DNMT3B (DNA Methyltransferase 3 Beta)
Key enzyme in de novo DNA methylation, critical for development and implicated in immunodeficiency, centromeric instability, and facial anomalies (ICF) syndrome and various cancers.
Gene Information Card
| Symbol | DNMT3B |
|---|---|
| Full Name | DNA methyltransferase 3 beta |
| Gene Type | Protein coding |
| Chromosomal Location | 20q11.21 |
| NCBI Gene ID | 1789 ncbi.nlm.nih.gov/gene/1789 |
| Ensembl ID | ENSG00000088305 |
| UniProt ID | Q9UBC3 |
| OMIM ID | 602900 |
| HGNC ID | 2979 |
| Aliases | ICF1, M.HsaIIIB, DNA MTase HsaIIIB |
Description
DNMT3B encodes a DNA methyltransferase that primarily establishes de novo DNA methylation patterns during embryonic development and in somatic tissues. It is essential for normal development, genomic imprinting, and silencing of repetitive elements. Mutations in DNMT3B cause Immunodeficiency, Centromeric instability, and Facial anomalies (ICF) syndrome type 1, and aberrant expression is linked to various cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Immunodeficiency, Centromeric instability, and Facial anomalies (ICF) syndrome type 1 | Loss-of-function mutations in DNMT3B lead to reduced DNA methylation at centromeric and pericentromeric regions, causing chromosomal instability and immune defects. | ClinVar, OMIM |
| Acute myeloid leukemia (AML) | Somatic mutations in DNMT3B (and DNMT3A) are recurrent in AML, leading to aberrant DNA methylation and altered gene expression that promotes leukemogenesis. | COSMIC, PubMed |
| Colorectal cancer | Overexpression of DNMT3B is observed in colorectal tumors, contributing to hypermethylation of tumor suppressor genes and genomic instability. | PubMed, COSMIC |
| Breast cancer | Elevated DNMT3B expression in breast cancer correlates with poor prognosis and may drive aberrant methylation of genes involved in cell cycle and apoptosis. | PubMed, COSMIC |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 20.1 | High |
| Bone marrow | 15.3 | Medium |
| Spleen | 12.8 | Medium |
| Lung | 8.5 | Low |
| Brain | 5.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| K-562 (leukemia) | 18.4 | High expression |
| HeLa (cervical cancer) | 12.1 | Moderate expression |
| A549 (lung cancer) | 9.3 | Low expression |
| HepG2 (liver cancer) | 7.8 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| p.Pro785Leu | Missense | Rare (ICF syndrome) | Impairs catalytic activity, leading to hypomethylation |
| p.Arg823Gln | Missense | Rare (ICF syndrome) | Disrupts DNA binding and reduces enzyme function |
| p.Val726Met | Missense | Somatic (AML) | Alters substrate specificity, contributes to aberrant methylation |
| p.Arg882His | Missense | Somatic (AML) | Dominant-negative effect, reduces methyltransferase activity |
Mutation functional classification
Loss of Function (LOF)
Most ICF syndrome mutations are loss-of-function, leading to reduced DNA methylation and genomic instability.
Gain of Function (GOF)
Some cancer-associated mutations may confer gain-of-function, increasing methylation at specific loci, though evidence is limited.
Dominant Negative (DN)
Certain mutations, like p.Arg882His in AML, exhibit dominant-negative effects by interfering with wild-type DNMT3B function.
View complete mutation data：
Gene Ontology (GO)
| • DNA binding | • DNA (cytosine-5-)-methyltransferase activity |
| • Chromatin binding | • Zinc ion binding |
| • Methyltransferase activity | • Nucleus |
| • Cytoplasm | • Regulation of gene expression by DNA methylation |
| • DNA methylation involved in embryo development | • Response to hypoxia |
Pathways
• DNA methylation
• Epigenetic regulation of gene expression
• Cellular response to DNA damage stimulus
• Developmental biology
Protein Summary
DNMT3B is a 853-amino acid protein that catalyzes the transfer of methyl groups to cytosine residues in CpG dinucleotides, establishing de novo methylation patterns. It contains a PWWP domain for chromatin targeting, a zinc finger domain for DNA binding, and a C-terminal methyltransferase domain. The protein interacts with DNMT3L and other chromatin modifiers to regulate gene silencing and genomic stability.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| DNMT3B Knockout HEK293 Cell Line | EDJ-KQ2278 | Human | 1789 | Details Get a Quote |
| DNMT3B Knockout A-549 Cell Line | EDJ-KQ22624 | Human | 1789 | Details Get a Quote |
| DNMT3B Knockout HCT 116 Cell Line | EDJ-KQ22625 | Human | 1789 | Details Get a Quote |
| DNMT3B Knockout HeLa Cell Line | EDJ-KQ22626 | Human | 1789 | Details Get a Quote |
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