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Gene | CBL |
Variant | Q365_E366insSK |
Impact List | insertion |
Protein Effect | loss of function |
Gene Variant Descriptions | CBL Q365_E366insSK results in the insertion of two amino acids in the linker region of the Cbl protein between amino acids 365 and 366 (UniProt.org). Q365_E366insSK results in a loss of E3-ligase activity, leading to activation of FLT3, and is transforming when expressed with FLT3 or KIT (PMID: 20622007). |
Associated Drug Resistance | |
Category Variants Paths |
CBL mutant CBL inact mut CBL Q365_E366insSK |
Transcript | NM_005188.4 |
gDNA | chr11:g.119277844_119277845insAGCAAG |
cDNA | c.1095_1095+1insAGCAAG |
Protein | p.Q365_E366insSK |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
NM_005188.3 | chr11:g.119277844_119277845insAGCAAG | c.1095_1095+1insAGCAAG | p.Q365_E366insSK | RefSeq | GRCh38/hg38 |
NM_005188 | chr11:g.119277844_119277845insAGCAAG | c.1095_1095+1insAGCAAG | p.Q365_E366insSK | RefSeq | GRCh38/hg38 |
NM_005188.4 | chr11:g.119277844_119277845insAGCAAG | c.1095_1095+1insAGCAAG | p.Q365_E366insSK | RefSeq | GRCh38/hg38 |
XM_011543057 | chr11:g.119277844_119277845insAGCAAG | c.1095_1095+1insAGCAAG | p.Q365_E366insSK | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
CBL Q365_E366insSK FLT3 wild-type | hematologic cancer | sensitive | Crenolanib | Preclinical - Cell culture | Actionable | In a preclinical study, Crenolanib inhibited growth of transformed hematologic cells expressing CBL Q365_E366insSK and wild-type FLT3 in culture (PMID: 31309543). | 31309543 |
CBL Q365_E366insSK FLT3 wild-type | hematologic cancer | sensitive | Quizartinib | Preclinical - Cell culture | Actionable | In a preclinical study, Vanflyta (quizartinib) inhibited growth of transformed hematologic cells expressing CBL Q365_E366insSK and wild-type FLT3 in culture (PMID: 31309543). | 31309543 |
CBL Q365_E366insSK FLT3 wild-type | hematologic cancer | sensitive | Gilteritinib | Preclinical - Cell culture | Actionable | In a preclinical study, Xospata (gilteritinib) inhibited growth of transformed hematologic cells expressing CBL Q365_E366insSK and wild-type FLT3 in culture (PMID: 31309543). | 31309543 |
CBL Q365_E366insSK FLT3 wild-type | hematologic cancer | sensitive | Midostaurin | Preclinical - Cell culture | Actionable | In a preclinical study, Rydapt (midostaurin) inhibited growth of transformed hematologic cells expressing CBL Q365_E366insSK and wild-type FLT3 in culture (PMID: 31309543). | 31309543 |
CBL Q365_E366insSK FLT3 wild-type | hematologic cancer | sensitive | Sorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, Nexavar (sorafenib) inhibited growth of transformed hematologic cells expressing CBL Q365_E366insSK and wild-type FLT3 in culture (PMID: 31309543). | 31309543 |
CBL Q365_E366insSK FLT3 wild-type | hematologic cancer | decreased response | Avapritinib | Preclinical - Cell culture | Actionable | In a preclinical study, Ayvakit (avapritinib) inhibited growth of transformed hematologic cells expressing CBL Q365_E366insSK and wild-type FLT3 in culture with reduced potency compared to other kinase inhibitors (PMID: 31309543). | 31309543 |
CBL Q365_E366insSK FLT3 pos | hematologic cancer | sensitive | Sorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, Nexavar (sorafenib) inhibited proliferation of cells expressing wild-type FLT3 and CBL Q365_E366insSK in culture (PMID: 31943762). | 31943762 |
CBL Q365_E366insSK FLT3 pos | hematologic cancer | sensitive | Gilteritinib | Preclinical - Cell culture | Actionable | In a preclinical study, Xospata (gilteritinib) inhibited proliferation of cells expressing wild-type FLT3 and CBL Q365_E366insSK in culture (PMID: 31943762). | 31943762 |
CBL Q365_E366insSK FLT3 pos | hematologic cancer | sensitive | Crenolanib | Preclinical - Cell culture | Actionable | In a preclinical study, Crenolanib inhibited proliferation of cells expressing wild-type FLT3 and CBL Q365_E366insSK in culture (PMID: 31943762). | 31943762 |
CBL Q365_E366insSK FLT3 pos | hematologic cancer | sensitive | Quizartinib | Preclinical - Cell culture | Actionable | In a preclinical study, Vanflyta (quizartinib) inhibited proliferation of cells expressing wild-type FLT3 and CBL Q365_E366insSK in culture (PMID: 31943762). | 31943762 |
CBL Q365_E366insSK FLT3 pos | hematologic cancer | sensitive | Midostaurin | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Rydapt (midostaurin) inhibited proliferation of cells expressing wild-type FLT3 and CBL Q365_E366insSK in culture, and inhibited leukemic growth and prolonged survival in cell line xenograft models expressing FLT3 and CBL Q365_E366insSK (PMID: 31943762). | 31943762 |
CBL Q365_E366insSK FLT3 pos | hematologic cancer | sensitive | Midostaurin + PRT062607 | Preclinical - Cell culture | Actionable | In a preclinical study, the addition of PRT062607 to treatment with Rydapt (midostaurin) resulted in enhanced inhibition of proliferation of cells expressing wild-type FLT3 and CBL Q365_E366insSK in culture (PMID: 31943762). | 31943762 |
CBL Q365_E366insSK FLT3 pos | hematologic cancer | sensitive | PRT062607 + Sorafenib | Preclinical - Cell culture | Actionable | In a preclinical study, the addition of PRT062607 to treatment with Nexavar (sorafenib) resulted in enhanced inhibition of proliferation of cells expressing wild-type FLT3 and CBL Q365_E366insSK in culture (PMID: 31943762). | 31943762 |
CBL Q365_E366insSK FLT3 pos | hematologic cancer | sensitive | PRT062607 + Quizartinib | Preclinical - Cell culture | Actionable | In a preclinical study, the addition of PRT062607 to treatment with Vanflyta (quizartinib) resulted in enhanced inhibition of proliferation of cells expressing wild-type FLT3 and CBL Q365_E366insSK in culture (PMID: 31943762). | 31943762 |
CBL Q365_E366insSK FLT3 pos | hematologic cancer | sensitive | Crenolanib + PRT062607 | Preclinical - Cell culture | Actionable | In a preclinical study, the addition of PRT062607 to treatment with Crenolanib resulted in enhanced inhibition of proliferation of cells expressing wild-type FLT3 and CBL Q365_E366insSK in culture (PMID: 31943762). | 31943762 |
CBL Q365_E366insSK FLT3 pos | hematologic cancer | sensitive | Gilteritinib + PRT062607 | Preclinical - Cell culture | Actionable | In a preclinical study, the addition of PRT062607 to treatment with Xospata (gilteritinib) resulted in enhanced inhibition of proliferation of cells expressing wild-type FLT3 and CBL Q365_E366insSK in culture (PMID: 31943762). | 31943762 |
CBL Q365_E366insSK FLT3 pos | hematologic cancer | sensitive | Entospletinib + Midostaurin | Preclinical - Cell culture | Actionable | In a preclinical study, the addition of Entospletinib to treatment with Rydapt (midostaurin) resulted in enhanced inhibition of proliferation of cells expressing wild-type FLT3 and CBL Q365_E366insSK in culture (PMID: 31943762). | 31943762 |