FOXP3

Chr XXLR

forkhead box P3

Also known as: AIID, DIETER, IPEX, JM2, PIDX, XPID

FOXP3 encodes a transcriptional regulator that is crucial for the development and suppressive function of regulatory T-cells, maintaining immune system homeostasis by controlling T-cell activation and cytokine production. Mutations cause X-linked immunodysregulation, polyendocrinopathy, and enteropathy (IPEX syndrome), which typically presents in infancy with severe autoimmunity affecting multiple organ systems including the gastrointestinal tract and endocrine glands. The gene shows X-linked recessive inheritance and is highly constrained against loss-of-function variants.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismXLRLOEUF 0.201 OMIM phenotype
Clinical SummaryFOXP3
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Gene-Disease Validity (ClinGen)
immune dysregulation-polyendocrinopathy-enteropathy-X-linked syndrome · XLDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.99). One damaged copy is likely sufficient to cause disease.
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Clinical Trials
12 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.20LOEUF
pLI 0.994
Z-score 3.63
OE 0.00 (0.000.20)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
1.67Z-score
OE missense 0.64 (0.550.75)
109 obs / 170.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.00 (0.000.20)
00.351.4
Missense OE0.64 (0.550.75)
00.61.4
Synonymous OE0.82
01.21.6
LoF obs/exp: 0 / 15.3Missense obs/exp: 109 / 170.4Syn Z: 1.19
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveFOXP3-related IPEX syndromeLOFXLR
DN
0.3892th %ile
GOF
0.3391th %ile
LOF
0.82top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.20

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

FOXP3 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

Malnutrition PregnancyMalnutrition in ChildrenMalnutrition (Calorie)

Early Life Malnutrition, Environmental Enteric Dysfunction and Microbiome Trajectories

RECRUITING
NCT07195006University of ZimbabweStarted 2025-01-27
Malnutrition in pregnancy as exposurePoor WASH living conditions as exposure
Prostate Cancer

Hypofractionated, Dose Escalation Radiotherapy for High Risk Adenocarcinoma of the Prostate

ACTIVE NOT RECRUITING
NCT01444820Phase PHASE3Sir Mortimer B. Davis - Jewish General HospitalStarted 2012-01
hypofractionationconventional
Breast AdenocarcinomaEstrogen Receptor- Negative Breast CancerEstrogen Receptor-positive Breast Cancer

Neoadjuvant Pembrolizumab + Decitabine Followed by Std Neoadj Chemo for Locally Advanced HER2- Breast Ca

ACTIVE NOT RECRUITING
NCT02957968Phase PHASE2Virginia Commonwealth UniversityStarted 2017-01-24
DoxorubicinCyclophosphamidePaclitaxel
Psoriasis VulgarisPsoriasisSkin Diseases

Residual Disease MEMory in PSOriasis Skin During EnstiLAR® and Narrow-band Ultraviolet B Therapy: The MEMPSOLAR Study

ACTIVE NOT RECRUITING
NCT05185258Phase PHASE4Aarhus University HospitalStarted 2022-02-16
EnstilarPlacebo-vehicle
Type 1 Diabetes Mellitus

Clinical Phase II/III Trial of Ustekinumab to Treat Type 1 Diabetes (UST1D2)

ACTIVE NOT RECRUITING
NCT03941132Phase PHASE2, PHASE3University of British ColumbiaStarted 2021-01-04
UstekinumabPlacebo
Type 1 Diabetes

Characterization of Autoreactive Regulatory and Conventional CD4 T Cells in Recent Onset Type 1 Diabetes and Control Individuals

RECRUITING
NCT06427421Phase NAAssistance Publique - Hôpitaux de ParisStarted 2025-05-06
Frequency of Treg and TeffsPhenotype of Treg and TeffsRNA seq analysis
Meningiomas

An Open-Label Phase II Study of Nivolumab or Nivolumab/Ipilimumab in Adult Participants With Progessive/ Recurrent Meningioma

ACTIVE NOT RECRUITING
NCT02648997Phase PHASE2Dana-Farber Cancer InstituteStarted 2016-03
Nivolumab - 240 mgIpilimumab - 1 mg/kgNivolumab - 480 mg
Cervical High Grade Squamous Intraepithelial LesionCervical Intraepithelial Neoplasia Grade 2/3CIN 2/3

Predicting Response In Cervical Intraepithelial Neoplasia to Topical Imiquimod Treatment

RECRUITING
NCT05405270Catharina Ziekenhuis EindhovenStarted 2022-06-01
Imiquimod3x vaginal swab for microbiome analysisExpectative management
IPEX

CD4^LVFOXP3 in Participants With IPEX

RECRUITING
NCT05241444Phase PHASE1Bacchetta, Rosa, MDStarted 2022-03-22
CD4^LVFOXP3
Lung Cancer (Diagnosis)Biomarkers / Blood

Circulating Immune Markers for Prognostic Evaluation in Postoperative Lung Cancer Patients

NOT YET RECRUITING
NCT07242482Zhao JunStarted 2025-12-17
Preoperative Peripheral Blood Immune Marker Analysis.
Advanced Solid Tumor

Dose Escalation Study of Immunomodulatory Nanoparticles

ACTIVE NOT RECRUITING
NCT04751786Phase PHASE1Radboud University Medical CenterStarted 2021-01-11
PRECIOUS-01
Immune System ToleranceDepressionObesity

ESAN II - Energy Sensing in Depression

RECRUITING
NCT05432362Phase NAMedical University of GrazStarted 2019-02-25
Aronia JuicePlacebo
Clinical Literature
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