Gene Variant Detail

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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

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Transcript NM_005188
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

Filtering

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  • Simple literal full or partial string matches
  • Separate multiple filter terms with a spaces, order doesn't matter (a b c and c b a are equivalent )
  • Filtering will only apply to rows that are already loaded on the page, filtering has no impact on query parameters
  • Use quotes to match a longer phrase which contains spaces "mtor c1483f"

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
CBL Y371H FLT3 wild-type hematologic cancer sensitive Quizartinib Preclinical - Cell culture Actionable In a preclinical study, Quizartinib (AC220) 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 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 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 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 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 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 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 Quizartinib Preclinical - Cell culture Actionable In a preclinical study, Quizartinib (AC220) inhibited 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 Quizartinib (AC220) 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 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 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
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
CBL mutant myelodysplastic/myeloproliferative neoplasm not applicable N/A Clinical Study Prognostic In clinical analyses, mutations in CBL were associated with adverse prognosis in patients with chronic myelomonocytic leukemia (PMID: 26230957, PMID: 23690417, PMID: 19901108). 26230957 19901108 23690417
CBL mutant bone marrow cancer sensitive Quizartinib Preclinical Actionable In a preclinical study, Quizartinib (AC220) reduced white blood cell counts and decreased myeloid cell invasion in a CBL mutant mouse model with myeloproliferative disorder (PMID: 22990016). 22990016
CBL mutant myelofibrosis not applicable N/A Guideline Prognostic CBL mutations are associated with inferior overall survival in patients with primary myelofibrosis (NCCN.org). detail...
Molecular Profile Protein Effect Treatment Approaches
CBL Y371H loss of function FLT3 Inhibitor
CBL Y371H FLT3 wild-type
CBL Y371H FLT3 pos