DNMT3A (DNA Methyltransferase 3 Alpha) Gene
Key epigenetic regulator in development and hematological malignancies
Gene Information Card
| Symbol | DNMT3A |
|---|---|
| Full Name | DNA methyltransferase 3 alpha |
| Gene Type | Protein coding |
| Chromosomal Location | 2p23.3 |
| NCBI Gene ID | 1788 ncbi.nlm.nih.gov/gene/1788 |
| Ensembl ID | ENSG00000119772 |
| UniProt ID | Q9Y6K1 |
| OMIM ID | 602769 |
| HGNC ID | 2978 |
| Aliases | DNMT3A2, M.HsaIIIA, TBRS |
Description
The DNMT3A gene encodes a DNA methyltransferase that catalyzes the addition of methyl groups to cytosine residues in CpG dinucleotides, playing a critical role in de novo DNA methylation. This enzyme is essential for establishing and maintaining epigenetic patterns during development and differentiation. DNMT3A is frequently mutated in hematological malignancies, particularly acute myeloid leukemia (AML), and germline mutations cause Tatton-Brown-Rahman syndrome, characterized by overgrowth and intellectual disability.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Acute Myeloid Leukemia | Somatic mutations (often R882) lead to reduced methyltransferase activity and altered DNA methylation, contributing to leukemogenesis. | COSMIC, ClinVar |
| Tatton-Brown-Rahman Syndrome | Germline loss-of-function mutations cause autosomal dominant overgrowth syndrome with intellectual disability. | OMIM, ClinVar |
| Clonal Hematopoiesis of Indeterminate Potential (CHIP) | Somatic DNMT3A mutations in hematopoietic stem cells confer a fitness advantage, increasing risk of hematologic cancers. | ClinVar, literature |
| Myelodysplastic Syndromes | Mutations are common and associated with poor prognosis, affecting methylation patterns in hematopoietic progenitors. | COSMIC, ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Bone Marrow | 12.4 | Medium |
| Spleen | 8.9 | Low |
| Thymus | 7.2 | Low |
| Brain | 5.1 | Low |
| Testis | 4.3 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| K-562 (leukemia) | 15.2 | High expression |
| MCF7 (breast cancer) | 8.7 | Moderate |
| HeLa (cervical cancer) | 6.3 | Low |
| A549 (lung cancer) | 5.8 | Low |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| R882H | Missense | ~20% in AML | Dominant-negative effect, reduces catalytic activity, alters methylation |
| R882C | Missense | ~10% in AML | Similar to R882H, impairs tetramer formation and activity |
| Frequent truncating mutations | Nonsense/frameshift | Variable | Loss of function, haploinsufficiency |
| Germline mutations (e.g., R749C) | Missense | Rare | Loss of function, causes TBRS |
Mutation functional classification
Loss of Function (LOF)
Many DNMT3A mutations, especially truncating variants, result in reduced or absent methyltransferase activity, leading to global hypomethylation and aberrant gene expression.
Gain of Function (GOF)
No clear gain-of-function mutations have been identified; most mutations are loss-of-function or dominant-negative.
Dominant Negative (DN)
The R882 hotspot mutations act in a dominant-negative manner, disrupting the tetrameric complex and reducing enzymatic activity even in the presence of wild-type allele.
View complete mutation data：
Gene Ontology (GO)
| • DNA (cytosine-5-)-methyltransferase activity | • Chromatin binding |
| • Zinc ion binding | • Methyltransferase activity |
| • Regulation of gene expression by epigenetic modification | • DNA methylation involved in embryo development |
Pathways
• DNA methylation
• Epigenetic regulation of gene expression
• Cellular response to DNA damage stimulus
Protein Summary
DNMT3A is a 912-amino acid protein containing a PWWP domain, a zinc finger domain, and a catalytic methyltransferase domain. It forms homo- and heterotetramers with DNMT3L, and its activity is regulated by post-translational modifications and interaction with chromatin. The protein is essential for de novo methylation during development and is involved in silencing of repetitive elements and imprinted genes.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| DNMT3A Knockout HEK293 Cell Line | EDJ-KQ1013 | Human | 1788 | Details Get a Quote |
| DNMT3A Knockout A-549 Cell Line | EDJ-KQ20080 | Human | 1788 | Details Get a Quote |
| DNMT3A Knockout HCT 116 Cell Line | EDJ-KQ20081 | Human | 1788 | Details Get a Quote |
| DNMT3A Knockout HeLa Cell Line | EDJ-KQ18292 | Human | 1788 | Details Get a Quote |
| DNMT3A (p.L422=) Point Mutation in HAP1 Cell Line | EDC03451 | Human | 1788 | Details Get a Quote |
| DNMT3A (c.1122+7G>A )Point Mutation in HAP1 Cell Line | EDC03452 | Human | 1788 | Details Get a Quote |
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