TISIDB

Summary
Symbol	FLT3
Name	fms-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 Location	13q12
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 [ TOP ]
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 [ TOP ]
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 [ TOP ]
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
Symbol	FLT3
Name	fms-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 Location	13q12
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

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Literatures describing the relation between FLT3 and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
23975756	Ovarian Cancinoma	Promote 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.
28895560	Acute Myeloid Leukemia	Promote immunity	The 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
Symbol	FLT3
Name	fms-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 Location	13q12
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

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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
29301958	CRISPR-Cas9	melanoma	B16F10	Pmel-1 T cell	NA/NS	NA/NS
29301958	CRISPR-Cas9	melanoma	B16F10	OT-1 T cell	NA/NS	NA/NS
28783722	CRISPR-Cas9	melanoma	Mel624	2CT-CRISPR	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX+Anti-PD1	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX	NA/NS	NA/NS
25691366	RNAi	Breast cancer	MCF7	Luc-CTL assay	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Primary screen	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Secondary screen	NA/NS	NA/NS

Summary
Symbol	FLT3
Name	fms-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 Location	13q12
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

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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
1	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	14	12	0.03	0.885
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	0.226	0.617
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.111	0.774
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	-0.357	0.419
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-0.708	0.571
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.082	0.955
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	1.193	0.0924
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	1.804	0.0797
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.549	0.619
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.496	0.272
11	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	2	0	0	1
12	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	2	8	0.035	0.952
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.406	0.108

> Mutation difference between responders and non-responders

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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
1	25765070	Non-small cell lung cancer (NSCLC)	all	Anti-PD-1 (pembrolizumab)	14	17	0	5.9	-5.9	1
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	0	33.3	-33.3	0.231
3	25765070	Non-small cell lung cancer (NSCLC)	non-smoking	Anti-PD-1 (pembrolizumab)	4	14	0	0	0	1
4	26359337	Melanoma	all	Anti-CTLA-4 (ipilimumab)	27	73	0	6.8	-6.8	0.32
5	26359337	Melanoma	BRAFi	Anti-CTLA-4 (ipilimumab)	0	14	0	7.1	-7.1	1
6	26359337	Melanoma	non-BRAFi	Anti-CTLA-4 (ipilimumab)	27	59	0	6.8	-6.8	0.304
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	23.8	11.8	12	0.427
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	37.5	0	37.5	0.209
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	15.4	18.2	-2.8	1
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	22.2	0	22.2	0.12
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	20	0	20	0.357
12	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	25	0	25	0.364
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	5.3	3.7	1.6	1
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	9.1	0	9.1	0.519
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	0	7.1	-7.1	0.467
16	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	11	13	0	0	0	1
17	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	6	1	0	0	0	1
18	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	5	12	0	0	0	1

Summary
Symbol	FLT3
Name	fms-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 Location	13q12
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 [ TOP ]

Summary
Symbol	FLT3
Name	fms-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 Location	13q12
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 [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	FLT3
Name	fms-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 Location	13q12
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 [ TOP ]

> Receptor [ TOP ]

Summary
Symbol	FLT3
Name	fms-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 Location	13q12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of FLT3 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	FLT3
Name	fms-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 Location	13q12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between FLT3 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	FLT3
Name	fms-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 Location	13q12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting FLT3 collected from DrugBank database.

> Drugs from DrugBank database

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Details on drugs targeting FLT3.

ID	Name	Drug Type	Targets	#Targets
DB00398	Sorafenib	Small Molecule	BRAF, FGFR1, FLT1, FLT3, FLT4, KDR, KIT, PDGFRB, RAF1, RET	10
DB01268	Sunitinib	Small Molecule	CSF1R, FLT1, FLT3, FLT4, KDR, KIT, PDGFRA, PDGFRB	8
DB05014	XL999	Small Molecule	FGFR1, FGFR3, FLT3, KDR, PDGFRB	5
DB05465	Tandutinib	Small Molecule	FLT3, PDGFD	2
DB06080	ABT-869	Small Molecule	CSF1R, FLT1, FLT3, FLT4, KDR, KIT	6
DB06469	Lestaurtinib	Small Molecule	FLT3	1
DB06595	Midostaurin	Small Molecule	FLT3, KDR, KIT, PDGFRA, PDGFRB, PRKCA	6
DB08901	Ponatinib	Small Molecule	ABL1, BCR, FGFR1, FGFR2, FGFR3, FGFR4, FLT3, KDR, KIT, LCK, LYN, P ......	15
DB09079	Nintedanib	Small Molecule	FGFR1, FGFR2, FGFR3, FLT1, FLT3, FLT4, KDR, LCK, LYN, SRC	10
DB12267	Brigatinib	Small Molecule	ABL1, ALK, EGFR, ERBB2, ERBB4, FLT3, IGF1R, INSR, MET	9
DB12742	Amuvatinib	Small Molecule	FLT3, KIT, MET, PDGFRA, RAD51, RET	6
DB12874	Quizartinib	Small Molecule	FLT3	1

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