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FLASH GENE
Symbol FOXL2 contributors: mct/shn - updated : 24-09-2011
HGNC name forkhead box L2
HGNC id 1092
Corresponding disease
BPES blepharophimosis, ptosis and epicanthus inversus
POF3 premature ovarian failure, 3
Location 3q22.3      Physical location : 138.663.066 - 138.665.982
Synonym name
  • pituitary forkhead factor, mouse homolog
  • forkhead transcription factor FOXL2
  • Synonym symbol(s) BPES, PFRK, PINTO, POF3, BPES1
    DNA
    TYPE anonymous DNA segment
    SPECIAL FEATURE
    text opposite orientation with PFOXIC
    STRUCTURE 2.91 kb     1 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Binding site
    text structure
  • bidirectional promoter activity (also for PFOXIC)
  • a FoxL2 response element (FLRE)
  • MAPPING cloned Y linked Y status provisional
    Map cen - D3S4544 - D3S1576 - FOXL2 - D3S3586 - D3S2435 - qter
    Physical map
    MGC3295 3q22.3 hypothetical protein MGC3295 NCK1 3q21 NCK adaptor protein 1 MGC34923 3q22.3 hypothetical protein MGC34923 NPM1P17 3q22.3 nucleophosmin 1 (nucleolar phosphoprotein B23, numatrin) pseudogene 17 SOX14 3q23 SRY (sex determining region Y)-box 14 LOC344829 3q22.3 similar to Heat shock cognate 71 kDa protein CLDN18 3q22.3 claudin 18 FLJ32844 3q22.3 hypothetical protein FLJ32844 alpha4GnT 3p14.3 hypothetical protein FLJ32844 DBR1 3q22.3 debranching enzyme homolog 1 (S. cerevisiae) HSPC056 3q22.3 HSPC056 protein TXL-2 3q22.3 thioredoxin-like 2 MRAS 3q22.3 muscle RAS oncogene homolog CHR3SYT 3q22.3 chr3 synaptotagmin BITE 3q22-q23 p10-binding protein FAIM 3q23 Fas apoptotic inhibitory molecule LOC256374 3q22.3 similar to peptidylprolyl isomerase A PIK3CB 3q22-q23 phosphoinositide-3-kinase, catalytic, beta polypeptide LOC391582 3 similar to ATP synthase lipid-binding protein, mitochondrial precursor (ATP synthase proteolipid P1) (ATPase protein 9) (ATPase subunit C) LOC389150 3 LOC389150 FOXL2 3q23 forkhead box L2 LOC389151 3 hypothetical gene supported by AK127998 LOC389152 3 hypothetical gene supported by AK128089 BPESC1 3q23 blepharophimosis, epicanthus inversus and ptosis, candidate 1 MRPS22 3q23 mitochondrial ribosomal protein S22 COPB2 3q23 coatomer protein complex, subunit beta 2 (beta prime) RBP2 3q23 retinol binding protein 2, cellular ACTGP1 3q22.3 actin, gamma pseudogene 1 RBP1 3q23 retinol binding protein 1, cellular NMNAT3 3q12.1-3q13.11 nicotinamide nucleotide adenylyltransferase 3 FLJ11827 3q22.3 hypothetical protein FLJ11827 CLSTN2 3q23-q24 calsyntenin 2 TRIM42 3q23-24 tripartite motif-containing 42 LOC391583 3 similar to 60S ribosomal protein L23a FLJ10618 3q23 hypothetical protein FLJ10618
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    1 - 2917 - 376 - -
    EXPRESSION
    Type
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Reproductivefemale systemovary    Homo sapiens
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Epithelialsecretoryglandularendocrine 
    cells
    SystemCellPubmedSpeciesStageRna symbol
     ovary Homo sapiens
    Reproductivegranulosa cell Homo sapiens
    Reproductiveoocyte
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period embryo, fetal
    Text mesenchyme of developing eyelids, fetal ovarian follicular and stromal cells
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a characteristic DNA-binding domain called forkhead (FHD)
  • a polyAlanine domain of 14 AAs
  • two loops-wings on the C terminal side of helix-turn-helix homeo domain
  • HOMOLOGY
    interspecies homolog to Pfrk
    ortholog to Foxl2, Mus musculus
    ortholog to Foxl2, Rattus norvegicus
    ortholog to FOX2, Pan troglodytes
    ortholog to foxl2, Danio rerio
    Homologene
    FAMILY
  • HNF-3 forkhead family of transcriptional activators
  • CATEGORY regulatory , DNA associated , transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,nucleus,chromatin/chromosome
    text polyalanine expansion inducing extensive nuclear and cytoplasmic protein aggregation, and retaining normal protein in the cytoplasm
    basic FUNCTION
  • transcriptional regulator of ovarian function and eyelid development via the inhibin/activin signaling pathway
  • playing a multiple role during fetal development and also latter during adult female fertility life
  • crucial actor in the ovarian differentiation process in different vertebrate species
  • playing a role in regulation of glycoprotein hormone alpha-subunit gene expression
  • playing a crucial role in ovarian development and maintenance
  • actor of the stress response
  • may play a role throughout female fertile life in follicular maturation and/or maintenance
  • able to directly activate SIRT1 transcription
  • induces significant granulosa cell death while the mutant version exhibited a minimal activity
  • essential for ovarian function and maintenance
  • may play a key role in granulosa cell homeostasis, the failure of which is central to ovarian ageing and tumorigenesis
  • key role for FOXL2 in the control of granulosa cell proliferation and stress response
  • CELLULAR PROCESS nucleotide, transcription, regulation
    PHYSIOLOGICAL PROCESS development
    text eyelids, maintenance of ovarian follicles
    PATHWAY
    metabolism
    signaling sensory transduction/vision
    a component
    INTERACTION
    DNA
  • direct transcriptional activator of the CYP19A1 gene through its ovarian-specific promoter 2
  • forkhead-binding element located just downstream of the SBE1 site of the follistatin gene (
  • RNA
    small molecule
    protein
  • DEAD box protein DP 103, DP103 (
  • FSHB interacting with FOXL2 (novel role for FOXL2 in activin A-regulated FSHB transcription)
  • Smad3
  • ubiquitin-conjugating enzyme E2I, UBE2I
  • antagonism between DMRT1 and FOXL2 for control of gonadal sex may therefore extend beyond mammals
  • DMRT1 maintains SOX9 and suppresses FOXL2 expression in postnatal Sertoli cells
  • cell & other
    REGULATION
    inhibited by SIRT1 (SIRT1 was able to inhibit FOXL2 transactivation and, eventually, its expression, we assessed the effect of nicotinamide on FOXL2 activity and expression)
    SIRT1 (its activity can be inhibited by SIRT1, which modulates its ability to regulate stress-related genes)
    ASSOCIATED DISORDERS
    corresponding disease(s) BPES , POF3
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional germinal mutation      
    mutation in premature ovarian failure
    tumoral somatic mutation      
    leading to a p.C134W change, was found in the majority of adult-type ovarian granulosa cell tumors (GCTs)
    constitutional       gain of function
    promotes cell accumulation in G1 phase and protects cells from oxidative damage
    Susceptibility to isolated premature ovarian failure (POF)
    Variant & Polymorphism other variant detected in a POF case without BPES
    Candidate gene female sex determining
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • mice lacking Foxl2 display gonadal dysgenesis, are small and show distinctive craniofacial morphology with upper eyelids absent (
  • Inducible deletion of Foxl2 in adult ovarian mouse follicles leads to immediate upregulation of testis-specific genes including the critical SRY target gene Sox9 (
  • Foxl2-null mice exhibit developmental defects in granulosa cells