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
109.20190905	current	GRCh38.p13 (GCF_000001405.39)	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 Functions

What's a GeneRIF?

These findings support an intrinsic role for human FOXP3 in controlling thymocyte maturation and peripheral expansion of Teff cells and reveal a previously undescribed pathogenic mechanism through an altered Teff cell compartment in patients with IPEX syndrome.
Title: Role of human forkhead box P3 in early thymic maturation and peripheral T-cell homeostasis.
study provides the first evidence that FOXP3 methylation is associated with chronic diesel exhaust particles exposure during childhood and increased risk for developing persistent wheezing and asthma
Title: Forkhead box protein 3 (FOXP3) hypermethylation is associated with diesel exhaust exposure and risk for childhood asthma.
High PD-L1, IDO, and FOXP3 Tregs expression was associated with high grade histology.
Title: Different pattern of PD-L1, IDO, and FOXP3 Tregs expression with survival in thymoma and thymic carcinoma.
It can now be certain that FOXP3 express not only in immune cells but also in tumor cells
Title: The expression of FOXP3 and its role in human cancers.
Our findings indicated that the AA genotype of Foxp3 in RA patients is associated with downregulation of Tregs and susceptibility to RA in the Iranian population.
Title: Polymorphism of Foxp3 gene affects the frequency of regulatory T cells and disease activity in patients with rheumatoid arthritis in Iranian population.
Findings indicate a direct role for Foxp3 in suppressing Th2-like Treg cells.
Title: A Mutation in the Transcription Factor Foxp3 Drives T Helper 2 Effector Function in Regulatory T Cells.
SNPs of the FOXP3 gene (rs3761549, rs3761548, rs3761547) were correlated with different clinical relapsing-remitting multiple sclerosis data.Significant differences in distribution of allele C rs3761547 were found in male MS patients in comparison to the male healthy group. No association was found for the other 2 SNPS.
Title: The FOXP3 rs3761547 Gene Polymorphism in Multiple Sclerosis as a Male-Specific Risk Factor.
Significant and independent associations between FOXP3 genetic variants and susceptibility to HPV infection and squamous intraepithelial lesion diagnosis and their role as biomarkers of HPV infection and cervical lesion management.
Title: FOXP3 immunoregulatory gene variants are independent predictors of human papillomavirus infection and cervical cancer precursor lesions.
As IPEX awareness and characterization have increased, so has identification of FOXP3 mutations, with at least 70 to date. Review.
Title: From IPEX syndrome to FOXP3 mutation: a lesson on immune dysregulation.
The lowered serum levels of IL-33 and Foxp3 in in recurrent pregnancy loss patients suggested that they might have an important role in the pathogenesis of the disease. Foxp3 rs2232365 SNP could be considered as a risk factor for recurrent pregnancy loss in Egyptian women.
Title: The association of IL-33 and Foxp3 gene polymorphisms with recurrent pregnancy loss in Egyptian women.

Submit: New GeneRIF Correction See all GeneRIFs (870)

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
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: 148 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_001114377.2 → 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, ENST00000376199.7

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_014009.4 → 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, ENST00000376207.9

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 details...

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

Reference GRCh38.p13 Primary Assembly

Genomic

NC_000023.11 Reference GRCh38.p13 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, ENST00000455775.7

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, ENST00000557224.6