Affinage

FOXP4

Forkhead box protein P4 · UniProt Q8IVH2

Length
680 aa
Mass
73.5 kDa
Annotated
2026-04-28
76 papers in source corpus 34 papers cited in narrative 33 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

FOXP4 is a forkhead box transcription factor that functions as both a transcriptional activator and repressor, regulating diverse developmental and homeostatic programs including neuronal migration, adipocyte thermogenesis, immune cell function, hair follicle stem cell niche maintenance, and spermatogonial proliferation. It binds target gene promoters through its forkhead DNA-binding domain to directly activate genes such as Slug, Snail, LEF-1, PTK7, SOX12, UCP1, GPX4, CYP26B1, and Il2ra/CD25, or repress targets such as FBXW7, thereby modulating Wnt/β-catenin signaling, EMT, ferroptosis, and regulatory T cell function (PMID:30930991, PMID:34590150, PMID:38740744, PMID:40789053, PMID:40794436, PMID:38293397, PMID:34384787). FOXP4 forms homo- and heterodimers with FOXP1 and FOXP2, and combinatorial loss-of-function studies demonstrate both redundant and non-redundant roles—for example, combined FOXP1/FOXP4 deletion in Tregs causes fatal autoimmunity whereas single knockouts do not, and combined FOXP1/FOXP4 loss destroys the hair follicle stem cell niche (PMID:40794436, PMID:35759955, PMID:25027557). Heterozygous loss-of-function variants in the FOXP4 forkhead domain cause an autosomal dominant neurodevelopmental disorder with speech/language delays and congenital abnormalities (PMID:33110267).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 2002 High

    Identification of FOXP4 as a new Foxp subfamily member established that a third forkhead transcription factor with structural similarity to FOXP1/FOXP2 is expressed in lung, neural, and gut tissues during embryonic development.

    Evidence cDNA cloning, Northern hybridization, and immunohistochemistry in mouse embryonic tissues

    PMID:12617805 PMID:14516685

    Open questions at the time
    • No functional assay performed
    • No target genes identified
    • Dimerization with FOXP1/FOXP2 not tested
  2. 2008 Medium

    Mapping FOXP4 expression alongside FOXP1 and FOXP2 in the developing forebrain revealed overlapping but distinct domains, raising the hypothesis that combinatorial heterodimerization among Foxp proteins diversifies transcriptional output in neural development.

    Evidence Immunohistochemistry and in situ hybridization in developing rat brain

    PMID:18561326

    Open questions at the time
    • Heterodimerization inferred but not directly demonstrated in brain tissue
    • No loss-of-function or target gene data
  3. 2010 Medium

    The first loss-of-function study showed FOXP4 is required for Purkinje cell dendritic arborization maintenance at a specific developmental window, establishing a cell-autonomous neural function beyond expression mapping.

    Evidence siRNA knockdown in organotypic cerebellar slice cultures with morphological analysis

    PMID:20951773

    Open questions at the time
    • Downstream transcriptional targets in Purkinje cells unknown
    • In vivo conditional knockout not performed
    • Relationship to FOXP2 in cerebellum not tested
  4. 2012 High

    Conditional deletion in T cells revealed that FOXP4 is dispensable for T cell development but required for robust cytokine recall responses during infection, establishing its first immune function.

    Evidence CD4-Cre conditional knockout mice challenged with T. gondii and LCMV, with cytokine and flow cytometry readouts

    PMID:22912696

    Open questions at the time
    • Direct transcriptional targets in T cells not identified
    • Mechanism of cytokine regulation unknown
    • Relationship to FOXP1 in T cells not tested
  5. 2014 Medium

    Overexpression studies demonstrated that FOXP1/FOXP2/FOXP4 homo- and heterodimers differentially regulate neuronal development gene sets, providing the first evidence that dimerization partner identity determines transcriptional output.

    Evidence Stable transfection of FOXP1/2/4 ORFs in HEK293 cells with qPCR of target genes

    PMID:25027557

    Open questions at the time
    • Overexpression system; endogenous dimerization stoichiometry unknown
    • No co-IP confirming specific dimer combinations in this study
    • Neuronal relevance not validated in neuronal cells
  6. 2015 High

    Triple conditional knockout of FOXP1/2/4 in islet cells revealed collective requirement for alpha cell proliferation and glucagon secretion, identifying cyclin genes as downstream cell-cycle mediators and linking Foxp factors to glucose homeostasis.

    Evidence Pax6-Cre triple conditional KO mice with IPGTT, immunohistochemistry, and gene expression profiling

    PMID:26021489

    Open questions at the time
    • Individual contributions of FOXP4 vs FOXP1/FOXP2 not dissected
    • Direct promoter binding to cyclin genes not shown
  7. 2019 Medium

    ChIP and luciferase assays identified Slug and Snail as direct FOXP4 transcriptional targets in cancer cells, establishing FOXP4 as a transcriptional activator of EMT master regulators and defining its first validated promoter-binding events.

    Evidence ChIP and dual luciferase reporter assays in HCC and breast cancer cell lines with gain/loss-of-function and Snail rescue

    PMID:30930991 PMID:31040716

    Open questions at the time
    • Genome-wide binding profile not determined
    • Whether FOXP4 activates EMT in normal developmental contexts unknown
    • Dimer partner requirements at these promoters not tested
  8. 2020 High

    Functional validation of FOXP4 forkhead domain variants from patients with neurodevelopmental delay demonstrated that pathogenic mutations abolish transcriptional repressor activity and/or cause protein mislocalization, establishing FOXP4 haploinsufficiency as a cause of a Mendelian neurodevelopmental syndrome.

    Evidence Luciferase repressor assays and subcellular localization analysis of multiple patient variants in cell lines

    PMID:33110267

    Open questions at the time
    • Endogenous target genes affected by these variants in neurons not identified
    • Animal model of specific patient variants not generated
    • Whether heterodimer formation with FOXP1/FOXP2 is disrupted not tested
  9. 2021 High

    Discovery that HSF1 directly induces FOXP4 expression, and FOXP4 in turn directly controls UCP1 transcription, placed FOXP4 within the thermogenic regulatory cascade linking heat shock signaling to mitochondrial uncoupling in adipocytes.

    Evidence ChIP for HSF1 at FOXP4 promoter, luciferase validation, oxygen consumption in isolated adipocytes, in vivo thermogenic stimulation

    PMID:34384787

    Open questions at the time
    • Full set of FOXP4 thermogenic target genes beyond UCP1 not defined
    • Whether FOXP4 dimerizes with FOXP1 in adipocytes unknown
  10. 2021 Medium

    FoxP4 knockdown in zebra finch Area X impaired vocal learning with features distinct from FoxP2 knockdown, demonstrating non-redundant roles of individual Foxp family members in a learned vocal behavior.

    Evidence Lentivirus-mediated knockdown in juvenile zebra finches with song analysis

    PMID:31641053

    Open questions at the time
    • Downstream gene targets in Area X not identified
    • Whether FoxP4 acts as monomer or heterodimer in song nuclei unknown
  11. 2022 High

    Stage-specific conditional knockout revealed that FOXP4 promotes early beige adipocyte differentiation but restrains thermogenesis in mature beige cells, establishing opposing context-dependent roles within a single cell lineage.

    Evidence Beige adipocyte-specific conditional knockout mice with cold exposure and UCP1/thermogenesis assays

    PMID:35297993

    Open questions at the time
    • Molecular basis for the switch from pro-differentiation to anti-thermogenic role not identified
    • Target gene changes at each stage not fully characterized
  12. 2022 High

    Co-IP and conditional knockout studies demonstrated that FOXP1 and FOXP4 form a physical complex in hair follicle stem cells, where combined loss destroys the inner bulge niche by downregulating Fgf18 and Bmp6 and inducing niche cell apoptosis—the first demonstration of a FOXP1/FOXP4 heterodimer with defined in vivo function.

    Evidence Co-immunoprecipitation, hair follicle-specific single and double conditional knockout mice, apoptosis and gene expression assays

    PMID:35759955

    Open questions at the time
    • Direct binding of FOXP1/FOXP4 complex to Fgf18/Bmp6 promoters not shown
    • Whether FOXP2 participates in this niche not addressed
  13. 2023 High

    Foxp4 loss-of-function in the developing cortex disrupted N-cadherin-based adherens junctions in radial glial cells and impaired neuronal migration, with rescue by N-cadherin overexpression identifying adherens junction maintenance as a key mechanism through which FOXP4 governs cortical development.

    Evidence siRNA and dominant-negative inhibition in vivo with N-cadherin rescue, immunostaining in mouse cortex

    PMID:36646976

    Open questions at the time
    • Whether FOXP4 directly transcribes N-cadherin or acts through intermediary genes not resolved
    • Relationship to the neurodevelopmental syndrome variants not tested
  14. 2024 High

    Multiple studies expanded the catalogue of direct FOXP4 transcriptional targets to include PTK7, SOX12, FBXW7, GPX4, and CYP26B1, connecting FOXP4 to Wnt signaling, cancer stemness, ferroptosis resistance, and alcohol-responsive enhancer-mediated gene regulation across diverse cancer types.

    Evidence ChIP-seq, ChIP-qPCR, luciferase reporters, epistasis/rescue experiments, PDO models, and xenografts across ovarian, gastric, thyroid, colorectal, and esophageal cancer systems

    PMID:38293397 PMID:38740744 PMID:39047223 PMID:40228145 PMID:40789053

    Open questions at the time
    • No consensus FOXP4-specific binding motif distinct from general forkhead motif established
    • Relative importance of activator vs repressor function across contexts not systematically defined
  15. 2025 High

    Conditional deletion studies in Tregs revealed that FOXP1 and FOXP4 bind the Il2ra promoter and are jointly required for CD25 expression and Treg suppressive function; individual FOXP4 deletion is insufficient to cause autoimmunity, demonstrating functional redundancy with FOXP1 in immune tolerance.

    Evidence FOXP3-Cre single and double Foxp1/Foxp4 knockout mice with ChIP, flow cytometry, and suppression assays

    PMID:40794436

    Open questions at the time
    • Genome-wide FOXP4 binding in Tregs not mapped
    • Whether FOXP2 compensates in single KOs not addressed
    • Structural basis for FOXP1/FOXP4 heterodimer at Il2ra not determined

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: the genome-wide binding landscape and chromatin remodeling activity of FOXP4, the structural basis for selective homo- vs heterodimerization with FOXP1/FOXP2, and how FOXP4 switches between activator and repressor modes in different cellular contexts.
  • No genome-wide ChIP-seq in non-cancer primary cells
  • No crystal structure of FOXP4 forkhead domain or FOXP4-containing heterodimers
  • Molecular switch mechanism for activator/repressor duality unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 13 GO:0003677 DNA binding 10
Localization
GO:0005634 nucleus 2
Pathway
R-HSA-1266738 Developmental Biology 4 R-HSA-162582 Signal Transduction 3 R-HSA-168256 Immune System 2
Partners
FOXP1FOXP2HSF1YAP1

Evidence

Reading pass · 33 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2002 FOXP4 (mouse Foxp4) was identified as a new member of the Foxp subfamily of winged-helix transcription factors, encoding a 685-amino-acid protein similar to Foxp1 and Foxp2, expressed in pulmonary, neural, and gut tissues during embryonic development, with exclusive expression in intestinal epithelial cells. cDNA cloning, Northern hybridization, immunohistochemistry with polyclonal antisera Mechanisms of development / Gene expression patterns High 12617805 14516685
2003 FoxP4 is a forkhead transcription factor expressed in adult heart, brain, lung, liver, kidney, and testis, with embryonic expression peaking at E11 in lung and gut. Northern hybridization, in situ hybridization Biochimica et biophysica acta Medium 12818433
2008 Foxp4 is expressed in the developing rat forebrain (striatum, cortex, thalamus) in patterns partially overlapping but distinct from Foxp1 and Foxp2; given that Foxp1/2/4 can heterodimerize, combinatorial Foxp actions may regulate forebrain development. Immunohistochemistry, in situ hybridization in developing rat brain Journal of neuroscience research Medium 18561326
2010 Foxp4 is required for maintenance of Purkinje cell dendritic arborization in the mouse cerebellum; siRNA knockdown at postnatal day 10 impaired organization of PC dendritic arbors and disrupted Bergmann glial fiber association, whereas knockdown at P5 had no effect on early dendritic remodeling. siRNA knockdown in organotypic cerebellar slice culture, morphological analysis Neuroscience Medium 20951773
2012 Foxp4 is dispensable for T cell development and peripheral T cell homeostasis, but is required for robust cytokine recall responses in vivo following pathogenic infection; Foxp4 expression increases upon T cell activation. CD4Cre-mediated conditional knockout in mice, infection models (T. gondii, LCMV), flow cytometry, cytokine measurement PloS one High 22912696
2014 FOXP1, FOXP2, and FOXP4 homo- and heterodimerization differentially regulates transcription of FOXP2 target genes (CER1, SFRP4, WISP2, PRICKLE1, NCOR2, SNW1, NEUROD2, PAX3, EFNB3, SLIT1) involved in early neuronal development in HEK293 cells. Stable transfection of FOXP1/2/4 open reading frames in HEK293 cells, real-time PCR of target gene expression Journal of molecular neuroscience Medium 25027557
2015 FOXP1, FOXP2, and FOXP4 are collectively required for islet alpha cell proliferation and glucagon secretion; triple conditional knockout (Pax6-Cre) mice exhibit hypoglycemia, hypoglucagonaemia, reduced alpha cell mass, decreased cyclin expression (Ccna2, Ccnb1, Ccnd2) and increased Cdkn1a, while beta cell insulin secretion remains normal. Triple conditional knockout mice (Pax6-Cre), IPGTT, radioimmunoassay, immunohistochemistry, isolated islet gene expression, glucose-stimulated hormone secretion Diabetologia High 26021489
2015 FOXP4 knockdown reduces NSCLC cell growth and invasion and induces cell cycle arrest; miR-138 directly targets and downregulates FOXP4 expression; the effect of FOXP4 knockdown on cancer growth is independent of EZH2 overexpression, placing FOXP4 in a separate downstream branch from EZH2 in miR-138 signaling. Lentiviral shRNA knockdown, dual luciferase reporter assay, cell proliferation/invasion/cell cycle assays, EZH2 overexpression epistasis Tumour biology Medium 25994569
2019 FOXP4 promotes hepatocellular carcinoma cell migration and invasion through EMT by transcriptionally activating Slug; ChIP and luciferase reporter assays confirmed direct FOXP4 binding to the Slug promoter. ChIP, qChIP, luciferase reporter assay, gain/loss-of-function in HCC cell lines Oncology letters Medium 30930991
2019 FOXP4 promotes breast cancer cell migration and invasion through EMT by transcriptionally activating Snail; ChIP and luciferase assays confirmed direct FOXP4 regulation of the Snail promoter; Snail overexpression partially rescues FOXP4 inhibition effects. ChIP, qChIP, dual luciferase reporter assay, gain/loss-of-function, rescue experiments Cancer management and research Medium 31040716
2019 PAX5 transcriptionally activates both FOXP4-AS1 and FOXP4 in prostate cancer; FOXP4-AS1 post-transcriptionally upregulates FOXP4 by sponging miR-3184-5p as a competing endogenous RNA (ceRNA); FOXP4-AS1 is located in the cytoplasm of PCa cell lines. Luciferase reporter assay, RIP, subcellular fractionation, overexpression/knockdown, ChIP Cell death & disease Medium 31209207
2019 FOXP4-AS1 promotes osteosarcoma development by binding to LSD1 and EZH2, thereby downregulating LATS1 expression; RIP assay confirmed the FOXP4-AS1/LSD1/EZH2 interaction. RIP assay, overexpression/knockdown, proliferation/migration/invasion assays Biochemical and biophysical research communications Low 29859193
2020 Heterozygous loss-of-function variants in the forkhead box DNA-binding domain of FOXP4 cause an autosomal dominant neurodevelopmental disorder with speech/language delays, growth abnormalities, and congenital abnormalities; luciferase assays demonstrated loss of transcriptional repressor activity for pathogenic variants, and aberrant subcellular localization was observed for a subset of variants. Luciferase transcriptional repressor assay, subcellular localization analysis, clinical cohort Genetics in medicine High 33110267
2020 FOXP4-AS1 positively regulates FOXP4 expression in ESCC by: (1) acting as ceRNA sponging miR-3184-5p, and (2) interacting with IGF2BP2 to stabilize FOXP4 mRNA; YY1 transcriptionally activates both FOXP4-AS1 and FOXP4. RIP, RNA pulldown, luciferase reporter assay, mRNA stability assay, ChIP for YY1 Cell biology international Medium 32159250
2021 FOXP4 directly promotes transcription of β-catenin in ESCC; FOXP4-AS1 upregulates FOXP4 by enriching MLL2 and H3K4me3 at the FOXP4 promoter, acting as a molecular scaffold, promoting Wnt pathway activation. ChIP, RIP, luciferase reporter assay, functional cell assays Frontiers in oncology Medium 34970490
2021 FoxP4 regulates thermogenic programs in adipocytes: FoxP4 is induced by heat shock factor protein 1 (HSF1) binding to a heat shock response element in the FoxP4 proximal promoter; FoxP4 directly controls uncoupling protein 1 (UCP1) levels and regulates brown/beige fat gene expression and oxygen consumption. ChIP assay, luciferase reporter assay, gain/loss-of-function, oxygen consumption measurement in isolated adipocytes, in vivo thermogenic stimulation Journal of lipid research High 34384787
2021 FOXP4 is required for human spermatogonial stem cell (SSC) proliferation; conditional inactivation of FOXP4 in human SSC lines suppressed proliferation and activated apoptosis. Conditional gene inactivation (RNAi) in human SSC lines, proliferation and apoptosis assays, single-cell RNA sequencing analysis Asian journal of andrology Medium 36018067
2021 FOXP4 inhibits squamous differentiation of cervical intraepithelial neoplasia cells via an ELF3-dependent pathway; downregulation of FOXP4 induced squamous differentiation in CIN1-derived HPV16-positive W12 cells and HaCaT cells, both dependent on ELF3. siRNA knockdown, organotypic raft cultures, monolayer cultures, immunohistochemistry Cancer science Medium 35838233
2021 In zebra finch Area X, FoxP4 knockdown impairs vocal learning with features partly similar to but distinct from FoxP2 knockdown, indicating FoxP4 plays a non-redundant role in song learning; FoxP1, FoxP2, and FoxP4 differentially affect spectral and temporal song features when individually manipulated. Lentivirus-mediated knockdown of FoxP4 in Area X of juvenile zebra finches, song analysis The Journal of neuroscience Medium 31641053
2021 miR-491-5p suppresses FOXP4 in NSCLC; FOXP4 knockdown decreases TGF-β and its downstream targets MMP-2 and MMP-9, linking FOXP4 to TGF-β/MMP signaling in lung cancer cell migration. Dual luciferase assay, shRNA knockdown, Western blot, functional proliferation/migration assays Experimental and therapeutic medicine Low 33936279
2022 Foxp1 and Foxp4 form a complex in vitro and in vivo in hair follicle stem cells; hair follicle-specific Foxp4 deficiency causes precocious HFSC activation; combined Foxp1/4 double knockout induces apoptosis of K6+ inner bulge (niche) cells and downregulates Fgf18 and Bmp6, resulting in HFSC niche destruction and hair loss. Co-immunoprecipitation (complex formation), conditional knockout mice, immunohistochemistry, apoptosis assays, gene expression Stem cells High 35759955
2022 FOXP4 differentially governs beige adipocyte differentiation and thermogenesis: depletion in progenitors impairs early beige cell differentiation, whereas ablation in differentiated beige adipocytes potentiates thermogenesis and UCP1-mediated uncoupling upon cold exposure; this effect is specific to beige but not brown adipocytes. Beige adipocyte-specific conditional knockout mice, cold exposure, UCP1 measurement, functional thermogenesis assays Development High 35297993
2022 FOXP4 directly binds the promoter of LEF-1 and activates Wnt signaling in laryngeal squamous cell carcinoma; ChIP and luciferase assays confirmed FOXP4 transcriptional regulation of LEF-1. ChIP, luciferase reporter assay, gain/loss-of-function, microarray, EMT analysis Molecular medicine reports Medium 34590150
2023 Knockdown or dominant-negative inhibition of Foxp4 in mice disrupts N-cadherin apical condensation in radial glial cells (RGCs), impairs adherens junctions in the ventricular zone, leads to ectopic neurogenesis and deficient radial migration of cortical neurons; N-cadherin overexpression rescues the ectopic differentiation and migration defects. siRNA knockdown, dominant-negative inhibition in vivo, immunostaining, N-cadherin rescue overexpression Neuroscience bulletin High 36646976
2024 FOXP4 is a direct transcriptional target of YAP1 in gastric cancer; FOXP4 maintains cancer cell stemness and promotes peritoneal metastasis by transcriptionally activating SOX12; a small-molecule screen identified 42-(2-tetrazolyl)rapamycin as a FOXP4 inhibitor. RNA sequencing, ChIP (YAP1-FOXP4 binding), loss-of-function/gain-of-function for stemness, spheroid formation, SOX12 functional studies, in vivo xenograft, small-molecule inhibitor screen Cancer research High 39047223
2024 FOXP4 directly induces expression of PTK7 (a Wnt co-receptor) in ovarian cancer, causing abnormal Wnt/β-catenin pathway activation that drives malignant phenotype; disruption of the FOXP4-Wnt feedback loop by inactivating Wnt signaling or reducing FOXP4 reduces malignancy, reversed by PTK7 restoration. RNA sequencing in FOXP4-deficient cells, ChIP (FOXP4 binding to PTK7 promoter implied), functional assays, rescue with PTK7 Cell death & disease Medium 38740744
2024 FOXP4 transcriptionally represses FBXW7 (a tumor suppressor) in thyroid cancer; ChIP confirmed FOXP4 protein binding to the FBXW7 promoter; FBXW7 overexpression mitigates FOXP4-mediated malignant phenotypes. ChIP assay, gain/loss-of-function, luciferase reporter assay, in vivo murine tumor model Heliyon Medium 38293397
2024 METTL14 mediates N6-methyladenosine (m6A) modification of FOXP4 mRNA during HBV infection, enhancing FOXP4 mRNA stability and increasing FOXP4 protein levels; upregulated FOXP4 activates the PI3K/AKT pathway in HCC cells. m6A modification analysis of FOXP4 mRNA, mRNA stability assay, PI3K/AKT pathway readout Journal of Cancer Medium 39513116
2024 FOXP4 promotes radioresistance in colorectal cancer by transcriptionally activating GPX4 via binding to the GPX4 promoter through its forkhead domain, thereby suppressing ferroptosis; doxorubicin promotes FOXP4 ubiquitination and degradation, reversing radioresistance. ChIP (forkhead domain binding to GPX4 promoter), ferroptosis assays, PDO models, xenograft, doxorubicin ubiquitination assay Advanced science High 40789053
2024 Androgen/AR signaling suppresses FOXP4 expression in endometrial carcinoma cells; FOXP4 overexpression promotes, while FOXP4 knockdown reduces, malignant behaviors; DHT/AR-mediated suppression of cancer cell malignancy is restored by FOXP4 overexpression, placing FOXP4 downstream of AR signaling. AR-transfected ECC cell lines, DHT treatment, ovariectomized Pten-mutant mice, gain/loss-of-function, rescue with FOXP4 Communications biology Medium 38890503
2024 Alcohol-responsive enhancer variant rs10223516 modulates FOXP4 expression via long-range chromatin interaction; FOXP4 transcriptionally activates CYP26B1 and MYC in esophageal cancer; upregulated FOXP4 promotes ESCC development in vivo. ChIP-seq, RNA-seq, luciferase reporter (enhancer activity), chromatin interaction assay, in vivo FOXP4 overexpression model Cancer research Medium 40228145
2025 Combined but not individual deletion of FOXP1 and FOXP4 from FOXP3+ Tregs causes lymphoproliferation, autoimmunity, and early lethality; FOXP1 and FOXP4 bind to the Il2ra promoter to regulate CD25 expression in Tregs; FOXP4 has a non-redundant but insufficient role in Treg suppressive function. FOXP3-Cre-mediated conditional single and double Foxp1/Foxp4 knockout mice, ChIP (Il2ra promoter binding), flow cytometry, suppression assays, germinal center analysis JCI insight High 40794436
2025 FOXP4 is expressed in anterior segment structures (iris, ciliary body, cornea, periocular mesenchyme); a hypomorphic missense variant (p.Q478R in the forkhead domain) retains transcriptional activity but mislocalizes to cytosolic aggregates, suggesting protein instability; FOXP4 is required for anterior segment development. Exome sequencing, YFP-tagged protein localization in HEK-293T and ARPE-19 cells, SRPX2-luciferase reporter assay, embryonic mouse eye immunostaining Investigative ophthalmology & visual science Medium 40637512

Source papers

Stage 0 corpus · 76 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2019 LncRNA FOXP4-AS1 is activated by PAX5 and promotes the growth of prostate cancer by sequestering miR-3184-5p to upregulate FOXP4. Cell death & disease 103 31209207
2018 CircRNA ZNF609 functions as a competitive endogenous RNA to regulate FOXP4 expression by sponging miR-138-5p in renal carcinoma. Journal of cellular physiology 97 30478938
2019 Circular RNA circABCC4 as the ceRNA of miR-1182 facilitates prostate cancer progression by promoting FOXP4 expression. Journal of cellular and molecular medicine 71 31270953
2002 Foxp4: a novel member of the Foxp subfamily of winged-helix genes co-expressed with Foxp1 and Foxp2 in pulmonary and gut tissues. Mechanisms of development 70 14516685
2003 FoxP4, a novel forkhead transcription factor. Biochimica et biophysica acta 66 12818433
2021 Exosomal miR-101-3p and miR-423-5p inhibit medulloblastoma tumorigenesis through targeting FOXP4 and EZH2. Cell death and differentiation 62 34294888
2015 MicroRNA-338-3p inhibits cell proliferation in hepatocellular carcinoma by target forkhead box P4 (FOXP4). International journal of clinical and experimental pathology 57 25755720
2016 Up-regulation of microRNA-491-5p suppresses cell proliferation and promotes apoptosis by targeting FOXP4 in human osteosarcoma. Cell proliferation 55 27704627
2014 Transcriptional regulation by FOXP1, FOXP2, and FOXP4 dimerization. Journal of molecular neuroscience : MN 52 25027557
2008 Expression of Foxp4 in the developing and adult rat forebrain. Journal of neuroscience research 52 18561326
2019 Upregulation of FoxP4 in HCC promotes migration and invasion through regulation of EMT. Oncology letters 49 30930991
2020 LncRNA FOXP4-AS1 Is Involved in Cervical Cancer Progression via Regulating miR-136-5p/CBX4 Axis. OncoTargets and therapy 48 32256085
2015 The FOXP1, FOXP2 and FOXP4 transcription factors are required for islet alpha cell proliferation and function in mice. Diabetologia 48 26021489
2018 FOXP4-AS1 participates in the development and progression of osteosarcoma by downregulating LATS1 via binding to LSD1 and EZH2. Biochemical and biophysical research communications 46 29859193
2015 FOXP4 modulates tumor growth and independently associates with miR-138 in non-small cell lung cancer cells. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 40 25994569
2018 Circular RNA circMYO9B facilitates breast cancer cell proliferation and invasiveness via upregulating FOXP4 expression by sponging miR-4316. Archives of biochemistry and biophysics 35 29702064
2012 Replication and fine mapping for association of the C2orf43, FOXP4, GPRC6A and RFX6 genes with prostate cancer in the Chinese population. PloS one 35 22662242
2020 CircRNA_0058063 functions as a ceRNA in bladder cancer progression via targeting miR-486-3p/FOXP4 axis. Bioscience reports 34 32181485
2020 Exosomal miR-3180-3p inhibits proliferation and metastasis of non-small cell lung cancer by downregulating FOXP4. Thoracic cancer 33 33350095
2012 Foxp4 is dispensable for T cell development, but required for robust recall responses. PloS one 33 22912696
2002 Foxp4: a novel member of the Foxp subfamily of winged-helix genes co-expressed with Foxp1 and Foxp2 in pulmonary and gut tissues. Gene expression patterns : GEP 33 12617805
2015 Differential coexpression of FoxP1, FoxP2, and FoxP4 in the Zebra Finch (Taeniopygia guttata) song system. The Journal of comparative neurology 30 25556631
2020 YY1-induced upregulation of FOXP4-AS1 and FOXP4 promote the proliferation of esophageal squamous cell carcinoma cells. Cell biology international 28 32159250
2019 Differential Song Deficits after Lentivirus-Mediated Knockdown of FoxP1, FoxP2, or FoxP4 in Area X of Juvenile Zebra Finches. The Journal of neuroscience : the official journal of the Society for Neuroscience 26 31641053
2010 Foxp4 is essential in maintenance of Purkinje cell dendritic arborization in the mouse cerebellum. Neuroscience 26 20951773
2019 Upregulation of FOXP4 in breast cancer promotes migration and invasion through facilitating EMT. Cancer management and research 25 31040716
2021 CircRPPH1 serves as a sponge for miR-296-5p to enhance progression of breast cancer by regulating FOXP4 expression. American journal of translational research 21 34377235
2020 Heterozygous variants that disturb the transcriptional repressor activity of FOXP4 cause a developmental disorder with speech/language delays and multiple congenital abnormalities. Genetics in medicine : official journal of the American College of Medical Genetics 21 33110267
2019 The carcinogenic complex lncRNA FOXP4-AS1/EZH2/LSD1 accelerates proliferation, migration and invasion of gastric cancer. European review for medical and pharmacological sciences 20 31646567
2021 LncRNA FOXP4-AS1 Promotes Progression of Ewing Sarcoma and Is Associated With Immune Infiltrates. Frontiers in oncology 18 34765540
2020 LncRNA SNHG16 Promotes the Progression of Laryngeal Squamous Cell Carcinoma by Mediating miR-877-5p/FOXP4 Axis. OncoTargets and therapy 18 32547087
2019 Upregulation of long non-coding RNA FOXP4-AS1 and its regulatory network in hepatocellular carcinoma. OncoTargets and therapy 18 31695417
2021 miR-491-5p inhibits the proliferation and migration of A549 cells by FOXP4. Experimental and therapeutic medicine 16 33936279
2021 LncRNA FOXP4-AS1 Promotes the Progression of Esophageal Squamous Cell Carcinoma by Interacting With MLL2/H3K4me3 to Upregulate FOXP4. Frontiers in oncology 16 34970490
2024 FOXP4-AS1 promotes CD8+ T cell exhaustion and esophageal cancer immune escape through USP10-stabilized PD-L1. Immunologic research 15 38687433
2024 FOXP4-mediated induction of PTK7 activates the Wnt/β-catenin pathway and promotes ovarian cancer development. Cell death & disease 15 38740744
2019 LncRNA LOC105372579 promotes proliferation and epithelial-mesenchymal transition in hepatocellular carcinoma via activating miR-4316/FOXP4 signaling. Cancer management and research 15 31114338
2024 FOXP4 Is a Direct YAP1 Target That Promotes Gastric Cancer Stemness and Drives Metastasis. Cancer research 13 39047223
2021 Long non-coding RNA FOXP4-AS1 facilitates the biological functions of hepatocellular carcinoma cells via downregulating ZC3H12D by mediating H3K27me3 through recruitment of EZH2. Cell biology and toxicology 13 34545456
2019 MiR-3196, a p53-responsive microRNA, functions as a tumor suppressor in hepatocellular carcinoma by targeting FOXP4. American journal of cancer research 13 31911853
2015 Association of FOXP4 Gene with Prostate Cancer and the Cumulative Effects of rs4714476 and 8q24 in Chinese Men. Clinical laboratory 13 26642711
2021 circ‑0000212 promotes cell proliferation of colorectal cancer by sponging miR‑491 and modulating FOXP4 expression. Molecular medicine reports 11 33649850
2020 MicroRNA-4651 represses hepatocellular carcinoma cell growth and facilitates apoptosis via targeting FOXP4. Bioscience reports 10 32436934
2023 FOXP4 promotes proliferation of human spermatogonial stem cells. Asian journal of andrology 9 36018067
2020 Long noncoding RNA LINC00858 promotes the proliferation, migration and invasion of gastric cancer cells via the miR-363-3p/FOXP4 axis. European review for medical and pharmacological sciences 9 33015780
2019 MicroRNA-299-3p/FOXP4 Axis Regulates the Proliferation and Migration of Oral Squamous Cell Carcinoma. Technology in cancer research & treatment 9 31500519
2021 FOXP4 promotes laryngeal squamous cell carcinoma progression through directly targeting LEF‑1. Molecular medicine reports 8 34590150
2023 LncRNA FOXP4-AS1 silencing inhibits metastasis and epithelial-mesenchymal transition in nasopharyngeal carcinoma via miR-136-5p/MAPK1. Anti-cancer drugs 7 36961080
2022 FOXP4-AS1 Inhibits Papillary Thyroid Carcinoma Proliferation and Migration Through the AKT Signaling Pathway. Frontiers in oncology 7 35720005
2022 FOXP4 inhibits squamous differentiation of atypical cells in cervical intraepithelial neoplasia via an ELF3-dependent pathway. Cancer science 7 35838233
2024 Emerging roles of long non-coding RNA FOXP4-AS1 in human cancers: From molecular biology to clinical application. Heliyon 6 39539976
2022 LncRNA FOXP4-AS promotes the progression of non-small cell lung cancer by regulating the miR-3184-5p/EIF5A axis. Journal of tissue engineering and regenerative medicine 6 34921595
2022 Downregulation of microRNA‑423‑5p suppresses TGF‑β1‑induced EMT by targeting FOXP4 in airway fibrosis. Molecular medicine reports 6 35642665
2021 LncRNA RP11-116G8.5 promotes the progression of lung squamous cell carcinoma through sponging miR-3150b-3p/miR-6870-5p to upregulate PHF12/FOXP4. Pathology, research and practice 6 34500373
2021 The forkhead box transcription factor FoxP4 regulates thermogenic programs in adipocytes. Journal of lipid research 5 34384787
2024 Prediction and assessment of deleterious and disease causing nonsynonymous single nucleotide polymorphisms (nsSNPs) in human FOXP4 gene: An in - silico study. Heliyon 4 38994097
2022 Foxp1 and Foxp4 Deletion Causes the Loss of Follicle Stem Cell Niche and Cyclic Hair Shedding by Inducing Inner Bulge Cell Apoptosis. Stem cells (Dayton, Ohio) 4 35759955
2018 Retracted: Long Noncoding RNA SOX2OT Accelerates the Carcinogenesis of Wilms' Tumor Through ceRNA Through miR-363/FOXP4 Axis. DNA and cell biology 4 30481065
2024 Polymorphisms of IFN signaling genes and FOXP4 influence the severity of COVID-19. BMC infectious diseases 3 38429664
2024 METTL14 Induced N6-Methyladenosine Modification of FOXP4 mRNA in HBV-HCC. Journal of Cancer 3 39513116
2023 Inhibition of Foxp4 Disrupts Cadherin-based Adhesion of Radial Glial Cells, Leading to Abnormal Differentiation and Migration of Cortical Neurons in Mice. Neuroscience bulletin 3 36646976
2022 The FOXP4-AS1/miR-3130-3p/SP4 feedback loop is associated with prostate cancer. Cellular and molecular biology (Noisy-le-Grand, France) 3 37114256
2025 Patients-Derived Organoids Sequencing-based FOXP4 Facilitates Radioresistance by Transcriptionally Modifying GPX4 to Regulate ferroptosis in Colorectal Cancer. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 2 40789053
2025 Normal Treg homeostasis and suppressive function require both FOXP1 and FOXP4. JCI insight 2 40794436
2024 Transcription factor FOXP4 inversely governs tumor suppressor genes and contributes to thyroid cancer progression. Heliyon 2 38293397
2024 Participation of Long Noncoding RNA FOXP4-AS1 in the Development and Progression of Endometrioid Carcinoma with Epigenetically Silencing DUSP5. Cancer biotherapy & radiopharmaceuticals 2 38512300
2024 Androgen-responsive FOXP4 is a target for endometrial carcinoma. Communications biology 2 38890503
2024 Incomplete Thermal Ablation-Induced FOXP4-Mediated Promotion of Malignant Progression in Liver Cancer via NDST2. Journal of hepatocellular carcinoma 2 39429915
2022 FOXP4 differentially controls cold-induced beige adipocyte differentiation and thermogenesis. Development (Cambridge, England) 2 35297993
2023 The essential role of forkhead box P4 (FOXP4) in thyroid cancer: a study related to The Cancer Genome Atlas and experimental data. Endocrine connections 1 36752821
2023 Hsa_circ_0017956 Acts as miR-758-3p Sponge to Facilitate the Progression of Non-small-Cell Lung Cancer by Regulating FOXP4 Expression. Molecular biotechnology 1 36763305
2022 Corrigendum: LncRNA FOXP4-AS1 promotes the progression of esophageal squamous cell carcinoma by interacting with MLL2/H3K4me3 to upregulate FOXP4. Frontiers in oncology 1 36313704
2026 LncRNA FOXP4-AS1 facilitates colorectal cancer invasion and migration by enhancing USP7 interaction with ZEB1. Scientific reports 0 41486276
2025 Cis-Regulatory Alterations in FOXP4 Modulate Esophageal Cancer Susceptibility Induced by Chronic Alcohol Exposure. Cancer research 0 40228145
2025 FOXP4 Variants Are Associated With Plateau Iris and Angle Closure Glaucoma. Investigative ophthalmology & visual science 0 40637512
2025 LINC00917 Promotes Bone Metastasis of Breast Cancer by Targeting the miR-491-5p/FOXP4 Axis. Breast cancer (Dove Medical Press) 0 41133246