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Gene | FLT3 |
Variant | D835H |
Impact List | missense |
Protein Effect | gain of function |
Gene Variant Descriptions | FLT3 D835H lies within the protein kinase domain activation loop of the Flt3 protein (PMID: 11290608). D835H results in constitutive phosphorylation of Flt3 and activation of Stat5, Erk signaling, leading to transformation of cultured cells (PMID: 15256420). |
Associated Drug Resistance | |
Category Variants Paths |
FLT3 mutant FLT3 act mut FLT3 D835H FLT3 mutant FLT3 exon20 FLT3 D835X FLT3 D835H |
Transcript | NM_004119.3 |
gDNA | chr13:g.28018505C>G |
cDNA | c.2503G>C |
Protein | p.D835H |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
NM_004119.2 | chr13:g.28018505C>G | c.2503G>C | p.D835H | RefSeq | GRCh38/hg38 |
NM_004119.3 | chr13:g.28018505C>G | c.2503G>C | p.D835H | RefSeq | GRCh38/hg38 |
NM_004119 | chr13:g.28018505C>G | c.2503G>C | p.D835H | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
FLT3 D835H | acute myeloid leukemia | sensitive | Crenolanib | Preclinical | Actionable | In a preclinical study, Crenolanib (CP-868596) inhibited Flt3 phosphorylation and induced apoptosis in leukemia cells expressing FLT3 D835H (PMID: 24623852). | 24623852 |
FLT3 D835H | hematologic cancer | sensitive | Pacritinib | Preclinical - Cell culture | Actionable | In a preclinical study, Vonjo (pacritinib) inhibited viability in a transformed cell line expressing FLT3 D835H in culture (PMID: 31102119). | 31102119 |
FLT3 D835H | hematologic cancer | sensitive | Dubermatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Dubermatinib (TP-0903) inhibited growth of transformed cells expressing FLT3 D835H in culture (PMID: 33268594). | 33268594 |
FLT3 D835H | hematologic cancer | predicted - sensitive | Olverembatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing FLT3 D835H 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 |