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Gene | FLT3 |
Variant | N841K |
Impact List | missense |
Protein Effect | unknown |
Gene Variant Descriptions | FLT3 N841K lies within the activation loop of the protein kinase domain of the Flt3 protein (PMID: 25837374). N841K has been demonstrated to occur as a secondary resistance mutation in the context of FLT3 internal tandem duplication (FLT3-ITD) mutations (PMID: 25847190, PMID: 25487917), but has not been biochemically characterized and therefore, its effect on Flt3 protein function is unknown (PubMed, Oct 2023). |
Associated Drug Resistance | Y |
Category Variants Paths |
FLT3 mutant FLT3 exon20 FLT3 N841K |
Transcript | NM_004119.3 |
gDNA | chr13:g.28018485G>C |
cDNA | c.2523C>G |
Protein | p.N841K |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
NM_004119 | chr13:g.28018485G>C | c.2523C>G | p.N841K | RefSeq | GRCh38/hg38 |
NM_004119.3 | chr13:g.28018485G>C | c.2523C>G | p.N841K | RefSeq | GRCh38/hg38 |
NM_004119.2 | chr13:g.28018485G>C | c.2523C>G | p.N841K | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
FLT3 exon 14 ins FLT3 N841K | Advanced Solid Tumor | resistant | Pexidartinib | Preclinical | Actionable | In a preclinical study, transformed cells expressing FLT3-ITD along with FLT3 N841K were resistant to PLX3397 in culture (PMID: 25847190). | 25847190 |
FLT3 exon 14 ins FLT3 N841K | 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 N841K in culture (PMID: 35395091). | 35395091 |
FLT3 exon 14 ins FLT3 N841K | 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 N841K in culture (PMID: 32040554). | 32040554 |
FLT3 exon 14 ins FLT3 N841K | 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 N841K in culture (PMID: 32040554). | 32040554 |
FLT3 exon 14 ins FLT3 N841K | acute myeloid leukemia | resistant | Quizartinib | Preclinical - Cell culture | Actionable | In a preclinical study, acute myeloid leukemia cells harboring FLT3 ITD with FLT3 N841K were resistant to Vanflyta (quizartinib) in culture (PMID: 32040554). | 32040554 |
FLT3 exon 14 ins FLT3 N841K | acute myeloid leukemia | resistant | Sorafenib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, FLT3 N841K was identified as a secondary resistance mutation in FLT3 ITD-positive acute myeloid leukemia cell line xenograft models that progressed on Nexavar (sorafenib) (PMID: 35344039). | 35344039 |
FLT3 exon 14 ins FLT3 N841K | acute myeloid leukemia | resistant | Crenolanib + Sorafenib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, FLT3 N841K was identified as a secondary resistance mutation in FLT3 ITD-positive acute myeloid leukemia cell line xenograft models that progressed on the combination of Crenolanib (CP-868596) and Nexavar (sorafenib) (PMID: 35344039). | 35344039 |
FLT3 exon 14 ins FLT3 N841K | 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 N841K in culture (PMID: 37992684). | 37992684 |
FLT3 exon 14 ins FLT3 F691L FLT3 N841K | Advanced Solid Tumor | resistant | Pexidartinib | Preclinical | Actionable | In a preclinical study, transformed cells expressing a compound FLT3-ITD/F691L/N841K mutation were resistant to PLX3397 in culture (PMID: 25847190). | 25847190 |