Browse FLT3

Summary
SymbolFLT3
Namefms-related tyrosine kinase 3
Aliases FLK2; CD135; FLK-2; CD135 antigen; FL cytokine receptor; fetal liver kinase 2; fms-like tyrosine kinase 3; g ......
Chromosomal Location13q12
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Basic function annotation.
> Subcellular Location, Domain and Function
> Gene Ontology
> KEGG and Reactome Pathway
> Subcellular Location, Domain and Function
 
Subcellular Location Membrane; Single-pass type I membrane protein. Endoplasmic reticulum lumen. Note=Constitutively activated mutant forms with internal tandem duplications are less efficiently transported to the cell surface and a significant proportion is retained in an immature form in the endoplasmic reticulum lumen. The activated kinase is rapidly targeted for degradation.
Domain PF00047 Immunoglobulin domain
PF07714 Protein tyrosine kinase
Function

Tyrosine-protein kinase that acts as cell-surface receptor for the cytokine FLT3LG and regulates differentiation, proliferation and survival of hematopoietic progenitor cells and of dendritic cells. Promotes phosphorylation of SHC1 and AKT1, and activation of the downstream effector MTOR. Promotes activation of RAS signaling and phosphorylation of downstream kinases, including MAPK1/ERK2 and/or MAPK3/ERK1. Promotes phosphorylation of FES, FER, PTPN6/SHP, PTPN11/SHP-2, PLCG1, and STAT5A and/or STAT5B. Activation of wild-type FLT3 causes only marginal activation of STAT5A or STAT5B. Mutations that cause constitutive kinase activity promote cell proliferation and resistance to apoptosis via the activation of multiple signaling pathways.

> Gene Ontology
 
Biological Process GO:0001776 leukocyte homeostasis
GO:0002244 hematopoietic progenitor cell differentiation
GO:0002318 myeloid progenitor cell differentiation
GO:0002320 lymphoid progenitor cell differentiation
GO:0002328 pro-B cell differentiation
GO:0002521 leukocyte differentiation
GO:0006644 phospholipid metabolic process
GO:0007259 JAK-STAT cascade
GO:0007260 tyrosine phosphorylation of STAT protein
GO:0014065 phosphatidylinositol 3-kinase signaling
GO:0014066 regulation of phosphatidylinositol 3-kinase signaling
GO:0014068 positive regulation of phosphatidylinositol 3-kinase signaling
GO:0018108 peptidyl-tyrosine phosphorylation
GO:0018212 peptidyl-tyrosine modification
GO:0019216 regulation of lipid metabolic process
GO:0030098 lymphocyte differentiation
GO:0030183 B cell differentiation
GO:0031099 regeneration
GO:0031100 animal organ regeneration
GO:0031960 response to corticosteroid
GO:0032943 mononuclear cell proliferation
GO:0033674 positive regulation of kinase activity
GO:0035726 common myeloid progenitor cell proliferation
GO:0035924 cellular response to vascular endothelial growth factor stimulus
GO:0038084 vascular endothelial growth factor signaling pathway
GO:0042113 B cell activation
GO:0042509 regulation of tyrosine phosphorylation of STAT protein
GO:0042531 positive regulation of tyrosine phosphorylation of STAT protein
GO:0043405 regulation of MAP kinase activity
GO:0043406 positive regulation of MAP kinase activity
GO:0043410 positive regulation of MAPK cascade
GO:0043550 regulation of lipid kinase activity
GO:0043551 regulation of phosphatidylinositol 3-kinase activity
GO:0043552 positive regulation of phosphatidylinositol 3-kinase activity
GO:0045834 positive regulation of lipid metabolic process
GO:0045860 positive regulation of protein kinase activity
GO:0046425 regulation of JAK-STAT cascade
GO:0046427 positive regulation of JAK-STAT cascade
GO:0046651 lymphocyte proliferation
GO:0046777 protein autophosphorylation
GO:0048015 phosphatidylinositol-mediated signaling
GO:0048017 inositol lipid-mediated signaling
GO:0048545 response to steroid hormone
GO:0048872 homeostasis of number of cells
GO:0050730 regulation of peptidyl-tyrosine phosphorylation
GO:0050731 positive regulation of peptidyl-tyrosine phosphorylation
GO:0051384 response to glucocorticoid
GO:0070661 leukocyte proliferation
GO:0071383 cellular response to steroid hormone stimulus
GO:0071384 cellular response to corticosteroid stimulus
GO:0071385 cellular response to glucocorticoid stimulus
GO:0071396 cellular response to lipid
GO:0071407 cellular response to organic cyclic compound
GO:0071900 regulation of protein serine/threonine kinase activity
GO:0071902 positive regulation of protein serine/threonine kinase activity
GO:0090218 positive regulation of lipid kinase activity
GO:0097028 dendritic cell differentiation
GO:0097696 STAT cascade
GO:1903725 regulation of phospholipid metabolic process
GO:1903727 positive regulation of phospholipid metabolic process
GO:1904892 regulation of STAT cascade
GO:1904894 positive regulation of STAT cascade
Molecular Function GO:0004713 protein tyrosine kinase activity
GO:0004714 transmembrane receptor protein tyrosine kinase activity
GO:0004896 cytokine receptor activity
GO:0005021 vascular endothelial growth factor-activated receptor activity
GO:0019199 transmembrane receptor protein kinase activity
GO:0035257 nuclear hormone receptor binding
GO:0035258 steroid hormone receptor binding
GO:0035259 glucocorticoid receptor binding
GO:0051427 hormone receptor binding
Cellular Component GO:0005788 endoplasmic reticulum lumen
> KEGG and Reactome Pathway
 
KEGG hsa04060 Cytokine-cytokine receptor interaction
hsa04640 Hematopoietic cell lineage
Reactome R-HSA-1280215: Cytokine Signaling in Immune system
R-HSA-168256: Immune System
R-HSA-449147: Signaling by Interleukins
Summary
SymbolFLT3
Namefms-related tyrosine kinase 3
Aliases FLK2; CD135; FLK-2; CD135 antigen; FL cytokine receptor; fetal liver kinase 2; fms-like tyrosine kinase 3; g ......
Chromosomal Location13q12
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Literatures that report relations between FLT3 and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.
> Text Mining
 
  Literatures describing the relation between FLT3 and anti-tumor immunity in human cancer.
PMID Cancer type Relation to immunity Evidence sentences
23975756Ovarian CancinomaPromote immunity (T cell function)When combined with GVAX or FVAX vaccination (consisting of irradiated ID8 cells expressing granulocyte macrophage colony-stimulating factor or FLT3 ligand) and costimulation by agonistic α-4-1BB or TLR 9 ligand, antibody-mediated blockade of PD-1 or PD-L1 triggered rejection of ID8 tumors in 75% of tumor-bearing mice. This therapeutic effect was associated with increased proliferation and function of tumor antigen-specific effector CD8(+) T cells, inhibition of suppressive regulatory T cells (Treg) and MDSC, upregulation of effector T-cell signaling molecules, and generation of T memory precursor cells.
28895560Acute Myeloid LeukemiaPromote immunityThe fms-related tyrosine kinase 3 (FLT3) receptor has been extensively studied over the past two decades with regard to oncogenic alterations that do not only serve as prognostic markers but also as therapeutic targets in acute myeloid leukemia (AML).
Summary
SymbolFLT3
Namefms-related tyrosine kinase 3
Aliases FLK2; CD135; FLK-2; CD135 antigen; FL cytokine receptor; fetal liver kinase 2; fms-like tyrosine kinase 3; g ......
Chromosomal Location13q12
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.
> High-throughput Screening
  Statistical results of FLT3 in screening data sets for detecting immune reponses.
PMID Screening System Cancer Type Cell Line Data Set Statistical Results Relation to immunity
29301958CRISPR-Cas9 melanomaB16F10Pmel-1 T cell NA/NSNA/NS
29301958CRISPR-Cas9 melanomaB16F10OT-1 T cell NA/NSNA/NS
28783722CRISPR-Cas9 melanomaMel6242CT-CRISPR NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX+Anti-PD1 NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX NA/NSNA/NS
25691366RNAiBreast cancerMCF7Luc-CTL assay NA/NSNA/NS
24476824shRNAmelanomaB16Primary screen NA/NSNA/NS
24476824shRNAmelanomaB16Secondary screen NA/NSNA/NS
Summary
SymbolFLT3
Namefms-related tyrosine kinase 3
Aliases FLK2; CD135; FLK-2; CD135 antigen; FL cytokine receptor; fetal liver kinase 2; fms-like tyrosine kinase 3; g ......
Chromosomal Location13q12
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets.
> Expression difference between responders and non-responders
> Mutation difference between responders and non-responders
> Expression difference between responders and non-responders
 
Points in the above scatter plot represent the expression difference of FLT3 in various data sets.
No PMID Cancer type Group Drug # Res # NRes Log2 (Fold Change) P value Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)14120.030.885
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)650.2260.617
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)87-0.1110.774
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 916-0.3570.419
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 59-0.7080.571
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470.0820.955
729033130MelanomaallAnti-PD-1 (nivolumab) 26231.1930.0924
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 15111.8040.0797
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 11120.5490.619
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 480.4960.272
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 280.0350.952
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 68230-0.4060.108
> Mutation difference between responders and non-responders
 
Points in the above scatter plot represent the mutation difference of FLT3 in various data sets.
No PMID Cancer type Group Drug # Res # NRes % Mut/Res % Mut/NRes % Diff (R vs NR) Pval Anno
125765070Non-small cell lung cancer (NSCLC)allAnti-PD-1 (pembrolizumab) 141705.9-5.91
225765070Non-small cell lung cancer (NSCLC)smokingAnti-PD-1 (pembrolizumab) 103033.3-33.30.231
325765070Non-small cell lung cancer (NSCLC)non-smokingAnti-PD-1 (pembrolizumab) 4140001
426359337MelanomaallAnti-CTLA-4 (ipilimumab) 277306.8-6.80.32
526359337MelanomaBRAFiAnti-CTLA-4 (ipilimumab) 01407.1-7.11
626359337Melanomanon-BRAFiAnti-CTLA-4 (ipilimumab) 275906.8-6.80.304
726997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)211723.811.8120.427
826997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)8637.5037.50.209
926997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)131115.418.2-2.81
1028552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 91622.2022.20.12
1128552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 59200200.357
1228552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 47250250.364
1329033130MelanomaallAnti-PD-1 (nivolumab) 38275.33.71.61
1429033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 22139.109.10.519
1529033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 161407.1-7.10.467
1629301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 11130001
1729301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 610001
1829301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 5120001
Summary
SymbolFLT3
Namefms-related tyrosine kinase 3
Aliases FLK2; CD135; FLK-2; CD135 antigen; FL cytokine receptor; fetal liver kinase 2; fms-like tyrosine kinase 3; g ......
Chromosomal Location13q12
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of FLT3. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.
> Lymphocyte
 
Summary
SymbolFLT3
Namefms-related tyrosine kinase 3
Aliases FLK2; CD135; FLK-2; CD135 antigen; FL cytokine receptor; fetal liver kinase 2; fms-like tyrosine kinase 3; g ......
Chromosomal Location13q12
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of FLT3. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by FLT3.
> Immunoinhibitor
> Immunostimulator
> MHC molecule
> Immunoinhibitor
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolFLT3
Namefms-related tyrosine kinase 3
Aliases FLK2; CD135; FLK-2; CD135 antigen; FL cytokine receptor; fetal liver kinase 2; fms-like tyrosine kinase 3; g ......
Chromosomal Location13q12
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of FLT3. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene.
> Chemokine
> Receptor
> Chemokine
 
> Receptor
 
Summary
SymbolFLT3
Namefms-related tyrosine kinase 3
Aliases FLK2; CD135; FLK-2; CD135 antigen; FL cytokine receptor; fetal liver kinase 2; fms-like tyrosine kinase 3; g ......
Chromosomal Location13q12
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of FLT3 expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolFLT3
Namefms-related tyrosine kinase 3
Aliases FLK2; CD135; FLK-2; CD135 antigen; FL cytokine receptor; fetal liver kinase 2; fms-like tyrosine kinase 3; g ......
Chromosomal Location13q12
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between FLT3 and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolFLT3
Namefms-related tyrosine kinase 3
Aliases FLK2; CD135; FLK-2; CD135 antigen; FL cytokine receptor; fetal liver kinase 2; fms-like tyrosine kinase 3; g ......
Chromosomal Location13q12
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting FLT3 collected from DrugBank database.
> Drugs from DrugBank database
 

  Details on drugs targeting FLT3.
ID Name Drug Type Targets #Targets
DB00398SorafenibSmall MoleculeBRAF, FGFR1, FLT1, FLT3, FLT4, KDR, KIT, PDGFRB, RAF1, RET10
DB01268SunitinibSmall MoleculeCSF1R, FLT1, FLT3, FLT4, KDR, KIT, PDGFRA, PDGFRB8
DB05014XL999Small MoleculeFGFR1, FGFR3, FLT3, KDR, PDGFRB5
DB05465TandutinibSmall MoleculeFLT3, PDGFD2
DB06080ABT-869Small MoleculeCSF1R, FLT1, FLT3, FLT4, KDR, KIT6
DB06469LestaurtinibSmall MoleculeFLT31
DB06595MidostaurinSmall MoleculeFLT3, KDR, KIT, PDGFRA, PDGFRB, PRKCA6
DB08901PonatinibSmall MoleculeABL1, BCR, FGFR1, FGFR2, FGFR3, FGFR4, FLT3, KDR, KIT, LCK, LYN, P ......15
DB09079NintedanibSmall MoleculeFGFR1, FGFR2, FGFR3, FLT1, FLT3, FLT4, KDR, LCK, LYN, SRC10
DB12267BrigatinibSmall MoleculeABL1, ALK, EGFR, ERBB2, ERBB4, FLT3, IGF1R, INSR, MET9
DB12742AmuvatinibSmall MoleculeFLT3, KIT, MET, PDGFRA, RAD51, RET6
DB12874QuizartinibSmall MoleculeFLT31