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| Gene | FLT3 |
| Variant | D835A |
| Impact List | missense |
| Protein Effect | gain of function |
| Gene Variant Descriptions | FLT3 D835A lies within the activation loop in the protein kinase domain of the Flt3 protein (PMID: 25837374). D835A results in constitutive phosphorylation of Flt3 and activation of Stat5, Erk signaling, leading to transformation of cultured cells (PMID: 15256420). |
| Associated Drug Resistance | |
| Category Variants Paths |
FLT3 mutant FLT3 act mut FLT3 D835A FLT3 mutant FLT3 exon20 FLT3 D835X FLT3 D835A |
| Transcript | NM_004119.3 |
| gDNA | chr13:g.28018504T>G |
| cDNA | c.2504A>C |
| Protein | p.D835A |
| Source Database | RefSeq |
| Genome Build | GRCh38/hg38 |
| Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
|---|---|---|---|---|---|
| NM_004119.3 | chr13:g.28018504T>G | c.2504A>C | p.D835A | RefSeq | GRCh38/hg38 |
| NM_004119.2 | chr13:g.28018504T>G | c.2504A>C | p.D835A | RefSeq | GRCh38/hg38 |
| NM_004119 | chr13:g.28018504T>G | c.2504A>C | p.D835A | RefSeq | GRCh38/hg38 |
| Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
|---|---|---|---|---|---|---|---|
| FLT3 D835A | hematologic cancer | sensitive | Midostaurin | Preclinical - Cell culture | Actionable | In a preclinical study, Rydapt (midostaurin) inhibited Flt3 autophosphorylation and viability in transformed cells expressing FLT3 D835A in culture (PMID: 28077790). | 28077790 |
| FLT3 D835A | hematologic cancer | sensitive | Midostaurin | Preclinical - Cell culture | Actionable | In a preclinical study, Rydapt (midostaurin) treatment decreased viability in a cell line expressing FLT3 D835A in culture (PMID: 40196870). | 40196870 |
| FLT3 D835A | hematologic cancer | sensitive | Lestaurtinib | Preclinical - Cell culture | Actionable | In a preclinical study, Lestaurtinib (CEP-701) inhibited Flt3 autophosphorylation and viability in transformed cells expressing FLT3 D835A in culture (PMID: 28077790). | 28077790 |
| FLT3 D835A | hematologic cancer | no benefit | AG1295 | Preclinical - Cell culture | Actionable | In a preclinical study, AG1295 did not inhibit viability of transformed cells expressing FLT3 D835A in culture (PMID: 28077790). | 28077790 |
| FLT3 D835A | hematologic cancer | no benefit | Linifanib | Preclinical - Cell culture | Actionable | In a preclinical study, Linifanib (ABT-869) did not inhibit viability of transformed cells expressing FLT3 D835A in culture (PMID: 28077790). | 28077790 |
| FLT3 D835A | hematologic cancer | conflicting | Quizartinib | Preclinical - Cell culture | Actionable | In a preclinical study, Vanflyta (quizartinib) did not inhibit viability of transformed cells expressing FLT3 D835A in culture (PMID: 28077790). | 28077790 |
| FLT3 D835A | hematologic cancer | conflicting | Quizartinib | Preclinical - Cell culture | Actionable | In a preclinical study, Vanflyta (quizartinib) treatment decreased viability in a cell line expressing FLT3 D835A in culture (PMID: 40196870). | 40196870 |
| FLT3 D835A | hematologic cancer | no benefit | Sunitinib | Preclinical - Cell culture | Actionable | In a preclinical study, Sutent (sunitinib) did not inhibit viability of transformed cells expressing FLT3 D835A in culture (PMID: 28077790). | 28077790 |
| FLT3 D835A | hematologic cancer | no benefit | Sorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, Nexavar (sorafenib) did not inhibit viability in transformed cells expressing FLT3 D835A in culture (PMID: 28077790). | 28077790 |
| FLT3 D835A | hematologic cancer | no benefit | Tamatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Tamatinib (R406) did not inhibit viability of transformed cells expressing FLT3 D835A in culture (PMID: 28077790). | 28077790 |
| FLT3 D835A | hematologic cancer | sensitive | KW-2449 | Preclinical - Cell culture | Actionable | In a preclinical study, KW-2449 inhibited Flt3 autophosphorylation and viability in transformed cells expressing FLT3 D835A in culture (PMID: 28077790). | 28077790 |
| FLT3 D835A | hematologic cancer | sensitive | Gilteritinib | Preclinical - Cell culture | Actionable | In a preclinical study, Xospata (gilteritinib) treatment decreased viability in a cell line expressing FLT3 D835A in culture (PMID: 40196870). | 40196870 |