Table 2.
Biochemical impact of mutations in DNMT3A found in cancer patients
| Residue (murine) | AA | Disease | Domain | Consequence | Refs |
|---|---|---|---|---|---|
| 308 (304) | Q | AML | PWWP | H3 | 159 |
| 664 (660) | E | AML | Motif II | Cat | 60 |
| 710 (706) | C | sAML from MDS | Motif IV | Cat, DNA, AdoMet (−) | 60 |
| 714 (710) | C | AML | Following motif IV | AdoMet | 60 |
| 720 (716) | N | T-ALL | Following motif IV | Cat, DNA | 60 |
| 729 (725) | R | AML | Catalytic | DNA | 106 |
| 733 (729) | E | AML, CMML | Catalytic | DNA | 106 |
| 771 (767) | R | AML, MDS, SM | Catalytic | DNA | 106 |
| 792 (788) | R | T-ALL | Motif VIII | Cat, DNA (+) | 60 |
| 826 (822) | K | MDS | Catalytic | DNAMulti | 167 |
| 841 (837) | K | AML | Catalytic | DNAMulti | 167 |
| 856 (852) | E | T-ALL | Catalytic | DNA (+) | 167 |
| 860 (856) | W | AML | Catalytic | Cat | 105 |
| 879 (875) | N | AML | Catalytic | Cat | 105 |
| 882 (878) | R | AML | In front of motif X | Cat, DNA | 60 |
AA, amino acid; AdoMet, S-adenosyl methionine reduced AdoMet binding; AdoMet (−), no AdoMet binding; AML, acute myeloid leukaemia; Cat, reduced catalytic activity; CMML, chronic myelomonocytic leukaemia; DNA, reduced DNA binding; DNA (+), enhanced DNA binding; DNAMulti, loss of ability to multimerize on DNA; DNMT3A, DNA methyltransferase 3A; H3, insensitive to H3 peptide; MDS, myelodysplastic syndrome; PWWP, Pro-Trp-Trp-Pro; sAML, secondary AML; SM, systemic mastocytosis; T-ALL, T cell acute lymphoblastic leukaemia.