TET3 (Tet Methylcytosine Dioxygenase 3): Gene, Function, and Disease Associations
A comprehensive overview of the TET3 gene, its protein product, expression patterns, mutations, and clinical significance.
Gene Information Card
| Symbol | TET3 |
|---|---|
| Full Name | Tet methylcytosine dioxygenase 3 |
| Gene Type | Protein coding |
| Chromosomal Location | 2p13.1 |
| NCBI Gene ID | 200424 ncbi.nlm.nih.gov/gene/200424 |
| Ensembl ID | ENSG00000170522 |
| UniProt ID | O43151 |
| OMIM ID | 613555 |
| HGNC ID | 28313 |
| Aliases | FLJ39037, MGC119567, MGC119569, MGC119570, bA119F7.1 |
Description
TET3 (Tet methylcytosine dioxygenase 3) is a member of the TET family of enzymes that catalyze the conversion of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), initiating active DNA demethylation. TET3 plays critical roles in epigenetic regulation, gene expression, and development, particularly in the nervous system and during zygotic reprogramming. It is involved in various cellular processes including stem cell differentiation, neuronal function, and immune response. Dysregulation of TET3 has been implicated in several diseases, including cancers and neurodevelopmental disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Neurodevelopmental disorder with microcephaly and structural brain anomalies | Loss-of-function mutations in TET3 impair DNA demethylation, leading to aberrant gene expression during brain development. | ClinVar, OMIM |
| Acute myeloid leukemia (AML) | Reduced TET3 expression or somatic mutations contribute to altered DNA methylation patterns, promoting leukemogenesis. | COSMIC, PubMed |
| Colorectal cancer | TET3 downregulation leads to decreased 5hmC levels, affecting tumor suppressor gene expression. | COSMIC, PubMed |
| Hepatocellular carcinoma | TET3 expression is reduced, correlating with poor prognosis and increased metastasis. | PubMed |
| Immunodeficiency | TET3 mutations may affect immune cell function, leading to immune dysregulation. | ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Lung | 8.2 | Low |
| Liver | 6.1 | Low |
| Kidney | 7.8 | Low |
| Testis | 15.3 | Medium |
| Spleen | 5.4 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 18.2 | High expression |
| HeLa | 12.5 | Moderate expression |
| K562 | 9.8 | Low expression |
| MCF7 | 7.3 | Low expression |
| HepG2 | 6.5 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1123C>T (p.Arg375Ter) | Nonsense | Rare | Loss of function, truncated protein |
| c.1480A>G (p.Thr494Ala) | Missense | Rare | Altered catalytic activity |
| c.2015T>C (p.Leu672Pro) | Missense | Rare | Potential dominant-negative effect |
| c.2542del (p.Glu848LysfsTer3) | Frameshift | Rare | Loss of function |
Mutation functional classification
Loss of Function (LOF)
Most TET3 mutations are loss-of-function, leading to reduced 5hmC levels and aberrant gene expression.
Gain of Function (GOF)
No clear gain-of-function mutations have been reported; TET3 primarily acts as a tumor suppressor.
Dominant Negative (DN)
Some missense mutations may exert dominant-negative effects by interfering with wild-type TET3 function.
View complete mutation data：
Gene Ontology (GO)
| • DNA binding | • Metal ion binding |
| • Oxidoreductase activity | • Dioxygenase activity |
| • Methylcytosine dioxygenase activity | • Nucleus |
| • Cytoplasm | • DNA demethylation |
| • Regulation of gene expression | • Cellular response to DNA damage stimulus |
Pathways
• DNA demethylation
• Epigenetic regulation
• Gene expression regulation
• Cellular response to hypoxia
Protein Summary
The TET3 protein is a 179-amino acid enzyme (UniProt O43151) that belongs to the TET family. It contains a CXXC-type zinc finger domain and a catalytic domain that requires Fe2+ and 2-oxoglutarate for activity. TET3 catalyzes the oxidation of 5-methylcytosine to 5-hydroxymethylcytosine, and further to 5-formylcytosine and 5-carboxylcytosine, facilitating DNA demethylation. It is predominantly localized in the nucleus and is highly expressed in brain and testis. TET3 is essential for zygotic reprogramming and neuronal differentiation. Its dysregulation is linked to cancer and neurodevelopmental disorders.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TET3 Knockout HEK293 Cell Line | EDJ-KQ15686 | Human | 200424 | Details Get a Quote |
| TET3 Knockout HeLa Cell Line | EDJ-KQ18111 | Human | 200424 | Details Get a Quote |
| TET3 Knockout A-549 Cell Line | EDJ-KQ46600 | Human | 200424 | Details Get a Quote |
| TET3 Knockout HCT 116 Cell Line | EDJ-KQ46601 | Human | 200424 | Details Get a Quote |
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