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FLASH GENE
Symbol FOXP1 contributors: mct - updated : 02-02-2016
HGNC name forkhead box P1
HGNC id 3823
Corresponding disease
DLCRM distal limb contractures with mental retardation
MRLA mental retardation with language impairment and autistic features
Location 3p13      Physical location : 71.004.736 - 71.633.140
Synonym name
  • glutamine rich factor 1
  • fork head-related protein like B
  • PAX5/FOXP1 fusion protein
    • Synonym symbol(s) QRF1, 12CC4, FLJ23741, HSPC215, MGC12942, hFKH1B
    DNA
    TYPE functioning gene
    STRUCTURE 628.41 kb     21 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    Physical map
    LRIG1 3p14 leucine-rich repeats and immunoglobulin-like domains 1 TA-KRP 3p14 T-cell activation kelch repeat protein SUCLG2 3p14.3 succinate-CoA ligase, GDP-forming, beta subunit LOC375350 3p14.3 COP9 pseudogene LOC151645 3p14.3 protease (prosome, macropain) 26S subunit, ATPase, 1 pseudogene FLJ25161 3p14.3-p14.2 hypothetical protein FLJ25161 LOC152122 3p14.2 hypothetical LOC152122 MGC34132 3p14.2 hypothetical protein MGC34132 TMF1 3p21-p12 TATA element modulatory factor 1 UBE1C 3p24.3-p13 ubiquitin-activating enzyme E1C (UBA3 homolog, yeast) JWA 3p14 ubiquitin-activating enzyme E1C (UBA3 homolog, yeast) LMOD3 3p14.1 leiomodin 3 (fetal) GRSP1 3p14.2 leiomodin 3 (fetal) MITF 3p14.1-p12.3 microphthalmia-associated transcription factor LOC391543 3 similar to KIAA1839 protein FOXP1 3p14.1 forkhead box P1 LOC391544 3 similar to MGC39820 protein GPR27 3p21-p14 G protein-coupled receptor 27 PROK2 3p21.1 prokineticin 2 RYBP 3p13 RING1 and YY1 binding protein LOC339875 3p14.2 hypothetical LOC339875 FLJ10539 3p14.2 hypothetical protein FLJ10539 LOC317753 3p14 proteasome 26S non-ATPase subunit 12 pseudogene LOC389129 3 similar to CG9996-PA PPP4R2 3q28 protein phosphatase 4, regulatory subunit 2 FLJ10213 3p14.1 hypothetical protein FLJ10213 LOC344709 3p14.1 similar to hypothetical protein FLJ38348 SEMACAP3 3p13 similar to hypothetical protein FLJ38348 LOC391546 3 similar to Heat shock protein HSP 90-beta (HSP 84) (HSP 90) ALDRP 3p12 aldehyde reductase (aldose reductase) pseudogene CNTN3 3p26 contactin 3 (plasmacytoma associated) LOC344715 3p14.1 similar to long myosin light chain kinase LOC344716 3p14.1 similar to seven transmembrane helix receptor LOC391548 3 similar to olfactory receptor GA_x6K02T2PVTD-14054886-14053957 LOC339879 3p14.1 similar to mannosyltransferase LOC389130 3 similar to Alkaline sphingomyelinase LOC389131 3 LOC389131 LOC391549 3 similar to chromosome 11 open reading frame2; chromosome 11 open reading frame2
    RNA
    TRANSCRIPTS type messenger
    text at least four isoforms
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    21 - 6222 - 677 - 2011 21924763
  • also called FOXP1a
  • during differentiation, exon 18b is entirely skipped, resulting in the exclusive inclusion of exon 18 and expression of the “canonical” FOXP1 isoform
    • 7 - 937 - 114 - 2011 21924763
    - - 7202 - 676 - 2011 21924763
    - - 7150 - 693 - 2011 21924763
    - - 6502 - 601 - 2011 21924763
    - - 6899 - 677 - 2011 21924763
    - - 6394 - 577 - 2011 21924763
    - - 6840 - 679 - 2011 21924763
    - - 7007 - 677 - 2011 21924763
    21 splicing - - - - 2011 21924763
  • exon 18b, in FOXP1 transcripts in place of exon 18
  • stimulates the expression of transcription factor genes required for pluripotency, including POU5F1, NANOG, NR5A2, and GDF3, while concomitantly repressing genes required for embryonic stem cell (ESC) differentiation
  • during differentiation, exon 18b is entirely skipped, resulting in the exclusive inclusion of exon 18 and expression of the “canonical” FOXP1 isoform
    		•
    EXPRESSION
    Type
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveesophagus    
     intestine    
    Nervousbrain     Homo sapiens
     brainbasal nucleistriatum highly Homo sapiens
     braindiencephalonthalamus   Homo sapiens
     brainforebraincerebral cortex   Homo sapiens
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Nervousneuron Homo sapiensFetal
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period fetal
    Text in the developing CNS, including the striatum, cerebral cortex, and thalamus
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a forkhead (winged helix) domain with two loops wings in the C terminal side of helix-turn-helix homeodomain
  • a second DNA-binding motif
  • a C2H2 zinc finger
  • nuclear localization signals (NLS)
  • coiled-coil region
  • PEST sequences and potential transactivation domains
    • HOMOLOGY
    intraspecies paralog to FOXP3
    homolog to FOXP2
    Homologene
    FAMILY
  • HNF-3 FKH family of transcriptional regulators
    • CATEGORY transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,nucleus,chromatin/chromosome
    intracellular,nucleus,nucleolus
    basic FUNCTION
  • transcriptional repressor playing an important role in the specification and differentiation of lung epithelium
  • androgen-responsive transcription factor that negatively regulates androgen receptor signaling in prostate cancer cells
  • crucial regulator of lung and esophageal development, underscoring the necessity of this transcription factor in the development of anterior foregut-derived tissues
  • FOXP1 and FOXP2 may be involved in the determination of the cell type identities during late embryogenesis
  • androgen-regulated gene, could be involved in the regulatory feedback loops for AR signaling
  • essential transcriptional regulator for thymocyte development and the generation of quiescent naive T cells
  • essential for the development of B cells, quiescent naive T cells and monocytes
  • may play a role in the development of verbal and motor skill
  • opposing transcriptional activities of FOXP1 and NFATC4 maintaining cardiomyocyte homeostasis
  • critical roles for FOXP1 in the specification of cell lineages in early development
  • FOXP1-regulated pathways might be important mediators of neuronal-glial cell communication
  • is physiologically downregulated in germinal center B-cell and aberrant expression of FOXP1 impairs mechanisms triggered by B-cell activation, potentially contributing to B-cell lymphomagenesis
  • represents an important modulator of FOXO-induced transcription, promoting cellular survival
  • is crucial for maintaining the quiescence of hair follicle stem cells
  • is essential for the angiogenic function of endothelial cells and functions as a suppressor of the inhibitory guidance cue SEMA5B, suggesting an important function of FOXP1 in the regulation of neovascularization
  • is a critical negative regulator of CD4(+) follicular helper T cells (T(FH) cells) differentiation
  • may play a central role in various cognitive and social processes
  • IKZF1 and FOXP1 are transcription factors that play key roles in normal lymphopoiesis and lymphoid malignancies
    • CELLULAR PROCESS nucleotide, transcription, regulation
    cell organization/biogenesis
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA binding
    RNA
    small molecule
    protein
  • directly interacts with AR and negatively regulates AR signaling ligand-dependently
  • functional interaction between NCOR2 and FOXP1 is required for cardiac growth and regulation of macrophage differentiation
  • FOXP1 and FOXP2 can physically interact and can repress the transcription of common targets in vivo by occupying the same binding sites
  • transcription regulatory role for FOXP1 on the PITX3 gene in mammalian stem cells
  • FOXP1 may compensate for the loss of FOXP2 and a level of redundancy exists between these two genes
  • FOXP1 regulates the quiescent stem cell state in the hair follicle stem cell niche by controlling FGF18 expression (pMID: 23946441)
  • SEMA5B acts as a FOXP1- dependent suppressor of endothelial cell proliferation, migration and sprouting, mediating the effects of FOXP1
  • is dependent upon, and cooperates with NFKB1 signaling to promote B-cell expansion and survival
  • interactions between FOXP1 and ESR1 may play a pivotal role in the progression of ovarian cancer
  • GPR132 is a novel target for FOXP1
    • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) MRLA , DLCRM
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral   LOH    
    in neoplastic cells, see TSG3G
    tumoral fusion      
    with IGHG1, t(3;14)(p14;q32) in diffuse large B-cell lymphoma
    constitutional germinal mutation      
    in sporadic autism spectrum disorders
    tumoral     --over  
    its expression negatively correlated with MKI67 expression in clear cell renal cell carcinomas
    tumoral fusion      
    with PAX5 in t(3;9)(p13;p13) recurrent in both childhood and in adult B-ALL
    tumoral     --low  
    is a common event in high-risk neuroblastoma pathogenesis and may contribute to tumor progression and unfavorable patient outcome
    constitutional       loss of function
    in autism spectrum disorder, gross motor delay, intellectual disability, expressive language impairment
    Susceptibility
  • to vitiligo
  • to language impairment, and autism spectrum disorders
    • Variant & Polymorphism SNP
  • rs17008713, located within FOXP1 associated with Vitiligo
  • nonsense mutation [p.R525X]) in the conserved forkhead DNA-binding domain associated with language impairment and autism (FOXP1 haploinsufficiency affects language development and possibly causes language impairment, and autism spectrum disorders (ASD) by disrupting this regulatory interaction)
  • FOXP1 variants are responsible for a more global cognitive phenotype, encompassing language impairment, intellectual disability, ASD and motor development delay
    • Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS