FOXP3 forkhead box P3 [Homo sapiens] - Gene

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Summary

Official Symbol: FOXP3provided by HGNC
Official Full Name: forkhead box P3provided by HGNC
Primary source: HGNC:6106
Locus tag: JM2
See related: Ensembl:ENSG00000049768; HPRD:02242; MIM:300292; Vega:OTTHUMG00000024135
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; MGC141961; MGC141963
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]

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Genomic context

Location :: Xp11.23

Sequence :: Chromosome: X; NC_000023.10 (49106897..49121288, complement)

See FOXP3 in Epigenomics, MapViewer

Chromosome X - NC_000023.10 Genomic Context describing neighboring genes

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Genomic regions, transcripts, and products

Genomic Sequence

Go to nucleotideGraphics FASTA GenBank

Go to reference sequence details

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Bibliography

GeneRIFs: Gene References Into Functions What's a GeneRIF?

Treatment with 89SrCl2 could decrease the amount of CD4+ CD25+ T cells and down-regulate Foxp3 mRNA expression in cancer patients with bone metastases.
Title: [Effects of 89SrCl2 treatment on CD4+ CD25+ regulatory T cells and its Foxp3 mRNA expression in cancer patients with bone metastases].
FOXP3-positive Treg cells accumulate at the tumor invasion zone in renal cell carcinoma
Title: Localization of FOXP3-positive cells in renal cell carcinoma.
FOXP3 probably has a relationship with lymph node metastasis of gastric cancer.
Title: Correlation between elevated FOXP3 expression and increased lymph node metastasis of gastric cancer.
Hepatitis C virus core protein-expressing Jurkat cells show an up-regulation of FOXP3.
Title: Up-regulation of FOXP3 and induction of suppressive function in CD4+ Jurkat T-cells expressing hepatitis C virus core protein.
An association study of single nucleotide polymorphisms of the FOXP3 intron-1 and the risk of Psoriasis vulgaris.
Title: An association study of single nucleotide polymorphisms of the FOXP3 intron-1 and the risk of Psoriasis vulgaris.
When the Foxp3 gene was knocked down, some Treg-associated surface markers were significantly altered, which affected the function of Tregs.
Title: [Effects of Foxp3 knockdown on the functions of human regulatory T cells].
Our data show a decreased Foxp3 expression and an increased ROR gamma t expression in COPD patients and normal smokers that parallels the aggravation of the disease.
Title: The expression of Foxp3 and ROR gamma t in lung tissues from normal smokers and chronic obstructive pulmonary disease patients.
The levels of inflammatory factors are associated with the variation of Foxp3+Tregs in COPD.
Title: Relationship between the anti-inflammatory properties of salmeterol/fluticasone and the expression of CD4⁺CD25⁺Foxp3⁺ regulatory T cells in COPD.
Our data identify SIRT1 as a negative regulator of Treg function via deacetylation of three novel target sites in Foxp3
Title: Three novel acetylation sites in the Foxp3 transcription factor regulate the suppressive activity of regulatory T cells.
The FOXP3 gene, which regulates expression of T regulatory lymphocytes, is more likely to display increased methylation among children with obstructive sleep apnea who exhibit increased systemic inflammatory responses.
Title: DNA methylation in inflammatory genes among children with obstructive sleep apnea.

Submit: New GeneRIF Correction See all (401)

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Phenotypes

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

Review eQTL and phenotype association data in this region using PheGenI

Diabetes mellitus, type I, susceptibility to

MIM: 222100

Immunodysregulation, polyendocrinopathy, and enteropathy, X-linked

MIM: 304790

IPEX (immune dysregulation, polyendocrinopathy, enteropathy, X-linked) syndrome is characterized by systemic autoimmunity, typically beginning in the first year of life. Presentation is most commonly the clinical triad of watery diarrhea, eczematous dermatitis, and endocrinopathy (most commonly insulin-dependent diabetes mellitus). Most children have other autoimmune phenomena including Coombs-positive anemia, autoimmune thrombocytopenia, autoimmune neutropenia, and tubular nephropathy. Without aggressive immunosuppression or bone marrow transplantation, the majority of affected males die within the first one to two years of life from metabolic derangements or sepsis; a few with a milder phenotype have survived into the second or third decade of life.

Diagnosis Testing

Diagnosis is based on clinical features and on the identification of a mutation in FOXP3. Molecular genetic testing is clinically available for FOXP3, the only gene in which mutations are known to cause IPEX syndrome. Approximately 25% of males with symptoms suggestive of IPEX syndrome have mutations identified in FOXP3.

Genetic Counseling

IPEX syndrome is inherited in an X-linked manner. The risk to sibs of the proband depends on the carrier status of the mother. If the mother of the proband is a carrier, the chance of transmitting the disease-causing mutation in each pregnancy is 50%. Males who inherit the mutation will be affected; females who inherit the mutation are carriers and will not be affected. Affected males pass the disease-causing mutation to all of their daughters and none of their sons. Carrier testing for at-risk relatives and prenatal testing for pregnancies at risk are possible for families in which the disease-causing mutation has been identified.

References

PMID: 20301297

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Interactions

Products	Interactant	Other Gene	Source	Pubs	Description
Q9BZS1	O94916	NFAT5	HPRD	PubMed
Q9BZS1	Q13469	NFATC2	HPRD	PubMed
Q9BZS1	Q01196	RUNX1	HPRD	PubMed
BioGRID:119170	BioGRID:109315	HDAC1	BioGRID	PubMed	Affinity Capture-Western
BioGRID:119170	BioGRID:109316	HDAC2	BioGRID	PubMed	Co-localization
BioGRID:119170	BioGRID:115106	HDAC4	BioGRID	PubMed	Co-localization
BioGRID:119170	BioGRID:119613	HDAC7	BioGRID	PubMed	Affinity Capture-Western
BioGRID:119170	BioGRID:115083	HDAC9	BioGRID	PubMed	Affinity Capture-Western
BioGRID:119170	BioGRID:122146	IKZF4	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex; Two-hybrid
BioGRID:119170	BioGRID:115779	KAT5	BioGRID	PubMed	Affinity Capture-Western
BioGRID:119170	BioGRID:123914	KAT8	BioGRID	PubMed	Reconstituted Complex
BioGRID:119170	BioGRID:110845	NFATC1	BioGRID	PubMed	Affinity Capture-Luminescence
BioGRID:119170	BioGRID:110846	NFATC2	BioGRID	PubMed	Co-localization
BioGRID:119170	BioGRID:111898	REL	BioGRID	PubMed	Affinity Capture-Luminescence

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General gene information

Markers

FOXP3_3345 (e-PCR)
- UniSTS:462200

NoName (e-PCR)
- UniSTS:485823

RH99318 (e-PCR)
- UniSTS:85188

NoName (e-PCR)
- UniSTS:481760

Genotypes

See FOXP3 SNP Geneview Report
See FOXP3 SNP Genotype Report
See FOXP3 SNP Variation Viewer Report

Homology

Homologs of the FOXP3 gene: The FOXP3 gene is conserved in , dog, cow, mouse, and rat.
Map Viewer (Mouse, Rat)

Pathways from BioSystems

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

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
DNA binding, bending	IBA Inferred from Biological aspect of Ancestor more info
NF-kappaB binding	NAS Non-traceable Author Statement more info	PubMed
NFAT protein binding	IPI Inferred from Physical Interaction more info	PubMed
chromatin binding	IBA Inferred from Biological aspect of Ancestor more info
double-stranded DNA binding	IBA Inferred from Biological aspect of Ancestor 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
protein heterodimerization activity	IBA Inferred from Biological aspect of Ancestor more info
protein homodimerization activity	IPI Inferred from Physical Interaction more info	PubMed
sequence-specific DNA binding	IDA Inferred from Direct Assay more info	PubMed
sequence-specific DNA binding transcription factor activity	IDA Inferred from Direct Assay more info	PubMed
sequence-specific DNA binding transcription factor activity	NAS Non-traceable Author Statement more info	PubMed
sequence-specific distal enhancer binding RNA polymerase II transcription factor activity	IBA Inferred from Biological aspect of Ancestor more info
transcription corepressor activity	IBA Inferred from Biological aspect of Ancestor more info
zinc ion binding	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
B cell homeostasis	IBA Inferred from Biological aspect of Ancestor more info
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	IBA Inferred from Biological aspect of Ancestor more info
NOT camera-type eye development	IRD Inferred from Rapid Divergence more info
NOT caudate nucleus development	IRD Inferred from Rapid Divergence more info
cerebellum development	IBA Inferred from Biological aspect of Ancestor more info
NOT cerebral cortex development	IRD Inferred from Rapid Divergence more info
chromatin remodeling	NAS Non-traceable Author Statement more info	PubMed
cytokine production	IEA Inferred from Electronic Annotation more info
embryo development	IBA Inferred from Biological aspect of Ancestor more info
NOT growth	IRD Inferred from Rapid Divergence more info
NOT lung alveolus development	IRD Inferred from Rapid Divergence more info
myeloid cell homeostasis	IBA Inferred from Biological aspect of Ancestor more info
negative regulation of CREB 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 proliferation	IDA Inferred from Direct Assay 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	IBA Inferred from Biological aspect of Ancestor 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	IBA Inferred from Biological aspect of Ancestor 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	IBA Inferred from Biological aspect of Ancestor more info
negative regulation of interferon-gamma production	IDA Inferred from Direct Assay more info	PubMed
negative regulation of interleukin-10 production	IDA Inferred from Direct Assay 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-4 production	IDA Inferred from Direct Assay more info	PubMed
negative regulation of interleukin-5 production	IBA Inferred from Biological aspect of Ancestor more info
negative regulation of interleukin-6 production	IBA Inferred from Biological aspect of Ancestor more info
negative regulation of isotype switching to IgE isotypes	IBA Inferred from Biological aspect of Ancestor more info
negative regulation of sequence-specific DNA binding transcription factor activity	IDA Inferred from Direct Assay more info	PubMed
negative regulation of transcription, DNA-dependent	IDA Inferred from Direct Assay more info	PubMed
negative regulation of tumor necrosis factor production	IBA Inferred from Biological aspect of Ancestor more info
pattern specification process	IBA Inferred from Biological aspect of Ancestor more info
positive regulation of CD4-positive, CD25-positive, alpha-beta regulatory T cell differentiation	IBA Inferred from Biological aspect of Ancestor more info
positive regulation of T cell anergy	IBA Inferred from Biological aspect of Ancestor more info
NOT positive regulation of epithelial cell proliferation involved in lung morphogenesis	IRD Inferred from Rapid Divergence more info
positive regulation of histone acetylation	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of immature T cell proliferation in thymus	IBA Inferred from Biological aspect of Ancestor more info
NOT positive regulation of mesenchymal cell proliferation	IRD Inferred from Rapid Divergence more info
positive regulation of peripheral T cell tolerance induction	IBA Inferred from Biological aspect of Ancestor more info
positive regulation of transcription from RNA polymerase II promoter	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of transcription, DNA-dependent	IDA Inferred from Direct Assay more info	PubMed
positive regulation of transcription, DNA-dependent	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of transcription, DNA-dependent	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of transforming growth factor beta1 production	IBA Inferred from Biological aspect of Ancestor more info
post-embryonic development	IBA Inferred from Biological aspect of Ancestor more info
NOT putamen development	IRD Inferred from Rapid Divergence more info
regulation of immunoglobulin production	IEA Inferred from Electronic Annotation more info
regulation of isotype switching to IgG isotypes	IBA Inferred from Biological aspect of Ancestor more info
regulation of transcription, DNA-dependent	NAS Non-traceable Author Statement more info	PubMed
response to virus	IEP Inferred from Expression Pattern more info
NOT righting reflex	IRD Inferred from Rapid Divergence more info
NOT skeletal muscle tissue development	IRD Inferred from Rapid Divergence more info
NOT smooth muscle tissue development	IRD Inferred from Rapid Divergence more info
tolerance induction to self antigen	IBA Inferred from Biological aspect of Ancestor more info
NOT vocal learning	IRD Inferred from Rapid Divergence more info

Component	Evidence Code	Pubs
cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
cytoplasm	NAS Non-traceable Author Statement more info	PubMed
intracellular	IEA Inferred from Electronic Annotation more info
nucleus	IDA Inferred from Direct Assay more info	PubMed
nucleus	NAS Non-traceable Author Statement more info	PubMed
protein complex	NAS Non-traceable Author Statement more info	PubMed
transcription factor complex	IBA Inferred from Biological aspect of Ancestor more info

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General protein information

Preferred Names: forkhead box protein P3

Names: forkhead box protein P3; scurfin; FOXP3delta7; immunodeficiency, polyendocrinopathy, enteropathy, X-linked; immune dysregulation, polyendocrinopathy, enteropathy, X-linked

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NCBI Reference Sequences (RefSeq)

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

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, ENST00000376199

Conserved Domains (1) summary

cd00059
Location:302 – 374
Blast Score: 276

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 ...
NM_014009.3 → NP_054728.2 forkhead box protein P3 isoform a

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, OTTHUMP00000025832, ENST00000376207, OTTHUMT00000060814

Conserved Domains (1) summary

cd00059
Location:337 – 409
Blast Score: 277

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 ...

RefSeqs of Annotated Genomes: Build 37.3

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

Reference GRCh37.p5 Primary Assembly

Genomic

NC_000023.10 Reference GRCh37.p5 Primary Assembly

Range

49106897..49121288, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000155.1 Alternate HuRef

Range

46763332..46777541, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

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Related Sequences

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	AF235097.2 (57906..71784)	None
genomic	CH471224.1	EAW50671.1
		EAW50672.1
		EAW50673.1
genomic	GN344065.1	CAY55968.1
genomic	JA738833.1	CCF77062.1
mRNA	AF277993.1	AAG53607.1
mRNA	AJ005891.1	CAA06748.1
mRNA	AK292052.1	BAF84741.1
mRNA	AK299988.1	BAG61809.1
mRNA	BC113401.1	AAI13402.1
mRNA	BC113403.1	AAI13404.1
mRNA	BC143785.1	AAI43786.1
mRNA	BC143786.1	AAI43787.1
mRNA	BQ184335.1	None
mRNA	DB342786.1	None
mRNA	DQ010327.1	AAY27088.1
mRNA	EF534714.1	ABQ15210.1
mRNA	EU855812.1	ACJ46653.1
other-genetic	BC111853.2	AAI11854.1
other-genetic	HQ258232.1	ADR82986.1

Protein Accession	Links
Protein Accession	GenPept Link	UniProtKB Link
Q9BZS1.1	GenPept	UniProtKB/Swiss-Prot:Q9BZS1

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Additional Links

Epigenomics
MIM 300292
FOXP3 @ LOVD FOXP3
FOXP3base: Mutation registry for Immunodysregulation, polyendocrinopathy, and enteropathy, X-linked; IPEX FOXP3base/
GeneTests for MIM: 300292
CCHMC - Human Genetics Mutation Database FOXP3
Resource of Asian Primary Immunodeficiency Diseases (RAPID) AGID_61
UCSC UCSC
UniGene Hs.247700