FOXP3

Summary

FOXP3 (forkhead box P3, HGNC:6106) is a protein-coding gene on chromosome Xp11.23, encoding Forkhead box protein P3 (Q9BZS1). Transcriptional regulator which is crucial for the development and inhibitory function of regulatory T-cells (Treg). In precision oncology, FOXP3 EXPRESSION confers sensitivity to Epirubicin in Breast Cancer (CIViC Level B).

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.

Source: NCBI Gene 50943 — RefSeq curated summary.

At a glance

• Gene–disease (curated): immune dysregulation-polyendocrinopathy-enteropathy-X-linked syndrome (Definitive, ClinGen)
• GWAS associations: 1
• Clinical variants (ClinVar): 468 total — 30 pathogenic, 21 likely-pathogenic
• Phenotypes (HPO): 79
• Druggable target: yes
• Precision-oncology evidence (CIViC): 1 curated variant–drug association
• Transcription factor: yes — 63 downstream targets (CollecTRI)
• MANE Select transcript: NM_014009

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6106
Approved symbol	FOXP3
Name	forkhead box P3
Location	Xp11.23
Locus type	gene with protein product
Status	Approved
Aliases	JM2, XPID, AIID, PIDX, DIETER, SCURFIN
Ensembl gene	ENSG00000049768
Ensembl biotype	protein_coding
OMIM	300292
Entrez	50943

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 9 protein_coding, 1 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000376197, ENST00000376199, ENST00000376207, ENST00000455775, ENST00000518685, ENST00000557224, ENST00000651307, ENST00000652559, ENST00000684155, ENST00000905168, ENST00000905169

RefSeq mRNA: 2 — MANE Select: NM_014009 NM_001114377, NM_014009

CCDS: CCDS14323, CCDS48109

Canonical transcript exons

ENST00000376207 — 12 exons

Exon	Start	End
ENSE00000670078	49257427	49257565
ENSE00000670083	49255715	49255802
ENSE00000670085	49255429	49255509
ENSE00000670087	49253917	49254067
ENSE00000670089	49253126	49253202
ENSE00000867139	49256925	49257012
ENSE00000867140	49256751	49256855
ENSE00000867141	49251664	49251765
ENSE00000978820	49257664	49257768
ENSE00001316456	49258296	49258527
ENSE00001865473	49250438	49251483
ENSE00003849914	49264661	49264710

Expression profiles

Bgee: expression breadth ubiquitous, 155 present calls, max score 90.33.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 2.8539 / max 511.6983, expressed in 86 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
199270	2.7968	86
199269	0.0572	13

Top tissues by expression

274 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	90.33	silver quality
parotid gland	UBERON:0001831	80.11	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	79.84	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	78.89	gold quality
vena cava	UBERON:0004087	78.57	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	78.29	silver quality
superficial temporal artery	UBERON:0001614	78.20	gold quality
triceps brachii	UBERON:0001509	77.79	gold quality
gluteal muscle	UBERON:0002000	77.29	gold quality
tendon of biceps brachii	UBERON:0008188	76.57	silver quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	75.12	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	75.05	gold quality
inferior olivary complex	UBERON:0002127	74.85	gold quality
biceps brachii	UBERON:0001507	74.33	gold quality
cerebellar vermis	UBERON:0004720	74.08	gold quality
lymph node	UBERON:0000029	73.69	gold quality
body of tongue	UBERON:0011876	72.35	gold quality
caecum	UBERON:0001153	72.04	gold quality
vermiform appendix	UBERON:0001154	71.88	gold quality
pharyngeal mucosa	UBERON:0000355	70.96	gold quality
pericardium	UBERON:0002407	70.82	gold quality
pons	UBERON:0000988	70.42	silver quality
medulla oblongata	UBERON:0001896	69.71	gold quality
blood	UBERON:0000178	69.48	gold quality
saphenous vein	UBERON:0007318	69.40	gold quality
tongue	UBERON:0001723	69.20	gold quality
nipple	UBERON:0002030	69.12	gold quality
inferior vagus X ganglion	UBERON:0005363	68.36	gold quality
ventral tegmental area	UBERON:0002691	68.31	gold quality
subthalamic nucleus	UBERON:0001906	68.10	gold quality

Single-cell (SCXA)

Detected in 8 experiment(s), a significant marker in 8.

Experiment	Marker?	Max mean expression
E-CURD-120	yes	1201.62
E-CURD-85	yes	890.78
E-CURD-95	yes	585.02
E-CURD-77	yes	400.52
E-CURD-89	yes	365.84
E-MTAB-8911	yes	315.34
E-CURD-122	yes	47.57
E-ANND-3	yes	5.47

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

63 targets.

Target	Regulation
ADAM2
APOA2	Repression
APOC3	Repression
BIRC3	Repression
BRCA1	Repression
CASP3	Repression
CASP9	Repression
CAT
CCR4	Activation
CD101
CD74
CDKN1A	Unknown
CEL
CREM	Activation
CTLA4	Unknown
DAB2	Activation
ERBB2	Unknown
FASLG	Unknown
FCGR3A	Activation
GATA3	Activation
GHRHR
H1-5
HLA-E	Repression
HMOX1	Activation
IFI16	Repression
IFNG	Activation
IGSF3
IKZF2
IL10	Unknown
IL17A	Activation

Upstream regulators (CollecTRI, top): AHR, ATF2, BCL11B, CBX1, CBX3, CREB1, DNMT1, DNMT3A, DNMT3B, EGR1, ETS1, ETS2, EZH2, FOXO1, FOXO3, GATA3, H4C2, HAND1, HES1, HIF1A, ID3, IKZF2, IRF1, IRF6, IRF7, JUN, JUNB, KAT2B, KLF10, KLF14, KLF2, LGALS9, MBD2, MECP2, MED12, MSC, NFATC1, NFATC2, NFKB1, NFKB

miRNA regulators (miRDB)

63 targeting FOXP3, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-6748-5P	100.00	65.81	1057
HSA-MIR-10401-5P	99.99	65.79	948
HSA-MIR-6759-5P	99.99	66.54	785
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-6793-5P	99.97	65.95	758
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-4658	99.77	64.94	514
HSA-MIR-6790-5P	99.77	65.24	505
HSA-MIR-12130	99.75	65.47	452
HSA-MIR-377-5P	99.70	65.28	712
HSA-MIR-6086	99.70	65.38	699
HSA-MIR-6512-3P	99.65	66.07	1468
HSA-MIR-6720-5P	99.65	66.22	1459
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-4649-3P	99.56	66.90	1783
HSA-MIR-17-3P	99.55	66.77	1311
HSA-MIR-1252-3P	99.55	67.71	2862
HSA-MIR-186-3P	99.51	66.24	1685
HSA-MIR-1275	99.47	67.90	2749
HSA-MIR-3191-3P	99.45	63.94	356
HSA-MIR-3911	99.38	66.95	1087
HSA-MIR-4318	99.38	66.94	1505
HSA-MIR-7974	99.24	65.48	1137
HSA-MIR-7854-3P	99.08	66.26	1117
HSA-MIR-4711-3P	98.97	66.87	1020

Literature-anchored findings (GeneRIF, showing 40)

• The ability of scurfin to bind DNA, and presumably repress transcription, plays a paramount role in determining the amplitude of the response of CD4 T cells to activation. (PMID:11483607)
• novel mutations of FOXP3 in two Japanese patients with immune dysregulation, polyendocrinopathy, enteropathy, X linked syndrome (IPEX) (PMID:11768393)
• Random X inactivation was found in the T lymphocytes of a carrier of a FOXP3 mutation (Ala384Thr)with an affected son. (PMID:12296863)
• FoxP3 is expressed predominantly in Tr cells and that it may serve as a master regulator of this cell population. (PMID:14597769)
• characterization of the underlying FOXP3 mutation in two families with features consistent with IPEX; analysis elucidated the molecular basis of IPEX in one family and provided evidence for an autosomal locus, suggesting genetic heterogeneity (PMID:14671208)
• impact of disease-causing missense mutations on the three-dimensional structure, stability, and surface electrostatic charge distribution of the forkhead domains is examined (PMID:14997560)
• TGF-beta-mediated induction of Foxp3 in CD4+CD25- T cells results in the development of T cells with regulatory functions. (PMID:15100250)
• Foxp3 regulatory gene expression may have a role in graft-versus-host disease (PMID:15172973)
• Allelic variation in or near the coding regions of the FOXP3 gene does not have a major role in the inherited susceptibility to the common form of type 1 diabetes. (PMID:15220219)
• Human cord blood CD25+CD4+ T cells preferentially transcribed Foxp3, which governs the regulatory function of this subset i (PMID:15246158)
• FoxP3 protein, but not mRNA, was specifically expressed by cord blood CD4-CD25 derived T-cells (PMID:15374887)
• FOXP3 is a crucial regulatory gene for the development and function of CD25(+)CD4(+) regulatory T cells (PMID:15466453)
• FOXP3 expression in humans, unlike mice, may not be specific for cells with a regulatory phenotype and may be only a consequence of activation status. (PMID:15620457)
• The relative expression of FOXP3 protein mrNA was estimated by the ratio of the Foxp3 value to the HPRT value. (PMID:15674359)
• Multiple sclerosis patients have abnormalities in FOXP3 message and protein expression levels in peripheral CD4+ CD25+ T cells that are quantitatively related to a reduction in functional suppression induced during suboptimal T-cell receptor ligation. (PMID:15952173)
• Gene expression of regulatory T cells transcription factor FOXP3 was reduced in chronic graft-versus-host disease patients (PMID:15972448)
• FOXP3 mRNA expression levels in allostimulated CD25 cells and CD25 cells and in peripheral blood mononuclear cells. (PMID:16003241)
• Initiation and suppressive function of FOXP3 and regulatory T cells in the context of allergic asthma. Review. (PMID:16091206)
• Ectopic expression of FOXP3 in human CD4+ T cells does not act as a molecular switch to induce regulatory T cells in vitro (PMID:16211090)
• The determination of FOXP3+/CD8+ ratio can be a helpful tool to discriminate graft versus hosst disease from infectious inflammation after allogeneic stem cell transplantation. (PMID:16278306)
• High expression levels of FoxP3 is associated with ovarian cancer (PMID:16322292)
• Costimulation of effector T cells with anti-CD3 and TLR5 ligand flagellin resulted in enhanced proliferation and production of IL-2, and potently increased their suppressive capacity and enhanced expression of FOXP3. (PMID:16339542)
• Increased expression of interleukin-10 and transforming growth factor-beta1 mRNA was also detected in patients with TB but did not correlate with regulatory T-cell markers. (PMID:16339919)
• analysis of transcriptional regulation by FOXP3 [review] (PMID:16368541)
• Increase of functional FOXP3 in T cells in cancer patients is a response to the process of malignant transformation. (PMID:16410445)
• Fox3p expression is inherent feature of the function of type 1 regulatory T cells specific for desmoglein-3, the autoantigen of pemphigus vulgaris. (PMID:16493082)
• reveals the structure of the human FOXP3 promoter and provides new insights in mechanisms of addressing T regulatory cell-inducing signals useful for promoting immune tolerance (PMID:16517728)
• Increased IL-10 and Foxp3 induction in cord blood mononuclear cells of non-atopic compared to atopic mothers, may indicate an increased capacity to respond to microbial stimuli. (PMID:16551363)
• The data support the conclusion that the neoplastic cells in CTCL do not express the T(reg) marker FOXP3. (PMID:16557241)
• The finding of reduced endometrial Foxp3 implicates impaired differentiation of uterine T cells into the Treg phenotype as a key determinant of fertility in women. (PMID:16574699)
• These data are the first to demonstrate differences in function and FOXP3 expression of CD4(+)CD25(+) T cells from patients with RR- and SP-MS. (PMID:16583400)
• Expression of Foxp3 in non-small cell lung cancer patients is significantly higher in tumor tissues than in normal tissues, especially in tumors smaller than 30 mm (PMID:16596204)
• Most patients lacked FOXP3-expressing cells, further solidifying the association between FOXP3 deficiency and immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome. (PMID:16617117)
• IL-2 treatment resulted in anincrease in FOXP3 expression in CD3+ T cells. CD56+CD3- natural killer (NK) cells in cancer. (PMID:16645171)
• HTLV-1-associated myelopathy/tropical spastic paraparesis was associated with lower expression of Foxp3 in leukocytes; suggests impaired Foxp3 expression may contribute to development of inflammatory disease in HTLV-1 infection (PMID:16652285)
• Regulatory T cells (T(regs)) containing FOXP3+ were increased in HIV patients after HAART therapy. (PMID:16728694)
• These findings indicate that forkhead box protein P3 mutations in immune dysregulation, polyendocrinopathy, enteropathy, X-linked patients result in heterogeneous biological abnormalities, leading to a dysfunction in regulatory and effector T cells. (PMID:16741580)
• Measurement of mRNA expression levels of specific marker FOXP3 in synovial fluid of rheumatic joints confirms the presence of regulatory CD25(bright)CD4+ T cells. (PMID:16764698)
• The orderly regulation of trafficking receptors in FOXP3-positive T cells according to stages of differentiation and activation is potentially important for their tissue-specific migration and regulation of immune responses in humans. (PMID:16818738)
• Prognostic significance of FOXP3-positive regulatory T cells in overall survival in follicular lymphoma. (PMID:16825494)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Foxp3	ENSMUSG00000039521
rattus_norvegicus	Foxp3	ENSRNOG00000011702

Paralogs (41): FOXC1 (ENSG00000054598), FOXJ2 (ENSG00000065970), FOXF1 (ENSG00000103241), FOXN1 (ENSG00000109101), FOXM1 (ENSG00000111206), FOXP1 (ENSG00000114861), FOXO3 (ENSG00000118689), FOXA2 (ENSG00000125798), FOXA1 (ENSG00000129514), FOXJ1 (ENSG00000129654), FOXK2 (ENSG00000141568), FOXO1 (ENSG00000150907), FOXH1 (ENSG00000160973), FOXQ1 (ENSG00000164379), FOXK1 (ENSG00000164916), FOXD4 (ENSG00000170122), FOXA3 (ENSG00000170608), FOXB1 (ENSG00000171956), FOXR1 (ENSG00000176302), FOXL1 (ENSG00000176678), FOXC2 (ENSG00000176692), FOXE1 (ENSG00000178919), FOXS1 (ENSG00000179772), FOXL2 (ENSG00000183770), FOXO4 (ENSG00000184481), FOXD4L1 (ENSG00000184492), FOXD4L4 (ENSG00000184659), FOXD2 (ENSG00000186564), FOXI2 (ENSG00000186766), FOXE3 (ENSG00000186790), FOXD3 (ENSG00000187140), FOXD4L3 (ENSG00000187559), FOXR2 (ENSG00000189299), FOXJ3 (ENSG00000198815), FOXO6 (ENSG00000204060), FOXB2 (ENSG00000204612), FOXD4L5 (ENSG00000204779), FOXI3 (ENSG00000214336), FOXL3 (ENSG00000248767), FOXD1 (ENSG00000251493)

Protein

Protein identifiers

Forkhead box protein P3 — Q9BZS1 (reviewed: Q9BZS1)

Alternative names: Scurfin

All UniProt accessions (5): A0A494BZV0, A0A494C0B0, Q9BZS1, A0A804HK12, B7ZLG1

UniProt curated annotations — full annotation on UniProt →

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. Mediates transcriptional repression of IL2 via its association with histone acetylase KAT5 and histone deacetylase HDAC7. Can activate the expression of TNFRSF18, IL2RA and CTLA4 and repress the expression of IL2 and IFNG via its association with transcription factor RUNX1. Inhibits the differentiation of IL17 producing helper T-cells (Th17) by antagonizing RORC function, leading to down-regulation of IL17 expression, favoring Treg development. Inhibits the transcriptional activator activity of RORA. Can repress the expression of IL2 and IFNG via its association with transcription factor IKZF4.

Subunit / interactions. Homodimer. Dimerization is essential for its transcriptional regulator activity. 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.

Subcellular location. Nucleus. Cytoplasm.

Post-translational modifications. 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 and USP44; leading to increase in protein stability. 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. Acetylation on lysine residues stabilizes FOXP3 and promotes differentiation of T-cells into induced regulatory T-cells (iTregs) associated with suppressive functions. Acetylation is mediated by a coordinated action of KAT5 and EP300/p300 acetyltransferases: EP300/p300 is required to enhance KAT5 autoacetylation, promoting acetylation of FOXP3 by KAT5. Deacetylated by SIRT1. 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.

Disease relevance. 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. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The fork-head DNA-binding domain is essential for dimerization and interaction with NFATC2. The leucine zipper (ZIP) is required for dimerization and transcriptional repression.

Induction. Down-regulated in regulatory T-cells (Treg) during inflammation. Up-regulated by FOXO3.

Isoforms (4)

UniProt ID	Names	Canonical?
Q9BZS1-1	1	yes
Q9BZS1-2	2
Q9BZS1-3	3
Q9BZS1-4	4

RefSeq proteins (2): NP_001107849, NP_054728* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001766	Fork_head_dom	Domain
IPR013087	Znf_C2H2_type	Domain
IPR030456	TF_fork_head_CS_2	Conserved_site
IPR032354	FOXP-CC	Domain
IPR036388	WH-like_DNA-bd_sf	Homologous_superfamily
IPR036390	WH_DNA-bd_sf	Homologous_superfamily
IPR047413	FH_FOXP3	Domain
IPR050998	FOXP	Family

Pfam: PF00250, PF16159

UniProt features (67 total): mutagenesis site 15, sequence variant 11, region of interest 5, modified residue 5, cross-link 5, short sequence motif 4, helix 4, chain 3, splice variant 3, strand 3, site 2, compositionally biased region 1, propeptide 1, domain 1, zinc finger region 1, sequence conflict 1, DNA-binding region 1, turn 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
3QRF	X-RAY DIFFRACTION	2.8
4WK8	X-RAY DIFFRACTION	3.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BZS1-F1	58.29	0.17

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (2): 51–52 (cleavage); 417–418 (cleavage; by pcsk1 or pcsk2)

Post-translational modifications (10): 19, 31, 263, 268, 418, 250, 252, 263, 268, 393

Mutagenesis-validated functional residues (15):

Position	Phenotype
69	decrease in nuclear export; when associated with a-71, a-74 and a-76.
71	decrease in nuclear export; when associated with a-69, a-74 and a-76.
74	decrease in nuclear export; when associated with a-69, a-71 and a-76.
76	decrease in nuclear export; when associated with a-69, a-71 and a-74.
95–96	loss of interaction with rora.
242	decrease in nuclear export; when associated with a-246 and a-248.
246	decrease in nuclear export; when associated with a-242 and a-248.
248	decrease in nuclear export; when associated with a-242 and a-246.
348	no loss of dna-binding. disrupts dimerization but does not affect dna-binding; when associated with t-370. disrupts dime
370	disrupts dimerization but does not affect dna-binding; when associated with q-348. disrupts dimerization, does not affec
372	disrupts dimerization, does not affect dna-binding, causes dysregulated expression of a subset of foxp3 target genes and
415–416	loss of nuclear localization.
418	decrease in phosphorylation, significant decrease in transcriptional repressor activity and reduced interaction with pp1
418	slight increase in transcriptional repressor activity.
422	significant decrease in phosphorylation and transcriptional repressor activity; when associated with a-418.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-8877330	RUNX1 and FOXP3 control the development of regulatory T lymphocytes (Tregs)
R-HSA-8939256	RUNX1 regulates transcription of genes involved in WNT signaling

MSigDB gene sets: 531 (showing top): GOBP_ENDOTHELIAL_CELL_DEVELOPMENT, GOBP_REGULATION_OF_CELL_ACTIVATION, RRAGTTGT_UNKNOWN, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_REGULATION_OF_DNA_RECOMBINATION, GOBP_REGULATION_OF_LEUKOCYTE_PROLIFERATION, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_NEGATIVE_REGULATION_OF_CELL_DEVELOPMENT, GOBP_POSITIVE_REGULATION_OF_ADAPTIVE_IMMUNE_RESPONSE, GOBP_NEGATIVE_REGULATION_OF_ADAPTIVE_IMMUNE_RESPONSE, GOBP_B_CELL_HOMEOSTASIS, GOBP_REGULATION_OF_ALPHA_BETA_T_CELL_ACTIVATION, GOBP_POSITIVE_REGULATION_OF_HEMOPOIESIS, GOBP_MYELOID_CELL_HOMEOSTASIS, GOBP_TOLERANCE_INDUCTION

GO Biological Process (75): B cell homeostasis (GO:0001782), negative regulation of cytokine production (GO:0001818), myeloid cell homeostasis (GO:0002262), CD4-positive, CD25-positive, alpha-beta regulatory T cell lineage commitment (GO:0002362), T cell mediated immunity (GO:0002456), tolerance induction to self antigen (GO:0002513), regulation of T cell anergy (GO:0002667), positive regulation of T cell anergy (GO:0002669), negative regulation of chronic inflammatory response (GO:0002677), negative regulation of T cell cytokine production (GO:0002725), positive regulation of peripheral T cell tolerance induction (GO:0002851), T cell anergy (GO:0002870), chromatin remodeling (GO:0006338), regulation of DNA-templated transcription (GO:0006355), regulation of transcription by RNA polymerase II (GO:0006357), transcription by RNA polymerase II (GO:0006366), inflammatory response (GO:0006954), negative regulation of cell population proliferation (GO:0008285), response to virus (GO:0009615), establishment of endothelial blood-brain barrier (GO:0014045), obsolete negative regulation of NF-kappaB transcription factor activity (GO:0032088), response to lipopolysaccharide (GO:0032496), negative regulation of type II interferon production (GO:0032689), negative regulation of interleukin-10 production (GO:0032693), negative regulation of interleukin-17 production (GO:0032700), negative regulation of interleukin-2 production (GO:0032703), negative regulation of interleukin-4 production (GO:0032713), negative regulation of interleukin-5 production (GO:0032714), negative regulation of interleukin-6 production (GO:0032715), negative regulation of tumor necrosis factor production (GO:0032720), positive regulation of interleukin-4 production (GO:0032753), obsolete negative regulation of CREB transcription factor activity (GO:0032792), positive regulation of CD4-positive, CD25-positive, alpha-beta regulatory T cell differentiation (GO:0032831), transforming growth factor beta1 production (GO:0032905), positive regulation of transforming growth factor beta1 production (GO:0032914), immature T cell proliferation in thymus (GO:0033080), positive regulation of immature T cell proliferation in thymus (GO:0033092), CD4-positive, alpha-beta T cell proliferation (GO:0035739), T cell activation (GO:0042110), negative regulation of T cell proliferation (GO:0042130)

GO Molecular Function (18): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA-binding transcription repressor activity, RNA polymerase II-specific (GO:0001227), DNA-binding transcription activator activity, RNA polymerase II-specific (GO:0001228), DNA binding (GO:0003677), DNA-binding transcription factor activity (GO:0003700), transcription corepressor activity (GO:0003714), zinc ion binding (GO:0008270), histone acetyltransferase binding (GO:0035035), protein homodimerization activity (GO:0042803), histone deacetylase binding (GO:0042826), sequence-specific DNA binding (GO:0043565), NF-kappaB binding (GO:0051059), NFAT protein binding (GO:0051525), sequence-specific double-stranded DNA binding (GO:1990837), protein binding (GO:0005515), identical protein binding (GO:0042802), metal ion binding (GO:0046872)

GO Cellular Component (6): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), protein-containing complex (GO:0032991)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Transcriptional regulation by RUNX1	2

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA polymerase II transcription regulatory region sequence-specific DNA binding	4
cellular anatomical structure	4
T cell anergy	2
positive regulation of T cell tolerance induction	2
DNA-templated transcription	2
regulation of DNA-templated transcription	2
DNA-binding transcription factor activity, RNA polymerase II-specific	2
enzyme binding	2
RNA polymerase II-specific DNA-binding transcription factor binding	2
lymphocyte homeostasis	1
cytokine production	1
regulation of cytokine production	1
negative regulation of gene expression	1
negative regulation of multicellular organismal process	1
immune system process	1
homeostasis of number of cells	1
CD4-positive, CD25-positive, alpha-beta regulatory T cell differentiation	1
CD4-positive, alpha-beta T cell lineage commitment	1
lymphocyte mediated immunity	1
adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains	1
tolerance induction	1
regulation of T cell tolerance induction	1
regulation of lymphocyte anergy	1
regulation of T cell anergy	1
positive regulation of lymphocyte anergy	1
chronic inflammatory response	1
regulation of chronic inflammatory response	1
negative regulation of inflammatory response	1
T cell cytokine production	1
negative regulation of T cell mediated immunity	1
negative regulation of cytokine production involved in immune response	1
regulation of T cell cytokine production	1
peripheral T cell tolerance induction	1
positive regulation of peripheral tolerance induction	1
positive regulation of T cell mediated immunity	1
regulation of peripheral T cell tolerance induction	1
lymphocyte anergy	1
T cell tolerance induction	1
chromatin organization	1
regulation of gene expression	1

Protein interactions and networks

STRING

4058 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FOXP3	RUNX1	Q01196	989
FOXP3	HIF1A	Q16665	988
FOXP3	KAT5	Q92993	986
FOXP3	CD4	P01730	979
FOXP3	STAT3	P40763	965
FOXP3	IL10	P22301	952
FOXP3	IFNG	P01579	950
FOXP3	IL17A	Q16552	949
FOXP3	IL2	P01585	947
FOXP3	CTLA4	P16410	947
FOXP3	CD8A	P01732	946
FOXP3	HDAC9	Q9UKV0	942
FOXP3	HDAC7	Q8WUI4	936
FOXP3	TBX21	Q9UL17	931
FOXP3	CD28	P10747	930

IntAct

120 interactions, top by confidence:

A	B	Type	Score
RBPMS	FOXP3	psi-mi:“MI:0915”(physical association)	0.740
FOXP3	RBPMS	psi-mi:“MI:0915”(physical association)	0.740
FOXP3	PRR20E	psi-mi:“MI:0915”(physical association)	0.740
PRR20E	FOXP3	psi-mi:“MI:0915”(physical association)	0.740
STUB1	UBA1	psi-mi:“MI:0220”(ubiquitination reaction)	0.730
FOXP3	STUB1	psi-mi:“MI:0915”(physical association)	0.640
FOXP3	STUB1	psi-mi:“MI:0914”(association)	0.640
FOXP3	STUB1	psi-mi:“MI:0403”(colocalization)	0.640
PRR20D	FOXP3	psi-mi:“MI:0915”(physical association)	0.600
FOXP3	EZH2	psi-mi:“MI:2364”(proximity)	0.600
EZH2	FOXP3	psi-mi:“MI:2364”(proximity)	0.600
EZH2	FOXP3	psi-mi:“MI:0915”(physical association)	0.600
FOXP3	EZH2	psi-mi:“MI:0915”(physical association)	0.600
	NFATC2	psi-mi:“MI:0914”(association)	0.590
FOXP3	hspa1a_hspa1b_human-1	psi-mi:“MI:0915”(physical association)	0.580

BioGRID (128): FOXP3 (Two-hybrid), PRR20A (Two-hybrid), SIVA1 (Two-hybrid), SIVA1 (Affinity Capture-Western), SIVA1 (Phenotypic Enhancement), FOXP3 (Affinity Capture-Western), FOXP3 (Affinity Capture-Western), FOXP3 (Biochemical Activity), SIRT1 (Affinity Capture-Western), FOXP3 (Affinity Capture-Western), FOXP3 (Affinity Capture-MS), FOXP1 (Affinity Capture-MS), HOXD13 (Affinity Capture-MS), AKAP8 (Affinity Capture-MS), FOXP4 (Affinity Capture-MS)

ESM2 similar proteins: A0A1W2PPF3, A0A3B3IT52, E9Q3T6, O02747, O13161, O42173, O57374, O73622, O95238, P01103, P01104, P09632, P0C7M4, P10242, P14837, P17278, P30561, P31538, P41738, P46200, Q1KKS8, Q28G02, Q32NH9, Q4JM65, Q5REX1, Q5WM45, Q66IG8, Q68EH7, Q6U8D7, Q6ZTZ1, Q7T1K4, Q8BIL2, Q8BKE5, Q8CFH6, Q8IWB6, Q8JIT7, Q8NHV9, Q8R4S2, Q8R4S4, Q8R4S5

Diamond homologs: A4IFD2, F1QDF8, F1R8Z9, O00409, O13606, O15409, O42097, P0CF24, P23512, P32314, P32315, P33205, P33206, P35582, P35583, P55316, P55317, P56260, P58462, P58463, P84961, Q00939, Q01167, Q07342, Q16676, Q17381, Q1A1A1, Q1A1A2, Q1A1A3, Q1A1A4, Q1A1A5, Q1A1A6, Q28D67, Q28EM1, Q28G71, Q28HT3, Q2LE08, Q32NH9, Q33BP8, Q3BJS3

SIGNOR signaling

17 interactions.

A	Effect	B	Mechanism
LCK	down-regulates	FOXP3	phosphorylation
STAT5A	up-regulates	FOXP3
STAT3	down-regulates	FOXP3
SMAD3	up-regulates	FOXP3
FOXP3	“up-regulates quantity by expression”	IL10	“transcriptional regulation”
FOXP3	up-regulates	T-reg_differentiation
2-hydroxyglutarate	“down-regulates activity”	FOXP3	“chemical inhibition”
DNMT1	“down-regulates quantity by repression”	FOXP3	“transcriptional regulation”
GSK3B	“down-regulates quantity by destabilization”	FOXP3	phosphorylation
SCF-betaTRCP	“down-regulates quantity by destabilization”	FOXP3	polyubiquitination
FOXP3	“up-regulates quantity by expression”	CCL5	“transcriptional regulation”
FOXP3	“up-regulates quantity by expression”	CD274	“transcriptional regulation”
“9-cis-retinoic acid”	“up-regulates activity”	FOXP3	“transcriptional regulation”

Disease & clinical

Cancer significance

Clinical variants and AI predictions

ClinVar

468 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	30
Likely pathogenic	21
Uncertain significance	171
Likely benign	129
Benign	39

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1098427	NM_014009.4(FOXP3):c.224C>T (p.Pro75Leu)	Pathogenic
11407	NM_014009.4(FOXP3):c.1189C>T (p.Arg397Trp)	Pathogenic
11408	NM_014009.4(FOXP3):c.1290_*12delinsTG (p.Pro431fs)	Pathogenic
11409	NM_014009.4(FOXP3):c.1112T>G (p.Phe371Cys)	Pathogenic
11411	NM_014009.4(FOXP3):c.1293_1294del (p.Ter432ThrextTer?)	Pathogenic
11413	NM_014009.4(FOXP3):c.751_753del (p.Glu251del)	Pathogenic
11414	NM_014009.4(FOXP3):c.227del (p.Leu76fs)	Pathogenic
11415	NM_014009.4(FOXP3):c.1117_1118delinsGC (p.Phe373Ala)	Pathogenic
11417	FOXP3, 543C-T	Pathogenic
11418	NM_014009.4(FOXP3):c.3G>A (p.Met1Ile)	Pathogenic
11419	NM_014009.4(FOXP3):c.1099T>C (p.Phe367Leu)	Pathogenic
1436074	NM_014009.4(FOXP3):c.2T>A (p.Met1Lys)	Pathogenic
1460125	NM_014009.4(FOXP3):c.736-2A>T	Pathogenic
1505816	NM_014009.4(FOXP3):c.1087A>G (p.Ile363Val)	Pathogenic
1685829	NM_014009.4(FOXP3):c.1234del (p.Glu412fs)	Pathogenic
211046	NM_014009.4(FOXP3):c.727del (p.Glu243fs)	Pathogenic
2675750	NM_014009.4(FOXP3):c.1110G>A (p.Met370Ile)	Pathogenic
280381	NM_014009.4(FOXP3):c.210+1G>C	Pathogenic
3233258	NM_014009.4(FOXP3):c.116_122dup (p.Gly43fs)	Pathogenic
372368	NM_014009.4(FOXP3):c.1009C>T (p.Arg337Ter)	Pathogenic
3724235	NM_014009.4(FOXP3):c.906del (p.Asp303fs)	Pathogenic
4710758	NM_014009.4(FOXP3):c.816+7G>C	Pathogenic
4710759	NM_014009.4(FOXP3):c.816+5G>A	Pathogenic
4732563	NM_014009.4(FOXP3):c.711_712del (p.Glu237fs)	Pathogenic
4763913	NM_014009.4(FOXP3):c.766A>G (p.Met256Val)	Pathogenic
575607	NM_014009.4(FOXP3):c.210+1G>T	Pathogenic
578790	NM_014009.4(FOXP3):c.694T>G (p.Cys232Gly)	Pathogenic
810691	NM_014009.4(FOXP3):c.691C>A (p.Gln231Lys)	Pathogenic
834992	NM_014009.4(FOXP3):c.210+1G>A	Pathogenic
952674	NM_014009.4(FOXP3):c.142C>T (p.Arg48Ter)	Pathogenic

SpliceAI

1488 predictions. Top by Δscore:

Variant	Effect	Δscore
X:49251479:GCGTT:G	acceptor_gain	1.0000
X:49251480:CGTT:C	acceptor_gain	1.0000
X:49251480:CGTTC:C	acceptor_gain	1.0000
X:49251481:GTT:G	acceptor_gain	1.0000
X:49251482:TT:T	acceptor_gain	1.0000
X:49251482:TTC:T	acceptor_loss	1.0000
X:49251483:TCTG:T	acceptor_loss	1.0000
X:49251484:C:CA	acceptor_loss	1.0000
X:49251484:C:CC	acceptor_gain	1.0000
X:49251495:C:CT	acceptor_gain	1.0000
X:49251495:C:T	acceptor_gain	1.0000
X:49251496:G:T	acceptor_gain	1.0000
X:49251762:TGGC:T	acceptor_gain	1.0000
X:49251766:C:CC	acceptor_gain	1.0000
X:49253124:AC:A	donor_gain	1.0000
X:49253125:CC:C	donor_gain	1.0000
X:49253125:CCCAG:C	donor_gain	1.0000
X:49253201:CT:C	acceptor_gain	1.0000
X:49253202:TCTGT:T	acceptor_loss	1.0000
X:49253203:C:CC	acceptor_gain	1.0000
X:49254068:C:CC	acceptor_gain	1.0000
X:49254068:CTG:C	acceptor_loss	1.0000
X:49255428:CCA:C	donor_gain	1.0000
X:49255506:CCAG:C	acceptor_gain	1.0000
X:49255507:CAG:C	acceptor_gain	1.0000
X:49255507:CAGC:C	acceptor_gain	1.0000
X:49255508:AG:A	acceptor_gain	1.0000
X:49255509:GC:G	acceptor_loss	1.0000
X:49255510:C:CC	acceptor_gain	1.0000
X:49255512:G:C	acceptor_gain	1.0000

AlphaMissense

2797 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:49251412:C:A	W406C	1.000
X:49251412:C:G	W406C	1.000
X:49251413:C:G	W406S	1.000
X:49251414:A:G	W406R	1.000
X:49251414:A:T	W406R	1.000
X:49251445:A:C	F395L	1.000
X:49251445:A:T	F395L	1.000
X:49251446:A:C	F395C	1.000
X:49251446:A:G	F395S	1.000
X:49251447:A:G	F395L	1.000
X:49251456:G:C	H392D	1.000
X:49251458:A:G	L391P	1.000
X:49251460:A:C	S390R	1.000
X:49251460:A:T	S390R	1.000
X:49251462:T:G	S390R	1.000
X:49251464:A:G	L389P	1.000
X:49251464:A:T	L389Q	1.000
X:49251466:G:C	N388K	1.000
X:49251466:G:T	N388K	1.000
X:49251468:T:C	N388D	1.000
X:49251469:G:C	H387Q	1.000
X:49251469:G:T	H387Q	1.000
X:49251470:T:G	H387P	1.000
X:49251471:G:C	H387D	1.000
X:49251474:G:T	R386S	1.000
X:49251476:A:T	I385N	1.000
X:49251664:C:A	K382N	1.000
X:49251664:C:G	K382N	1.000
X:49251667:C:A	W381C	1.000
X:49251667:C:G	W381C	1.000

dbSNP variants (sampled 300 via entrez): RS1000077362 (X:49252504 T>C), RS1000901082 (X:49262140 G>A), RS1001170701 (X:49265363 G>A), RS1001269582 (X:49262762 C>A), RS1001683545 (X:49255404 C>T), RS1001747352 (X:49254946 T>G), RS1002017383 (X:49257484 G>A), RS1003688412 (X:49259574 C>T), RS1003763723 (X:49259153 A>G), RS1004031988 (X:49261620 G>A), RS1004105634 (X:49261262 G>A), RS1004347761 (X:49252327 G>A), RS1005611207 (X:49254776 C>T), RS1005980708 (X:49256354 A>G), RS1006058240 (X:49254366 A>G)

Disease associations

OMIM: gene MIM:300292 | disease phenotypes: MIM:304790, MIM:236500, MIM:222100, MIM:160150

GenCC curated gene-disease

Disease	Classification	Inheritance
immune dysregulation-polyendocrinopathy-enteropathy-X-linked syndrome	Definitive	X-linked

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
immune dysregulation-polyendocrinopathy-enteropathy-X-linked syndrome	Definitive	XL

Mondo (7): immune dysregulation-polyendocrinopathy-enteropathy-X-linked syndrome (MONDO:0010580), multinucleated neurons-anhydramnios-renal dysplasia-cerebellar hypoplasia-hydranencephaly syndrome (MONDO:0009359), hydrops fetalis (MONDO:0015193), type 1 diabetes mellitus (MONDO:0005147), centronuclear myopathy (MONDO:0018947), monogenic diabetes (MONDO:0015967), neurodevelopmental disorder (MONDO:0700092)

Orphanet (6): Immune dysregulation-polyendocrinopathy-enteropathy-X-linked syndrome (Orphanet:37042), Multinucleated neurons-anhydramnios-renal dysplasia-cerebellar hypoplasia-hydranencephaly syndrome (Orphanet:500135), Hydrops fetalis (Orphanet:1041), Centronuclear myopathy (Orphanet:595), Rare genetic diabetes mellitus (Orphanet:183625), NON RARE IN EUROPE: Diabetes mellitus type 1 (Orphanet:243377)

HPO phenotypes

79 total (30 of 79 shown, HPO-id order):

HPO	Term
HP:0000099	Glomerulonephritis
HP:0000100	Nephrotic syndrome
HP:0000818	Abnormality of the endocrine system
HP:0000821	Hypothyroidism
HP:0000836	Hyperthyroidism
HP:0000964	Eczematoid dermatitis
HP:0001019	Erythroderma
HP:0001025	Urticaria
HP:0001250	Seizure
HP:0001263	Global developmental delay
HP:0001287	Meningitis
HP:0001369	Arthritis
HP:0001419	X-linked recessive inheritance
HP:0001508	Failure to thrive
HP:0001531	Failure to thrive in infancy
HP:0001581	Recurrent skin infections
HP:0001596	Alopecia
HP:0001744	Splenomegaly
HP:0001873	Thrombocytopenia
HP:0001875	Decreased total neutrophil count
HP:0001880	Increased total eosinophil count
HP:0001890	Autoimmune hemolytic anemia
HP:0001891	Iron deficiency anemia
HP:0001903	Anemia
HP:0001904	Autoimmune neutropenia
HP:0001970	Tubulointerstitial nephritis
HP:0001973	Autoimmune thrombocytopenia
HP:0002013	Vomiting
HP:0002024	Malabsorption
HP:0002028	Chronic diarrhea

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST004785_40	Vitiligo	1.000000e-09

MeSH disease descriptors (5)

Descriptor	Name	Tree numbers
D003922	Diabetes Mellitus, Type 1	C18.452.394.750.124; C19.246.267; C20.111.327
D015160	Hydrops Fetalis	C12.050.703.277.060.480; C15.378.295.480; C15.378.420.826.100.350; C16.300.060.480; C16.320.365.826.100.350; C20.306.480; C23.888.277.395
D065886	Neurodevelopmental Disorders	F03.625
C565507	Hydranencephaly with Renal Aplasia-Dysplasia (supp.)
C580192	Immune Dysregulation, Polyendocrinopathy, Enteropathy, X-Linked Syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6195516 (PROTEIN-PROTEIN INTERACTION)

Clinical evidence (CIViC)

Drug × variant × indication: 1 predictive associations from 1 curated evidence items.

Variant	Therapy	Indication	Effect	Level	CIViC
FOXP3 EXPRESSION	Epirubicin	Breast Cancer	Sensitivity/Response	CIViC B	EID928

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB clinical annotations

2 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs3761548	Toxicity	3	tacrolimus	Kidney Transplantation
rs3761548	Efficacy	3	methotrexate	Psoriasis

PharmGKB variants

5 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs3761548	FOXP3	3	2.50	2	tacrolimus;methotrexate
rs3761547	FOXP3		0.00	0
rs3761549	FOXP3		0.00	0
rs2232365	FOXP3		0.00	0
rs2280883	FOXP3		0.00	0

CTD chemical–gene interactions

50 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	increases methylation, decreases methylation, increases expression, affects methylation, increases abundance	3
Particulate Matter	increases abundance, increases expression, increases methylation, affects methylation	3
2-(1’H-indole-3’-carbonyl)thiazole-4-carboxylic acid methyl ester	affects expression, increases expression	2
Decitabine	affects cotreatment, increases expression, decreases expression, decreases reaction, increases methylation (+1 more)	2
Arsenic Trioxide	affects localization, increases expression	2
Fulvestrant	increases expression, increases methylation, increases reaction	2
Arsenic	decreases expression, increases expression, decreases reaction, affects cotreatment	2
Carbon Monoxide	affects methylation, increases abundance, increases methylation	2
Ozone	affects methylation, increases abundance, decreases methylation	2
Polycyclic Aromatic Hydrocarbons	decreases expression, increases abundance, increases methylation	2
Aflatoxin B1	increases methylation	2
deoxynivalenol	increases expression	1
trichostatin A	affects cotreatment, increases expression, decreases reaction	1
2,4,5,2’,4’,5’-hexachlorobiphenyl	increases activity	1
sodium arsenite	decreases expression, decreases reaction, increases methylation	1
ferrous chloride	decreases expression	1
1-hydroxypyrene	decreases expression, increases abundance	1
fumonisin B1	decreases expression	1
4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)imidazole	increases expression, decreases reaction	1
2-palmitoylglycerol	increases expression	1
obeticholic acid	increases expression	1
abrine	increases expression	1
Grape Seed Proanthocyanidins	affects cotreatment, decreases expression	1
dorsomorphin	decreases expression, decreases reaction	1
Fingolimod Hydrochloride	decreases expression	1
Acetylcysteine	decreases expression, decreases reaction	1
Amiodarone	increases expression	1
Benzo(a)pyrene	affects methylation	1
Calcitriol	increases expression	1
Catechin	affects cotreatment, decreases expression	1

ChEMBL screening assays

4 unique, capped per target: 4 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL6092590	Binding	PROTAC activity at VHL/Foxp3 (unknown origin) transfected in HEK293T cells assessed as induction of Foxp3 degradation by measuring reduction in protein level at 10 to 1000 nM incubated for 24 hrs by Western blot analysis	Discovery of a proteolysis targeting chimera (PROTAC) as a potent regulator of FOXP3. — Bioorg Med Chem Lett

Cellosaurus cell lines

14 cell lines: 9 cancer cell line, 3 embryonic stem cell, 2 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_A2D3	SEES3-1V human FOXP3, clone1	Embryonic stem cell	Male
CVCL_A2D4	SEES3-1V human FOXP3, clone2	Embryonic stem cell	Male
CVCL_A2D5	SEES3-1V human FOXP3, clone3	Embryonic stem cell	Male
CVCL_B8GJ	Abcam HCT 116 FOXP3 KO	Cancer cell line	Male
CVCL_B9IT	Abcam A-549 FOXP3 KO	Cancer cell line	Male
CVCL_C3GV	SW780 FOXP3	Cancer cell line	Female
CVCL_C3GW	SW780 FOXP3Delta3	Cancer cell line	Female
CVCL_C3GX	T24 FOXP3	Cancer cell line	Female
CVCL_C3GY	T24 FOXP3Delta3	Cancer cell line	Female
CVCL_C3GZ	293T FOXP3	Transformed cell line	Female

Clinical trials (associated diseases)

300 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00145353	PHASE4	UNKNOWN	Insulin NovoRapid Versus Actrapid in Treatment of Type 1 Diabetic Patients During Daily Adjustment of Insulin Dose
NCT00145379	PHASE4	COMPLETED	The Effect of Metformin in Overweight Patients With Dysregulated Type 1 Diabetes Mellitus
NCT00206401	PHASE4	COMPLETED	Lantus in the Treatment of Type 1 Diabetes Children
NCT00276393	PHASE4	COMPLETED	Treatment Trial Evaluating Long Acting Insulin in Type 1 Diabetes
NCT00291772	PHASE4	COMPLETED	Continuous Subcutaneous Infusion of Pramlintide and Insulin
NCT00315952	PHASE4	COMPLETED	Study to Estimate the Effects of Inhaled Versus Intravenous (IV) Infusion of Human Insulin in Subjects With Type 1 Diabetes
NCT00340613	PHASE4	COMPLETED	Lunch Time Insulin Injection by School Nurse for Poorly Controlled Diabetes
NCT00346996	PHASE4	COMPLETED	Insulin Analogues and Severe Hypoglycaemia
NCT00360984	PHASE4	COMPLETED	Prevention of Severe Hypoglycemia in Type 1 Diabetes
NCT00372086	PHASE4	COMPLETED	Rosiglitazone and Insulin in T1DM Adolescents
NCT00442767	PHASE4	COMPLETED	Post-meal Insulin Dosing With Adjuvant Pre-meal Pramlintide in Children With Type 1 Diabetes Mellitus
NCT00453934	PHASE4	TERMINATED	Patient Preference of h-Patch vs. Pen or Needle/Syringe as Insulin Administration Device
NCT00461331	PHASE4	COMPLETED	Comparison of Insulins Aspart and Lispro in Insulin Pumps
NCT00472875	PHASE4	UNKNOWN	Do Sulphonylureas Preserve Cortical Function During Hypoglycaemia?
NCT00497536	PHASE4	COMPLETED	Pharmacokinetics of IAsp Following CSII in Patients With T1DM
NCT00502138	PHASE4	COMPLETED	A Pilot Study of Continuous Subcutaneous Pramlintide Infusion Therapy in Patients With Type 1 Diabetes
NCT00505882	PHASE4	WITHDRAWN	Efficacy of Pramlintide on Prevention of Weight Gain Early Onset of Type 1 Diabetes
NCT00530023	PHASE4	COMPLETED	Feasibility Study for Training Pump Naïve Subjects To Use The Paradigm® System And Evaluate Effectiveness
NCT00542399	PHASE4	COMPLETED	Comparing the Metabolic Control of Once to Twice-daily Insulin Detemir Injections
NCT00564395	PHASE4	COMPLETED	Detemir: Role in Type 1 Diabetes
NCT00814476	PHASE4	COMPLETED	The Effects of Regular Home Use Vs Diabetic Team- Supported Use of the Medtronic CareLink Therapy Management System.
NCT00898534	PHASE4	COMPLETED	Effect of Immediate Hemoglobin A1c on Glycemic Control in Children With Type I Diabetes Mellitus
NCT00913497	PHASE4	COMPLETED	The Effect of Insulin Glulisine Compared With Insulin Aspart on Breakfast Post Prandial Glucose Levels in Prepubertal Children
NCT00978796	PHASE4	COMPLETED	Assessing Glucose Effects of Sitagliptin (Januvia) in Adult Patients With Type 1 Diabetes
NCT01019486	PHASE4	COMPLETED	Regadenoson Blood Flow in Type 1 Diabetes (RABIT1D)
NCT01235819	PHASE4	COMPLETED	Comparison Between GLP 1 Analogues and DPP 4 Inhibitors in Type 1 Diabetes Mellitus
NCT01269034	PHASE4	COMPLETED	New Onset Type 1 Diabetes: Role of Exenatide
NCT01269047	PHASE4	COMPLETED	Use of Exenatide and Pramlintide to Decrease Post-prandial Hyperglycemia
NCT01280682	PHASE4	COMPLETED	Immune Intervention With Rituximab to Preserve Beta Cell Function in Early Onset Type 1 Diabetes
NCT01331343	PHASE4	COMPLETED	Effectiveness Study of the Guardian RT in Type 1 Diabetics
NCT01351857	PHASE4	COMPLETED	Diabetes Care Management Compared to Standard Diabetes Care in Adolescents and Young Adults With Type 1 Diabetes
NCT01390480	PHASE4	COMPLETED	Effects of Vitamin D Supplementation in Subjects With New Onset of Type 1 Diabetes
NCT01400659	PHASE4	COMPLETED	Pizza-Salami Study in Children and Adolescents With Type 1 Diabetes
NCT01454700	PHASE4	COMPLETED	Effect of CSII and CGM on Progression of Late Diabetic Complications
NCT01488136	PHASE4	COMPLETED	Use of Diazoxide in Acute Hypoglycaemia
NCT01497912	PHASE4	COMPLETED	Treatment Effects of Atorvastatin on Hemostasis and Skin Microcirculation in Patients With Type 1 Diabetes
NCT01526733	PHASE4	COMPLETED	Randomized, Double Blind, 2 Way Crossover Study of CSII With, Versus Without, Pretreatment With Human Hyaluronidase
NCT01668485	PHASE4	COMPLETED	Mechanisms of Glucose Counterregulation in Pancreatic Islet Transplantation
NCT01678235	PHASE4	COMPLETED	Insulin Glulisine and Aspart in Postprandial Glycemic Control After High-GI Meal in Children With Type 1 Diabetes Mellitus
NCT01718093	PHASE4	COMPLETED	A Pilot Study to Assess the Glucose Lowering Effect of Metformin and Sitagliptin in Adolescents With Type 1 Diabetes