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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 exon20 FLT3 D835X FLT3 D835V FLT3 mutant FLT3 act mut FLT3 D835V |
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 |
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 | HQP1351 | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing FLT3 D835V demonstrated decreased proliferation in response to GZD824 (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) resulted in reduced cell viability in transformed cells expressing FLT3 D835V in culture (PMID: 32040554). | 32040554 |