bHSH)
(2) Zinc finger DNA-binding domains
(2.1) Nuclear receptor (Cys4)
subfamily 1
subfamily 2
subfamily 3
subfamily 4
subfamily 5
subfamily 6
subfamily 0
(2.2) Other Cys4
(2.3) Cys2His2
(2.4) Cys6
(2.5) Alternating composition
(2.6) WRKY
(3) Helix-turn-helix domains
(3.1) Homeodomain
Antennapedia
ANTP class
protoHOX
Hox-like
metaHOX
NK-like
other
(3.2) Paired box
(3.3) Fork head / winged helix
(3.4) Heat shock factors
(3.5) Tryptophan clusters
(3.6) TEA domain
  • transcriptional enhancer factor
(4) β-Scaffold factors with minor groove contacts
(4.1) Rel homology region
(4.2) STAT
(4.3) p53-like
(4.4) MADS box
(4.6) TATA-binding proteins
(4.7) High-mobility group
(4.9) Grainyhead
(4.10) Cold-shock domain
(4.11) Runt
(0) Other transcription factors
(0.2) HMGI(Y)
(0.3) Pocket domain
(0.5) AP-2/EREBP-related factors
(0.6) Miscellaneous
see also transcription factor/coregulator deficiencies


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