FOXP3 forkhead box P3 [Homo sapiens (human)] - Gene

Summary

Official Symbol: FOXP3provided by HGNC
Official Full Name: forkhead box P3provided by HGNC
Primary source: HGNC:HGNC:6106
See related: Ensembl:ENSG00000049768 MIM:300292
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: JM2; AIID; IPEX; PIDX; XPID; DIETER
Summary: 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]
Expression: Ubiquitous expression in appendix (RPKM 2.2), lymph node (RPKM 1.8) and 25 other tissues See more
Orthologs: mouse all

Genomic context

Location:: Xp11.23

Exon count:: 12

Annotation release	Status	Assembly	Chr	Location
109	current	GRCh38.p12 (GCF_000001405.38)	X	NC_000023.11 (49250436..49264932, complement)
105	previous assembly	GRCh37.p13 (GCF_000001405.25)	X	NC_000023.10 (49106897..49122200, complement)

Chromosome X - NC_000023.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

review article: propose a model whereby modulations in metabolic programming lead to changes in DNA methylation at the Foxp3 locus to allow Foxp3 expression following the reversal of anergy.
Title: Anergy into T regulatory cells: an integration of metabolic cues and epigenetic changes at the Foxp3 conserved non-coding sequence 2.
Study suggests that asthma is significantly associated with higher differentially methylated regions within the promoter region of Foxp3 and positively linked with average exposure to CO,NO2, and PM2.5 during the 90 days prior to the blood draw.
Title: Exposure to NO2, CO, and PM2.5 is linked to regional DNA methylation differences in asthma.
There was a significant positive correlation between the expression of EBI3 and Foxp3 mRNA in the sarcoidosis group (r=0.786, P<0.001). Conclusion: IL-35 may be involved in the inflammatory process of sarcoidosis and play an important role in the pathogenesis of the disease.
Title: [The plasma level and gene expression in peripheral blood of interleukin-35 in patients with sarcoidosis and its clinical significance].
TGF-b, IL-10, and Foxp3 mRNA levels were significantly higher in patients with breast cancer than in healthy controls (P < 0.05). In summary, our results suggest that nutritional status, especially BMI, may strongly affect systematic immune function in patients with breast cancer
Title: Low BMI is correlated with increased TGF-β and IL-10 mRNA levels in the peripheral blood of breast cancer patients.
FOXP3 represses the ability of hnRNPF to bind to its target pre-mRNA and thus modulates RNA alternative splicing
Title: FOXP3 interacts with hnRNPF to modulate pre-mRNA alternative splicing.
Results are in line with the hypothesis that in the early phase of ALS, neuroprotective helper T cells infiltrate in the affected areas in the lumbar spinal cord. This was reflected in higher peripheral percentage of CD4(+) helper T cells and higher expression of FOXP3 and IL-2Ralpha.
Title: Evaluation of regulatory T lymphocytes and IL2Ra and FOXP3 gene expression in peripheral mononuclear cells from patients with amyotrophic lateral sclerosis.
RUNX3, a CD8(+) lineage-specific transcription factor, binds at the FOXP3-promoter to induce its transcription.
Title: Transcriptional regulation of FOXP3 requires integrated activation of both promoter and CNS regions in tumor-induced CD8+ Treg cells.
Multivariate analysis of OS only found CD8(+)/Foxp3(+) ratio to be independent prognostic factor (P = 0.022) om spinal chordoma.
Title: Clinicopathologic implications of CD8+/Foxp3+ ratio and miR-574-3p/PD-L1 axis in spinal chordoma patients.
Authors have demonstrated that excessive amounts of STAT5 may bind more TET2 to the FOXP3-TSDR and upregulate FOXP3 expression via DNA demethylation. Study improved the mechanism of FOXP3-TSDR hypomethylation in tumor-infiltrating CD4(+) T cells of CRC patients.
Title: STAT5 and TET2 Cooperate to Regulate FOXP3-TSDR Demethylation in CD4+ T Cells of Patients with Colorectal Cancer.
Treg cells from asthmatic patients expressed more FOXP3 as well as GATA3; the expression level of GATA3 negatively correlated with FEV1%pred. Increased expressions of USP21 and PIM2 in Treg cells from asthmatic patients were found.
Title: The Imbalance of FOXP3/GATA3 in Regulatory T Cells from the Peripheral Blood of Asthmatic Patients.

Submit: New GeneRIF Correction See all GeneRIFs (841)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Diabetes mellitus type 1 MedGen: C0011854 OMIM: 222100 GeneReviews: Not available	Compare labs
Insulin-dependent diabetes mellitus secretory diarrhea syndrome MedGen: C0342288 OMIM: 304790 GeneReviews: IPEX Syndrome	Compare labs

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Tat	tat	HIV-1 Tat upregulates the expression of forkhead box P3 (FOXP3) in human primary T cells	PubMed
	tat	Subjects immunized with HIV-1 Tat increase the percentage of FOXP3 expression in the CD4+/CD25+ T cells	PubMed

Go to the HIV-1, Human Interaction Database

Pathways from BioSystems

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Allograft Rejection, organism-specific biosystem (from WikiPathways)
Allograft Rejection, organism-specific biosystemThis pathway illustrates molecular interactions involved in the fundamental adaptive immune response for allograft destruction. This pathway was adapted in large part from the KEGG pathway http://www...
Calcineurin-regulated NFAT-dependent transcription in lymphocytes, organism-specific biosystem (from Pathway Interaction Database)
Calcineurin-regulated NFAT-dependent transcription in lymphocytes, organism-specific biosystem
Calcineurin-regulated NFAT-dependent transcription in lymphocytes
IL2 signaling events mediated by STAT5, organism-specific biosystem (from Pathway Interaction Database)
IL2 signaling events mediated by STAT5, organism-specific biosystem
IL2 signaling events mediated by STAT5
Inflammatory bowel disease (IBD), organism-specific biosystem (from KEGG)
Inflammatory bowel disease (IBD), organism-specific biosystemInflammatory bowel disease (IBD), which includes Crohn disease (CD) and ulcerative colitis (UC), is characterized by chronic inflammation of the gastrointestinal tract due to environmental and geneti...
Inflammatory bowel disease (IBD), conserved biosystem (from KEGG)
Inflammatory bowel disease (IBD), conserved biosystemInflammatory bowel disease (IBD), which includes Crohn disease (CD) and ulcerative colitis (UC), is characterized by chronic inflammation of the gastrointestinal tract due to environmental and geneti...
TGF-beta Signaling Pathway, organism-specific biosystem (from WikiPathways)
TGF-beta Signaling Pathway, organism-specific biosystemThe signal transduction mechanisms underlying the pathophysiological activities of transforming growth factor-? (TGF-?) have been extensively studied since its discovery nearly 30 years ago. TGF-? li...
Th17 cell differentiation, organism-specific biosystem (from KEGG)
Th17 cell differentiation, organism-specific biosystemInterleukin (IL)-17-producing helper T (Th17) cells serve as a subset of CD4+ T cells involved in epithelial cell- and neutrophil mediated immune responses against extracellular microbes and in the p...
Th17 cell differentiation, conserved biosystem (from KEGG)
Th17 cell differentiation, conserved biosystemInterleukin (IL)-17-producing helper T (Th17) cells serve as a subset of CD4+ T cells involved in epithelial cell- and neutrophil mediated immune responses against extracellular microbes and in the p...

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

FOXP3_3345 (e-PCR)
- UniSTS:462200

NoName (e-PCR)
- UniSTS:485823

RH99318 (e-PCR)
- UniSTS:85188

NoName (e-PCR)
- UniSTS:481760

Homology

Homologs of the FOXP3 gene: The FOXP3 gene is conserved in Rhesus monkey, dog, cow, mouse, rat, and frog.
Orthologs from Annotation Pipeline: 136 organisms have orthologs with human gene FOXP3
Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
DNA binding	IMP Inferred from Mutant Phenotype more info	PubMed
DNA-binding transcription factor activity	IDA Inferred from Direct Assay more info	PubMed
DNA-binding transcription factor activity	NAS Non-traceable Author Statement more info	PubMed
DNA-binding transcription factor activity, RNA polymerase II-specific	ISA Inferred from Sequence Alignment more info
DNA-binding transcription factor activity, RNA polymerase II-specific	ISM Inferred from Sequence Model more info	PubMed
NF-kappaB binding	NAS Non-traceable Author Statement more info	PubMed
NFAT protein binding	IPI Inferred from Physical Interaction more info	PubMed
RNA polymerase II proximal promoter sequence-specific DNA binding	ISS Inferred from Sequence or Structural Similarity more info
histone acetyltransferase binding	IPI Inferred from Physical Interaction more info	PubMed
histone deacetylase binding	IPI Inferred from Physical Interaction more info	PubMed
metal ion binding	IEA Inferred from Electronic Annotation more info
protein binding	IPI Inferred from Physical Interaction more info	PubMed
protein homodimerization activity	IDA Inferred from Direct Assay more info	PubMed
protein homodimerization activity	IPI Inferred from Physical Interaction more info	PubMed
sequence-specific DNA binding	IDA Inferred from Direct Assay more info	PubMed
transcription corepressor activity	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
B cell homeostasis	IEA Inferred from Electronic Annotation more info
CD4-positive, CD25-positive, alpha-beta regulatory T cell lineage commitment	TAS Traceable Author Statement more info	PubMed
T cell activation	IDA Inferred from Direct Assay more info	PubMed
T cell homeostasis	NAS Non-traceable Author Statement more info	PubMed
T cell mediated immunity	IEA Inferred from Electronic Annotation more info
T cell receptor signaling pathway	IEA Inferred from Electronic Annotation more info
chromatin remodeling	NAS Non-traceable Author Statement more info	PubMed
cytokine production	IEA Inferred from Electronic Annotation more info
myeloid cell homeostasis	IEA Inferred from Electronic Annotation more info
negative regulation of CREB transcription factor activity	IDA Inferred from Direct Assay more info	PubMed
negative regulation of DNA-binding transcription factor activity	IDA Inferred from Direct Assay more info	PubMed
negative regulation of NF-kappaB transcription factor activity	IDA Inferred from Direct Assay more info	PubMed
negative regulation of T cell cytokine production	IDA Inferred from Direct Assay more info	PubMed
negative regulation of T cell cytokine production	IMP Inferred from Mutant Phenotype more info	PubMed
negative regulation of T cell proliferation	IDA Inferred from Direct Assay more info	PubMed
negative regulation of T cell proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
negative regulation of T-helper 17 cell differentiation	IMP Inferred from Mutant Phenotype more info	PubMed
negative regulation of activated T cell proliferation	NAS Non-traceable Author Statement more info	PubMed
negative regulation of cell proliferation	IDA Inferred from Direct Assay more info	PubMed
negative regulation of chronic inflammatory response	IEA Inferred from Electronic Annotation more info
negative regulation of cytokine biosynthetic process	IDA Inferred from Direct Assay more info	PubMed
negative regulation of cytokine secretion	IDA Inferred from Direct Assay more info	PubMed
negative regulation of histone acetylation	IEA Inferred from Electronic Annotation more info
negative regulation of histone deacetylation	IGI Inferred from Genetic Interaction more info	PubMed
negative regulation of immune response	IDA Inferred from Direct Assay more info	PubMed
negative regulation of interferon-gamma biosynthetic process	IEA Inferred from Electronic Annotation more info
negative regulation of interferon-gamma production	IDA Inferred from Direct Assay more info	PubMed
negative regulation of interferon-gamma production	IMP Inferred from Mutant Phenotype more info	PubMed
negative regulation of interleukin-10 production	IDA Inferred from Direct Assay more info	PubMed
negative regulation of interleukin-17 production	IMP Inferred from Mutant Phenotype more info	PubMed
negative regulation of interleukin-2 biosynthetic process	IMP Inferred from Mutant Phenotype more info	PubMed
negative regulation of interleukin-2 production	IDA Inferred from Direct Assay more info	PubMed
negative regulation of interleukin-2 production	IMP Inferred from Mutant Phenotype more info	PubMed
negative regulation of interleukin-4 production	IDA Inferred from Direct Assay more info	PubMed
negative regulation of interleukin-5 production	IEA Inferred from Electronic Annotation more info
negative regulation of interleukin-6 production	IEA Inferred from Electronic Annotation more info
negative regulation of isotype switching to IgE isotypes	IEA Inferred from Electronic Annotation more info
negative regulation of transcription by RNA polymerase II	IEA Inferred from Electronic Annotation more info
negative regulation of transcription, DNA-templated	IDA Inferred from Direct Assay more info	PubMed
negative regulation of transcription, DNA-templated	IMP Inferred from Mutant Phenotype more info	PubMed
negative regulation of tumor necrosis factor production	IEA Inferred from Electronic Annotation more info
positive regulation of CD4-positive, CD25-positive, alpha-beta regulatory T cell differentiation	TAS Traceable Author Statement more info	PubMed
positive regulation of T cell anergy	IEA Inferred from Electronic Annotation more info
positive regulation of histone acetylation	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of immature T cell proliferation in thymus	IEA Inferred from Electronic Annotation more info
positive regulation of interleukin-4 production	IEA Inferred from Electronic Annotation more info
positive regulation of peripheral T cell tolerance induction	IEA Inferred from Electronic Annotation more info
positive regulation of transcription by RNA polymerase II	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of transcription, DNA-templated	IDA Inferred from Direct Assay more info	PubMed
positive regulation of transcription, DNA-templated	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of transcription, DNA-templated	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of transforming growth factor beta1 production	IEA Inferred from Electronic Annotation more info
regulation of T cell anergy	ISS Inferred from Sequence or Structural Similarity more info
regulation of Wnt signaling pathway	TAS Traceable Author Statement more info
regulation of isotype switching to IgG isotypes	IEA Inferred from Electronic Annotation more info
regulation of regulatory T cell differentiation	TAS Traceable Author Statement more info
regulation of transcription, DNA-templated	NAS Non-traceable Author Statement more info	PubMed
response to virus	IEP Inferred from Expression Pattern more info	PubMed
tolerance induction to self antigen	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
cytoplasm	IDA Inferred from Direct Assay more info	PubMed
nucleoplasm	IDA Inferred from Direct Assay more info
nucleoplasm	TAS Traceable Author Statement more info
nucleus	IDA Inferred from Direct Assay more info	PubMed
protein-containing complex	NAS Non-traceable Author Statement more info	PubMed

General protein information

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Preferred Names: forkhead box protein P3

Names: FOXP3delta7; immune dysregulation, polyendocrinopathy, enteropathy, X-linked; immunodeficiency, polyendocrinopathy, enteropathy, X-linked; scurfin

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_007392.1 RefSeqGene

Range

5001..19392

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_62

mRNA and Protein(s)

NM_001114377.1 → NP_001107849.1 forkhead box protein P3 isoform b

See identical proteins and their annotated locations for NP_001107849.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks an in-frame segment of the coding region, compared to variant 1. It encodes a shorter isoform (b), that is missing an internal segment compared to isoform a.

Source sequence(s)

AF277993, BQ184335, DB342786

Consensus CDS

CCDS48109.1

UniProtKB/Swiss-Prot

Q9BZS1

Related

ENSP00000365372.2, ENST00000376199.6

Conserved Domains (3) summary

cd00059
Location:302 → 374

FH; Forkhead (FH), also known as a "winged helix". FH is named for the Drosophila fork head protein, a transcription factor which promotes terminal rather than segmental development. This family of transcription factor domains, which bind to B-DNA as ...

pfam07793
Location:1 → 111

DUF1631; Protein of unknown function (DUF1631)

pfam16159
Location:158 → 225

FOXP-CC; FOXP coiled-coil domain
NM_014009.3 → NP_054728.2 forkhead box protein P3 isoform a

See identical proteins and their annotated locations for NP_054728.2

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longer transcript, and encodes the longer isoform (a).

Source sequence(s)

AF277993, BQ184335, DB342786

Consensus CDS

CCDS14323.1

UniProtKB/Swiss-Prot

Q9BZS1

Related

ENSP00000365380.4, ENST00000376207.8

Conserved Domains (2) summary

pfam00250
Location:337 → 410

Forkhead; Forkhead domain

pfam16159
Location:193 → 260

FOXP-CC; FOXP coiled-coil domain

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p12 Primary Assembly

Genomic

NC_000023.11 Reference GRCh38.p12 Primary Assembly

Range

49250436..49264932 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_006724533.2 → XP_006724596.2 forkhead box protein P3 isoform X1

See identical proteins and their annotated locations for XP_006724596.2

UniProtKB/TrEMBL

B7ZLG1

Related

ENSP00000396415.3, ENST00000455775.6

Conserved Domains (2) summary

cd00059
Location:360 → 432

FH; Forkhead (FH), also known as a "winged helix". FH is named for the Drosophila fork head protein, a transcription factor which promotes terminal rather than segmental development. This family of transcription factor domains, which bind to B-DNA as ...

pfam16159
Location:216 → 283

FOXP-CC; FOXP coiled-coil domain
XM_017029567.1 → XP_016885056.1 forkhead box protein P3 isoform X2

Related

ENSP00000451208.1, ENST00000557224.5