FOXL2
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| Location (UCSC) | Chr 3: 138.94 – 138.95 Mb | Chr 9: 98.84 – 98.84 Mb | |||||||
| PubMed search | [3] | [4] | |||||||
| View/Edit Human | View/Edit Mouse |
Forkhead box protein L2 is a protein that in humans is encoded by the FOXL2 gene.[5][6]
Function
FOXL2 (OMIM 605597) is a transcription factor belonging to the forkhead box (FOX) superfamily, characterized by the forkhead box/winged-helix DNA-binding domain. FOXL2 plays an important role in ovarian development and function.[6] In postnatal ovaries FOXL2 regulates granulosa cell differentiation and supports the growth of the pre-ovulatory follicles during adult life.[7] In addition, the FOXL2 protein will prevent the formation of testes by suppressing expression of SOX9.[8] In mice, FOXL2 is also expressed in pituitary cells[9] where it is required for FSH expression.[10]
Regulation
FOXL2 has several
Clinical significance
Sex determination
FOXL2 is involved in sex determination. FOXL2
Eyebrow thickness
Several SNPs (Single Variant Polymorphisms) in the genomic region 3q23 overlapping the forkhead box L2 (FOXL2) were found associated with eyebrow thickness. In Europeans, East Asians, and South Asians, the derived allele is above ~90% frequency, and in Africans, it is above ~75%. Native Americans, particularly Peruvians, have a relatively high frequency of the homozygous ancestral allele, which significantly decreases eyebrow thickness. All primates and archaic humans share the ancestral allele.[15]
Blepharophimosis–ptosis–epicanthus inversus syndrome
Mutations in this gene are a cause of
Adult granulosa cell tumors
A missense mutation in the FOXL2 gene, C134W, is typically found in adult
Endometriosis
In addition to ovarian expression of FOXL2, there have been recent studies to suggest that overexpression of FOXL2 has been implicated in
Other deregulations
One study has found that FOXL2 is required for SF-1-induced ovarian AMH regulation by interactions between FOXL2 protein and SF-1; a mutated FOXL2 could not interact with SF-1 normally and thus could not regulate ovarian AMH as normal.[19]
In a knockout study in mice, the granulosa cells of the ovaries failed to undergo the squamous-to-cuboidal transition, which led to the arrest of folliculogenesis.[20]
See also
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000183770 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000050397 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- PMID 1941972.
- ^ a b c "Entrez Gene: FOXL2 forkhead box L2".
- ^ PMID 26791928.
- PMID 28193729.
- PMID 16840539.
- PMID 21700720.
- PMID 22022399.
- PMID 22544055.
- S2CID 14305820.*Lay summary in: Borrell B (December 10, 2009). "Ovaries reveal their inner testes". Nature News.
- S2CID 12076748.
- PMID 26926045.
- PMID 19515849.
- PMID 21632871.
- S2CID 25004354.
- PMID 27414805.
- S2CID 31658647.
Further reading
- Vaiman D, Schibler L, Oustry-Vaiman A, Pailhoux E, Goldammer T, Stevanovic M, et al. (February 1999). "High-resolution human/goat comparative map of the goat polled/intersex syndrome (PIS): the human homologue is contained in a human YAC from HSA3q23". Genomics. 56 (1): 31–9. S2CID 1446666.
- Kaestner KH, Knochel W, Martinez DE (January 2000). "Unified nomenclature for the winged helix/forkhead transcription factors". Genes & Development. 14 (2): 142–6. S2CID 26488600.
- Crisponi L, Deiana M, Loi A, Chiappe F, Uda M, Amati P, et al. (February 2001). "The putative forkhead transcription factor FOXL2 is mutated in blepharophimosis/ptosis/epicanthus inversus syndrome". Nature Genetics. 27 (2): 159–66. S2CID 26750194.
- De Baere E, Dixon MJ, Small KW, Jabs EW, Leroy BP, Devriendt K, et al. (July 2001). "Spectrum of FOXL2 gene mutations in blepharophimosis-ptosis-epicanthus inversus (BPES) families demonstrates a genotype--phenotype correlation". Human Molecular Genetics. 10 (15): 1591–600. PMID 11468277.
- Dollfus H, Kumaramanickavel G, Biswas P, Stoetzel C, Quillet R, Denton M, et al. (July 2001). "Identification of a new TWIST mutation (7p21) with variable eyelid manifestations supports locus homogeneity of BPES at 3q22". Journal of Medical Genetics. 38 (7): 470–2. PMID 11474656.
- Yamada T, Hayasaka S, Matsumoto M, Esa T, Hayasaka Y, Endo M (2002). "Heterozygous 17-bp deletion in the forkhead transcription factor gene, FOXL2, in a Japanese family with blepharophimosis-ptosis-epicanthus inversus syndrome". Journal of Human Genetics. 46 (12): 733–6. S2CID 39171567.
- Kosaki K, Ogata T, Kosaki R, Sato S, Matsuo N (March 2002). "A novel mutation in the FOXL2 gene in a patient with blepharophimosis syndrome: differential role of the polyalanine tract in the development of the ovary and the eyelid". Ophthalmic Genetics. 23 (1): 43–7. S2CID 2502871.
- Bell R, Murday VA, Patton MA, Jeffery S (2002). "Two families with blepharophimosis/ptosis/epicanthus inversus syndrome have mutations in the putative forkhead transcription factor FOXL2". Genetic Testing. 5 (4): 335–8. PMID 11960581.
- Harris SE, Chand AL, Winship IM, Gersak K, Aittomäki K, Shelling AN (August 2002). "Identification of novel mutations in FOXL2 associated with premature ovarian failure". Molecular Human Reproduction. 8 (8): 729–33. PMID 12149404.
- De Baere E, Lemercier B, Christin-Maitre S, Durval D, Messiaen L, Fellous M, et al. (August 2002). "FOXL2 mutation screening in a large panel of POF patients and XX males". Journal of Medical Genetics. 39 (8): 43e–43. PMID 12161610.
- Ramírez-Castro JL, Pineda-Trujillo N, Valencia AV, Muñetón CM, Botero O, Trujillo O, et al. (November 2002). "Mutations in FOXL2 underlying BPES (types 1 and 2) in Colombian families". American Journal of Medical Genetics. 113 (1): 47–51. PMID 12400065.
- Cocquet J, Pailhoux E, Jaubert F, Servel N, Xia X, Pannetier M, et al. (December 2002). "Evolution and expression of FOXL2". Journal of Medical Genetics. 39 (12): 916–21. PMID 12471206.
- De Baere E, Beysen D, Oley C, Lorenz B, Cocquet J, De Sutter P, et al. (February 2003). "FOXL2 and BPES: mutational hotspots, phenotypic variability, and revision of the genotype-phenotype correlation". American Journal of Human Genetics. 72 (2): 478–87. PMID 12529855.
- Mazumdar A, Kumar R (January 2003). "Estrogen regulation of Pak1 and FKHR pathways in breast cancer cells". FEBS Letters. 535 (1–3): 6–10. S2CID 28855687.
- Fokstuen S, Antonarakis SE, Blouin JL (March 2003). "FOXL2-mutations in blepharophimosis-ptosis-epicanthus inversus syndrome (BPES); challenges for genetic counseling in female patients". American Journal of Medical Genetics. Part A. 117A (2): 143–6. S2CID 41583322.
- Dollfus H, Stoetzel C, Riehm S, Lahlou Boukoffa W, Bediard Boulaneb F, Quillet R, et al. (February 2003). "Sporadic and familial blepharophimosis -ptosis-epicanthus inversus syndrome: FOXL2 mutation screen and MRI study of the superior levator eyelid muscle". Clinical Genetics. 63 (2): 117–20. S2CID 19151109.
- Udar N, Yellore V, Chalukya M, Yelchits S, Silva-Garcia R, Small K (September 2003). "Comparative analysis of the FOXL2 gene and characterization of mutations in BPES patients". Human Mutation. 22 (3): 222–8. S2CID 24771690.
- Crisponi L, Uda M, Deiana M, Loi A, Nagaraja R, Chiappe F, et al. (May 2004). "FOXL2 inactivation by a translocation 171 kb away: analysis of 500 kb of chromosome 3 for candidate long-range regulatory sequences". Genomics. 83 (5): 757–64. PMID 15081106.
- L'Hôte D, Georges A, Todeschini AL, Kim JH, Benayoun BA, Bae J, et al. (July 2012). "Discovery of novel protein partners of the transcription factor FOXL2 provides insights into its physiopathological roles". Human Molecular Genetics. 21 (14): 3264–74. PMID 22544055.
- Georges A, L'Hôte D, Todeschini AL, Auguste A, Legois B, Zider A, et al. (November 2014). "The transcription factor FOXL2 mobilizes estrogen signaling to maintain the identity of ovarian granulosa cells". eLife. 3. PMID 25369636.
- Elzaiat M, Todeschini AL, Caburet S, Veitia RA (February 2017). "The genetic make-up of ovarian development and function: the focus on the transcription factor FOXL2". Clinical Genetics. 91 (2): 173–182. S2CID 30962804.
External links
- FOXL2+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
- GeneReviews/NCBI/NIH/UW entry on Blepharophimosis, Ptosis, and Epicanthus Inversus