Forkhead box L2

Forkhead box L2
Identifiers
Symbols	FOXL2 ; BPES; BPES1; PFRK; PINTO; POF3
External IDs	OMIM: 605597 MGI: 1349428 HomoloGene: 74992 GeneCards: FOXL2 Gene
Gene ontology Molecular function • RNA polymerase II core promoter proximal region sequence-specific DNA binding • RNA polymerase II transcription factor activity, sequence-specific DNA binding • transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding • DNA binding • transcription factor activity, sequence-specific DNA binding • protein binding • estrogen receptor binding • ubiquitin conjugating enzyme binding • cysteine-type endopeptidase regulator activity involved in apoptotic process Cellular component • nucleus Biological process • negative regulation of transcription from RNA polymerase II promoter • ovarian follicle development • extraocular skeletal muscle development • apoptotic DNA fragmentation • regulation of transcription from RNA polymerase II promoter • transcription from RNA polymerase II promoter • anatomical structure morphogenesis • female somatic sex determination • cell differentiation • menstruation • positive regulation of apoptotic process • positive regulation of cysteine-type endopeptidase activity involved in apoptotic process • negative regulation of transcription, DNA-templated • positive regulation of transcription, DNA-templated • positive regulation of transcription from RNA polymerase II promoter • embryonic eye morphogenesis • granulosa cell differentiation Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	668	26927
Ensembl	ENSG00000183770	ENSMUSG00000050397
UniProt	P58012	O88470
RefSeq (mRNA)	NM_023067	NM_012020
RefSeq (protein)	NP_075555	NP_036150
Location (UCSC)	Chr 3: 138.94 – 138.95 Mb	Chr 9: 98.96 – 98.96 Mb
PubMed search

Forkhead box protein L2 is a protein that in humans is encoded by the FOXL2 gene.^[1][2]

Function

FOXL2 is a forkhead transcription factor. The protein contains a fork-head DNA-binding domain and may play a role in ovarian development and function.^[2]

Clinical significance

This protein is involved in sex determination. Female missing the FOXL2 gene appear male. FOXL2 knockout in mature mouse ovaries cause them to develop into testes, however oocytes are still formed.^[3]

Mutations in this gene are a cause of blepharophimosis syndrome and premature ovarian failure 3.^[2]

See also

• FOX proteins

References

1. de Die-Smulders CE, Engelen JJ, Donk JM, Fryns JP (Oct 1991). "Further evidence for the location of the BPES gene at 3q2". Journal of Medical Genetics 28 (10): 725. doi:10.1136/jmg.28.10.725. PMC 1017067. PMID 1941972.
2. "Entrez Gene: FOXL2 forkhead box L2".
3. Uhlenhaut NH, Jakob S, Anlag K, Eisenberger T, Sekido R, Kress J, Treier AC, Klugmann C, Klasen C, Holter NI, Riethmacher D, Schütz G, Cooney AJ, Lovell-Badge R, Treier M (Dec 2009). "Somatic sex reprogramming of adult ovaries to testes by FOXL2 ablation". Cell 139 (6): 1130–42. doi:10.1016/j.cell.2009.11.021. PMID 20005806. Lay summary – Nature News.

Further reading

• Vaiman D, Schibler L, Oustry-Vaiman A, Pailhoux E, Goldammer T, Stevanovic M, Furet JP, Schwerin M, Cotinot C, Fellous M, Cribiu EP (Feb 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. doi:10.1006/geno.1998.5691. PMID 10036183.
• Kaestner KH, Knochel W, Martinez DE (Jan 2000). "Unified nomenclature for the winged helix/forkhead transcription factors". Genes & Development 14 (2): 142–6. doi:10.1101/gad.14.2.142. PMID 10702024.
• Crisponi L, Deiana M, Loi A, Chiappe F, Uda M, Amati P, Bisceglia L, Zelante L, Nagaraja R, Porcu S, Ristaldi MS, Marzella R, Rocchi M, Nicolino M, Lienhardt-Roussie A, Nivelon A, Verloes A, Schlessinger D, Gasparini P, Bonneau D, Cao A, Pilia G (Feb 2001). "The putative forkhead transcription factor FOXL2 is mutated in blepharophimosis/ptosis/epicanthus inversus syndrome". Nature Genetics 27 (2): 159–66. doi:10.1038/84781. PMID 11175783.
• De Baere E, Dixon MJ, Small KW, Jabs EW, Leroy BP, Devriendt K, Gillerot Y, Mortier G, Meire F, Van Maldergem L, Courtens W, Hjalgrim H, Huang S, Liebaers I, Van Regemorter N, Touraine P, Praphanphoj V, Verloes A, Udar N, Yellore V, Chalukya M, Yelchits S, De Paepe A, Kuttenn F, Fellous M, Veitia R, Messiaen L (Jul 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. doi:10.1093/hmg/10.15.1591. PMID 11468277.
• Dollfus H, Kumaramanickavel G, Biswas P, Stoetzel C, Quillet R, Denton M, Maw M, Perrin-Schmitt F (Jul 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. doi:10.1136/jmg.38.7.470. PMC 1757180. 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. doi:10.1007/s100380170009. PMID 11776388.
• Kosaki K, Ogata T, Kosaki R, Sato S, Matsuo N (Mar 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. doi:10.1076/opge.23.1.43.2202. PMID 11910558.
• 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. doi:10.1089/109065701753617499. PMID 11960581.
• Harris SE, Chand AL, Winship IM, Gersak K, Aittomäki K, Shelling AN (Aug 2002). "Identification of novel mutations in FOXL2 associated with premature ovarian failure". Molecular Human Reproduction 8 (8): 729–33. doi:10.1093/molehr/8.8.729. PMID 12149404.
• De Baere E, Lemercier B, Christin-Maitre S, Durval D, Messiaen L, Fellous M, Veitia R (Aug 2002). "FOXL2 mutation screening in a large panel of POF patients and XX males". Journal of Medical Genetics 39 (8): e43. doi:10.1136/jmg.39.8.e43. PMC 1735205. PMID 12161610.
• Ramírez-Castro JL, Pineda-Trujillo N, Valencia AV, Muñetón CM, Botero O, Trujillo O, Vásquez G, Mora BE, Durango N, Bedoya G, Ruiz-Linares A (Nov 2002). "Mutations in FOXL2 underlying BPES (types 1 and 2) in Colombian families". American Journal of Medical Genetics 113 (1): 47–51. doi:10.1002/ajmg.10741. PMID 12400065.
• Cocquet J, Pailhoux E, Jaubert F, Servel N, Xia X, Pannetier M, De Baere E, Messiaen L, Cotinot C, Fellous M, Veitia RA (Dec 2002). "Evolution and expression of FOXL2". Journal of Medical Genetics 39 (12): 916–21. doi:10.1136/jmg.39.12.916. PMC 1757225. PMID 12471206.
• De Baere E, Beysen D, Oley C, Lorenz B, Cocquet J, De Sutter P, Devriendt K, Dixon M, Fellous M, Fryns JP, Garza A, Jonsrud C, Koivisto PA, Krause A, Leroy BP, Meire F, Plomp A, Van Maldergem L, De Paepe A, Veitia R, Messiaen L (Feb 2003). "FOXL2 and BPES: mutational hotspots, phenotypic variability, and revision of the genotype-phenotype correlation". American Journal of Human Genetics 72 (2): 478–87. doi:10.1086/346118. PMC 379240. PMID 12529855.
• Mazumdar A, Kumar R (Jan 2003). "Estrogen regulation of Pak1 and FKHR pathways in breast cancer cells". FEBS Letters 535 (1-3): 6–10. doi:10.1016/S0014-5793(02)03846-2. PMID 12560069.
• Fokstuen S, Antonarakis SE, Blouin JL (Mar 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. doi:10.1002/ajmg.a.10024. PMID 12567411.
• Dollfus H, Stoetzel C, Riehm S, Lahlou Boukoffa W, Bediard Boulaneb F, Quillet R, Abu-Eid M, Speeg-Schatz C, Francfort JJ, Flament J, Veillon F, Perrin-Schmitt F (Feb 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. doi:10.1034/j.1399-0004.2003.00011.x. PMID 12630957.
• Udar N, Yellore V, Chalukya M, Yelchits S, Silva-Garcia R, Small K (Sep 2003). "Comparative analysis of the FOXL2 gene and characterization of mutations in BPES patients". Human Mutation 22 (3): 222–8. doi:10.1002/humu.10251. PMID 12938087.
• Crisponi L, Uda M, Deiana M, Loi A, Nagaraja R, Chiappe F, Schlessinger D, Cao A, Pilia G (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. doi:10.1016/j.ygeno.2003.11.010. PMID 15081106.

External links

• FOXL2 protein, human at the US National Library of Medicine Medical Subject Headings (MeSH)
• GeneReviews/NCBI/NIH/UW entry on Blepharophimosis, Ptosis, and Epicanthus Inversus