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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.
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.
In plain words · 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.
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.
A de novo methyltransferase working with DNMT3L during development and in haematopoietic stem cells; the R882H mutant acts dominantly to reduce methylation.
No product in this corpus aims at DNA methyltransferase 3A (DNMT3A) yet. Inhibitors are shaped to fit the enzyme's active site so the reaction the cancer relies on stops.
Broadly expressed or essential: HPA finds the RNA at low tissue specificity; the 2 medicines aimed at it (Azacitidine, Decitabine) act on the wild-type protein, so normal tissue is exposed and the therapeutic window comes from the tumour's faster division or its dependence on the protein. HPA DNMT3A: RNA low tissue specificity; high antibody staining in 37 normal tissues; highest cancer staining head and neck cancer (4 of 4 high). Distribution: 2 cancer families in the corpus carry a prevalence row, label threshold or catalogue link for it (Leukaemia, Myeloid neoplasms); Open Targets associates it with 7 specific cancer types at or above 0.5 (acute myeloid leukemia, myelodysplastic syndrome, myeloid leukemia, chronic myelomonocytic leukemia, ebv-positive nodal t- and nk-cell lymphoma, myelodysplastic syndrome with excess blasts and more). (Rule 7 of scripts/fetch-target-specificity.ts.)
Sources: Human Protein Atlas DNMT3A tissue; Open Targets ENSG00000119772 associations
First described 1999. Earliest sequence paper UniProt cites for the protein: Xie et al, Gene, 1999, "Cloning, expression and chromosome locations of the human DNMT3 gene family". Source.
A de novo methyltransferase working with DNMT3L during development and in haematopoietic stem cells; the R882H mutant acts dominantly to reduce methylation.
RNA: low tissue specificity, detected in all normal tissues.
Medium: Adipose tissue, Caudate, Cerebral cortex, Heart muscle, Hippocampus, Prostate, Spleen.
Human Protein Atlas version 25.1, antibody staining at reliability approved, enhanced or supported; used under CC BY-SA 3.0. Staining counts are patients per level in the atlas cohort, not population prevalence.
| Cancer | Prevalence | Measure | Note | Source |
|---|---|---|---|---|
| Acute myeloid leukaemia | 22.1% | DNMT3A mutation, exon sequencing of 281 de novo AML cases (62 mutated) | 33.7% in intermediate-risk cytogenetics and absent in favourable-risk disease; R882 the commonest site | doi.org |
Approximate, population-level figures; the measure column says what was counted. Ranges show the midpoint as a bar.
Query for this target: (TITLE:"DNA methyltransferase 3A" OR ABSTRACT:"DNA methyltransferase 3A" OR TITLE:"DNMT3A" OR ABSTRACT:"DNMT3A") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about DNA methyltransferase 3A (DNMT3A), not a curated reading list.
Shares RHOA G17V, Clonal haematopoiesis (CHIP), Nodal T-follicular helper cell lymphoma, angioimmunoblastic type (angioimmunoblastic T-cell lymphoma), Epigenetic reprogramming.
Shares RHOA G17V, Clonal haematopoiesis (CHIP), Nodal T-follicular helper cell lymphoma, angioimmunoblastic type (angioimmunoblastic T-cell lymphoma), Epigenetic reprogramming.
Shares Clonal haematopoiesis (CHIP), Nodal T-follicular helper cell lymphoma, angioimmunoblastic type (angioimmunoblastic T-cell lymphoma), Epigenetic reprogramming, Non-Hodgkin lymphoma (all types).
Shares Decitabine, Azacitidine, Myelodysplastic syndromes / neoplasms (MDS).
Shares Decitabine, Azacitidine, Acute myeloid leukaemia.
Shares Azacitidine, Myelodysplastic syndromes / neoplasms (MDS), Acute myeloid leukaemia.
Shares Decitabine, Azacitidine, Myelodysplastic syndromes / neoplasms (MDS).
Shares TET2, RHOA G17V, Nodal T-follicular helper cell lymphoma, angioimmunoblastic type (angioimmunoblastic T-cell lymphoma), Peripheral T-cell lymphomas (including cutaneous T-cell lymphoma).