TET2

Chr 4AR

tet methylcytosine dioxygenase 2

Also known as: IMD75, KIAA1546, MDS

NCBI Gene: 54790 ENSG00000168769 UniProt: Q6N021 OMIM: 612839

The protein is a methylcytosine dioxygenase that catalyzes the conversion of 5-methylcytosine to 5-hydroxymethylcytosine and plays a key role in active DNA demethylation, an important epigenetic modification involved in transcriptional regulation. Mutations cause autosomal recessive immunodeficiency 75 and are associated with myelodysplastic syndrome, primarily affecting the immune and hematopoietic systems. The gene is extremely intolerant to loss-of-function variants, indicating that complete loss of protein function has severe consequences.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

The protein encoded by this gene is a methylcytosine dioxygenase that catalyzes the conversion of methylcytosine to 5-hydroxymethylcytosine. The encoded protein is involved in myelopoiesis, and defects in this gene have been associated with several myeloproliferative disorders. Two variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2011]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Immunodeficiency 75MIM #619126

Myelodysplastic syndrome, somaticMIM #614286

UniProtPolycythemia vera

Clinical highlights

Gene-disease validity (ClinGen)

pulmonary arterial hypertension · ADModerateconsider for supplementary testing

Active trials

744

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.38

LOEUF

LOF

Mechanism· predicted

📖

GeneReview available — TET2

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.38LOEUF

pLI 0.000

Z-score -1.06

OE 1.14 (0.95–1.38)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

1.62Z-score

OE missense 0.86 (0.81–0.91)

872 obs / 1017.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?1.14 (0.95–1.38)

0≤0.351.4

Missense OE?0.86 (0.81–0.91)

0≤0.61.4

Synonymous OE?0.90

0≤1.21.6

LoF obs/exp: 76 / 66.7Missense obs/exp: 872 / 1017.2Syn Z: 1.49

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

TET2 · protein map & ClinVar variants

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

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

📖

GeneReview available — TET2

Authoritative clinical overview · NCBI Bookshelf · Recommended first read

Open GeneReview ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

Leukemia, Myeloid, AcuteMyeloid DysplasiaOvarian Epithelial Cancer

Genetic Landscape in Women with Metastatic Ovarian Cancer Before and During Treatment with PARP Inhibitors

RECRUITING

NCT06785077Phase NAEuropean Institute of OncologyStarted 2020-10-02

buccal cellsbone marrow cellsperipheral blood cells

Peripheral T-Cell Lymphoma

Real-world Outcomes of Peripheral T-cell Lymphoma: A Multicenter Retrospective and Prospective Cohort Study

RECRUITING

NCT07270861Fudan UniversityStarted 2025-11-15

Observational

AMLIDH1 MutationTreatment

Venetoclax in Combination With Ivosidenib and Azacitidine for Newly Diagnosed IDH1-Mutated AML

RECRUITING

NCT06611839Phase PHASE1, PHASE2Institute of Hematology & Blood Diseases Hospital, ChinaStarted 2025-10-17

Ivosidenib, Venetoclax, Azacitidine

Chronic Myeloid Leukemia, Chronic PhaseWithdrawal;Drug

Efficacy and Safety of TKIs' Withdrawal After a Two-step Dose Reduction in Patients with Chronic Myeloid Leukemia

ACTIVE NOT RECRUITING

NCT04147533Phase PHASE2Masaryk UniversityStarted 2020-06-16

Imatinib withdrawalDasatinibNilotinib

Polycythemia Vera

Pegylated Interferon α-2b in Combination With Ruxolitinib for Treating Hydroxyurea-resistant/Intolerant PV

RECRUITING

NCT05870475Phase PHASE2Institute of Hematology & Blood Diseases Hospital, ChinaStarted 2023-06-30

RuxolitinibPegylated interferon α-2b

Bone Marrow Failure DisordersVEXAS SyndromeHemoglobinurea, Paroxysmal

Molecular and Clinical Analysis of Bone Marrow Failure: A Secondary Research Study

ENROLLING BY INVITATION

NCT07102849National Heart, Lung, and Blood Institute (NHLBI)Started 2025-09-09

Giant Cell ArteritisTemporal ArteritisClonal Hematopoiesis of Indeterminate Potential

Clonal Hematopoiesis in Giant Cell Arteritis

NOT YET RECRUITING

NCT06244069ASST Fatebenefratelli SaccoStarted 2024-03

Temporal arterial biopsyWhole exome sequencingSingle cell transcriptomics

Clonal HematopoiesisClonal Hematopoiesis of Indeterminate PotentialClonal Cytopenia of Undetermined Significance (CCUS)

CHIP in Health and Disease

NOT YET RECRUITING

NCT07780552VASCage GmbHStarted 2026-10

Acute Lymphatic LeukemiaLymphoma

More Than Just X-Rays - Imaging of Chemotherapy-induced Morphological and Functional Cardiovascular and Lung Changes After Childhood ALL and Other Cancers - a Monocentric Late Effects Study (MaximALL)

RECRUITING

NCT07705178Phase NAUniversity of Erlangen-Nürnberg Medical SchoolStarted 2026-07-14

QOL assessment, NeuropsychologicalSpirometryDLCO measurement

Chronic Myelomonocytic Leukemia

Relevance of Peripheral Cells in the Pathophysiology of Chronic Myelomonocytic Leukemia (CMML)

RECRUITING

NCT03280888Centre Hospitalier Universitaire de NiceStarted 2014-11-05

ST-elevation Myocardial Infarction (STEMI)Clonal Hematopoiesis of Indeterminate Potential (CHIP)

Clonal Hematopoiesis of Indeterminate Potential and Infarct Severity in ST-Elevation Myocardial Infarction

NOT YET RECRUITING

NCT07615023Medical University InnsbruckStarted 2026-06-20

Clonal hematopoiesis assessment and cardiac magnetic resonance imaging