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FOXP3 Gene(Protein Coding)

Forkhead Box P3

GCID:
GC0XM049250
GIFtS:
71
Genes Participants
UDN Logo

Aliases for FOXP3 Gene

Aliases for FOXP3 Gene

  • Forkhead Box P3 2 3 5
  • Immune Dysregulation, Polyendocrinopathy, Enteropathy, X-Linked 2 3
  • Scurfin 3 4
  • IPEX 3 4
  • Immunodeficiency, Polyendocrinopathy, Enteropathy, X-Linked 3
  • FOXP3delta7 3
  • DIETER 3
  • AIID 3
  • PIDX 3
  • XPID 3
  • JM2 3

External Ids for FOXP3 Gene

Previous HGNC Symbols for FOXP3 Gene

  • IPEX

Previous GeneCards Identifiers for FOXP3 Gene

  • GC0XM047890
  • GC0XM047348
  • GC0XM047913
  • GC0XM048133
  • GC0XM048863
  • GC0XM048993
  • GC0XM049106
  • GC0XM046763

Summaries for FOXP3 Gene

Entrez Gene Summary for FOXP3 Gene

  • The protein encoded by this gene is a member of the forkhead/winged-helix family of transcriptional regulators. Defects in this gene are the cause of immunodeficiency polyendocrinopathy, enteropathy, X-linked syndrome (IPEX), also known as X-linked autoimmunity-immunodeficiency syndrome. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

GeneCards Summary for FOXP3 Gene

FOXP3 (Forkhead Box P3) is a Protein Coding gene. Diseases associated with FOXP3 include immunodysregulation, polyendocrinopathy, and enteropathy, x-linked and immune dysregulation, polyendocrinopathy, enteropathy, x-linked syndrome. Among its related pathways are Allograft rejection and NF-kappaB Signaling. GO annotations related to this gene include transcription factor activity, sequence-specific DNA binding and sequence-specific DNA binding. An important paralog of this gene is FOXK2.

UniProtKB/Swiss-Prot for FOXP3 Gene

  • Transcriptional regulator which is crucial for the development and inhibitory function of regulatory T-cells (Treg). Plays an essential role in maintaining homeostasis of the immune system by allowing the acquisition of full suppressive function and stability of the Treg lineage, and by directly modulating the expansion and function of conventional T-cells. Can act either as a transcriptional repressor or a transcriptional activator depending on its interactions with other transcription factors, histone acetylases and deacetylases. The suppressive activity of Treg involves the coordinate activation of many genes, including CTLA4 and TNFRSF18 by FOXP3 along with repression of genes encoding cytokines such as interleukin-2 (IL2) and interferon-gamma (IFNG). Inhibits cytokine production and T-cell effector function by repressing the activity of two key transcription factors, RELA and NFATC2 (PubMed:15790681). Mediates transcriptional repression of IL2 via its association with histone acetylase KAT5 and histone deacetylase HDAC7 (PubMed:17360565). Can activate the expression of TNFRSF18, IL2RA and CTLA4 and repress the expression of IL2 and IFNG via its association with transcription factor RUNX1 (PubMed:17377532). Inhibits the differentiation of IL17 producing helper T-cells (Th17) by antagonizing RORC function, leading to down-regulation of IL17 expression, favoring Treg development (PubMed:18368049). Inhibits the transcriptional activator activity of RORA (PubMed:18354202). Can repress the expression of IL2 and IFNG via its association with transcription factor IKZF4 (By similarity).

Gene Wiki entry for FOXP3 Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for FOXP3 Gene

Genomics for FOXP3 Gene

Products:

  1. Regulatory Element

Regulatory Elements for FOXP3 Gene

Enhancers for FOXP3 Gene
GeneHancer Identifier Score Enhancer Sources TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Other Gene Targets for Enhancer

Enhancers around FOXP3 on UCSC Golden Path with GeneCards custom track

Promoters for FOXP3 Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters

ENSRs around FOXP3 on UCSC Golden Path with GeneCards custom track

Transcription factor binding sites by QIAGEN in the FOXP3 gene promoter:

Genomic Location for FOXP3 Gene

Chromosome:
X
Start:
49,250,436 bp from pter
End:
49,269,727 bp from pter
Size:
19,292 bases
Orientation:
Minus strand

Genomic View for FOXP3 Gene

Genes around FOXP3 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
FOXP3 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for FOXP3 Gene
GeneLoc Logo Genomic Neighborhood • Exon Structure • Gene Density

RefSeq DNA sequence for FOXP3 Gene

Proteins for FOXP3 Gene

Products:

  1. Antibody
  2. Protein
  3. Assay

  • Protein details for FOXP3 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9BZS1-FOXP3_HUMAN
    Recommended name:
    Forkhead box protein P3
    Protein Accession:
    Q9BZS1
    Secondary Accessions:
    • A5HJT1
    • B7ZLG0
    • B9UN80
    • O60827
    • Q14DD8
    • Q4ZH51

    Protein attributes for FOXP3 Gene

    Size:
    431 amino acids
    Molecular mass:
    47244 Da
    Quaternary structure:
    • Homodimer (By similarity). Interacts with IKZF3. Isoform 1 (via LXXLL motif), but not isoform 2, interacts with isoform 4 of RORA (via AF-2 motif). Interacts with STUB1, HSPA8 and HSPA1A/B. Interacts with PPP1CA, PPP1CB and PPP1CG. Interacts with KAT5 and HDAC7. Interacts with HDAC9 in the absence of T-cell stimulation. Interacts with USP7. Interacts with isoform 2 of ZFP90 and can form a complex with TRIM28 in the presence of isoform 2 of ZFP90. Interacts with RUNX1. Interacts with RORC. Interacts with RELA and NFATC2. Interacts with RUNX2, RUNX3 and IKZF4 (By similarity).

    Three dimensional structures from OCA and Proteopedia for FOXP3 Gene

    Alternative splice isoforms for FOXP3 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for FOXP3 Gene

Proteomics data for FOXP3 Gene at MOPED

Protein Expression for FOXP3 Gene

See protein expression from ProteomicsDB, MOPED, PaxDb, and MaxQB

Post-translational modifications for FOXP3 Gene

  • Acetylation on lysine residues stabilizes FOXP3 and promotes differentiation of T-cells into induced regulatory T-cells (iTregs) associated with suppressive functions. Deacetylated by SIRT1.
  • Phosphorylation at Ser-418 regulates its transcriptional repressor activity and consequently, regulatory T-cells (Treg) suppressive function. Dephosphorylated at Ser-418 by protein phosphatase 1 (PP1) in Treg cells derived from patients with rheumatoid arthritis. Phosphorylation by CDK2 negatively regulates its transcriptional activity and protein stability (By similarity).
  • Polyubiquitinated, leading to its proteasomal degradation in regulatory T-cells (Treg) which is mediated by STUB1 in a HSPA1A/B-dependent manner. Deubiquitinated by USP7 leading to increase in protein stability.
  • Undergoes proteolytic cleavage in activated regulatory T-cells (Treg), and can be cleaved at either the N- or C-terminal site, or at both sites.
  • Ubiquitination at Lys 250, Lys 252, Lys 263, Lys 268, and Lys 393
  • Modification sites at PhosphoSitePlus

Other Protein References for FOXP3 Gene

ENSEMBL proteins:
REFSEQ proteins:

Antibody Products

  • Cell Signaling Technology (CST) Antibodies for FOXP3 (FOXP3)

No data available for DME Specific Peptides for FOXP3 Gene

Domains & Families for FOXP3 Gene

Gene Families for FOXP3 Gene

HGNC:

Protein Domains for FOXP3 Gene

InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for FOXP3 Gene

GenScript: Design optimal peptide antigens:

Graphical View of Domain Structure for InterPro Entry

Q9BZS1

UniProtKB/Swiss-Prot:

FOXP3_HUMAN :
  • Contains 1 fork-head DNA-binding domain.
  • Contains 1 C2H2-type zinc finger.
Domain:
  • Contains 1 fork-head DNA-binding domain.
Similarity:
  • Contains 1 C2H2-type zinc finger.
genes like me logo Genes that share domains with FOXP3: view

Function for FOXP3 Gene

Products:

  1. Animal Model
  2. CRISPR
  3. miRNA
  4. Inhibitory RNA
  5. Clone
  6. Cell Line
  7. Flow Cytometry

Molecular function for FOXP3 Gene

UniProtKB/Swiss-Prot Function:
Transcriptional regulator which is crucial for the development and inhibitory function of regulatory T-cells (Treg). Plays an essential role in maintaining homeostasis of the immune system by allowing the acquisition of full suppressive function and stability of the Treg lineage, and by directly modulating the expansion and function of conventional T-cells. Can act either as a transcriptional repressor or a transcriptional activator depending on its interactions with other transcription factors, histone acetylases and deacetylases. The suppressive activity of Treg involves the coordinate activation of many genes, including CTLA4 and TNFRSF18 by FOXP3 along with repression of genes encoding cytokines such as interleukin-2 (IL2) and interferon-gamma (IFNG). Inhibits cytokine production and T-cell effector function by repressing the activity of two key transcription factors, RELA and NFATC2 (PubMed:15790681). Mediates transcriptional repression of IL2 via its association with histone acetylase KAT5 and histone deacetylase HDAC7 (PubMed:17360565). Can activate the expression of TNFRSF18, IL2RA and CTLA4 and repress the expression of IL2 and IFNG via its association with transcription factor RUNX1 (PubMed:17377532). Inhibits the differentiation of IL17 producing helper T-cells (Th17) by antagonizing RORC function, leading to down-regulation of IL17 expression, favoring Treg development (PubMed:18368049). Inhibits the transcriptional activator activity of RORA (PubMed:18354202). Can repress the expression of IL2 and IFNG via its association with transcription factor IKZF4 (By similarity).
UniProtKB/Swiss-Prot Induction:
Down-regulated in regulatory T-cells (Treg) during inflammation.

Gene Ontology (GO) - Molecular Function for FOXP3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0003700 transcription factor activity, sequence-specific DNA binding IEA,NAS 11138001
GO:0042803 protein homodimerization activity IPI 16920951
GO:0051525 NFAT protein binding IPI 16873067
genes like me logo Genes that share ontologies with FOXP3: view

Phenotypes for FOXP3 Gene

MGI mutant phenotypes for FOXP3:
inferred from 27 alleles
GenomeRNAi human phenotypes for FOXP3:
genes like me logo Genes that share phenotypes with FOXP3: view

Human Phenotype Ontology for FOXP3 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for FOXP3 Gene

MGI Knock Outs for FOXP3:

Animal Model Products

miRNA for FOXP3 Gene

miRTarBase miRNAs that target FOXP3

Inhibitory RNA Products

Flow Cytometry Products

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targets and HOMER Transcription for FOXP3 Gene

Localization for FOXP3 Gene

Subcellular locations from UniProtKB/Swiss-Prot for FOXP3 Gene

Nucleus. Cytoplasm. Note=Predominantly expressed in the cytoplasm in activated conventional T-cells whereas predominantly expressed in the nucleus in regulatory T-cells (Treg). The 41 kDa form derived by proteolytic processing is found exclusively in the chromatin fraction of activated Treg cells (By similarity). {ECO:0000250 UniProtKB:Q99JB6, ECO:0000269 PubMed:22678915}.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for FOXP3 Gene COMPARTMENTS Subcellular localization image for FOXP3 gene
Compartment Confidence
nucleus 5
cytosol 2
extracellular 2
golgi apparatus 2
plasma membrane 2
cytoskeleton 1

No data available for Gene Ontology (GO) - Cellular Components for FOXP3 Gene

Pathways & Interactions for FOXP3 Gene

genes like me logo Genes that share pathways with FOXP3: view

SIGNOR curated interactions for FOXP3 Gene

Is inactivated by:

Gene Ontology (GO) - Biological Process for FOXP3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000122 negative regulation of transcription from RNA polymerase II promoter IEA --
GO:0001782 B cell homeostasis IEA --
GO:0002262 myeloid cell homeostasis IEA --
GO:0002361 CD4-positive, CD25-positive, alpha-beta regulatory T cell differentiation IMP --
GO:0002362 CD4-positive, CD25-positive, alpha-beta regulatory T cell lineage commitment TAS 18368049
genes like me logo Genes that share ontologies with FOXP3: view

Drugs & Compounds for FOXP3 Gene

Products:

  1. Drug

(3) Drugs for FOXP3 Gene - From: Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials

(3) Additional Compounds for FOXP3 Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with FOXP3: view

Transcripts for FOXP3 Gene

Products:

  1. CRISPR
  2. miRNA
  3. Inhibitory RNA
  4. Clone
  5. Flow Cytometry

mRNA/cDNA for FOXP3 Gene

(8) REFSEQ mRNAs :
(10) Additional mRNA sequences :
(6) Selected AceView cDNA sequences:
(6) Ensembl transcripts including schematic representations, and UCSC links where relevant :

Unigene Clusters for FOXP3 Gene

Forkhead box P3:
Representative Sequences:

Inhibitory RNA Products

Flow Cytometry Products

Alternative Splicing Database (ASD) splice patterns (SP) for FOXP3 Gene

ExUns: 1a · 1b ^ 2a · 2b · 2c ^ 3 ^ 4a · 4b ^ 5 ^ 6a · 6b ^ 7 ^ 8 ^ 9 ^ 10 ^ 11 ^ 12a · 12b
SP1:
SP2: -
SP3: -
SP4: -
SP5: - -

Relevant External Links for FOXP3 Gene

GeneLoc Exon Structure for
FOXP3
ECgene alternative splicing isoforms for
FOXP3

Expression for FOXP3 Gene

Products:

  1. Primer

mRNA expression in normal human tissues for FOXP3 Gene

mRNA expression in normal human tissues for FOXP3 Gene
mRNA expression by BioGPS for FOXP3 GenemRNA expression by GTEx for FOXP3 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for FOXP3 Gene

This gene is overexpressed in Whole Blood (x10.5).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, and MOPED for FOXP3 Gene



SOURCE GeneReport for Unigene cluster for FOXP3 Gene Hs.247700

genes like me logo Genes that share expression patterns with FOXP3: view

Primer Products

No data available for Protein differential expression in normal tissues , mRNA Expression by UniProt/SwissProt and Protein tissue co-expression partners for FOXP3 Gene

Orthologs for FOXP3 Gene

This gene was present in the common ancestor of animals.

Orthologs for FOXP3 Gene

Organism Taxonomy Gene Similarity Type Details
cow
(Bos Taurus)
 Mammalia FOXP3 35
  • 89.25 (n)
  • 90.02 (a)
FOXP3 36
  • 90 (a)
 OneToOne
dog
(Canis familiaris)
 Mammalia FOXP3 35
  • 89.69 (n)
  • 90.93 (a)
FOXP3 36
  • 91 (a)
 OneToOne
mouse
(Mus musculus)
 Mammalia Foxp3 35
  • 85.05 (n)
  • 86.92 (a)
Foxp3 16
Foxp3 36
  • 87 (a)
 OneToOne
rat
(Rattus norvegicus)
 Mammalia Foxp3 35
  • 84.3 (n)
  • 86.48 (a)
oppossum
(Monodelphis domestica)
 Mammalia FOXP3 36
  • 42 (a)
 OneToOne
platypus
(Ornithorhynchus anatinus)
 Mammalia FOXP3 36
  • 59 (a)
 OneToOne
chimpanzee
(Pan troglodytes)
 Mammalia FOXP3 36
  • 98 (a)
 OneToOne
lizard
(Anolis carolinensis)
 Reptilia FOXP3 36
  • 62 (a)
 OneToOne
tropical clawed frog
(Silurana tropicalis)
 Amphibia foxp3 35
  • 55.56 (n)
  • 45.13 (a)
rainbow trout
(Oncorhynchus mykiss)
 Actinopterygii Omy.4467 35
zebrafish
(Danio rerio)
 Actinopterygii foxp3a 36
  • 28 (a)
 OneToMany
foxp3b 36
  • 30 (a)
 OneToMany
fruit fly
(Drosophila melanogaster)
 Insecta FoxP 36
  • 22 (a)
 OneToMany
worm
(Caenorhabditis elegans)
 Secernentea fkh-7 36
  • 14 (a)
 ManyToMany
fkh-8 36
  • 17 (a)
 ManyToMany
Species with no ortholog for FOXP3:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • chicken (Gallus gallus)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for FOXP3 Gene

ENSEMBL:
Gene Tree for FOXP3 (if available)
TreeFam:
Gene Tree for FOXP3 (if available)

Paralogs for FOXP3 Gene

Paralogs for FOXP3 Gene

(5) SIMAP similar genes for FOXP3 Gene using alignment to 2 proteins:

genes like me logo Genes that share paralogs with FOXP3: view

Variants for FOXP3 Gene

Sequence variations from dbSNP and Humsavar for FOXP3 Gene

SNP ID Clin Chr 0X pos Sequence Context AA Info Type
VAR_011331 Immunodeficiency polyendocrinopathy, enteropathy, X-linked syndrome (IPEX)
VAR_011332 Immunodeficiency polyendocrinopathy, enteropathy, X-linked syndrome (IPEX)
rs28935477 Immunodeficiency polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) 49,251,441(-) TTGTG(C/T)GGGTG reference, synonymous-codon, missense
VAR_023569 Immunodeficiency polyendocrinopathy, enteropathy, X-linked syndrome (IPEX)
rs2232364 -- 49,259,888(-) TGGAA(C/T)GGGGA intron-variant

Structural Variations from Database of Genomic Variants (DGV) for FOXP3 Gene

Variant ID Type Subtype PubMed ID
esv32909 CNV Gain+Loss 17666407
nsv528292 CNV Gain 19592680
nsv469734 CNV Complex 16826518
nsv471602 CNV Gain 15918152
nsv6895 CNV Insertion 18451855
esv21578 CNV Gain 19812545

Variation tolerance for FOXP3 Gene

Residual Variation Intolerance Score: 66.7% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 1.23; 24.61% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for FOXP3 Gene

HapMap Linkage Disequilibrium report
FOXP3
Human Gene Mutation Database (HGMD)
FOXP3

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for FOXP3 Gene

Disorders for FOXP3 Gene

MalaCards: The human disease database

(47) MalaCards diseases for FOXP3 Gene - From: OMIM, ClinVar, GeneTests, Orphanet, Swiss-Prot, DISEASES, Novoseek, and GeneCards

- elite association - COSMIC cancer census association via MalaCards
Search FOXP3 in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

FOXP3_HUMAN
  • Immunodeficiency polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) [MIM:304790]: Characterized by neonatal onset insulin-dependent diabetes mellitus, infections, secretory diarrhea, thrombocytopenia, anemia and eczema. It is usually lethal in infancy. {ECO:0000269 PubMed:11120765, ECO:0000269 PubMed:11137992, ECO:0000269 PubMed:11137993, ECO:0000269 PubMed:11768393}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Relevant External Links for FOXP3

Genetic Association Database (GAD)
FOXP3
Human Genome Epidemiology (HuGE) Navigator
FOXP3
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
FOXP3
genes like me logo Genes that share disorders with FOXP3: view

No data available for Genatlas for FOXP3 Gene

Publications for FOXP3 Gene

  1. Disruption of a new forkhead/winged-helix protein, scurfin, results in the fatal lymphoproliferative disorder of the scurfy mouse. (PMID: 11138001) Brunkow M.E. … Ramsdell F. (Nat. Genet. 2001) 2 3 4 67
  2. Up-regulation of Foxp3 inhibits cell proliferation, migration and invasion in epithelial ovarian cancer. (PMID: 19628330) Zhang H.Y. … Sun H. (Cancer Lett. 2010) 3 23
  3. TGF-beta and 'adaptive' Foxp3(+) regulatory T cells. (PMID: 19648226) Chen W. … Konkel J.E. (J Mol Cell Biol 2010) 3 23
  4. Regulation of Treg functionality by acetylation-mediated Foxp3 protein stabilization. (PMID: 19996091) van Loosdregt J. … Coffer P.J. (Blood 2010) 3 23
  5. Enhanced lesional Foxp3 expression and peripheral anergic lymphocytes indicate a role for regulatory T cells in Indian post-kala-azar dermal leishmaniasis. (PMID: 20032994) Ganguly S. … Chatterjee M. (J. Invest. Dermatol. 2010) 3 23

Products for FOXP3 Gene

  • Addgene plasmids for FOXP3

Sources for FOXP3 Gene

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