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FLT3 D835V - 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 D835V Advanced Solid Tumor resistant Pexidartinib Preclinical Actionable In a preclinical study, transformed cells expressing FLT3 D835V were resistant to PLX3397 in culture (PMID: 25847190). 25847190
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 FLT3 D835V in culture (PMID: 27158668). 27158668
FLT3 D835V hematologic cancer predicted - sensitive Olverembatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing FLT3 D835V demonstrated decreased proliferation in response to Olverembatinib (HQP1351) in culture, but were less sensitive to treatment than cells expressing other FLT3 kinase domain mutations (PMID: 32247263). 32247263
FLT3 D835V hematologic cancer sensitive Gilteritinib Preclinical - Cell culture Actionable In a preclinical study, Xospata (gilteritinib) inhibited viability of cultured cells expressing FLT3 D835V (PMID: 38231480). 38231480
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 D835V in culture (PMID: 32040554). 32040554
FLT3 D835V hematologic cancer resistant Quizartinib Preclinical - Cell culture Actionable In a preclinical study, cultured cells expressing FLT3 D835V were resistant to treatment with Vanflyta (quizartinib) (PMID: 38231480). 38231480
FLT3 D835V hematologic cancer sensitive Foretinib Preclinical - Cell culture Actionable In a preclinical study, Foretinib (GSK1363089) inhibited viability of cultured cells expressing FLT3 D835V (PMID: 38231480). 38231480
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 D835V in culture (PMID: 38231480). 38231480
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 D835V in culture (PMID: 38231480). 38231480
FLT3 D835V acute myeloid leukemia decreased response Quizartinib Preclinical - Cell culture Actionable In a preclinical study, primary patient-derived acute myeloid leukemia blasts harboring FLT3 D835V were less sensitive to Vanflyta (quizartinib) in culture (PMID: 38231480). 38231480