Missing content? – Request curation!
Request curation for specific Genes, variants, or PubMed publications.
Have questions, comments or suggestions? - Let us know!
Email us at : ckbsupport@jax.org
Gene | DNMT3A |
Variant | R882H |
Impact List | missense |
Protein Effect | loss of function |
Gene Variant Descriptions | DNMT3A R882H lies within the SAM-dependent MTase C5-type domain of the Dnmt3a protein (UniProt.org). R882H disrupts the tetramerization ability of the Dnmt3a protein, resulting in reduced DNA binding affinity and altered catalytic activity in in vitro assays (PMID: 22722925), and results in hypomethylation, cytokine-independent growth, increased cell proliferation and impaired differentiation in cultured cells (PMID: 31164355, PMID: 32015320). |
Associated Drug Resistance |
Transcript | NM_022552.4 |
gDNA | chr2:g.25234373C>T |
cDNA | c.2645G>A |
Protein | p.R882H |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
XM_017003526.1 | chr2:g.25234373C>T | c.2645G>A | p.R882H | RefSeq | GRCh38/hg38 |
XM_017003526 | chr2:g.25234373C>T | c.2645G>A | p.R882H | RefSeq | GRCh38/hg38 |
XM_005264175 | chr2:g.25234373C>T | c.2645G>A | p.R882H | RefSeq | GRCh38/hg38 |
NM_022552 | chr2:g.25234373C>T | c.2645G>A | p.R882H | RefSeq | GRCh38/hg38 |
XM_005264175.5 | chr2:g.25234373C>T | c.2645G>A | p.R882H | RefSeq | GRCh38/hg38 |
NM_022552.4 | chr2:g.25234373C>T | c.2645G>A | p.R882H | RefSeq | GRCh38/hg38 |
NM_175629.2 | chr2:g.25234373C>T | c.2645G>A | p.R882H | RefSeq | GRCh38/hg38 |
NM_175629 | chr2:g.25234373C>T | c.2645G>A | p.R882H | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
DNMT3A R882H NRAS G12D | acute myeloid leukemia | sensitive | I-BET151 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, an acute myeloid leukemia cell line harboring DNMT3A R882H and NRAS G12D mutations demonstrated reduced proliferation and downregulation of a DNMT3A R882H associated gene expression profile upon I-BET151 treatment in culture, and I-BET151 treatment delayed the onset of leukemia symptoms and improved survival in xenograft mouse models derived from these cells (PMID: 31164355). | 31164355 |
DNMT3A R882H NRAS G12D | acute myeloid leukemia | sensitive | I-BET151 + Trametinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, an acute myeloid leukemia cell line xenograft model harboring DNMT3A R882H and NRAS G12D treated with combined I-BET151 and Mekinist (trametinib) demonstrated impaired disease progression and improved survival superior to either therapy alone (PMID: 31164355). | 31164355 |
DNMT3A R882H NRAS G12D | acute myeloid leukemia | sensitive | Trametinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, an acute myeloid leukemia cell line xenograft model harboring DNMT3A R882H and NRAS G12D was sensitive to Mekinist (trametinib), demonstrating impaired disease progression and improved survival (PMID: 31164355). | 31164355 |
Molecular Profile | Protein Effect | Treatment Approaches |
---|---|---|
DNMT3A R882H | loss of function | |
DNMT3A R882H NRAS G12D |