FOXP3

Chr XXLR

forkhead box P3

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

NCBI Gene: 50943ENSG00000049768UniProt: Q9BZS1OMIM: 300292

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]

GeneReviewsOMIMResearchGenerating clinical summary…
LOFmechanismXLRLOEUF 0.201 OMIM phenotype
Clinical Summary— FOXP3
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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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ClinVar Variants
7 unique Pathogenic / Likely Pathogenic· 31 VUS of 98 total submissions
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Clinical Trials
12 active or recruiting trials — potential therapeutic options may be available
Explore recent and relevant literature in Research Assistant →
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GeneReview available — FOXP3
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

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

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

Missense Constraint?
1.67Z-score
OE missense 0.64 (0.55–0.75)
109 obs / 170.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.00 (0.00–0.20)
0≤0.351.4
Missense OE?0.64 (0.55–0.75)
0≤0.61.4
Synonymous OE?0.82
0≤1.21.6
LoF obs/exp: 0 / 15.3Missense obs/exp: 109 / 170.4Syn Z: 1.19
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveFOXP3-related IPEX syndromeLOFXLR

This gene — mechanism propensity

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 · 57% of P/LP variants are LoF · 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

98 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic5
Likely Pathogenic2
VUS31
Likely Benign26
Benign8
5
Pathogenic
2
Likely Pathogenic
31
VUS
26
Likely Benign
8
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
2
1
2
0
5
Likely Pathogenic
2
0
0
0
2
VUS
0
25
4
2
31
Likely Benign
0
2
11
13
26
Benign
0
0
8
0
8
Total428251572

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

1 pathogenic / likely-pathogenic (of 2) ClinVar copy-number / structural variants overlap FOXP3 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →

Protein Context — Lollipop Plot

FOXP3 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Advanced Non-Small Cell Lung Cancer (NSCLC)

Immunodynamics-Guided Optimization of Individualized Immunochemotherapy in Advanced Driver-Negative NSCLC: A Randomized Trial

NOT YET RECRUITING
NCT07190027Phase PHASE1, PHASE2First Affiliated Hospital of Wenzhou Medical UniversityStarted 2025-11
Arm 1： Standard Synchronous GroupArm 2：Fixed Delay GroupArm 3： Individualized Delay Group
Diabetes MellitusPancreas TransplantationAllograft Rejection

The Norwegian Pancreas Transplantation (PTx) Study

ENROLLING BY INVITATION
NCT01957696Oslo University HospitalStarted 2013-09
Advanced Solid Tumor

Dose Escalation Study of Immunomodulatory Nanoparticles

ACTIVE NOT RECRUITING
NCT04751786Phase PHASE1Radboud University Medical CenterStarted 2021-01-11
PRECIOUS-01
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
IPEX

CD4^LVFOXP3 in Participants With IPEX

RECRUITING
NCT05241444Phase PHASE1Bacchetta, Rosa, MDStarted 2022-03-22
CD4^LVFOXP3
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
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
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
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.
Immune System ToleranceDepressionObesity

ESAN II - Energy Sensing in Depression

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

DC Migration Study to Evaluate TReg Depletion In GBM Patients With and Without Varlilumab

ACTIVE NOT RECRUITING
NCT03688178Phase PHASE2Annick Desjardins, MDStarted 2020-08-26
Human CMV pp65-LAMP mRNA-pulsed autologous DCsTemozolomideVarlilumab

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients