Gene Variant Detail

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Gene FLT3
Variant D835V
Impact List missense
Protein Effect gain of function
Gene Variant Descriptions FLT3 D835V lies within the protein kinase domain activation loop of the Flt3 protein (PMID: 11290608). D835V results in constitutive phosphorylation of Flt3 and activation of Stat5, Erk signaling, leading to transformation of cultured cells (PMID: 15256420), and has been demonstrated to promote secondary drug resistance in the context of FLT3 internal tandem duplication (FLT3-ITD) mutations (PMID: 22504184, PMID: 29187377).
Associated Drug Resistance Y
Category Variants Paths

FLT3 mutant FLT3 act mut FLT3 D835V

FLT3 mutant FLT3 exon20 FLT3 D835X FLT3 D835V

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Transcript NM_004119.3
gDNA chr13:g.28018504T>A
cDNA c.2504A>T
Protein p.D835V
Source Database RefSeq
Genome Build GRCh38/hg38
Transcript gDNA cDNA Protein Source Database Genome Build
NM_004119 chr13:g.28018504T>A c.2504A>T p.D835V RefSeq GRCh38/hg38
NM_004119.2 chr13:g.28018504T>A c.2504A>T p.D835V RefSeq GRCh38/hg38
NM_004119.3 chr13:g.28018504T>A c.2504A>T p.D835V RefSeq GRCh38/hg38

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
FLT3 exon 14 ins FLT3 D835V Advanced Solid Tumor resistant Pexidartinib Preclinical Actionable In a preclinical study, transformed cells expressing FLT3-ITD along with FLT3 D835V were resistant to PLX3397 in culture (PMID: 25847190). 25847190
FLT3 exon 14 ins FLT3 D835V Advanced Solid Tumor sensitive MRX-2843 Preclinical - Cell culture Actionable In a preclinical study, MRX-2843 inhibited Flt3 signaling, resulted in growth inhibition in Quizartinib (AC220)-resistant transformed cells over expressing both FLT3 internal tandem duplication (ITD) and D835V in culture (PMID: 27158668). 27158668
FLT3 exon 14 ins FLT3 D835V hematologic cancer predicted - sensitive HQP1351 Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing FLT3-ITD and FLT3 D835V demonstrated decreased proliferation in response to GZD824 (HQP1351) in culture, but were less sensitive to treatment than cells co-expressing FLT3-ITD with other FLT3 kinase domain mutations (PMID: 32247263). 32247263
FLT3 exon 14 ins FLT3 D835V hematologic cancer sensitive KX2-391 Preclinical - Cell culture Actionable In a preclinical study, KX2-391 treatment inhibited cell viability and decreased downstream signaling in cells expressing a FLT3-ITD mutation with FLT3 D835V in culture (PMID: 34217323). 34217323
FLT3 exon 14 ins FLT3 D835V hematologic cancer sensitive FF-10101 Preclinical - Cell culture Actionable In a preclinical study, FF-10101 treatment inhibited growth of transformed hematologic cells expressing FLT3-ITD and FLT3 D835V in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins FLT3 D835V acute myeloid leukemia sensitive FF-10101 Preclinical - Cell culture Actionable In a preclinical study, FF-10101 treatment inhibited growth of acute myeloid leukemia cells harboring FLT3-ITD and FLT3 D835V in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins FLT3 D835V hematologic cancer sensitive Gilteritinib Preclinical - Cell culture Actionable In a preclinical study, Xospata (gilteritinib) inhibited viability of cultured cells expressing FLT3-ITD with FLT3 D835V (PMID: 38231480). 38231480
FLT3 exon 14 ins FLT3 D835V hematologic cancer sensitive Gilteritinib Preclinical - Cell culture Actionable In a preclinical study, Xospata (gilteritinib) resulted in reduced cell viability in transformed cells expressing FLT3 ITD with FLT3 D835V in culture (PMID: 32040554). 32040554
FLT3 exon 14 ins FLT3 D835V hematologic cancer sensitive Gilteritinib Preclinical - Cell culture Actionable In a preclinical study, Xospata (gilteritinib) treatment inhibited growth of transformed hematologic cells expressing FLT3-ITD and FLT3 D835V in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins FLT3 D835V hematologic cancer sensitive Crenolanib Preclinical - Cell culture Actionable In a preclinical study, Crenolanib (CP-868596) treatment inhibited growth of transformed hematologic cells expressing FLT3-ITD and FLT3 D835V in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins FLT3 D835V hematologic cancer sensitive Crenolanib Preclinical - Cell culture Actionable In a preclinical study, transformed hematologic cells expressing FLT3-ITD and FLT3 D835V were sensitive to Crenolanib (CP-868596) treatment in culture (PMID: 34768286). 34768286
FLT3 exon 14 ins FLT3 D835V hematologic cancer resistant Quizartinib Preclinical - Cell culture Actionable In a preclinical study, cells expressing FLT3-ITD with FLT3 D835V were resistant to treatment with Vanflyta (quizartinib) in culture (PMID: 38231480). 38231480
FLT3 exon 14 ins FLT3 D835V hematologic cancer resistant Quizartinib Preclinical - Cell culture Actionable In a preclinical study, transformed hematologic cells expressing FLT3-ITD and FLT3 D835V were resistant to treatment with Vanflyta (quizartinib) in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins FLT3 D835V hematologic cancer sensitive Midostaurin Preclinical - Cell culture Actionable In a preclinical study, Rydapt (midostaurin) treatment inhibited growth of transformed hematologic cells expressing FLT3-ITD and FLT3 D835V in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins FLT3 D835V hematologic cancer sensitive Midostaurin Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing FLT3-ITD and FLT3 D835V were sensitive to Rydapt (midostaurin) treatment in culture (PMID: 34768286). 34768286
FLT3 exon 14 ins FLT3 D835V acute myeloid leukemia sensitive Gilteritinib Preclinical - Cell culture Actionable In a preclinical study, Xospata (gilteritinib) inhibited viability of primary patient-derived acute myeloid leukemia blasts harboring FLT3-ITD with FLT3 D835V in culture (PMID: 38231480). 38231480
FLT3 exon 14 ins FLT3 D835V acute myeloid leukemia sensitive Gilteritinib Preclinical - Cell culture Actionable In a preclinical study, Xospata (gilteritinib) resulted in reduced cell viability in acute myeloid leukemia cells harboring FLT3 ITD with FLT3 D835V in culture (PMID: 32040554). 32040554
FLT3 exon 14 ins FLT3 D835V acute myeloid leukemia resistant Quizartinib Preclinical - Cell culture Actionable In a preclinical study, acute myeloid leukemia cells harboring FLT3 ITD with FLT3 D835V were resistant to Vanflyta (quizartinib) in culture (PMID: 32040554). 32040554
FLT3 exon 14 ins FLT3 D835V acute myeloid leukemia resistant Quizartinib Preclinical - Cell culture Actionable In a preclinical study, primary patient-derived acute myeloid leukemia blasts harboring FLT3-ITD with FLT3 D835V were less sensitive to Vanflyta (quizartinib) in culture (PMID: 38231480). 38231480
FLT3 exon 14 ins FLT3 D835V hematologic cancer sensitive Lestaurtinib Preclinical - Cell culture Actionable In a preclinical study, Lestaurtinib (CEP-701) inhibited proliferation of transformed cells expressing FLT3-ITD and FLT3 D835V in culture (PMID: 34768286). 34768286
FLT3 exon 14 ins FLT3 D835V hematologic cancer resistant Sorafenib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing FLT3-ITD and FLT3 D835V demonstrated resistance to Nexavar (sorafenib) in culture (PMID: 34768286). 34768286
FLT3 exon 14 ins FLT3 D835V hematologic cancer resistant Pacritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing FLT3-ITD and FLT3 D835V demonstrated resistance to Vonjo (pacritinib) in culture (PMID: 34768286). 34768286
FLT3 exon 14 ins FLT3 D835V hematologic cancer resistant Sitravatinib Preclinical - Cell line xenograft Actionable In a preclinical study, transformed hematologic cells expressing a FLT3-ITD mutation with FLT3 D835V were resistant to treatment with Sitravatinib (MGCD516) in culture and in a cell line xenograft model (PMID: 36691065). 36691065
FLT3 exon 14 ins FLT3 D835V acute myeloid leukemia sensitive RMC-4550 Preclinical - Cell culture Actionable In a preclinical study, RMC-4550 inhibited viability in an acute myeloid leukemia cell line harboring FLT3 ITD and expressing FLT3 D835V in culture (PMID: 37992684). 37992684
FLT3 exon 14 ins FLT3 D835V hematologic cancer sensitive Foretinib Preclinical - Cell culture Actionable In a preclinical study, Foretinib (GSK1363089) inhibited viability of cultured cells expressing FLT3-ITD with FLT3 D835V (PMID: 38231480). 38231480
FLT3 exon 14 ins FLT3 D835V acute myeloid leukemia sensitive Foretinib Preclinical - Cell culture Actionable In a preclinical study, Foretinib (GSK1363089) inhibited viability of primary patient-derived acute myeloid leukemia blasts harboring FLT3-ITD with FLT3 D835V in culture (PMID: 38231480). 38231480
FLT3 exon 14 ins FLT3 F691L FLT3 D835V hematologic cancer predicted - resistant FF-10101 Preclinical - Cell culture Actionable In a preclinical study, transformed hematologic cells expressing FLT3-ITD with FLT3 F691L and D835V were moderately resistant to treatment with FF-10101 in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins FLT3 F691L FLT3 D835V hematologic cancer resistant Gilteritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing FLT3 ITD with FLT3 D835V and FLT3 F691L were resistant to Xospata (gilteritinib) in culture (PMID: 32040554). 32040554
FLT3 exon 14 ins FLT3 D698N FLT3 D835V hematologic cancer predicted - resistant FF-10101 Preclinical - Cell culture Actionable In a preclinical study, transformed hematologic cells expressing FLT3-ITD with FLT3 D698N and D835V were moderately resistant to treatment with FF-10101 in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins FLT3 D698N FLT3 D835V hematologic cancer resistant Gilteritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing FLT3 ITD with FLT3 D835V and FLT3 D698N were resistant to Xospata (gilteritinib) in culture (PMID: 32040554). 32040554
FLT3 exon 14 ins FLT3 Y693C FLT3 D835V hematologic cancer resistant FF-10101 Preclinical - Cell culture Actionable In a preclinical study, transformed hematologic cells expressing FLT3-ITD with FLT3 Y693C and D835V were resistant to treatment with FF-10101 in culture (PMID: 35395091). 35395091
FLT3 exon 14 ins FLT3 Y693C FLT3 D835V hematologic cancer resistant Gilteritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing FLT3 ITD with FLT3 D835V and FLT3 Y693C were resistant to Xospata (gilteritinib) in culture (PMID: 32040554). 32040554
FLT3 exon 14 ins FLT3 G697S FLT3 D835V hematologic cancer resistant Gilteritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing FLT3 ITD with FLT3 D835V and FLT3 G697S were resistant to Xospata (gilteritinib) in culture (PMID: 32040554). 32040554
FLT3 exon 14 ins FLT3 Y693N FLT3 D835V hematologic cancer resistant Gilteritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing FLT3 ITD with FLT3 D835V and FLT3 Y693N were resistant to Xospata (gilteritinib) in culture (PMID: 32040554). 32040554