Gene: FLT3

Alternate names for this Gene: CD135|FLK-2|FLK2|STK1

Gene Summary: This gene encodes a class III receptor tyrosine kinase that regulates hematopoiesis. This receptor is activated by binding of the fms-related tyrosine kinase 3 ligand to the extracellular domain, which induces homodimer formation in the plasma membrane leading to autophosphorylation of the receptor. The activated receptor kinase subsequently phosphorylates and activates multiple cytoplasmic effector molecules in pathways involved in apoptosis, proliferation, and differentiation of hematopoietic cells in bone marrow. Mutations that result in the constitutive activation of this receptor result in acute myeloid leukemia and acute lymphoblastic leukemia.

Gene is located in Chromosome: 13

Location in Chromosome : 13q12.2

Description of this Gene: fms related receptor tyrosine kinase 3

Type of Gene: protein-coding

rs76428106 in FLT3 gene and AUTOIMMUNE DISEASE, MULTISYSTEM, INFANTILE-ONSET, 1 PMID 30595370 2019 Leveraging Polygenic Functional Enrichment to Improve GWAS Power.

rs76428106 in FLT3 gene and AUTOIMMUNE DISEASE, MULTISYSTEM, INFANTILE-ONSET, 2 PMID 30595370 2019 Leveraging Polygenic Functional Enrichment to Improve GWAS Power.

rs76428106 in FLT3 gene and AUTOIMMUNE DISEASE, SUSCEPTIBILITY TO, 6 PMID 30595370 2019 Leveraging Polygenic Functional Enrichment to Improve GWAS Power.

rs1933437 in FLT3 gene and Age at menarche PMID 30595370 2019 Leveraging Polygenic Functional Enrichment to Improve GWAS Power.

rs76428106 in FLT3 gene and Autoimmune Diseases PMID 30595370 2019 Leveraging Polygenic Functional Enrichment to Improve GWAS Power.

rs34061361 in FLT3 gene and Blood basophil count (lab test) PMID 27863252 2016 The Allelic Landscape of Human Blood Cell Trait Variation and Links to Common Complex Disease.

rs1933437 in FLT3 gene and Body mass index PMID 30108127 2018 A Large Multiethnic Genome-Wide Association Study of Adult Body Mass Index Identifies Novel Loci.

PMID 29273807 2018 Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity.

PMID 26426971 2015 The Influence of Age and Sex on Genetic Associations with Adult Body Size and Shape: A Large-Scale Genome-Wide Interaction Study.

PMID 30239722 2019 Meta-analysis of genome-wide association studies for body fat distribution in 694 649 individuals of European ancestry.

PMID 25673413 2015 Genetic studies of body mass index yield new insights for obesity biology.

PMID 30595370 2019 Leveraging Polygenic Functional Enrichment to Improve GWAS Power.

rs34061361 in FLT3 gene and Eosinophil count procedure PMID 27863252 2016 The Allelic Landscape of Human Blood Cell Trait Variation and Links to Common Complex Disease.

rs2504235 in FLT3 gene and Gilles de la Tourette syndrome PMID 30818990 2019 Interrogating the Genetic Determinants of Tourette's Syndrome and Other Tic Disorders Through Genome-Wide Association Studies.

rs34061361 in FLT3 gene and Granulocyte count PMID 27863252 2016 The Allelic Landscape of Human Blood Cell Trait Variation and Links to Common Complex Disease.

rs76428106 in FLT3 gene and Hypothyroidism PMID 30595370 2019 Leveraging Polygenic Functional Enrichment to Improve GWAS Power.

rs1057519726 in FLT3 gene and Leukemia, Myelocytic, Acute PMID 23714533 2013 The role of kinase inhibitors in the treatment of patients with acute myeloid leukemia.

PMID 22368270 2012 Sorafenib treatment of FLT3-ITD(+) acute myeloid leukemia: favorable initial outcome and mechanisms of subsequent nonresponsiveness associated with the emergence of a D835 mutation.

PMID 23783394 2013 The importance of relative mutant level for evaluating impact on outcome of KIT, FLT3 and CBL mutations in core-binding factor acute myeloid leukemia.

PMID 15863200 2005 Prognostic significance of FLT3 mutations in pediatric non-promyelocytic acute myeloid leukemia.

PMID 16573742 2006 Prospective study of 174 de novo acute myelogenous leukemias according to the WHO classification: subtypes, cytogenetic features and FLT3 mutations.

PMID 22504186 2012 Continuing aspirin in the perioperative patient.

PMID 16371029 2006 Novel observation of three FLT3 codons mutated in tandem in an elderly acute myeloid leukaemia patient.

PMID 23261068 2013 Mutational landscape of AML with normal cytogenetics: biological and clinical implications.

PMID 23321257 2013 Prospective evaluation of gene mutations and minimal residual disease in patients with core binding factor acute myeloid leukemia.

PMID 22504184 2012 Validation of ITD mutations in FLT3 as a therapeutic target in human acute myeloid leukaemia.

PMID 23430109 2013 Activity of ponatinib against clinically-relevant AC220-resistant kinase domain mutants of FLT3-ITD.

PMID 24619500 2014 Reversal of acquired drug resistance in FLT3-mutated acute myeloid leukemia cells via distinct drug combination strategies.

PMID 23878140 2013 Gene expression analysis of AML patients with CBFB/MYH11 rearrangement and FLT3 N676K mutation showed a trend toward a specific expression profile.

PMID 16410449 2006 Point mutations in the juxtamembrane domain of FLT3 define a new class of activating mutations in AML.

PMID 14737077 2004 Acquisition of FLT3 or N-ras mutations is frequently associated with progression of myelodysplastic syndrome to acute myeloid leukemia.

PMID 16091740 2005 Roles of tyrosine residues 845, 892 and 922 in constitutive activation of murine FLT3 kinase domain mutant.

PMID 16990784 2006 The other novel mutation, FLT3 K663Q, is the first AML-associated gain-of-function mutation located outside the JM and AL domains.

PMID 22504183 2012 Crowding induces live cell extrusion to maintain homeostatic cell numbers in epithelia.

PMID 20733134 2010 Phase IIB trial of oral Midostaurin (PKC412), the FMS-like tyrosine kinase 3 receptor (FLT3) and multi-targeted kinase inhibitor, in patients with acute myeloid leukemia and high-risk myelodysplastic syndrome with either wild-type or mutated FLT3.

PMID 11290608 2001 Activating mutation of D835 within the activation loop of FLT3 in human hematologic malignancies.

PMID 25157968 2014 Prospective enterprise-level molecular genotyping of a cohort of cancer patients.

PMID 17606455 2007 Impact of FLT3 mutations and secondary cytogenetic changes on the outcome of patients with newly diagnosed acute promyelocytic leukemia treated with a single agent arsenic trioxide regimen.

PMID 24046014 2013 Crenolanib is active against models of drug-resistant FLT3-ITD-positive acute myeloid leukemia.

PMID 19657110 2009 Recurring mutations found by sequencing an acute myeloid leukemia genome.

PMID 15256420 2004 Variable sensitivity of FLT3 activation loop mutations to the small molecule tyrosine kinase inhibitor MLN518.

PMID 16857985 2006 A phase 2 trial of the FLT3 inhibitor lestaurtinib (CEP701) as first-line treatment for older patients with acute myeloid leukemia not considered fit for intensive chemotherapy.

PMID 14604974 2004 Mutations in the tyrosine kinase domain of FLT3 define a new molecular mechanism of acquired drug resistance to PTK inhibitors in FLT3-ITD-transformed hematopoietic cells.

PMID 19840437 2009 [FMS-like tyrosine kinase 3 gene mutations in acute myeloid leukemia].

PMID 15374878 2005 FLT3 inhibition selectively kills childhood acute lymphoblastic leukemia cells with high levels of FLT3 expression.

PMID 17047150 2007 Prolonged exposure to FLT3 inhibitors leads to resistance via activation of parallel signaling pathways.

PMID 17889720 2007 Sensitivity toward sorafenib and sunitinib varies between different activating and drug-resistant FLT3-ITD mutations.

PMID 22504185 2012 MicroRNAs in liver disease.

PMID 24046014 2013 In addition, crenolanib inhibited drug-resistant AML primary blasts with FLT3-ITD and D835H/Y mutations.

PMID 15625552 2005 A novel FLT3 activation loop mutation N841K in acute myeloblastic leukemia.

PMID 16990784 2006 FLT3 K663Q is a novel AML-associated oncogenic kinase: Determination of biochemical properties and sensitivity to Sunitinib (SU11248).

PMID 15667533 2005 Development of a human acute myeloid leukaemia screening panel and consequent identification of novel gene mutation in FLT3 and CCND3.

rs189992044 in FLT3 gene and Monocyte count procedure PMID 27863252 2016 The Allelic Landscape of Human Blood Cell Trait Variation and Links to Common Complex Disease.

PMID 28158719 2017 Genome-wide association of white blood cell counts in Hispanic/Latino Americans: the Hispanic Community Health Study/Study of Latinos.

PMID 29403010 2018 Genetic analysis of quantitative traits in the Japanese population links cell types to complex human diseases.

rs189992044 in FLT3 gene and Monocyte count result PMID 27863252 2016 The Allelic Landscape of Human Blood Cell Trait Variation and Links to Common Complex Disease.

PMID 28158719 2017 Genome-wide association of white blood cell counts in Hispanic/Latino Americans: the Hispanic Community Health Study/Study of Latinos.

PMID 29403010 2018 Genetic analysis of quantitative traits in the Japanese population links cell types to complex human diseases.

rs34061361 in FLT3 gene and Neutrophil count (procedure) PMID 27863252 2016 The Allelic Landscape of Human Blood Cell Trait Variation and Links to Common Complex Disease.

rs76428106 in FLT3 gene and RDW - Red blood cell distribution width result PMID 30595370 2019 Leveraging Polygenic Functional Enrichment to Improve GWAS Power.

rs76428106 in FLT3 gene and Red cell distribution width determination PMID 30595370 2019 Leveraging Polygenic Functional Enrichment to Improve GWAS Power.

rs34061361 in FLT3 gene and White Blood Cell Count procedure PMID 27863252 2016 The Allelic Landscape of Human Blood Cell Trait Variation and Links to Common Complex Disease.

PMID 30595370 2019 Leveraging Polygenic Functional Enrichment to Improve GWAS Power.