TET1 Gene: Function, Expression, and Clinical Significance
A comprehensive overview of the TET1 gene, including its genomic context, protein function, expression patterns, associated diseases, and mutation landscape.
Gene Information Card
| Symbol | TET1 |
|---|---|
| Full Name | Tet methylcytosine dioxygenase 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 10q21.3 |
| NCBI Gene ID | 80312 ncbi.nlm.nih.gov/gene/80312 |
| Ensembl ID | ENSG00000138336 |
| UniProt ID | Q8NFU7 |
| OMIM ID | 607783 |
| HGNC ID | HGNC:29421 |
| Aliases | CXXC6, LCX, bA119F7.1 |
Description
The TET1 gene encodes a member of the 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. TET1 is involved in gene expression control, development, and cellular differentiation. It is frequently dysregulated in various cancers and neurodevelopmental disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Acute Myeloid Leukemia | TET1 mutations or reduced expression lead to decreased 5-hmC levels, contributing to leukemogenesis. | COSMIC, ClinVar, PubMed |
| Myelodysplastic Syndromes | Loss-of-function mutations in TET1 impair DNA demethylation, affecting hematopoietic differentiation. | COSMIC, ClinVar |
| Glioblastoma | TET1 downregulation is associated with hypermethylation of tumor suppressor genes, promoting tumor progression. | PubMed |
| Hepatocellular Carcinoma | Reduced TET1 expression correlates with poor prognosis and increased cell proliferation. | PubMed |
| Neurodevelopmental Disorders | TET1 variants may affect neuronal gene expression, contributing to autism spectrum disorders and intellectual disability. | ClinVar, PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 10.2 | Medium |
| Testis | 8.5 | Medium |
| Thyroid | 6.1 | Low |
| Lung | 4.3 | Low |
| Liver | 2.0 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 12.5 | High expression |
| K562 | 8.0 | Moderate expression |
| MCF7 | 5.2 | Low expression |
| HepG2 | 3.1 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.4560_4561del (p.Gln1521Hisfs*2) | Frameshift | Rare | Loss of function |
| c.1123C>T (p.Arg375*) | Nonsense | Rare | Loss of function |
| c.2345A>G (p.Tyr782Cys) | Missense | Rare | Unknown/possibly damaging |
| c.3456_3460dup (p.Leu1154Profs*12) | Frameshift | Rare | Loss of function |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations in TET1, including frameshift and nonsense variants, result in reduced catalytic activity and decreased 5-hmC levels, contributing to tumorigenesis and developmental disorders.
Gain of Function (GOF)
Gain-of-function mutations in TET1 are rare and not well characterized. Some missense variants may increase enzymatic activity, but evidence is limited.
Dominant Negative (DN)
Dominant-negative effects have been suggested for certain TET1 mutations that interfere with wild-type protein function, but this mechanism is not firmly established.
View complete mutation data：
Gene Ontology (GO)
| • DNA binding | • Metal ion binding |
| • Oxidoreductase activity | • Methylcytosine dioxygenase activity |
| • Chromatin binding | • Regulation of gene expression |
| • DNA demethylation | • Cellular response to DNA damage stimulus |
Pathways
• DNA demethylation
• Epigenetic regulation of gene expression
• Cellular response to hypoxia
• Notch signaling pathway
Protein Summary
The TET1 protein is a 2136-amino acid enzyme that belongs to the TET family. It contains a CXXC zinc finger domain that binds to CpG islands, and a catalytic domain that oxidizes 5-methylcytosine to 5-hydroxymethylcytosine. TET1 is involved in maintaining DNA methylation homeostasis and regulating gene expression. It is predominantly localized in the nucleus and interacts with various chromatin modifiers. Its expression is tightly regulated during development and is often altered in cancer.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| Tet1 Knockout Kupffer Cell Line | EDJ-KQ88 | Mouse | 52463 | Details Get a Quote |
| TET1 Knockout HEK293 Cell Line | EDJ-KQ3116 | Human | 80312 | Details Get a Quote |
| TET1 Knockout A-549 Cell Line | EDJ-KQ24463 | Human | 80312 | Details Get a Quote |
| TET1 Knockout HCT 116 Cell Line | EDJ-KQ24464 | Human | 80312 | Details Get a Quote |
| TET1 Knockout HeLa Cell Line | EDJ-KQ57326 | Human | 80312 | Details Get a Quote |
