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Gene | FLT3 |
Variant | N676K |
Impact List | missense |
Protein Effect | gain of function |
Gene Variant Descriptions | FLT3 N676K lies within the protein kinase domain of the Flt3 protein (UniProt.org). N676K results in constitutive phosphorylation of Flt3, activation of Akt and Mapk signaling, leading to malignant hematological transformation in animal models (PMID: 26891877), and has been demonstrated to occur as a resistance mutation in the context of FLT3 internal tandem duplication (FLT3-ITD) mutations (PMID: 16150941). |
Associated Drug Resistance | Y |
Category Variants Paths |
FLT3 mutant FLT3 act mut FLT3 N676K FLT3 mutant FLT3 exon16 FLT3 N676K |
Transcript | NM_004119.3 |
gDNA | chr13:g.28028203G>C |
cDNA | c.2028C>G |
Protein | p.N676K |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
NM_004119.3 | chr13:g.28028203G>C | c.2028C>G | p.N676K | RefSeq | GRCh38/hg38 |
NM_004119.2 | chr13:g.28028203G>C | c.2028C>G | p.N676K | RefSeq | GRCh38/hg38 |
NM_004119 | chr13:g.28028203G>C | c.2028C>G | p.N676K | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
FLT3 exon 14 ins FLT3 N676K | acute myeloid leukemia | predicted - resistant | Midostaurin | Case Reports/Case Series | Actionable | In a clinical case study, a patient with acute myeloid leukemia harboring a FLT3-ITD mutation progressed on Rydapt (midostaurin) after 288 days and was found to have acquired a FLT3 N676K mutation, and resistance was also confirmed in patient-derived cells in culture (PMID: 16150941). | 16150941 |
FLT3 exon 14 ins FLT3 N676K | acute myeloid leukemia | predicted - resistant | Pexidartinib | Case Reports/Case Series | Actionable | In a Phase I/II trial, an acute myeloid leukemia patient harboring a FLT3-ITD was found to have acquired FLT3 N676K following relapse on Turalio (pexidartinib) treatment (PMID: 34103301; NCT01349049). | 34103301 |
FLT3 exon 14 ins FLT3 N676K | 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 N676K in culture (PMID: 35395091). | 35395091 |
FLT3 exon 14 ins FLT3 N676K | 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 N676K in culture (PMID: 32040554). | 32040554 |
FLT3 exon 14 ins FLT3 N676K | 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 N676K in culture (PMID: 35395091). | 35395091 |
FLT3 exon 14 ins FLT3 N676K | 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 N676K in culture (PMID: 35395091). | 35395091 |
FLT3 exon 14 ins FLT3 N676K | hematologic cancer | sensitive | Quizartinib | Preclinical - Cell culture | Actionable | In a preclinical study, Vanflyta (quizartinib) treatment inhibited growth of transformed hematologic cells expressing FLT3-ITD and FLT3 N676K in culture (PMID: 35395091). | 35395091 |
FLT3 exon 14 ins FLT3 N676K | 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 N676K in culture (PMID: 35395091). | 35395091 |