Gene

DNMT3A

DNA methyltransferase 3 alpha

Explore in graph →CI-GENE-00043700HGNC:2978 ENSG00000119772 NCBI 1788 CIViC Cancer geneApproved

Curated evidence

Clinical evidence (41)

CIViC items involving this gene, grouped by molecular profile and therapy, with native levels and directions. 50 items per page.

civicCuratedShowing 1–41 of 41 evidence items · levels, directions and significance as curated at the source; each row links to its CIViC record.

Therapy	Cancer	Type	Level	Direction · significance	Rating (1–5)	Status	Evidence	Source
DNMT3A Mutation7
(prognostic)	T Acute Lymphoblastic LeukemiaCURATED_BROADER	Prognostic	B	Supports Poor Outcome	4	accepted

Cohorts

Alteration frequency by cohort (149)

Frequency = cases affected / cases profiled within one cohort. Cohorts are never pooled.

cbioportalObserved149 cohort rows (showing 50, sorted by frequency) · frequency = affected / profiled, as published by each cohort; cohorts are not pooled. Hover a row badge for its release.

Cohort	Mapped cancer	Alteration	Affected (n)	Profiled (n)	Frequency (%)	Rank in cohort	Source
Colorectal Cancer (MSK, Cancer Discovery 2022) coadread_mskresistance_2022	Colorectal Adenocarcinoma	Ssm

Literature

Linked publications (12)

25 per page, newest first.

pubmedPublishedShowing 1–12 of 12 publications · bibliographic data as recorded by PubMed; abstracts are not reproduced.

DNMT3A mutations in acute myeloid leukemia.
· N Engl J Med · 2010 · PMID 21067377 · validated civic_curation pubmed
DNMT3A R882 mutations in patients with cytogenetically normal acute myeloid leukemia and myelodysplastic syndrome.
· Blood Cells Mol Dis · 2014 · PMID 24512939 · validated civic_curation pubmed
Genomic Classification and Prognosis in Acute Myeloid Leukemia.
· N Engl J Med · 2016 · PMID 27276561 · validated civic_curation pubmed
Do AML patients with DNMT3A exon 23 mutations benefit from idarubicin as compared to daunorubicin? A single center experience.
· Oncotarget · 2011 · PMID 22081665 · validated civic_curation pubmed

DNMT3A P904L1
5-Fluoro-2-Deoxycytidine + Azacitidine + Decitabine + GuadecitabineCombination	Myelodysplastic SyndromeCURATED_BROADER	Predictive	E	Supports Sensitivity Response	3	rejected	EID1134 Previously only reported in haematopoietic and lymphoid malignancies, P904 is a likely activating event, whose function has not been well characterized. In the tertiary protein structure, the mutation… (full text at CIViC) PMID 21415852 · Walter et al., 2011 · Open in CIViC	civic

DNMT3A P904L1

5-Fluoro-2-Deoxycytidine + Azacitidine + Decitabine + GuadecitabineCombination

Myelodysplastic SyndromeCURATED_BROADER

Predictive

Supports Sensitivity Response

rejected

EID1134

Previously only reported in haematopoietic and lymphoid malignancies, P904 is a likely activating event, whose function has not been well characterized. In the tertiary protein structure, the mutation… (full text at CIViC)

PMID 21415852 · Walter et al., 2011 · Open in CIViC

DNMT3A R88228
(prognostic)	Acute Myeloid LeukemiaCURATED_BROADER	Prognostic	B	Supports Poor Outcome	5	accepted	EID62 AML patients with DNMT3A mutations (59% of which were R882) showed worse survival (event-free and overall) outcome than those without DNMT3A mutation. PMID 21067377 · Ley et al., 2010 · Open in CIViC	civic
〃	Acute Myeloid LeukemiaCURATED_BROADER	Prognostic	B	Supports Poor Outcome	5	accepted	EID64 In AML patients with FLT3-ITD mutations, concurrent DNMT3A mutations (including R882) were associated with worse overall survival compared to those without DNMT3A mutation. PMID 21067377 · Ley et al., 2010 · Open in CIViC	civic
〃	Acute Myeloid LeukemiaCURATED_BROADER	Prognostic	B	Supports Poor Outcome	5	accepted	EID65 In cytogenetically normal AML patients, DNMT3A R882 mutations are associated with lower overall and disease free survival as compared to patients with wild type DNMT3A. PMID 24512939 · El Ghannam et al., 2014 · Open in CIViC	civic
(diagnostic)	Acute Myeloid LeukemiaCURATED_BROADER	Diagnostic	B	Supports Positive	5	accepted	EID112 DNMT3A mutations (59% of which were R882) were associated with an intermediate risk cytogenetic profile, normal cytogenetic profile, and M4 and M5 FAB subtypes. PMID 21067377 · Ley et al., 2010 · Open in CIViC	civic
(prognostic)	Acute Myeloid LeukemiaCURATED_BROADER	Prognostic	B	Does Not Support Poor Outcome	4	accepted	EID24 There is no difference in the complete remission rate of de novo AML patients with DNMT3A mutation compared to those who are wild type for DNMT3A. PMID 22081665 · LaRochelle et al., 2011 · Open in CIViC	civic
〃	Acute Myeloid LeukemiaCURATED_BROADER	Prognostic	B	Supports Poor Outcome	4	accepted	EID25 De novo AML patients with DNMT3A D882 mutation showed worse survival (event-free and overall) outcome than those without DNMT3A mutation. PMID 21067377 · Ley et al., 2010 · Open in CIViC	civic
〃	Acute Myeloid LeukemiaCURATED_BROADER	Prognostic	B	Does Not Support N/A	4	accepted	EID51 In young AML patients (<60 years old), DNMT3A mutation status (60% of which were R882) was not predictive of overall and relapse free survival in patients with NPM1 mutations and wildtype FLT3 or wild… (full text at CIViC) PMID 22490330 · Ribeiro et al., 2012 · Open in CIViC	civic
〃	Acute Myeloid LeukemiaCURATED_BROADER	Prognostic	B	Supports Poor Outcome	4	accepted	EID66 In older cytogenetically normal AML patients (>59 years), DNMT3A R882 mutation is prognostic for shorter disease free survival and overall survival compared to patients without the mutation. PMID 22291079 · Marcucci et al., 2012 · Open in CIViC	civic
〃	Acute Myeloid LeukemiaCURATED_BROADER	Prognostic	B	Supports Poor Outcome	4	accepted	EID67 In young AML patients (<60 years old), DNMT3A mutations were associated with significantly reduced overall survival and relapse free survival in patients wildtype for NPM1 and FLT3. PMID 22490330 · Ribeiro et al., 2012 · Open in CIViC	civic
〃	Acute Myeloid LeukemiaCURATED_BROADER	Prognostic	B	Supports Poor Outcome	4	accepted	EID68 In younger cytogenetically normal AML patients (<60 years), DNMT3A mutations other than R882 are prognostic for shorter disease free survival and overall survival compared to patients without the muta… (full text at CIViC) PMID 22291079 · Marcucci et al., 2012 · Open in CIViC	civic
〃	Acute Myeloid LeukemiaCURATED_BROADER	Prognostic	B	Does Not Support N/A	4	accepted	EID157 Complete remission rates did not differ between patients with wildtype or mutant DNMT3A (62% of which affected R882) and cytogenetically normal AML. PMID 22291079 · Marcucci et al., 2012 · Open in CIViC	civic
〃	Acute Myeloid LeukemiaCURATED_BROADER	Prognostic	B	Supports Poor Outcome	4	accepted	EID187 DNMT3A mutations (62% of which were R882) were associated with reduced disease-free survival in patients with cytogenetically normal AML. PMID 22291079 · Marcucci et al., 2012 · Open in CIViC	civic
(diagnostic)	Acute Myeloid LeukemiaCURATED_BROADER	Diagnostic	B	Supports Positive	3	accepted	EID4 Young AML patients (<60 years old) with DNMT3A mutations (60% of which were R882) were older in age, had higher white blood cell counts and had higher platelet counts than patients wildtype for DNMT3A… (full text at CIViC) PMID 22490330 · Ribeiro et al., 2012 · Open in CIViC	civic
〃	Acute Myeloid LeukemiaCURATED_BROADER	Diagnostic	B	Supports Positive	3	accepted	EID31 DNMT3A R882 mutations were associated with older age, higher white blood cell count, and FAB M4 and M5 subtypes compared to wildtype DNMT3A in a cohort of cytogenetically normal AML patients. PMID 24512939 · El Ghannam et al., 2014 · Open in CIViC	civic
(prognostic)	Acute Myeloid LeukemiaCURATED_BROADER	Prognostic	B	Does Not Support N/A	3	accepted	EID49 In a large cohort of AML patients (mean = 48 years), DNMT3A mutation (64.5% of which were R882) had no prognostic value on overall, relapse free and event free survival. PMID 23632886 · Gaidzik et al., 2013 · Open in CIViC	civic
〃	Acute Myeloid LeukemiaCURATED_BROADER	Prognostic	B	Does Not Support Poor Outcome	3	accepted	EID50 In a large cohort (n=1770) of AML patients (18-60 years old), DNMT3A mutation status (65.4% of which were R882) had no prognostic value for overall, relapse free and event free survival. This was true… (full text at CIViC) PMID 23632886 · Gaidzik et al., 2013 · Open in CIViC	civic
〃	Acute Myeloid LeukemiaCURATED_BROADER	Prognostic	B	Supports Poor Outcome	3	accepted	EID61 In a large cohort of young AML patients (18-60 years old), DNMT3A R882 mutations were associated with reduced relapse free survival in the entire cohort as well as the subset of patients with cytogene… (full text at CIViC) PMID 23632886 · Gaidzik et al., 2013 · Open in CIViC	civic
〃	Acute Myeloid LeukemiaCURATED_BROADER	Prognostic	B	Supports Poor Outcome	3	accepted	EID63 DNMT3A R882 mutation was associated with reduced relapse free and overall survival in ELN-unfavorable, cytogenetically normal AMLs. PMID 23632886 · Gaidzik et al., 2013 · Open in CIViC	civic
(diagnostic)	Acute Myeloid LeukemiaCURATED_BROADER	Diagnostic	B	Supports Negative	3	accepted	EID110 Therapy-related AML was less common in patients with DNMT3A mutations (64.5% of which were R882) than patients wildtype for DNMT3A in a large cohort of younger (18-60) AML patients. PMID 23632886 · Gaidzik et al., 2013 · Open in CIViC	civic
〃	Acute Myeloid LeukemiaCURATED_BROADER	Diagnostic	B	Supports Positive	3	accepted	EID114 DNMT3A mutations (64.5% R882) were associated with older age, higher white blood cell count and cytogenetically normal AML in a large cohort of younger (18-60) AML patients. PMID 23632886 · Gaidzik et al., 2013 · Open in CIViC	civic
〃	Acute Myeloid LeukemiaCURATED_BROADER	Diagnostic	B	Supports Positive	3	accepted	EID115 DNMT3A R882 mutations were associated with cytogenetically normal AML in a large cohort of younger (18-60) AML patients. PMID 23632886 · Gaidzik et al., 2013 · Open in CIViC	civic
(prognostic)	Acute Myeloid LeukemiaCURATED_BROADER	Prognostic	B	Supports Better Outcome	3	accepted	EID170 DNMT3A mutations were associated with achievement of complete remission in a large cohort of younger (18-60) AML patients. PMID 23632886 · Gaidzik et al., 2013 · Open in CIViC	civic
〃	Acute Myeloid LeukemiaCURATED_BROADER	Prognostic	B	Supports Poor Outcome	3	accepted	EID186 Complete remission rate was not different between young AML patients (<60 years old) with or without DNMT3A mutations (60% of which were R882). PMID 22490330 · Ribeiro et al., 2012 · Open in CIViC	civic
〃	Acute Myeloid LeukemiaCURATED_BROADER	Prognostic	B	Supports Poor Outcome	3	accepted	EID189 Young AML patients (415 patients; <60 years old) with DNMT3A R882 mutations (n=58) have shorter overall and relapse-free survival than patients with wildtype DNMT3A. PMID 22490330 · Ribeiro et al., 2012 · Open in CIViC	civic
(diagnostic)	Acute Myeloid LeukemiaCURATED_BROADER	Diagnostic	B	Supports Positive	2	rejected	EID3 DNMT3A R882 mutations occur most often in de novo AML patients with intermediate risk cytogenetics (39/194 intermediate risk patients vs 0/89 low and high risk). PMID 22081665 · LaRochelle et al., 2011 · Open in CIViC	civic
(prognostic)	Acute Myeloid LeukemiaCURATED_BROADER	Prognostic	B	Does Not Support Better Outcome	2	accepted	EID113 DNMT3A mutations (59% of which were R882) were associated with intermediate risk cytogenetics (including normal karyotype) and not favorable risk cytogenetic abnormalities (PML::RARA, RUNX1::RUNX1T1, … (full text at CIViC) PMID 21067377 · Ley et al., 2010 · Open in CIViC	civic
Daunorubicin	Acute Myeloid LeukemiaCURATED_BROADER	Predictive	B	Does Not Support Resistance	4	accepted	EID11 Daunorubicin treatment resulted in similar overall survival and disease free survival in de novo AML patients with DNMT3A R882 mutation compared to those who do not harbor this mutation. PMID 22081665 · LaRochelle et al., 2011 · Open in CIViC	civic
Idarubicin	Acute Myeloid LeukemiaCURATED_BROADER	Predictive	B	Supports Sensitivity Response	4	accepted	EID18 Idarubicin increases the overall survival and disease free survival in de novo AML patients with DNMT3A R882 mutation compared to those who do not harbor this mutation. PMID 22081665 · LaRochelle et al., 2011 · Open in CIViC	civic

DNMT3A R882H3
(oncogenic)	Acute Leukemia	Oncogenic	D	Supports Oncogenicity	5	submitted	EID7232 The DNMT3A mutational hotspot at Arg882 (DNMT3A(R882H)) cooperates with NRAS mutation to transform hematopoietic stem/progenitor cells and induce acute leukemia development. Mechanistically, DNMT3A(R8… (full text at CIViC) PMID 27344947 · Lu et al., 2016 · Open in CIViC	civic
(functional)	—UNRESOLVED	Functional	D	Supports Loss Of Function	4	submitted	EID13323 The DNMT3A R882H variant resulted had a statistically significant reduction in DNA methylation potential in NK-AML cells when compared to WT samples (p= 4.5 × 10-6), particularly when looking at focal… (full text at CIViC) PMID 24656771 · Russler-Germain et al., 2014 · Open in CIViC	civic
〃	—UNRESOLVED	Functional	D	Supports Dominant Negative	3	submitted	EID13324 Co-transfection in HEK293T cells revealed a potential dominant negative effect on methyltransferase function of the protein by creating inactive heterodimers that inhibit WT homotetramer formation. PMID 24656771 · Russler-Germain et al., 2014 · Open in CIViC	civic