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Gene | CBL |
Variant | Y371H |
Impact List | missense |
Protein Effect | loss of function |
Gene Variant Descriptions | CBL Y371H lies within the linker region of the Cbl protein (PMID: 20622007). Y371H results in a loss of Cbl ubiquitin ligase activity, leading to activation of FLT3, AKT, and STAT5, and transformation of cultured cells when co-expressed with FLT3 or KIT (PMID: 23696637, PMID: 20622007). |
Associated Drug Resistance | |
Category Variants Paths |
CBL mutant CBL exon8 CBL Y371H CBL mutant CBL inact mut CBL Y371H |
Transcript | NM_005188.4 |
gDNA | chr11:g.119278181T>C |
cDNA | c.1111T>C |
Protein | p.Y371H |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
XM_011543057 | chr11:g.119278181T>C | c.1111T>C | p.Y371H | RefSeq | GRCh38/hg38 |
NM_005188 | chr11:g.119278181T>C | c.1111T>C | p.Y371H | RefSeq | GRCh38/hg38 |
NM_005188.3 | chr11:g.119278181T>C | c.1111T>C | p.Y371H | RefSeq | GRCh38/hg38 |
NM_005188.4 | chr11:g.119278181T>C | c.1111T>C | p.Y371H | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
CBL Y371H FLT3 wild-type | hematologic cancer | sensitive | Crenolanib | Preclinical - Cell culture | Actionable | In a preclinical study, Crenolanib inhibited growth of transformed hematologic cells expressing CBL Y371H and wild-type FLT3 in culture (PMID: 31309543). | 31309543 |
CBL Y371H FLT3 wild-type | hematologic cancer | sensitive | Midostaurin | Preclinical | Actionable | In a preclinical study, Rydapt (midostaurin) inhibited growth of transformed hematologic cells expressing CBL Y371H and wild-type FLT3 in culture, reduced leukemia burden and prolonged survival in animal models (PMID: 31309543). | 31309543 |
CBL Y371H 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 Y371H and wild-type FLT3 in culture (PMID: 31309543). | 31309543 |
CBL Y371H 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 Y371H and wild-type FLT3 in culture (PMID: 31309543). | 31309543 |
CBL Y371H 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 Y371H and wild-type FLT3 in culture (PMID: 31309543). | 31309543 |
CBL Y371H 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 Y371H and wild-type FLT3 in culture with reduced potency compared to other kinase inhibitors (PMID: 31309543). | 31309543 |
CBL Y371H 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 Y371H in culture (PMID: 31943762). | 31943762 |
CBL Y371H 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 Y371H in culture, and inhibited leukemic growth and prolonged survival in cell line xenograft models expressing FLT3 and CBL Y371H (PMID: 31943762). | 31943762 |
CBL Y371H 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 Y371H in culture (PMID: 31943762). | 31943762 |
CBL Y371H 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 Y371H in culture (PMID: 31943762). | 31943762 |
CBL Y371H 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 Y371H in culture (PMID: 31943762). | 31943762 |
CBL Y371H 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 Y371H in culture (PMID: 31943762). | 31943762 |
CBL Y371H 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 Y371H in culture (PMID: 31943762). | 31943762 |
CBL Y371H 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 Y371H in culture (PMID: 31943762). | 31943762 |