TET2 Gene: Function, Mutations, and Associated Diseases
A comprehensive overview of the TET2 gene, its role in epigenetic regulation, clinical significance in myeloid malignancies, and expression patterns.
Gene Information Card
| Symbol | TET2 |
|---|---|
| Full Name | Tet methylcytosine dioxygenase 2 |
| Gene Type | Protein coding |
| Chromosomal Location | 4q24 |
| NCBI Gene ID | 54790 ncbi.nlm.nih.gov/gene/54790 |
| Ensembl ID | ENSG00000168769 |
| UniProt ID | Q6N021 |
| OMIM ID | 612839 |
| HGNC ID | 25941 |
| Aliases | KIAA1546, MDS, FLJ20032 |
Description
The TET2 gene encodes a member of the ten-eleven translocation (TET) family of methylcytosine dioxygenases. These enzymes catalyze the conversion of 5-methylcytosine (5-mC) to 5-hydroxymethylcytosine (5-hmC) and further oxidation products, playing a critical role in DNA demethylation and epigenetic regulation. TET2 is a tumor suppressor frequently mutated in various hematological malignancies, including myeloid leukemias and myelodysplastic syndromes. Mutations lead to loss of function, contributing to aberrant DNA methylation and hematopoietic dysregulation.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Myelodysplastic syndromes (MDS) | Loss-of-function mutations reduce 5-hmC levels, leading to aberrant DNA methylation and impaired hematopoietic differentiation. | Somatic mutations in ~20-25% of MDS cases (COSMIC, ClinVar). |
| Acute myeloid leukemia (AML) | Inactivating mutations disrupt normal hematopoiesis, promoting leukemogenesis through epigenetic dysregulation. | Found in ~10-20% of AML cases (COSMIC, ClinVar). |
| Chronic myelomonocytic leukemia (CMML) | Mutations impair TET2 enzymatic activity, contributing to monocytic proliferation and disease progression. | Present in ~40-50% of CMML cases (COSMIC, ClinVar). |
| Clonal hematopoiesis of indeterminate potential (CHIP) | Somatic TET2 mutations in hematopoietic stem cells confer a fitness advantage, leading to clonal expansion without overt malignancy. | Detected in healthy individuals, increasing with age (ClinVar). |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Bone Marrow | High | High expression in hematopoietic tissues. |
| Spleen | High | High expression in immune cells. |
| Lymph Node | High | High expression in lymphoid tissues. |
| Blood | Medium | Moderate expression in peripheral blood cells. |
| Brain | Low | Low expression in brain tissues. |
| Liver | Low | Low expression in liver. |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| K-562 (CML) | High | Chronic myeloid leukemia cell line. |
| HL-60 (AML) | High | Acute promyelocytic leukemia cell line. |
| MOLT-4 (ALL) | Medium | T-cell acute lymphoblastic leukemia cell line. |
| HeLa (Cervical Cancer) | Low | Low expression in non-hematopoietic cell line. |
| A549 (Lung Cancer) | Low | Low expression in epithelial cell line. |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.4504C>T (p.Arg1502*) | Nonsense | ~5% in myeloid malignancies | Truncating mutation leading to loss of catalytic domain. |
| c.3920_3921del (p.Leu1307fs) | Frameshift | ~3% in MDS | Frameshift causing premature stop codon. |
| c.5161C>T (p.Arg1721Trp) | Missense | ~2% in AML | Affects catalytic activity. |
| c.5649_5650insA (p.Leu1884fs) | Insertion | ~2% in CMML | Insertion leading to frameshift. |
Mutation functional classification
Loss of Function (LOF)
Most TET2 mutations are loss-of-function, reducing or abolishing enzymatic activity and decreasing 5-hmC levels.
Gain of Function (GOF)
No gain-of-function mutations have been reported; TET2 acts as a tumor suppressor.
Dominant Negative (DN)
Some missense mutations may exert dominant-negative effects by interfering with wild-type TET2 dimerization, but evidence is limited.
View complete mutation data：
Gene Ontology (GO)
| • DNA binding | • Metal ion binding |
| • Oxidoreductase activity | • Dioxygenase activity |
| • Chromatin binding | • Regulation of DNA methylation |
| • Cellular response to DNA damage stimulus |
Pathways
• DNA demethylation
• Epigenetic regulation
• Hematopoietic stem cell differentiation
• Cancer pathways
Protein Summary
The TET2 protein is a 2002-amino acid enzyme that belongs to the TET family. It contains a C-terminal catalytic domain that requires iron (Fe2+) and 2-oxoglutarate as cofactors to oxidize 5-methylcytosine to 5-hydroxymethylcytosine. TET2 is involved in maintaining DNA methylation homeostasis and gene expression regulation. It is predominantly expressed in hematopoietic cells and plays a crucial role in normal blood cell development. Loss of TET2 function due to mutations is a key event in the pathogenesis of various myeloid malignancies.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TET2 Knockout HEK293 Cell Line | EDJ-KQ17907 | Human | 54790 | Details Get a Quote |
| TET2 Knockout A-549 Cell Line | EDJ-KQ20037 | Human | 54790 | Details Get a Quote |
| TET2 Knockout HCT 116 Cell Line | EDJ-KQ20038 | Human | 54790 | Details Get a Quote |
| TET2 Knockout HeLa Cell Line | EDJ-KQ20039 | Human | 54790 | Details Get a Quote |
| TET2 Knockout THP-1 Cell Line | EDJ-KZ503 | Human | 54790 | Details Get a Quote |
