TET3

Chr 2

tet methylcytosine dioxygenase 3

Also known as: BEFAHRS, hCG_40738

NCBI Gene: 200424ENSG00000187605UniProt: O43151

Enables RNA polymerase II cis-regulatory region sequence-specific DNA binding activity; methyl-CpG binding activity; and zinc ion binding activity. Involved in positive regulation of transcription by RNA polymerase II and protein O-linked glycosylation. Predicted to be located in cytoplasm and male pronucleus. Predicted to be active in nucleus. Biomarker of esophagus squamous cell carcinoma. [provided by Alliance of Genome Resources, Jul 2025]

Primary Disease Associations & Inheritance

UniProtBeck-Fahrner syndrome
0
ClinVar variants
0
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— TET3
🧬
Gene-Disease Validity (ClinGen)
Beck-Fahrner syndrome · ARLimited

Limited evidence — not for standalone diagnostic reporting

2 total gene-disease associations curated

⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.09LOEUF
pLI 1.000
Z-score 6.75
OE 0.02 (0.01–0.09)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
2.88Z-score
OE missense 0.74 (0.70–0.79)
732 obs / 986.4 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.02 (0.01–0.09)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.74 (0.70–0.79)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.06
0≤1.21.6
LoF obs/exp: 1 / 55.1Missense obs/exp: 732 / 986.4Syn Z: -1.04

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

TET3 · protein map & ClinVar variants

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

Gene2Phenotype Curations

TET3-related DNA demethylation disorder

strong
ADLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

TET3-related DNA demethylation disorder

strong
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype

OMIM

No OMIM entries found.

📖
GeneReview available — TET3
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
TET3-overexpressing macrophages promote endometriosis.
Lv H et al.·J Clin Invest
2024
Interferon regulatory factor-1-expressing astrocytes are epigenetically controlled and exacerbate TBI-associated pathology in mice.
Cui W et al.·Sci Transl Med
2025
Delineation of a Human Mendelian Disorder of the DNA Demethylation Machinery: TET3 Deficiency.
Beck DB et al.·Am J Hum Genet
2020
TET3 is a common epigenetic immunomodulator of pathogenic macrophages.
Liu B et al.·J Clin Invest
2025
TET3-mediated DNA oxidation is essential for intestinal epithelial cell response to stressors.
Gonzalez EA et al.·Proc Natl Acad Sci U S A
2023
TET3-overexpressing macrophages are a unifying pathogenic feature with therapeutic potential in chronic inflammatory diseases.
Haji S et al.·J Clin Invest
2025Review
High-Fidelity CRISPR/Cas9-Based Gene-Specific Hydroxymethylation.
Xu X et al.·Methods Mol Biol
2021
Integrative Genomic and Transcriptomic Analysis Reveals Targetable Vulnerabilities in Angioimmunoblastic T-Cell Lymphoma.
Bouska A et al.·Am J Hematol
2025
MYC/TET3-Regulated TMEM65 Activates OXPHOS-SERPINB3 Pathway to Promote Progression and Cisplatin Resistance in Triple-Negative Breast Cancer.
Zhang YL et al.·Adv Sci (Weinh)
2025
TP53 and CDKN2A alterations define a poor prognostic subgroup in patients with nodal T follicular helper cell lymphoma.
Ito Y et al.·Leukemia
2025Cohort
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
The Tet3 degrader Bobcat339 ameliorates isoprenaline induced cardiac fibrosis and heart failure: animal and transcriptomic studies.
Liu S et al.·Life Sci
2026
Biochemical engineering of 5hmdC-DNA using a Tet3 double-mutant.
Sahin H et al.·Comput Struct Biotechnol J
2026🔓 Open Access
Targeting TET3 suppresses group 3 medulloblastoma stemness and progression via impairing hypomethylation of Otx2 super-enhancer.
Chen X et al.·Cell Rep Med
2025🔓 Open Access
Delivery of miR-29a/29c-3p by serum exosomes promotes osteogenesis through TET3-dependent Sox9 demethylation and PI3K/Akt activation.
Lin Q et al.·J Nanobiotechnology
2025🔓 Open Access
TET3-Mediated m5C Modification of CCAT2 Accelerates Cardiac Microvascular Endothelial Cell Damage in Acute Coronary Syndrome.
Liu JC et al.·Kaohsiung J Med Sci
2025
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools