# DNA methyltransferase 3A (DNMT3A)

Source: https://onco.cc/targets/dnmt3a/  
OnCo record `dnmt3a` (Target). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

DNMT3A writes new methyl marks on DNA; it is one of the most commonly mutated genes in acute myeloid leukaemia and is trapped by the hypomethylating drugs azacitidine and decitabine.

## Summary

DNA methyltransferase 3A establishes new (de novo) cytosine methylation. Loss-of-function mutations, most often at R882, are among the commonest events in acute myeloid leukaemia and in age-related clonal haematopoiesis. Azacitidine and decitabine are incorporated into DNA and covalently trap DNA methyltransferases, including DNMT3A, leading to their degradation and to demethylation.

## Fields

- Kind: Target
- Last checked: 2026-09-04
- Symbol: DNMT3A
- Class: enzyme
- Biology: A de novo methyltransferase working with DNMT3L during development and in haematopoietic stem cells; the R882H mutant acts dominantly to reduce methylation.
- Where found: Haematopoietic stem cells; Mutated in a large share of AML and in clonal haematopoiesis

## Notes

- Lymphoma, RHOA G17V and the epigenetic mutations of T-follicular-helper lymphoma: A single substitution, G17V, in the small GTPase RHOA produces a protein that does not bind GTP and that blocks the wild-type protein as well. It is specific to the tumour cell, whereas the TET2 mutations that accompany it are found in non-tumour haematopoietic cells too, which places the TET2 lesion earlier, in the stem cell, and makes this lymphoma a disease that grows out of clonal haematopoiesis. Frequency: RHOA G17V in 68% of angioimmunoblastic T-cell lymphoma samples, with every G17V case also carrying a TET2 mutation (Sakata-Yanagimoto 2014); independently, in 22 of 35 angioimmunoblastic cases, 67%, and 8 of 44 peripheral T-cell lymphoma not otherwise specified, 18%, alongside recurrent TET2, DNMT3A and IDH2 mutations and less frequent FYN, ATM, B2M and CD58 lesions (Palomero 2014). What it changes about treatment: Not through an approved test. The hypomethylating agents are used in this disease on the strength of the TET2 and DNMT3A biology rather than on a mutation result, and azacitidine-containing regimens have shown activity in T-follicular-helper histology specifically.

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/DNMT3A
- UniProt Q9Y6K1: DNMT3A: https://www.uniprot.org/uniprotkb/Q9Y6K1/entry
- HGNC:2978 DNMT3A: https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:2978
- ChEMBL target CHEMBL1992: https://www.ebi.ac.uk/chembl/explore/target/CHEMBL1992
- Sakata-Yanagimoto et al., Nat Genet 2014: somatic RHOA G17V in angioimmunoblastic T-cell lymphoma: https://doi.org/10.1038/ng.2872
- Palomero et al., Nat Genet 2014: recurrent mutations in epigenetic regulators, RHOA and FYN in peripheral T-cell lymphoma: https://doi.org/10.1038/ng.2873

## Connected records

- targets: [DNMT1 (DNA methyltransferase 1)](https://onco.cc/targets/dnmt1/), [TET2](https://onco.cc/targets/tet2/)
- cancers: [Acute myeloid leukaemia](https://onco.cc/cancers/aml/), [Myelodysplastic syndromes / neoplasms (MDS)](https://onco.cc/cancers/mds/), [Nodal T-follicular helper cell lymphoma, angioimmunoblastic type (angioimmunoblastic T-cell lymphoma)](https://onco.cc/cancers/angioimmunoblastic-t-cell-lymphoma/), [Non-Hodgkin lymphoma (all types)](https://onco.cc/cancers/non-hodgkin-lymphoma/), [Peripheral T-cell lymphomas (including cutaneous T-cell lymphoma)](https://onco.cc/cancers/peripheral-t-cell-lymphoma/)
- drugs: [Azacitidine](https://onco.cc/drugs/azacitidine/), [Decitabine](https://onco.cc/drugs/decitabine/)
- pathways: [Clonal haematopoiesis (CHIP)](https://onco.cc/pathways/clonal-haematopoiesis/), [Epigenetic reprogramming](https://onco.cc/pathways/epigenetic-reprogramming/)
- biomarkers: [RHOA G17V](https://onco.cc/biomarkers/rhoa-g17v/)

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