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Gene Symbol DNMT3A
Synonyms DNMT3A2 | HESJAS | M.HsaIIIA | TBRS
Gene Description DNMT3A, DNA methyltransferase 3 alpha, mediates DNA methylation and functions in modification of gene expression, and plays a role in hematopoietic differentiation (PMID: 28286768, PMID: 25693834). DNMT3A mutations are frequent in acute myeloid leukemia, and are recurrent in myelodysplastic syndromes (PMID: 28286768, PMID: 28003281).
NCBI Gene ID Chromosome Map Location Canonical Transcript Gene Role
1788 2 2p23.3 NM_022552 Tumor suppressor (PMID: 30606230)

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Variant Impact Protein Effect Variant Description Associated with drug Resistance
A121S missense unknown DNMT3A A121S does not lie within any known functional domains of the Dnmt3a protein (UniProt.org). A121S has been identified in the scientific literature (PMID: 26960398), but has not been biochemically characterized and therefore, its effect on Dnmt3a protein function is unknown (PubMed, Jul 2024).
A376T missense unknown DNMT3A A376T lies within the DNMT1 and DNMT3B-interacting region of the Dnmt3a protein (UniProt.org). A376T has been identified in the scientific literature (PMID: 23300180), but has not been biochemically characterized and therefore, its effect on Dnmt3a protein function is unknown (PubMed, Jul 2024).
A741V missense unknown DNMT3A A741V lies within the SAM-dependent MTase C5-type domain of the Dnmt3a protein (UniProt.org). A741V has been identified in sequencing studies (PMID: 21067377, PMID: 26373574, PMID: 32774506), but has not been biochemically characterized and therefore, its effect on Dnmt3a protein function is unknown (PubMed, Jul 2024).
A910V missense unknown DNMT3A A910V lies within the SAM-dependent MTase C5-type domain of the Dnmt3a protein (UniProt.org). A910V has been identified in sequencing studies (PMID: 24923295, PMID: 27534895, PMID: 21993668), but has not been biochemically characterized and therefore, its effect on Dnmt3a protein function is unknown (PubMed, Jul 2024).
act mut unknown gain of function DNMT3A act mut indicates that this variant results in a gain of function in the Dnmt3a protein. However, the specific amino acid change has not been identified.
amp none no effect DNMT3A amplification indicates an increased number of copies of the DNMT3A gene. However, the mechanism causing the increase is unspecified.
C497Y missense unknown DNMT3A C497Y lies within the ADD domain of the Dnmt3a protein (UniProt.org). C497Y has been identified in sequencing studies (PMID: 27276561, PMID: 25092143, PMID: 31004019), but has not been biochemically characterized and therefore, its effect on Dnmt3a protein function is unknown (PubMed, Jul 2024).
C911Y missense unknown DNMT3A C911Y lies within the SAM-dependent MTase C5-type domain of the Dnmt3a protein (Uniprot.org). C911Y has been identified in sequencing studies (PMID: 22722750, PMID: 36912186), but has not been biochemically characterized and therefore, its effect on Dnmt3a protein function is unknown (PubMed, Oct 2024).
D768A missense no effect - predicted DNMT3A D768A lies within the SAM-dependent MTase C5-type domain of the Dnmt3a protein (UniProt.org). D768A retains the ability to form DNA-bound Dnmt3a tetramers and leads to catalytic activity comparable to wild-type in in vitro assays (PMID: 21979949), and therefore, is predicted to have no effect on Dnmt3a protein function.
D811Y missense unknown DNMT3A D811Y lies within the SAM-dependent MTase C5-type domain of the Dnmt3a protein (UniProt.org). D811Y has been identified in the scientific literature (PMID: 26960398), but has not been biochemically characterized and therefore, its effect on Dnmt3a protein function is unknown (PubMed, Oct 2024).
D876G missense loss of function DNMT3A D876G lies within the SAM-dependent MTase C5-type domain of the Dnmt3a protein (UniProt.org). D876G disrupts Dnmt3a tetramer formation and leads to decreased Dnmt3a activity in in vitro assays (PMID: 22722925).
del deletion loss of function DNMT3A del indicates a deletion of the DNMT3A gene.
E240* nonsense loss of function - predicted DNMT3A E240* results in a premature truncation of the Dnmt3a protein at amino acid 240 of 912 (UniProt.org). E240* has not been characterized, however, due to the effects of other truncation mutations downstream of E240 (PMID: 28872462, PMID: 26595813, PMID: 35639959), is predicted to lead to a loss of Dnmt3a protein function.
E240fs frameshift loss of function - predicted DNMT3A E240fs results in a change in the amino acid sequence of the Dnmt3a protein beginning at aa 240 of 912, likely resulting in premature truncation of the functional protein (UniProt.org). E240fs has not been characterized, however, due to the effects of other truncation mutations downstream of E240 (PMID: 28872462, PMID: 26595813, PMID: 35639959), is predicted to lead to a loss of Dnmt3a protein function.
E285* nonsense loss of function - predicted DNMT3A E285* results in a premature truncation of the Dnmt3a protein at amino acid 285 of 912 (UniProt.org). E285* has not been characterized, however, due to the effects of other truncation mutations downstream of E285 (PMID: 28872462, PMID: 26595813, PMID: 35639959), is predicted to lead to a loss of Dnmt3a protein function.
E30A missense unknown DNMT3A E30A does not lie within any known functional domains of the Dnmt3a protein (UniProt.org). E30A has been identified in sequencing studies (PMID: 27486981, PMID: 37435532, PMID: 32060404), but has not been biochemically characterized and therefore, its effect on Dnmt3a protein function is unknown (PubMed, Oct 2024).
E477* nonsense loss of function - predicted DNMT3A E477* results in a premature truncation of the Dnmt3a protein at amino acid 477 of 912 (UniProt.org). E477* has not been characterized, however, due to the effects of other truncation mutations downstream of E477 (PMID: 28872462, PMID: 26595813, PMID: 35639959), is predicted to lead to a loss of Dnmt3a protein function.
E505* nonsense loss of function - predicted DNMT3A E505* results in a premature truncation of the Dnmt3a protein at amino acid 505 of 912 (UniProt.org). E505* has not been characterized, however, due to the effects of other truncation mutations downstream of E505 (PMID: 28872462, PMID: 26595813, PMID: 35639959), is predicted to lead to a loss of Dnmt3a protein function.
E616fs frameshift loss of function DNMT3A E616fs results in a change in the amino acid sequence of the Dnmt3a protein beginning at aa 616 of 912, likely resulting in premature truncation of the functional protein (UniProt.org). E616fs confers a loss of function to the Dnmt3a protein as demonstrated by failure to dimerize with wild-type Dnmt3a and loss of methyltransferase activity in in vitro assays (PMID: 28872462).
E664K missense unknown DNMT3A E664K lies within the SAM-dependent MTase C5-type domain of the Dnmt3A protein (UniProt.org). E664K has been identified in sequencing studies (PMID: 22749068, PMID: 31004019, PMID: 32269971), but has not been biochemically characterized and therefore, its effect on Dnmt3A protein function is unknown (PubMed, Oct 2024).
E733A missense loss of function DNMT3A E733A lies within the SAM-dependent MTase C5-type domain of the Dnmt3a protein (UniProt.org). E733A disrupts Dnmt3a tetramer formation (PMID: 21979949) and leads to reduced catalytic activity in in vitro assays (PMID: 36528185, PMID: 21979949).
F414S missense unknown DNMT3A F414S does not lie within any known functional domains of the Dnmt3a protein (UniProt.org). F414S has been identified in sequencing studies (PMID: 21720365), but has not been biochemically characterized and therefore, its effect on Dnmt3a protein function is unknown (PubMed, Oct 2024).
F731fs frameshift loss of function - predicted DNMT3A F731fs results in a change in the amino acid sequence of the Dnmt3a protein beginning at aa 731 of 912, likely resulting in premature truncation of the functional protein (UniProt.org). F731fs has not been characterized, however, due to the effects of other truncation mutations downstream of F731 (PMID: 35639959), is predicted to lead to a loss of Dnmt3a protein function.
F732A missense loss of function DNMT3A F732A lies within the SAM-dependent MTase C5-type domain of the Dnmt3a protein (UniProt.org). F732A disrupts Dnmt3a tetramer formation in an in vitro assay (PMID: 21979949) and in cell culture (PMID: 31582562) and leads to reduced catalytic activity in an in vitro assay (PMID: 21979949).
F732del deletion unknown DNMT3A F732del results in the deletion of an amino acid in the SAM-dependent MTase C5-type domain of the Dnmt3a protein at amino acid 732 (UniProt.org). F732del has been identified in sequencing studies (PMID: 28411256, PMID: 38359296), but has not been biochemically characterized and therefore, its effect on Dnmt3a protein function is unknown (PubMed, Oct 2024).
F751fs frameshift loss of function - predicted DNMT3A F751fs results in a change in the amino acid sequence of the Dnmt3a protein beginning at aa 751 of 912, likely resulting in premature truncation of the functional protein (UniProt.org). F751fs has not been characterized, however, due to the effects of other truncation mutations downstream of F751 (PMID: 35639959), is predicted to lead to a loss of Dnmt3a protein function.
F752V missense loss of function - predicted DNMT3A F752V lies within the SAM-dependent MTase C5-type domain of the Dnmt3a protein (UniProt.org). F752V (corresponds to F748V in mouse) retains DNA-binding ability but results in loss of methylation activity in in vitro assays (PMID: 31861499), and therefore, is predicted to lead to a loss of Dnmt3a protein function.
F772A missense gain of function - predicted DNMT3A F772A lies within the SAM-dependent MTase C5-type domain of the Dnmt3a protein (UniProt.org). F772A demonstrates higher catalytic activity compared to wild-type protein in an in vitro assay (PMID: 36528185), and therefore, is predicted to lead to a gain of Dnmt3a protein function.
F868S missense unknown DNMT3A F868S lies within the SAM-dependent MTase C5-type domain of the Dnmt3a protein (UniProt.org). F868S has been identified in sequencing studies (PMID: 28634182, PMID: 33255857, PMID: 38359296), but has not been biochemically characterized and therefore, its effect on Dnmt3a protein function is unknown (PubMed, Oct 2024).
F902S missense unknown DNMT3A F902S lies within the SAM-dependent MTase C5-type domain of the Dnmt3a protein (UniProt.org). F902S results in reduced interaction with Mbd1, Bach1, Brd1, Dnmt3b, and Foxk2 (Blood (2022) 140 (Supplement 1): 8727–8728), but has not been fully biochemically characterized and therefore, its effect on Dnmt3a protein function is unknown.
F909C missense unknown DNMT3A F909C lies within the SAM-dependent MTase C5-type domain of the Dnmt3a protein (UniProt.org). F909C has been identified in sequencing studies (PMID: 22817890, PMID: 21067377), but has not been biochemically characterized and therefore, its effect on Dnmt3a protein function is unknown (PubMed, Oct 2024).
G104E missense unknown DNMT3A G104E does not lie within any known functional domains of the Dnmt3a protein (UniProt.org). G104E has not been characterized in the scientific literature and therefore, its effect on Dnmt3a protein function is unknown (PubMed, Oct 2024).
G302del deletion unknown DNMT3A G302del results in the deletion of an amino acid in the PWWP domain of the Dnmt3a protein at amino acid 302 (UniProt.org). G302del has been identified in the scientific literature (PMID: 24659740), but has not been biochemically characterized and therefore, its effect on Dnmt3a protein function is unknown (PubMed, Oct 2024).
G543C missense unknown DNMT3A G543C lies within the ADD domain of the Dnmt3a protein (UniProt.org). G543C has been identified in the scientific literature (PMID: 32060404), but has not been biochemically characterized and therefore, its effect on Dnmt3a protein function is unknown (PubMed, Oct 2024).
G590fs frameshift loss of function - predicted DNMT3A G590fs results in a change in the amino acid sequence of the Dnmt3a protein beginning at aa 590 of 912, likely resulting in premature truncation of the functional protein (UniProt.org). G590fs has not been characterized, however, due to the effects of other truncation mutations downstream of G590 (PMID: 28872462, PMID: 26595813, PMID: 35639959), is predicted to lead to a loss of Dnmt3a protein function.
G685E missense unknown DNMT3A G685E lies within the SAM-dependent MTase C5-type domain of the Dnmt3a protein (UniProt.org). G685E has been identified in sequencing studies (PMID: 22842228), but has not been biochemically characterized and therefore, its effect on Dnmt3a protein function is unknown (PubMed, Oct 2024).
G699fs frameshift loss of function - predicted DNMT3A G699fs results in a change in the amino acid sequence of the Dnmt3a protein beginning at aa 699 of 912, likely resulting in premature truncation of the functional protein (UniProt.org). G699fs has not been characterized, however, due to the effects of other truncation mutations downstream of G699 (PMID: 28872462, PMID: 35639959), is predicted to lead to a loss of Dnmt3a protein function.
G707fs frameshift loss of function - predicted DNMT3A G707fs results in a change in the amino acid sequence of the Dnmt3a protein beginning at aa 707 of 912, likely resulting in premature truncation of the functional protein (UniProt.org). G707fs has not been characterized, however, due to the effects of other truncation mutations downstream of G707 (PMID: 28872462, PMID: 35639959), is predicted to lead to a loss of Dnmt3a protein function.
G746V missense unknown DNMT3A G746V lies within the SAM-dependent MTase C5-type domain of the Dnmt3a protein (UniProt.org). G746V has been identified in the scientific literature (PMID: 27147599), but has not been biochemically characterized and therefore, its effect on Dnmt3a protein function is unknown (PubMed, Oct 2024).
G890D missense unknown DNMT3A G890D lies within the SAM-dependent MTase C5-type domain of the Dnmt3a protein (UniProt.org). G890D has been identified in sequencing studies (PMID: 22749068, PMID: 25426838, PMID: 25426837), but has not been biochemically characterized and therefore, its effect on Dnmt3a protein function is unknown (PubMed, Oct 2024).
H739A missense no effect - predicted DNMT3A H739A lies within the SAM-dependent MTase C5-type domain of the Dnmt3a protein (UniProt.org). H739A retains the ability to form DNA-bound Dnmt3a tetramers and leads to catalytic activity comparable to wild-type in in vitro assays (PMID: 21979949), and therefore, is predicted to have no effect on Dnmt3a protein function.
H873A missense loss of function DNMT3A H873A lies within the dimer interface region of the Dnmt3a protein (PMID: 22722925). H873A disrupts the teramerization ability of the Dnmt3a protein, resulting in reduced DNA binding affinity, reduced methylation activity, and altered catalytic activity (PMID: 22722925).
H873R missense loss of function DNMT3A H873R lies within the dimer interface region of the Dnmt3a protein (PMID: 22722925). H873R disrupts the teramerization ability of the Dnmt3a protein, resulting in reduced DNA binding affinity, reduced methylation activity, and altered catalytic activity (PMID: 22722925).
I407T missense unknown DNMT3A I407T does not lie within any known functional domains of the Dnmt3a protein (UniProt.org). I407T has been identified in sequencing studies (PMID: 22642896), but has not been biochemically characterized and therefore, its effect on Dnmt3a protein function is unknown (PubMed, Oct 2024).
I643M missense unknown DNMT3A I643M lies within the SAM-dependent MTase C5-type domain of the Dnmt3a protein (UniProt.org). I643M has been identified in sequencing studies (PMID: 28634182), but has not been biochemically characterized and therefore, its effect on Dnmt3a protein function is unknown (PubMed, Oct 2024).
inact mut unknown loss of function DNMT3A inact mut indicates that this variant results in a loss of function of the Dnmt3a protein. However, the specific amino acid change has not been identified.
K299I missense unknown DNMT3A K299I lies within the PWWP domain of the Dnmt3a protein (UniProt.org). K299I (corresponds to K295I in mouse) results in hypermethylation of target DNA in culture (PMID: 29740169, PMID: 33986537), but decreased binding with H3K36me2/3, loss of DNA binding and interaction with oligonucleosomes, and loss of localization to heterochromatin in cultured cells in another study (PMID: 31634469), and therefore, its effect on Dnmt3a protein function is unknown.
K721R missense unknown DNMT3A K721R lies within the SAM-dependent MTase C5-type domain of the Dnmt3a protein (UniProt.org). K721R has not been characterized in the scientific literature and therefore, its effect on Dnmt3a protein function is unknown (PubMed, Oct 2024).
K829R missense unknown DNMT3A K829R lies within the SAM-dependent MTase C5-type domain of the Dnmt3a protein (UniProt.org). K829R has been identified in sequencing studies (PMID: 21067377), but has not been biochemically characterized and therefore, its effect on Dnmt3a protein function is unknown (PubMed, Oct 2024).
K841E missense loss of function DNMT3A K841E lies within the SAM-dependent MTase C5-type domain of the Dnmt3a protein (UniProt.org). K841E results in decreased Dnmt3a enzymatic activity, reduced cytosine methylation in the presence of wild-type Dnmt3a, and cytokine-independent growth in cell culture (PMID: 29414941).
K841Q missense unknown DNMT3A K841Q lies within the SAM-dependent MTase C5-type domain of the Dnmt3a protein (UniProt.org). K841Q has been identified in sequencing studies (PMID: 21067377), but has not been biochemically characterized and therefore, its effect on Dnmt3a protein function is unknown (PubMed, Oct 2024).
L723fs frameshift loss of function DNMT3A L723fs results in a change in the amino acid sequence of the Dnmt3a protein beginning at aa 723 of 912, likely resulting in premature truncation of the functional protein (UniProt.org). L723fs confers a loss of function to the Dnmt3a protein as demonstrated by failure to dimerize with wild-type Dnmt3a and loss of methyltransferase activity in in vitro assays (PMID: 28872462).
L737F missense unknown DNMT3A L737F lies within the SAM-dependent MTase C5-type domain of the Dnmt3a protein (UniProt.org). L737F has been identified in sequencing studies (PMID: 21720365, PMID: 32577167), but has not been biochemically characterized and therefore, its effect on Dnmt3a protein function is unknown (PubMed, Oct 2024).
L805* nonsense loss of function - predicted DNMT3A L805* results in a premature truncation of the Dnmt3a protein at amino acid 805 of 912 (UniProt.org). L805* has not been characterized, however, due to the effects of other truncation mutations downstream of L805 (PMID: 35639959), is predicted to lead to a loss of Dnmt3a protein function.
loss unknown loss of function DNMT3A loss indicates loss of the DNMT3A gene, mRNA, and protein.
M513I missense unknown DNMT3A M513I lies within the ADD domain of the Dnmt3a protein (UniProt.org). M513I has been identified in the scientific literature (PMID: 27276561), but has not been biochemically characterized and therefore, its effect on Dnmt3a protein function is unknown (PubMed, Oct 2024).
M880I missense unknown DNMT3A M880I lies within the SAM-dependent MTase C5-type domain of the Dnmt3a protein (UniProt.org). M880I has been identified in the scientific literature (PMID: 27276561), but has not been biochemically characterized and therefore, its effect on Dnmt3a protein function is unknown (PubMed, Oct 2024).
mutant unknown unknown DNMT3A mutant indicates an unspecified mutation in the DNMT3A gene.
N838D missense loss of function DNMT3A N838D lies within the SAM-dependent MTase C5-type domain of the Dnmt3a protein (UniProt.org). N838D results in reduced Dnmt3A enzymatic activity and decreased DNA methylation at commonly demethylated sites, and cytokine-independent growth in cell culture (PMID: 29414941).
N879A missense loss of function DNMT3A N879A lies within the dimer interface region of the Dnmt3a protein (PMID: 22722925). N879A disrupts the teramerization ability of the Dnmt3a protein, resulting in reduced DNA binding affinity, reduced methylation activity, and altered catalytic activity (PMID: 22722925).
over exp none no effect DNMT3A over exp indicates an over expression of the Dnmt3a protein. However, the mechanism causing the over expression is unspecified.
P569_A574del deletion unknown DNMT3A P569_A574del results in the deletion of six amino acids in the ADD domain of the Dnmt3a protein from amino acids 569 to 574 (UniProt.org). P569_A574del has not been characterized in the scientific literature and therefore, its effect on Dnmt3a protein function is unknown (PubMed, Oct 2024).
P59L missense unknown DNMT3A P59L does not lie within any known functional domains of the Dnmt3a protein (UniProt.org). P59L has been identified in the scientific literature (PMID: 27900369), but has not been biochemically characterized and therefore, its effect on Dnmt3a protein function is unknown (PubMed, Oct 2024).
P619Lfs*32 frameshift loss of function - predicted DNMT3A P619Lfs*32 indicates a shift in the reading frame starting at amino acid 619 and terminating 32 residues downstream causing a premature truncation of the 912 amino acid Dnmt3a protein (UniProt.org). P619Lfs*32 has not been characterized, however, due to the effects of other truncation mutations downstream of P619 (PMID: 28872462, PMID: 35639959), is predicted to lead to a loss of Dnmt3a protein function.
P709S missense loss of function - predicted DNMT3A P709S lies within the SAM-dependent MTase C5-type domain of the Dnmt3a protein (UniProt.org). P709S (corresponds to P705S in mouse) results in impaired global methylation and both decreased interaction with and inhibition of wild-type Dnmt3a in cell culture (PMID: 32856987), and therefore, is predicted to lead to a loss of Dnmt3a protein function.
P718L missense loss of function DNMT3A P718L lies within the SAM-dependent MTase C5-type domain of the Dnmt3a protein (UniProt.org). P718L results in reduced Dnmt3A enzymatic activity and decreased DNA methylation at commonly demethylated sites, and cytokine-independent growth in cell culture (PMID: 29414941).
P777R missense loss of function - predicted DNMT3A P777R lies within the SAM-dependent MTase C5-type domain of the Dnmt3a protein (UniProt.org). P777R (corresponds to P773R in mouse) retains DNA-binding ability but results in decreased methylation activity in in vitro assays (PMID: 31861499), and therefore, is predicted to lead to a loss of Dnmt3a protein function.
P904L missense loss of function DNMT3A P904L lies within the SAM-dependent MTase C5-type domain of the Dnmt3a protein (UniProt.org). P904L results in decreased methylation activity in an in vitro assay and failure to rescue mCA accumulation in cell culture (PMID: 33238114), increases methylation of non-CpG substrates but reduced methylation of CpG substrates in in vitro assays (PMID: 30705090), and leads to dysregulation of DNA methylation and gene expression, obesity, overgrowth, and neuronal defects in a transgenic mouse model expressing the corresponding mouse isoform (P900L) (PMID: 37952155).
Q237* nonsense loss of function - predicted DNMT3A Q237* results in a premature truncation of the Dnmt3a protein at amino acid 237 of 912 (UniProt.org). Q237* has not been characterized, however, due to the effects of other truncation mutations downstream of Q237 (PMID: 28872462, PMID: 26595813, PMID: 35639959), is predicted to lead to a loss of Dnmt3a protein function.
Q249* nonsense loss of function - predicted DNMT3A Q249* results in a premature truncation of the Dnmt3a protein at amino acid 249 of 912 (UniProt.org). Q249* has not been characterized, however, due to the effects of other truncation mutations downstream of Q249 (PMID: 28872462, PMID: 26595813, PMID: 35639959), is predicted to lead to a loss of Dnmt3a protein function.
Q485H missense unknown DNMT3A Q485H lies within the ADD domain of the Dnmt3a protein (UniProt.org). Q485H has been identified in sequencing studies (PMID: 27147599), but has not been biochemically characterized and therefore, its effect on Dnmt3a protein function is unknown (PubMed, Oct 2024).
Q515* nonsense loss of function DNMT3A Q515* results in a premature truncation within the ADD domain of the Dnmt3a protein at amino acid 515 of 912 (UniProt.org). Q515* confers a loss of function to the Dnmt3a protein as demonstrated by failure to dimerize with wild-type Dnmt3a and loss of methyltransferase activity in in vitro assays (PMID: 28872462).
Q606* nonsense loss of function - predicted DNMT3A Q606* results in a premature truncation of the Dnmt3a protein at amino acid 606 of 912 (UniProt.org). Q606* has not been characterized, however, due to the effects of other truncation mutations downstream of Q606 (PMID: 28872462, PMID: 26595813, PMID: 35639959), is predicted to lead to a loss of Dnmt3a protein function.
Q615* nonsense loss of function DNMT3A Q615* results in a premature truncation of the Dnmt3a protein at amino acid 615 of 912 (UniProt.org). Q615* confers a loss of function to the Dnmt3a protein as demonstrated by impaired myelomonocytic cell differentiation, colony formation, and methyltransferase activity in cell culture (PMID: 26595813).
Q886* nonsense loss of function - predicted DNMT3A Q886* results in a premature truncation of the Dnmt3a protein at amino acid 886 of 912 (UniProt.org). Q886* is predicted to lead to a loss of Dnmt3a protein function as demonstrated by decreased methylation of downstream target genes resulting in increased cell proliferation in culture (PMID: 35639959).
Q886E missense unknown DNMT3A Q886E lies within the SAM-dependent MTase C5-type domain of the Dnmt3a protein (UniProt.org). Q886E has been identified in the scientific literature (PMID: 27276561, PMID: 23251566, PMID: 29386642), but has not been biochemically characterized and therefore, its effect on Dnmt3a protein function is unknown (PubMed, Oct 2024).
R19W missense unknown DNMT3A R19W does not lie within any known functional domains of the Dnmt3a protein (UniProt.org). R19W has been identified in the scientific literature (PMID: 24793135, PMID: 23305405), but has not been biochemically characterized and therefore, its effect on Dnmt3a protein function is unknown (PubMed, Oct 2024).
R301W missense loss of function DNMT3A R301W lies within the PWWP domain of the Dnmt3a protein (UniProt.org). R301W results in decreased DNA binding and loss of Dnmt3a catalytic activity in in vitro assays, and a corresponding mouse variant (R297W) results in hypomethylation in cell culture (PMID: 36266353).
R320* nonsense loss of function - predicted DNMT3A R320* results in a premature truncation of the Dnmt3a protein at amino acid 320 of 912 (UniProt.org). R320* has not been characterized, however, due to the effects of other truncation mutations downstream of R320 (PMID: 28872462, PMID: 26595813, PMID: 35639959), is predicted to lead to a loss of Dnmt3a protein function.
R478Q missense unknown DNMT3A R478Q does not lie within any known functional domains of the Dnmt3a protein (UniProt.org). R478Q has not been characterized in the scientific literature and therefore, its effect on Dnmt3a protein function is unknown (PubMed, Oct 2024).
R556M missense unknown DNMT3A R556M lies within the ADD domain and PRC2/EED-EZH2 complex interacting region of the Dnmt3a protein (UniProt.org). R556M has been identified in sequencing studies (PMID: 31101826), but has not been biochemically characterized and therefore, its effect on Dnmt3a protein function is unknown (PubMed, Oct 2024).
R598* nonsense loss of function - predicted DNMT3A R598* results in a premature truncation of the Dnmt3a protein at amino acid 598 of 912 (UniProt.org). R598* has not been characterized, however, due to the effects of other truncation mutations downstream of R598 (PMID: 28872462, PMID: 26595813, PMID: 35639959), is predicted to lead to a loss of Dnmt3a protein function.
R635G missense loss of function - predicted DNMT3A R635G lies within the SAM-dependent MTase C5-type domain of the Dnmt3a protein (UniProt.org). R635G demonstrates reduced methylation of both CpG and non-CpG substrates in an in vitro assay (PMID: 30705090), and therefore, is predicted to lead to a loss of Dnmt3a protein function.
R635W missense loss of function DNMT3A R635W lies within the SAM-dependent MTase C5-type domain of the Dnmt3a protein (UniProt.org). R635W (corresponding to R631W in mouse) confers a loss of function on Dnmt3a as indicated by loss of methylation activity, failure to be activated by Dnmt3L, failure to bind DNA in in vitro assays (PMID: 31861499), and reduced TDG activity in an in vitro assay (Blood (2016) 128 (22): 1076).
R659H missense unknown DNMT3A R659H lies within the SAM-dependent MTase C5-type domain of the Dnmt3a protein (UniProt.org). R659H has been identified in the scientific literature (PMID: 21519343, PMID: 34815255, PMID: 35456436), but has not been biochemically characterized and therefore, its effect on Dnmt3a protein function is unknown (PubMed, Oct 2024).
R720C missense unknown DNMT3A R720C lies within the SAM-dependent MTase C5-type domain of the Dnmt3a protein (UniProt.org). R720C has been identified in sequencing studies (PMID: 29872864), but has not been biochemically characterized and therefore, its effect on Dnmt3a protein function is unknown (PubMed, Oct 2024).
R729A missense loss of function DNMT3A R729A lies within the SAM-dependent MTase C5-type domain of the Dnmt3a protein (UniProt.org). R729A disrupts Dnmt3a tetramer formation and leads to reduced catalytic activity in in vitro assays (PMID: 21979949).
R729Q missense unknown DNMT3A R729Q lies within the SAM-dependent MTase C5-type domain of the Dnmt3a protein (UniProt.org). R729Q has been identified in the scientific literature (PMID: 21067377, PMID: 28446434, PMID: 36219880), but has not been biochemically characterized and therefore, its effect on Dnmt3a protein function is unknown (PubMed, Oct 2024).
R729W missense loss of function - predicted DNMT3A R729W lies within the SAM-dependent MTase C5-type domain of the Dnmt3a protein (UniProt.org). R729W results in a loss of methylation activity in in vitro assays (PMID: 22722925), and therefore, is predicted to lead to a loss of Dnmt3a protein function.
R736A missense loss of function DNMT3A R736A lies within the SAM-dependent MTase C5-type domain of the Dnmt3a protein (UniProt.org). R736A retains the ability to form tetrameric complexes (PMID: 21979949), but leads to reduced Dnmt3a catalytic activity in in vitro assays (PMID: 36528185, PMID: 21979949).
R736C missense loss of function - predicted DNMT3A R736C lies within the SAM-dependent MTase C5-type domain of the Dnmt3a protein (UniProt.org). R736C leads to reduced catalytic activity in an in vitro assay (PMID: 36528185), and therefore, is predicted to lead to a loss of Dnmt3a protein function.
R736E missense loss of function - predicted DNMT3A R736E lies within the SAM-dependent MTase C5-type domain of the Dnmt3a protein (UniProt.org). R736E results in a loss of catalytic activity in an in vitro assay (PMID: 36528185), and therefore, is predicted to lead to a loss of Dnmt3a protein function.
R736F missense loss of function - predicted DNMT3A R736F lies within the SAM-dependent MTase C5-type domain of the Dnmt3a protein (UniProt.org). R736F results in a loss of catalytic activity in an in vitro assay (PMID: 36528185), and therefore, is predicted to lead to a loss of Dnmt3a protein function.
R736H missense unknown DNMT3A R736H lies within the SAM-dependent MTase C5-type domain of the Dnmt3a protein (UniProt.org). The functional effect of R736H is conflicting as it demonstrates processivity and activation by Dnmt3L similar to wild-type protein, increased activity at non-CpG sites but decreased activity at CpG sites in in vitro assays in one study (PMID: 30705090), but decreased methylation activity and reduced activation by Dnmt3L in other studies (PMID: 22722925, PMID: 33826797), and moderately decreased catalytic activity, wild-type CpG specificity, but increased activation by Dnmt3L in another study (PMID: 36528185), and therefore, its effect on Dnmt3a protein function is unknown.
R736K missense no effect - predicted DNMT3A R736K lies within the SAM-dependent MTase C5-type domain of the Dnmt3a protein (UniProt.org). R736K results in catalytic activity similar to wild-type in an in vitro assay (PMID: 36528185), and therefore, is predicted to have no effect on Dnmt3a protein function.
R736Q missense loss of function - predicted DNMT3A R736Q lies within the SAM-dependent MTase C5-type domain of the Dnmt3a protein (UniProt.org). R736Q results in a loss of catalytic activity in an in vitro assay (PMID: 36528185), and therefore, is predicted to lead to a loss of Dnmt3a protein function.
R736W missense loss of function - predicted DNMT3A R736W lies within the SAM-dependent MTase C5-type domain of the Dnmt3a protein (UniProt.org). R736W results in a loss of catalytic activity in an in vitro assay (PMID: 36528185), and therefore, is predicted to lead to a loss of Dnmt3a protein function.
R736Y missense loss of function - predicted DNMT3A R736Y lies within the SAM-dependent MTase C5-type domain of the Dnmt3a protein (UniProt.org). R736Y leads to reduced catalytic activity in an in vitro assay (PMID: 36528185), and therefore, is predicted to lead to a loss of Dnmt3a protein function.
R749C missense loss of function - predicted DNMT3A R749C lies within the SAM-dependent MTase C5-type domain of the Dnmt3a protein (UniProt.org). R749C results in expression and localization similar to wild-type, but results in decreased methyltransferase activity in an in vitro assay (PMID: 33238114), and therefore, is predicted to lead to a loss of Dnmt3a protein function.
R771* nonsense loss of function - predicted DNMT3A R771* results in a premature truncation of the Dnmt3a protein at amino acid 771 of 912 (UniProt.org). R771* has not been characterized, however, due to the effects of other truncation mutations downstream of R771 (PMID: 35639959), is predicted to lead to a loss of Dnmt3a protein function.
R771A missense loss of function DNMT3A R771A lies within the SAM-dependent MTase C5-type domain of the Dnmt3a protein (UniProt.org). R771A disrupts Dnmt3a tetramer formation and leads to reduced catalytic activity in in vitro assays (PMID: 21979949).
R771G missense unknown DNMT3A R771G lies within the SAM-dependent MTase C5-type domain of the Dnmt3a protein (UniProt.org). R771G results in increased methylation of non-CpG substrates (PMID: 30705090) but reduced methylation of CpG substrates relative to wild-type in in vitro assays in one study (PMID: 30705090), and increased methylation of a CpG substrate in an in vitro assay in another study (PMID: 33826797), and therefore, its effect on Dnmt3a protein function is unknown.
R771L missense loss of function - predicted DNMT3A R771L lies within the SAM-dependent MTase C5-type domain of the Dnmt3a protein (UniProt.org). R771L demonstrates loss of methylation activity in in vitro assays (PMID: 22722925, PMID: 31861499), and therefore, is predicted to lead to a loss of Dnmt3a protein function.
R771P missense loss of function - predicted DNMT3A R771P lies within the SAM-dependent MTase C5-type domain of the Dnmt3a protein (UniProt.org). R771P results in reduced methylation of both CpG and non-CpG substrates in an in vitro assay (PMID: 30705090), and therefore, is predicted to lead to a loss of Dnmt3a protein function.
R771Q missense unknown DNMT3A R771Q lies within the SAM-dependent MTase C5-type domain of the Dnmt3a protein (UniProt.org). R771Q increases methylation of both non-CpG and CpG substrates in an in vitro assay, however, results in a moderate decrease in global methylation in cultured embryonic stem cells (PMID: 30705090), and decreased methylation activity in an in vitro assay (PMID: 33826797), and therefore, its effect on Dnmt3a protein function is unknown.
R792Afs*10 frameshift loss of function - predicted DNMT3A R792Afs*10 indicates a shift in the reading frame starting at amino acid 792 and terminating 10 residues downstream causing a premature truncation of the 912 amino acid Dnmt3a protein (UniProt.org). R792Afs*10 has not been characterized, however, due to the effects of other truncation mutations downstream of R792 (PMID: 35639959), is predicted to lead to a loss of Dnmt3a protein function.
R792H missense loss of function DNMT3A R792H lies within the SAM-dependent MTase C5-type domain of the Dnmt3a protein (UniProt.org). R792H results in decreased Dnmt3a enzymatic activity, reduced cytosine methylation in the presence of wild-type Dnmt3a, and cytokine-independent growth in cell culture (PMID: 29414941).
R792S missense unknown DNMT3A R792S lies within the SAM-dependent MTase C5-type domain of the Dnmt3a protein (UniProt.org). R792S has not been characterized in the scientific literature and therefore, its effect on Dnmt3a protein function is unknown (PubMed, Oct 2024).
R803S missense unknown DNMT3A R803S lies within the SAM-dependent MTase C5-type domain of the Dnmt3a protein (UniProt.org). R803S has been identified in sequencing studies (PMID: 21067377, PMID: 31004019), but has not been biochemically characterized and therefore, its effect on Dnmt3a protein function is unknown (PubMed, Oct 2024).
R831Q missense loss of function DNMT3A R831Q lies within the SAM-dependent MTase C5-type domain of the Dnmt3a protein (UniProt.org). R831Q is predicted to confer a loss of function to Dnmt3a, as indicated by decreased DNA binding and decreased methyltransferase activity in vitro of a Dnmt3a-Dnmt3l heterotetramer (PMID: 32083663).
R836A missense loss of function - predicted DNMT3A R836A lies within the SAM-dependent MTase C5-type domain of the Dnmt3a protein (UniProt.org). R836A demonstrates methylation activity similar to wild-type protein in a chimeric Dnmt3a catalytic domain construct in an in vitro assay (PMID: 33826797), but results in altered substrate specificity leading to decreased CpG site methylation and increased non-CpG site methylation in in vitro assays and in cell culture (PMID: 29414941), and therefore, is predicted to lead to a loss of Dnmt3a protein function.
R836W missense loss of function - predicted DNMT3A R836W lies within the SAM-dependent MTase C5-type domain of the Dnmt3a protein (UniProt.org). R836W results in modestly reduced Dnmt3A activity and overall methylation, with increased non-CpG methylation, and cytokine-independent growth in cell culture (PMID: 29414941), and therefore, is predicted to lead to a loss of Dnmt3a protein function.
R882C missense loss of function DNMT3A R882C lies within the SAM-dependent MTase C5-type domain of the Dnmt3a protein (UniProt.org). R882C results in a loss of Dnmt3a protein function as indicated by genomic hypomethylation (PMID: 32015320, PMID: 31164355), which leads to altered gene expression profiles, reduced apoptosis, increased proliferation, cell transformation, and activation of hematopoietic stem cells in culture (PMID: 27010239, PMID: 31164355, PMID: 30245403, PMID: 32015320).
R882H missense loss of function 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), disrupts Tp53 inhibition of methylation (PMID: 31640986), and results in hypomethylation, cytokine-independent growth, increased cell proliferation and impaired differentiation in cultured cells (PMID: 31164355, PMID: 32015320).
R882P missense loss of function DNMT3A R882P lies within the SAM-dependent MTase C5-type domain of the Dnmt3a protein (UniProt.org). R882P results in a loss of Dnmt3a protein function as indicated by decreased catalytic activity of Dnmt3a and altered flanking sequence preferences in vitro assays (PMID: 31620784).
R882S missense loss of function DNMT3A R882S lies within the SAM-dependent MTase C5-type domain of the Dnmt3a protein (UniProt.org). R882S results in a loss of Dnmt3a protein function, as demonstrated by cytokine-independent growth and hypomethylation in cultured cells (PMID: 31164355).
R885A missense loss of function DNMT3A R885A lies within the SAM-dependent MTase C5-type domain of the Dnmt3a protein (UniProt.org). R885A confers a loss of function to Dnmt3a as demonstrated by loss of activity in in vitro assays (PMID: 22722925, PMID: 31582562) and decreased oligomer formation in culture (PMID: 31582562).
R899H missense unknown DNMT3A R899H lies within the SAM-dependent MTase C5-type domain of the Dnmt3a protein (UniProt.org). R899H has been identified in sequencing studies (PMID: 27276561, PMID: 29472349, PMID: 27881874), but has not been biochemically characterized and therefore, its effect on Dnmt3a protein function is unknown (PubMed, Oct 2024).
S352N missense unknown DNMT3A S352N lies within the DNMT1 and DNMT3B-interacting region of the Dnmt3a protein (UniProt.org). S352N has been identified in sequencing studies (PMID: 21993668), but has not been biochemically characterized and therefore, its effect on Dnmt3a protein function is unknown (PubMed, Oct 2024).
S714C missense loss of function DNMT3A S714C lies within the SAM-dependent MTase C5-type domain of the Dnmt3a protein (UniProt.org). S714C demonstrates reduced methylation of both CpG and non-CpG substrates in an in vitro assay, decreased global methylation in cultured embryonic stem cells (PMID: 30705090), and decreased methylation activity in a chimeric Dnmt3a catalytic domain construct in an in vitro assay (PMID: 33826797).
S837* nonsense loss of function - predicted DNMT3A S837* results in a premature truncation of the Dnmt3a protein at amino acid 837 of 912 (UniProt.org). S837* has not been characterized, however, due to the effects of other truncation mutations downstream of S837 (PMID: 35639959), is predicted to lead to a loss of Dnmt3a protein function.
S894R missense unknown DNMT3A S894R lies within the SAM-dependent MTase C5-type domain of the Dnmt3a protein (UniProt.org). S894R has not been characterized in the scientific literature and therefore, its effect on Dnmt3a protein function is unknown (PubMed, Oct 2024).
T835M missense loss of function DNMT3A T835M lies within the SAM-dependent MTase C5-type domain of the Dnmt3a protein (UniProt.org). T835M results in reduced Dnmt3A enzymatic activity and decreased DNA methylation at commonly demethylated sites, and cytokine-independent growth in cell culture (PMID: 29414941).
V296M missense unknown DNMT3A V296M lies within the PWWP domain of the Dnmt3a protein (UniProt.org). V296M has been identified in sequencing studies (PMID: 28634182, PMID: 38167262, PMID: 30108064), but has not been biochemically characterized and therefore, its effect on Dnmt3a protein function is unknown (PubMed, Oct 2024).
V636M missense unknown DNMT3A V636M lies within the SAM-dependent MTase C5-type domain of the Dnmt3a protein (UniProt.org). V636M has been identified in the scientific literature (PMID: 29386642, PMID: 27881874, PMID: 38300528), but has not been biochemically characterized and therefore, its effect on Dnmt3a protein function is unknown (PubMed, Oct 2024).
V649M missense unknown DNMT3A V649M lies within the SAM-dependent MTase C5-type domain of the Dnmt3a protein (UniProt.org). V649M has not been characterized in the scientific literature and therefore, its effect on Dnmt3a protein function is unknown (PubMed, Oct 2024).
V716D missense loss of function DNMT3A V716D lies within the SAM-dependent MTase C5-type domain of the Dnmt3a protein (UniProt.org). V716D results in decreased Dnmt3a enzymatic activity, reduced cytosine methylation in the presence of wild-type Dnmt3a, and cytokine-independent growth in cell culture (PMID: 29414941).
V716G missense loss of function DNMT3A V716G lies within the SAM-dependent MTase C5-type domain of the Dnmt3a protein (UniProt.org). V716G results in a loss of Dnmt3a methyltransferase activity in an in vitro assay and in cell culture, and fails to rescue cytosine methylation in DNA methyltransferases-deficient cells (PMID: 29414941).
V716I missense unknown DNMT3A V716I lies within the SAM-dependent MTase C5-type domain of the Dnmt3a protein (UniProt.org). V716I has been identified in sequencing studies (PMID: 31004019, PMID: 27534895, PMID: 28481359), but has not been biochemically characterized and therefore, its effect on Dnmt3a protein function is unknown (PubMed, Oct 2024).
V785M missense unknown DNMT3A V785M lies within the SAM-dependent MTase C5-type domain of the Dnmt3a protein (UniProt.org). V785M has been identified in sequencing studies (PMID: 22490330), but has not been biochemically characterized and therefore, its effect on Dnmt3a protein function is unknown (PubMed, Oct 2024).
W305* nonsense loss of function - predicted DNMT3A W305* results in a premature truncation of the Dnmt3a protein at amino acid 305 of 912 (UniProt.org). W305* has not been characterized, however, due to the effects of other truncation mutations downstream of W305 (PMID: 28872462, PMID: 26595813, PMID: 35639959), is predicted to lead to a loss of Dnmt3a protein function.
W306* nonsense loss of function - predicted DNMT3A W306* results in a premature truncation of the Dnmt3a protein at amino acid 306 of 912 (UniProt.org). W306* has not been characterized, however, due to the effects of other truncation mutations downstream of W306 (PMID: 28872462, PMID: 26595813, PMID: 35639959), is predicted to lead to a loss of Dnmt3a protein function.
W313* nonsense loss of function - predicted DNMT3A W313* results in a premature truncation of the Dnmt3a protein at amino acid 313 of 912 (UniProt.org). W313* has not been characterized, however, due to the effects of other truncation mutations downstream of W313 (PMID: 28872462, PMID: 26595813, PMID: 35639959), is predicted to lead to a loss of Dnmt3a protein function.
W409C missense unknown DNMT3A W409C does not lie within any known functional domains of the Dnmt3a protein (UniProt.org). W409C has been identified in sequencing studies (PMID: 36600554), but has not been biochemically characterized and therefore, its effect on Dnmt3a protein function is unknown (PubMed, Oct 2024).
W601* nonsense loss of function - predicted DNMT3A W601* results in a premature truncation of the Dnmt3a protein at amino acid 601 of 912 (UniProt.org). W601* has not been characterized, however, due to the effects of other truncation mutations downstream of W601 (PMID: 28872462, PMID: 26595813, PMID: 35639959), is predicted to lead to a loss of Dnmt3a protein function.
W860A missense loss of function DNMT3A W860A lies within the dimer interface region of the Dnmt3a protein (PMID: 22722925). W860A disrupts the tetramerization ability of the Dnmt3a protein, resulting in reduced DNA binding affinity, reduced methylation activity, and altered catalytic activity (PMID: 22722925).
W860R missense unknown DNMT3A W860R lies within the dimer interface region of the Dnmt3a protein (PMID: 22722925). W860R has been identified in the scientific literature (PMID: 27546487, PMID: 37240216), but has not been biochemically characterized and therefore, its effect on Dnmt3a protein function is unknown (PubMed, Oct 2024).
W893S missense loss of function - predicted DNMT3A W893S lies within the SAM-dependent MTase C5-type domain of the Dnmt3a protein (UniProt.org). W893S results in reduced methylation of CpG substrates relative to wild-type protein, but increased methylation of non-CpG substrates in in vitro assays (PMID: 30705090), and therefore, is predicted to lead to a loss of Dnmt3a protein function.
wild-type none no effect Wild-type DNMT3A indicates that no mutation has been detected within the DNMT3A gene.
Y436* nonsense loss of function - predicted DNMT3A Y436* results in a premature truncation of the Dnmt3a protein at amino acid 436 of 912 (UniProt.org). Y436* has not been characterized, however, due to the effects of other truncation mutations downstream of Y436 (PMID: 28872462, PMID: 26595813, PMID: 35639959), is predicted to lead to a loss of Dnmt3a protein function.
Y528_S535dup duplication unknown DNMT3A Y528_S535dup indicates the insertion of 8 duplicate amino acids, tyrosine (Y)-528 through serine (S)-535 in the ADD domain of the Dnmt3a protein (UniProt.org). Y528_S535dup has not been characterized in the scientific literature and therefore, its effect on Dnmt3a protein function is unknown (PubMed, Oct 2024).
Y533C missense unknown DNMT3A Y533C lies within the ADD domain of the Dnmt3a protein (UniProt.org). Y533C has been identified in sequencing studies (PMID: 27288520, PMID: 28194436, PMID: 28721364), but has not been biochemically characterized and therefore, its effect on Dnmt3a protein function is unknown (PubMed, Oct 2024).
Y735A missense loss of function - predicted DNMT3A Y735A lies within the SAM-dependent MTase C5-type domain of the Dnmt3a protein (UniProt.org). Y735A disrupts Dnmt3a tetramer formation and leads to reduced catalytic activity in in vitro assays (PMID: 21979949).
Y735C missense loss of function - predicted DNMT3A Y735C lies within the SAM-dependent MTase C5-type domain of the Dnmt3a protein (UniProt.org). Y735C results in expression and localization similar to wild-type, but results in decreased methyltransferase activity in vitro (PMID: 33238114) and therefore, is predicted to lead to a loss of Dnmt3a protein function.
Y735S missense unknown DNMT3A Y735S lies within the SAM-dependent MTase C5-type domain of the Dnmt3a protein (UniProt.org). Y735S has been identified in the scientific literature (PMID: 26290145, PMID: 27149842, PMID: 34788385), but has not been biochemically characterized and therefore, its effect on Dnmt3a protein function is unknown (PubMed, Oct 2024).
Y793* nonsense loss of function - predicted DNMT3A Y793* results in a premature truncation of the Dnmt3a protein at amino acid 793 of 912 (UniProt.org). Y793* has not been characterized, however, due to the effects of other truncation mutations downstream of Y793 (PMID: 35639959), is predicted to lead to a loss of Dnmt3a protein function.