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GeneE
50 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
FOXP3
forkhead box P3
Chromosome X Β· Xp11.23
NCBI Gene: 50943Ensembl: ENSG00000049768.19HGNC: HGNC:6106UniProt: Q9BZS1
1,170PubMed Papers
21Diseases
0Drugs
57Pathogenic Variants
FUNCTIONAL ROLE
Highly ConstrainedHub GeneTranscription Factor
RESEARCH IMPACT
Highly StudiedVariant-Rich
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
negative regulation of type II interferon productionpositive regulation of DNA-templated transcriptionpositive regulation of transcription by RNA polymerase IIDNA-binding transcription factor activityimmune dysregulation-polyendocrinopathy-enteropathy-X-linked syndrometype 1 diabetes mellitushydrops fetalisneurodegenerative disease
✦AI Summary

FOXP3 (forkhead box P3) is a transcription factor that serves as the master regulator of regulatory T cells (Tregs), which are essential for immune homeostasis and self-tolerance 1. FOXP3 functions as both a transcriptional activator and repressor, controlling the suppressive capacity of Tregs by activating genes like CTLA4 and TNFRSF18 while repressing pro-inflammatory cytokines including IL-2 and interferon-gamma 1. The protein operates through interactions with various transcription factors and chrX-modifying enzymes to coordinate immune suppression programs. Mutations in FOXP3 cause IPEX syndrome (Immunodeficiency, Polyendocrinopathy, Enteropathy, X-linked), a fatal disorder characterized by immune dysregulation, autoimmune enteropathy, and endocrinopathy 23. In cancer contexts, FOXP3 expression is complex and context-dependent, being found in both tumor-infiltrating Tregs that suppress anti-tumor immunity and in some tumor cells themselves, where its role varies across different cancer types 456. However, in humans, FOXP3 expression alone is insufficient to definitively identify regulatory T cells, as activated conventional T cells can transiently express FOXP3 without acquiring regulatory function 7.

Sources cited
1
FOXP3 is a transcription factor that regulates Treg phenotype and immune homeostasis
PMID: 28757603
2
FOXP3 mutations cause IPEX syndrome with immune dysregulation and autoimmune manifestations
PMID: 11137993
3
IPEX syndrome is caused by FOXP3 mutations affecting the forkhead domain
PMID: 11137992
4
FOXP3 is expressed in tumor microenvironments and affects anti-tumor immune responses
PMID: 35689826
5
FOXP3 expression in tumor cells has variable and context-dependent effects
PMID: 30630091
6
FOXP3 can be expressed in non-lymphoid cells and has tumor suppressor functions
PMID: 20498631
7
FOXP3 expression alone is insufficient to define regulatory T cells in humans
PMID: 38891073
Disease Associationsβ“˜21
immune dysregulation-polyendocrinopathy-enteropathy-X-linked syndromeOpen Targets
0.85Strong
type 1 diabetes mellitusOpen Targets
0.55Moderate
hydrops fetalisOpen Targets
0.50Moderate
neurodegenerative diseaseOpen Targets
0.45Moderate
azoospermiaOpen Targets
0.43Moderate
centronuclear myopathyOpen Targets
0.34Weak
Neurodevelopmental disorderOpen Targets
0.34Weak
multinucleated neurons-anhydramnios-renal dysplasia-cerebellar hypoplasia-hydranencephaly syndromeOpen Targets
0.27Weak
genetic disorderOpen Targets
0.19Weak
monogenic diabetesOpen Targets
0.15Weak
hepatocellular carcinomaOpen Targets
0.13Weak
systemic lupus erythematosusOpen Targets
0.13Weak
neoplasmOpen Targets
0.12Weak
breast cancerOpen Targets
0.12Weak
colorectal carcinomaOpen Targets
0.11Weak
asthmaOpen Targets
0.11Weak
non-small cell lung carcinomaOpen Targets
0.11Weak
rheumatoid arthritisOpen Targets
0.11Weak
cancerOpen Targets
0.11Weak
acute myeloid leukemiaOpen Targets
0.11Weak
Immunodeficiency polyendocrinopathy, enteropathy, X-linked syndromeUniProt
Pathogenic Variants57
NM_014009.4(FOXP3):c.1222G>A (p.Val408Met)Pathogenic
Insulin-dependent diabetes mellitus secretory diarrhea syndrome|FOXP3-related disorder
β˜…β˜…β˜†β˜†2025β†’ Residue 408
NM_014009.4(FOXP3):c.1010G>A (p.Arg337Gln)Pathogenic
Insulin-dependent diabetes mellitus secretory diarrhea syndrome|not provided|Neurodevelopmental disorder
β˜…β˜…β˜†β˜†2025β†’ Residue 337
NM_014009.4(FOXP3):c.1190G>A (p.Arg397Gln)Pathogenic
not provided|Insulin-dependent diabetes mellitus secretory diarrhea syndrome|FOXP3-related disorder
β˜…β˜…β˜†β˜†2025β†’ Residue 397
NM_014009.4(FOXP3):c.1150G>A (p.Ala384Thr)Pathogenic
Insulin-dependent diabetes mellitus secretory diarrhea syndrome
β˜…β˜…β˜†β˜†2024β†’ Residue 384
NM_014009.4(FOXP3):c.543-2A>GLikely pathogenic
Insulin-dependent diabetes mellitus secretory diarrhea syndrome
β˜…β˜…β˜†β˜†2024
NM_014009.4(FOXP3):c.751_753del (p.Glu251del)Pathogenic
Insulin-dependent diabetes mellitus secretory diarrhea syndrome|not provided
β˜…β˜…β˜†β˜†2024β†’ Residue 251
NM_014009.4(FOXP3):c.1040G>A (p.Arg347His)Pathogenic
Insulin-dependent diabetes mellitus secretory diarrhea syndrome|not provided
β˜…β˜…β˜†β˜†2023β†’ Residue 347
NM_014009.4(FOXP3):c.1189C>T (p.Arg397Trp)Pathogenic
Insulin-dependent diabetes mellitus secretory diarrhea syndrome|Hydrops fetalis
β˜…β˜…β˜†β˜†2021β†’ Residue 397
NM_014009.4(FOXP3):c.748_750del (p.Lys250del)Pathogenic
not provided|Insulin-dependent diabetes mellitus secretory diarrhea syndrome
β˜…β˜…β˜†β˜†2021β†’ Residue 250
NM_014009.4(FOXP3):c.1156C>T (p.Arg386Cys)Likely pathogenic
not provided
β˜…β˜…β˜†β˜†2021β†’ Residue 386
NM_014009.4(FOXP3):c.1015C>G (p.Pro339Ala)Pathogenic
not provided|Insulin-dependent diabetes mellitus secretory diarrhea syndrome
β˜…β˜…β˜†β˜†2020β†’ Residue 339
NM_014009.4(FOXP3):c.711_712del (p.Glu237fs)Pathogenic
Insulin-dependent diabetes mellitus secretory diarrhea syndrome
β˜…β˜†β˜†β˜†2025β†’ Residue 237
NM_014009.4(FOXP3):c.816+5G>APathogenic
Insulin-dependent diabetes mellitus secretory diarrhea syndrome
β˜…β˜†β˜†β˜†2025
NM_014009.4(FOXP3):c.816+7G>CPathogenic
Insulin-dependent diabetes mellitus secretory diarrhea syndrome
β˜…β˜†β˜†β˜†2025
NM_014009.4(FOXP3):c.646_647+2delLikely pathogenic
Insulin-dependent diabetes mellitus secretory diarrhea syndrome
β˜…β˜†β˜†β˜†2025
NM_014009.4(FOXP3):c.227del (p.Leu76fs)Pathogenic
Insulin-dependent diabetes mellitus secretory diarrhea syndrome
β˜…β˜†β˜†β˜†2025β†’ Residue 76
NM_014009.4(FOXP3):c.766A>G (p.Met256Val)Pathogenic
Insulin-dependent diabetes mellitus secretory diarrhea syndrome
β˜…β˜†β˜†β˜†2025β†’ Residue 256
NM_014009.4(FOXP3):c.-22-1G>ALikely pathogenic
Insulin-dependent diabetes mellitus secretory diarrhea syndrome
β˜…β˜†β˜†β˜†2025
NM_014009.4(FOXP3):c.906del (p.Asp303fs)Pathogenic
Insulin-dependent diabetes mellitus secretory diarrhea syndrome
β˜…β˜†β˜†β˜†2024β†’ Residue 303
NM_014009.4(FOXP3):c.116_122dup (p.Gly43fs)Pathogenic
Centronuclear myopathy
β˜…β˜†β˜†β˜†2024β†’ Residue 43
View on ClinVar β†—
Related Genes
IKZF1Protein interaction100%IKZF3Protein interaction100%CBFBProtein interaction98%BCL6Protein interaction98%CXCR5Protein interaction98%CD1DProtein interaction98%
Tissue Expression6 tissues
Bone Marrow
100%
Liver
51%
Lung
25%
Brain
21%
Ovary
14%
Heart
0%
Gene Interaction Network
Click a node to explore
FOXP3IKZF1IKZF3CBFBBCL6CXCR5CD1D
PROTEIN STRUCTURE
Preparing viewer…
PDB3QRF Β· 2.80 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.34Highly Constrained
pLIβ“˜
1.00Intolerant
Observed/Expected LoF0.16 [0.08–0.34]
RankingsWhere FOXP3 stands among ~20K protein-coding genes
  • #123of 20,598
    Most Researched1,170 Β· top 1%
  • #1,206of 5,498
    Most Pathogenic Variants57 Β· top quartile
  • #1,439of 17,882
    Most Constrained (LOEUF)0.34 Β· top 10%
Genes detectedFOXP3
Sources retrieved50 papers
Response timeβ€”
πŸ“„ Sources
50β–Ό
1
Human FOXP3 and tumour microenvironment.
PMID: 35689826
Immunology Β· 2023
1.00
2
The immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) is caused by mutations of FOXP3.
PMID: 11137993
Nat Genet Β· 2001
0.90
3
Alternative splicing, FOXP3 and cardiovascular disease.
PMID: 30981208
Aging (Albany NY) Β· 2019
0.82
4
Defining Human Regulatory T Cells beyond FOXP3: The Need to Combine Phenotype with Function.
PMID: 38891073
Cells Β· 2024
0.80
5
Optimized CRISPR-mediated gene knockin reveals FOXP3-independent maintenance of human Treg identity.
PMID: 34348163
Cell Rep Β· 2021
0.80