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Gene | FLT3 |
Variant | N676D |
Impact List | missense |
Protein Effect | unknown |
Gene Variant Descriptions | FLT3 N676D lies within the protein kinase domain of the Flt3 protein (UniProt.org). N676D has been demonstrated to occur as a secondary resistance mutation in the context of FLT3 internal tandem duplication (FLT3-ITD) mutations (PMID: 22875611, PMID: 15374944), 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 exon16 FLT3 N676D |
Transcript | NM_004119.3 |
gDNA | chr13:g.28028205T>C |
cDNA | c.2026A>G |
Protein | p.N676D |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
NM_004119.2 | chr13:g.28028205T>C | c.2026A>G | p.N676D | RefSeq | GRCh38/hg38 |
NM_004119 | chr13:g.28028205T>C | c.2026A>G | p.N676D | RefSeq | GRCh38/hg38 |
NM_004119.3 | chr13:g.28028205T>C | c.2026A>G | p.N676D | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
FLT3 exon 14 ins FLT3 N676D FLT3 Y842C | leukemia | sensitive | E6201 | Preclinical | Actionable | In a preclinical study, E6201 inhibited proliferation and induced apoptosis in FLT3 inhibitor-resistant leukemia cell lines harboring FLT3 N676D and Y842C in addition to FLT3 internal tandem duplications (ITD) in culture (PMID: 26822154). | 26822154 |
FLT3 exon 14 ins FLT3 N676D | Advanced Solid Tumor | resistant | Midostaurin | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells over expressing FLT3 ITD and N676D were resistant to Rydapt (midostaurin) in culture (PMID: 23392356). | 23392356 |
FLT3 exon 14 ins FLT3 N676D | Advanced Solid Tumor | decreased response | Quizartinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells over expressing FLT3 ITD and N676D demonstrated reduced sensitivity to Vanflyta (quizartinib) in culture (PMID: 23392356). | 23392356 |
FLT3 exon 14 ins FLT3 N676D | hematologic cancer | sensitive | SKI-G-801 | Preclinical - Cell culture | Actionable | In a preclinical study, cells co-expressing a FLT3 internal tandem duplication and FLT3 N676D were sensitive to SKI-G-801 in culture, demonstrating inhibition of cell growth and inhibition of Flt3 autophosphorylation (PMID: 24532805). | 24532805 |
FLT3 exon 14 ins FLT3 N676D | hematologic cancer | sensitive | HQP1351 | Preclinical - Cell culture | Actionable | In a preclinical study, GZD824 (HQP1351) inhibited growth of transformed cells expressing FLT3-ITD and FLT3 N676D in culture (PMID: 32247263). | 32247263 |
FLT3 exon 14 ins FLT3 N676D | hematologic cancer | sensitive | LT-171-861 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, LT-171-861 inhibited cell viability and decreased FLT3 phosphorylation in transformed cells expressing a FLT3-ITD mutation and FLT3 N676D in culture, and inhibited tumor growth and prolonged survival in cell line xenograft models (PMID: 33391463). | 33391463 |
FLT3 exon 14 ins FLT3 N676D | hematologic cancer | predicted - sensitive | PHI-101 | Preclinical - Biochemical | Actionable | In a preclinical study, PHI-101 demonstrated activity against FLT3 N676D in the context of a FLT3-ITD mutation in culture (Cancer Res 2020;80(16 Suppl):Abstract nr 4226). | detail... |
FLT3 N676D FLT3 D835Y | hematologic cancer | sensitive | SKI-G-801 | Preclinical - Cell culture | Actionable | In a preclinical study, cells co-expressing FLT3 D835Y and FLT3 N676D were sensitive to SKI-G-801 in culture, demonstrating inhibition of cell growth and inhibition of Flt3 autophosphorylation (PMID: 24532805). | 24532805 |