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FLT3 Gene

protein-coding GIFtS: 71
GCID: GC13M028577

Fms-Related Tyrosine Kinase 3

See related diseases
at

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(According to ¹HGNC, ²Entrez Gene,
³UniProtKB/Swiss-Prot, ⁴UniProtKB/TrEMBL, ⁵OMIM, ⁶GeneLoc, ⁷Ensembl, ⁸DME, ⁹miRBase, ¹⁰fRNAdb, ¹²H-InvDB, ¹³NCBI, ¹⁴NONCODE, and/or ¹⁵RNAdb)
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Aliases
Fms-Related Tyrosine Kinase 3¹ ²		FL Cytokine Receptor² ³
Fms-Like Tyrosine Kinase 3² ³		EC 2.7.10.1³ ⁸
Stem Cell Tyrosine Kinase 1² ³		Fetal Liver Kinase 2²
CD135² ³		Growth Factor Receptor Tyrosine Kinase Type III²
FLK-2² ³		Receptor-Type Tyrosine-Protein Kinase FLT3²
FLK2² ³		FLT-3³
STK-1² ³		Fetal Liver Kinase-2³
STK1² ³		EC 2.7.10⁸
CD135 Antigen² ³

External Ids:	HGNC: 3765¹	Entrez Gene: 2322²	Ensembl: ENSG00000122025⁷	OMIM: 136351⁵	UniProtKB: P36888³

Export aliases for FLT3 gene to outside databases

Previous GC identifers: GC13M026557 GC13M022557 GC13M027507 GC13M026375 GC13M027475 GC13M009398

(According to Entrez Gene, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
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Entrez Gene summary for FLT3 Gene:

This gene encodes a class III receptor tyrosine kinase that regulates hematopoiesis. The receptor consists of an

extracellular domain composed of five immunoglobulin-like domains, one transmembrane region, and a cytoplasmic

kinase domain split into two parts by a kinase-insert domain. The 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.

(provided by RefSeq, Jul 2008)

GeneCards Summary for FLT3 Gene:

FLT3 (fms-related tyrosine kinase 3) is a protein-coding gene. Diseases associated with FLT3 include leukemia, acute lymphoblastic, somatic, and minimally differentiated acute myeloblastic leukemia. GO annotations related to this gene include phosphatidylinositol 3-kinase binding and protein homodimerization activity. An important paralog of this gene is FLT4.

UniProtKB/Swiss-Prot: FLT3_HUMAN, P36888

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

summary for FLT3 Gene:

FMS-like receptor tyrosine kinase-3 (FLT3) is a member of the class III RTK (receptor tyrosine kinase)

family and is expressed primarily in hematopoietic progenitor cells. The expression within these cells

demonstrates that FLT3 has an important role in the pathogenesis of AML (acute myelogenous leukemia), under

which conditions wild type receptors are overexpressed or mutated forms of the receptor are present.

Inhibitors of both mutated and wild type receptors are therefore of interest in a therapeutic context.

Gene Wiki entry for FLT3 (CD135) Gene

(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 75), Regulatory elements and Epigenetics data according to QIAGEN, and/or SwitchGear Genomics)
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RefSeq DNA sequence:

NC_000013.11 NC_018924.2 NT_024524.15

Regulatory elements:

Regulatory transcription factor binding sites in the FLT3 gene promoter:
STAT5B Pax-5 AP-1 ATF-2 GATA-2 C/EBPalpha STAT3 c-Jun NF-kappaB1 Hlf
Other transcription factors

SwitchGear Promoter luciferase reporter plasmid: FLT3 promoter sequence

Search Chromatin IP Primers for FLT3

Epigenetics:

DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat FLT3

Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 13q12 Ensembl cytogenetic band: 13q12.2 HGNC cytogenetic band: 13q12

FLT3 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
FLT3 gene location

GeneLoc information about chromosome 13 GeneLoc Exon Structure

GeneLoc location for GC13M028577: view genomic region (about GC identifiers)

Start:	28,577,411 bp from pter	End:	28,674,729 bp from pter
Size:	97,319 bases	Orientation:	minus strand

(According to ¹UniProtKB, HORDE, ²neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Cloud-Clone Corp.,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Cloud-Clone Corp., Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, and/or Cloud-Clone Corp.)
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UniProtKB/Swiss-Prot: FLT3_HUMAN, P36888 (See protein sequence)

Recommended Name: Receptor-type tyrosine-protein kinase FLT3 precursor

Size: 993 amino acids; 112903 Da

Subunit: Monomer in the absence of bound FLT3LG. Homodimer in the presence of bound FLT3LG. Interacts with FIZ1

following ligand activation (By similarity). Interacts with FES, FER, LYN, FGR, HCK, SRC and GRB2. Interacts with

PTPRJ/DEP-1 and PTPN11/SHP2

Miscellaneous: Can be used as diagnostic tool to establish the exact cause of acute myeloid leukemia, and to

determine the optimal therapy

3 PDB 3D structures from and Proteopedia for FLT3:

1RJB (3D)

3QS7 (3D)

3QS9 (3D)

Secondary accessions: A0AVG9 B7ZLT7 B7ZLT8 F5H0A0 Q13414

Alternative splicing: 2 isoforms: P36888-1 P36888-2

Explore the universe of human proteins at neXtProt for FLT3: NX_P36888

Explore proteomics data for FLT3 at MOPED

Post-translational modifications:

N-glycosylated, contains complex N-glycans with sialic acid¹

Autophosphorylated on several tyrosine residues in response to FLT3LG binding. FLT3LG binding also increases

phosphorylation of mutant kinases that are constitutively activated. Dephosphorylated by PTPRJ/DEP-1, PTPN1,

PTPN6/SHP-1, and to a lesser degree by PTPN12. Dephosphorylation is important for export from the endoplasmic

reticulum and location at the cell membrane¹

Rapidly ubiquitinated by UBE2L6 and the E3 ubiquitin-protein ligase SIAH1 after autophosphorylation, leading to

its proteasomal degradation¹

Ubiquitination² at Lys614, Lys623

Glycosylation² at Asn43, Asn100, Asn151, Asn306, Asn323, Asn351, Asn354, Asn473, Asn502, Asn541

Modification sites at PhosphoSitePlus

Selected DME Specific Peptides for FLT3 (P36888) (see all 13)

VAVKMLK

RDLAARN

ALMSELK

WEIFSLG

See FLT3 Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

REFSEQ proteins: NP_004110.2

ENSEMBL proteins:

ENSP00000241453 ENSP00000370374 ENSP00000370369 ENSP00000438139

FLT3 Human Recombinant Protein Products:

	EMD Millipore Purified and/or Recombinant FLT3 Protein
	R&D Systems Recombinant & Natural Proteins for FLT3 (Flt-3/Flk-2)
	Enzo Life Sciences proteins for FLT3
	OriGene Purified Proteins for FLT3 OriGene Protein Over-expression Lysate for FLT3 OriGene MassSpec for FLT3 OriGene Custom Protein Services for FLT3
	GenScript Custom Purified and Recombinant Proteins Services for FLT3
	Novus Biologicals FLT3 Proteins Novus Biologicals FLT3 Lysate
	Sino Biological Recombinant Protein for FLT3 Sino Biological Cell Lysate for FLT3
	Browse ProSpec Recombinant Proteins
	Browse Proteins at Cloud-Clone Corp.

FLT3 Antibody Products:

	EMD Millipore Mono- and Polyclonal Antibodies for the study of FLT3
	R&D Systems Antibodies for FLT3 (Flt-3/Flk-2)
	Cell Signaling Technology (CST) Antibodies for FLT3
	OriGene Antibodies for FLT3 OriGene Custom Antibody Services for FLT3
	Novus Biologicals FLT3 Antibodies
	Search for Antibodies for FLT3 at Abcam
	Browse Antibodies at Cloud-Clone Corp.
	ThermoFisher Antibody for FLT3
	LSBio Antibodies in human, mouse, rat for FLT3

FLT3 Assay Products:

	Browse Kits and Assays available from EMD Millipore
	OriGene Custom Assay Services for FLT3
	R&D Systems ELISAs for FLT3 (Flt-3/Flk-2) (see all)
	GenScript FLT3-Activity-based Kinase Assay for Compound Screening
	Cell Signaling Technology (CST) Sandwich ELISA Kits for FLT3
	Browse Enzo Life Sciences for kits & assays
	Browse ELISAs at Cloud-Clone Corp. Browse CLIAs at Cloud-Clone Corp.

(According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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HGNC Gene Families:

CD: CD molecules

IGD: Immunoglobulin superfamily / Immunoglobulin-like domain containing

IUPHAR Guide to PHARMACOLOGY protein family classification: fms-related tyrosine kinase 3

PDGF (platelet-derived growth factor) receptor family

Selected InterPro protein domains (see all 12):

IPR017441 Protein_kinase_ATP_BS

IPR011009 Kinase-like_dom

IPR013783 Ig-like_fold

IPR000719 Prot_kinase_dom

IPR001824 Tyr_kinase_rcpt_3_CS

Graphical View of Domain Structure for InterPro Entry P36888

ProtoNet protein and cluster: P36888

2 Blocks protein domains:

IPB003599 Immunoglobulin subtype

IPB008266 Tyrosine protein kinase

UniProtKB/Swiss-Prot: FLT3_HUMAN, P36888

Domain: The juxtamembrane autoregulatory region is important for normal regulation of the kinase activity and for

maintaining the kinase in an inactive state in the absence of bound ligand. Upon tyrosine phosphorylation, it

mediates interaction with the SH2 domains of numerous signaling partners. In-frame internal tandem duplications

(ITDs) result in constitutive activation of the kinase. The activity of the mutant kinase can be stimulated

further by FLT3LG binding

Similarity: Belongs to the protein kinase superfamily. Tyr protein kinase family. CSF-1/PDGF receptor subfamily

Similarity: Contains 1 Ig-like C2-type (immunoglobulin-like) domain

Similarity: Contains 1 protein kinase domain

FLT3 for domains About GeneDecksing

(According to ¹UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or ²DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, inGenious Targeting Laboratory, genOway,
transcription factor targeting from QIAGEN and/or HOMER, miRNA Gene Targets from miRTarBase, shRNA from OriGene, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, SwitchGear Genomics, Gene Editing from DNA2.0, Clones from OriGene, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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Molecular Function:

UniProtKB/Swiss-Prot Summary: FLT3_HUMAN, P36888

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

Catalytic activity: ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate

Enzyme regulation: Present in an inactive conformation in the absence of bound ligand. FLT3LG binding leads to

dimerization and activation by autophosphorylation

Genatlas biochemistry entry for FLT3:

fms-related receptor tyrosine kinase 3,expressed on endothelial cell,duplicated in childhood acute myeloid

leukemia with poor prognosis and acute lymphoblastic leukemia but not in myelodysplastic syndrome

Enzyme Numbers (IUBMB): EC 2.7.10.1¹ ² EC 2.7.10²

Gene Ontology (GO): Selected molecular function terms (see all 10): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0004672	protein kinase activity	--	--
GO:0004713	protein tyrosine kinase activity	--	--
GO:0004714	transmembrane receptor protein tyrosine kinase activity	TAS	19549778
GO:0004896	cytokine receptor activity	ISS	--
GO:0005021	vascular endothelial growth factor-activated receptor activity	TAS	8394751

FLT3 for ontologies About GeneDecksing

Phenotypes:
2 GenomeRNAi human phenotypes for FLT3:

Decreased substrate adherent c

Decreased viability

7 MGI mutant phenotypes (inferred from 4 alleles) (MGI details for Flt3):

cellular	growth/size/body	hematopoietic system	homeostasis/metabolism	immune system
mortality/aging	tumorigenesis

FLT3 for phenotypes About GeneDecksing

Animal Models:
MGI mouse knock-out Flt3^tm1Irl for FLT3

inGenious Targeting Laboratory: Let us create your new Knockout/Knockin mouse model for FLT3

inGenious Targeting Laboratory: Contact us about creating complex and humanized mouse models for FLT3

genOway customized KO model: permanent, tissue-specific or time-controlled inactivation for FLT3

genOway customized Knockin model: humanization, point mutation, expression monitoring, etc. for FLT3

miRNA Products:		miRTarBase miRNAs that target FLT3: hsa-mir-335-5p (MIRT017462), hsa-mir-150-5p (MIRT007053)

		Block miRNA regulation of human, mouse, rat FLT3 using miScript Target Protectors
		Selected qRT-PCR Assays for microRNAs that regulate FLT3 (see all 33):
		hsa-miR-3194-5p hsa-miR-15a hsa-miR-1245 hsa-miR-139-5p hsa-miR-3074-3p hsa-miR-570 hsa-miR-3142 hsa-miR-424

		SwitchGear 3'UTR luciferase reporter plasmid: FLT3 3' UTR sequence

Inhib. RNA Products:		OriGene RNAi products in human, mouse, rat for FLT3
		Predesigned siRNA for gene silencing in human, mouse, rat FLT3

Gene Editing
Products:

DNA2.0 Custom Protein Engineering Service for FLT3

Clone Products:		OriGene clones in human, mouse for FLT3 (see all 8) OriGene ORF clones in mouse, rat for FLT3 OriGene custom cloning services - gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
		GenScript: all cDNA clones in your preferred vector: FLT3 (NM_004119)
		Sino Biological Human cDNA Clone for FLT3
		DNA2.0 Custom Codon Optimized Gene Synthesis Service for FLT3
		Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat FLT3

Cell Line Products:		GenScript Custom overexpressing Cell Line Services for FLT3
		Browse ESI BIO Cell Lines and PureStem Progenitors for FLT3

In Situ Assay
Products:

Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for FLT3

(According to UniProtKB, COMPARTMENTS Subcellular localization database, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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Subcellular locations from UniProtKB/Swiss-Prot

FLT3_HUMAN, P36888: 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

Subcellular locations from COMPARTMENTS:

Compartment	Confidence
endoplasmic reticulum	5
plasma membrane	4
extracellular	2
nucleus	2
peroxisome	1

About this image

Gene Ontology (GO): 5 cellular component terms (see first 5): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0005788	endoplasmic reticulum lumen	IEA	--
GO:0005887	integral component of plasma membrane	TAS	8394751
GO:0009986	cell surface	IEA	--
GO:0016020	membrane	--	--
GO:0016021	integral component of membrane	--	--

FLT3 for ontologies About GeneDecksing

(SuperPaths according to PathCards, Pathways according to R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to QIAGEN, and/or STRING, Interactions according to ¹UniProtKB, ²MINT, ³I2D, and/or ⁴STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene).
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SuperPaths for FLT3 About (see all 17)

See pathways by source

SuperPath

Contained pathways About

PEDF Induced Signaling

Endothelin-1 Signaling Pathway

0.46

Cytokine-cytokine receptor interaction

0.43

GPCR Pathway

Ras Pathway	0.73	Breast Cancer Regulation by Stathmin1	0.58
Paxillin Interactions	0.73	NFAT in Immune Response	0.58
GPCR Pathway	0.62	Estrogen Pathway	0.55
Pancreatic Adenocarcinoma	0.59	P2Y Receptor Signaling	0.38

ERK Signaling

Rho Family GTPases	0.61	Molecular Mechanisms of Cancer	0.51
ERK Signaling	0.61	ILK Signaling	0.49
MAPK Signaling	0.58

Nanog in Mammalian ESC Pluripotency

	Nanog in Mammalian ESC Pluripotency	0.61			14-3-3 Induced Intracellular Signaling	0.59
	GSK3 Signaling	0.61			eNOS Signaling	0.48

Actin Nucleation by ARP-WASP Complex

	Actin Nucleation and Branching	0.66			CDC42 Pathway	0.41
	Actin Nucleation by ARP-WASP Complex	0.66

Pathways by source See SuperPaths
Show all pathways

Selected Downloadable PowerPoint Slides of GeneGlobe Pathway Central Maps for FLT3 (see all 29)

	FLT3 Signaling
	MAPK Signaling
	Paxillin Interactions
	Endothelin-1 Signaling Pathway
	Molecular Mechanisms of Cancer

1 Cell Signaling Technology (CST) Pathway for FLT3

Tyrosine Kinases / Adaptors

1 GeneGo (Thomson Reuters) Pathway for FLT3

Development Flt3 signaling

1 PharmGKB Pathway for FLT3

Sorafenib Pharmacodynamics

5 Kegg Pathways (Kegg details for FLT3):

	Cytokine-cytokine receptor interaction
	Hematopoietic cell lineage
	Pathways in cancer
	Transcriptional misregulation in cancer
	Acute myeloid leukemia

FLT3 for pathways About GeneDecksing

Pathway & Disease-focused RT² Profiler PCR Arrays including FLT3:

Antigen Presenting Cells in human mouse rat

Lymphoma in human mouse rat

T-cell & B-cell Activation in human mouse rat

Interactions:

GeneGlobe Interaction Network for FLT3

STRING Interaction Network Preview (showing 5 interactants - click image to see 25)

Selected Interacting proteins for FLT3 (P36888^{1, 2, 3} ENSP00000241453⁴) via UniProtKB, MINT, STRING, and/or I2D (see all 35)

Interactant		Interaction Details
GeneCard	External ID(s)	Interaction Details
PIK3R1	P27986¹^,²^,³, ENSP00000274335⁴	EBI-3946257,EBI-79464 MINT-7103574 MINT-7103585 I2D: score=2 STRING: ENSP00000274335
PTPN11	Q06124²^,³, ENSP00000340944⁴	MINT-8030324 MINT-8030340 I2D: score=1 STRING: ENSP00000340944
IKBKG	Q9Y6K9¹^,³, ENSP00000358622⁴	EBI-3946257,EBI-81279 I2D: score=1 STRING: ENSP00000358622
SOCS1	O15524³, ENSP00000329418⁴	I2D: score=4 STRING: ENSP00000329418
INPP5D	Q92835³, ENSP00000352575⁴	I2D: score=3 STRING: ENSP00000352575

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Gene Ontology (GO): Selected biological process terms (see all 27): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0001776	leukocyte homeostasis	ISS	--
GO:0002318	myeloid progenitor cell differentiation	ISS	--
GO:0002320	lymphoid progenitor cell differentiation	--	--
GO:0002328	pro-B cell differentiation	ISS	--
GO:0002572	pro-T cell differentiation	IEA	--

FLT3 for ontologies About GeneDecksing

(Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience, ApexBio, HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB)
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Browse Small Molecules at EMD Millipore

Browse drugs & compounds from Enzo Life Sciences

Selected ApexBio Compounds for FLT3 (see all 12)

About this table

Compound	Action	CAS #
Amuvatinib (MP-470, HPK 56)	Multi-kinase inhibitor, inhibits PDGFR, c-Kit, and Flt3	[850879-09-3]
AST 487	high selectivity and potency toward FLT3	[630124-46-8]
Cabozantinib (XL184, BMS-907351)	Multi-target kinase inhibitor, inhibits c-Met, VEGFR2, and RET	[849217-68-1]
KW 2449	multiple-targeted inhibitor, mostly for Flt3	[1000669-72-6]
Lestaurtinib	Potent JAK2, FLT3 and TrkA inhibitor	[111358-88-4]
Linifanib (ABT-869)	ATP-competitive, multi-targeted RTK inhibitor	[796967-16-3]
Ponatinib (AP24534)	pan-BCR-ABL inhibitor	[943319-70-8]
Quizartinib (AC220)	Potent and selective FLT3 inhibitor	[950769-58-1]
SB1317	inhibits CDKs 1, 2, 7 and 9 together with JAK2 and FLT3	[937270-47-8]
SU5416	VEGF receptor inhibitor and an aryl hydrocarbon receptor (AHR) agonist	[204005-46-9]

Compounds for FLT3 available from Tocris Bioscience About this table

Compound	Action	CAS #
TCS 359	Potent FLT3 inhibitor	[301305-73-7]
5'-Fluoroindirubinoxime	FLT3 inhibitor; displays antiproliferative activity	[861214-33-7]

2 HMDB Compounds for FLT3 About this table

Compound	Synonyms	CAS #	PubMed Ids
ADP	adenosindiphosphorsaeure (see all 8)	58-64-0	--
Adenosine triphosphate	5'-(tetrahydrogen triphosphate) Adenosine (see all 24)	56-65-5	--

3 DrugBank Compounds for FLT3 About this table

Compound	Synonyms	CAS #	Type	Actions	PubMed Ids
Sunitinib	SU011248 (see all 2)	557795-19-4	target	multitarget	14654525 12531805 15304385 15180525 11752352 14753710
Sorafenib	--	284461-73-0	target	antagonist	17229632 17205056
Ponatinib	--	943319-70-8	target	inhibitor	23430109

1 IUPHAR Ligand for FLT3 (fms-related tyrosine kinase 3) About this table

Ligand	Type	Action	Affinity	Pubmed IDs
Fms-related tyrosine kinase 3 ligand	None	None		--

Selected Novoseek inferred chemical compound relationships for FLT3 gene (see all 40) About this table

Compound	-log (P-Val)	Hits	PubMed IDs for Articles with Shared Sentences (# sentences)
pkc 412	91.7	85	17330105 (5), 18071308 (5), 15956279 (4), 15150124 (4) (see all 27)
lestaurtinib	88.1	22	16868253 (4), 16857985 (2), 20141349 (2), 18341639 (2) (see all 7)
tyrosine	85.3	556	17851558 (7), 15345597 (4), 9737679 (3), 14726387 (3) (see all 99)
tandutinib	84.9	24	16902153 (4), 15256420 (3), 15242881 (3), 19625780 (3) (see all 6)
ag-1296	80.8	21	11455967 (7), 12357354 (2), 17050201 (2), 18509353 (2) (see all 6)
sunitinib	74.2	28	17889720 (4), 17041096 (3), 17591828 (1), 18192256 (1) (see all 20)
daniplestim	67.8	1	10781904 (1)
imatinib	67.8	30	18797870 (3), 14976243 (2), 15180525 (2), 11290609 (1) (see all 13)
sorafenib	67.5	37	17229632 (6), 18230792 (4), 17889720 (4), 17205056 (2) (see all 20)
su5416	62.1	11	15158089 (5), 12351406 (2), 17169805 (1), 12649163 (1) (see all 5)

FLT3 for compounds About GeneDecksing

(Secondary structures according to fRNAdb,
GenBank/EMBL/DDBJ Accessions according to
Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
RefSeq according to Entrez Gene,
DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
Conferences by KenesGroup, exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN, SwitchGear Genomics,
Tagged/untagged cDNA clones from OriGene, GenScript, DNA2.0, Vector BioLabs, Primers from OriGene, and/or QIAGEN )
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REFSEQ mRNAs for FLT3 gene:

NM_004119.2

Unigene Cluster for FLT3:

Fms-related tyrosine kinase 3

Hs.507590 [show with all ESTs]

Unigene Representative Sequence: NM_004119

5 Ensembl transcripts including schematic representations, and UCSC links where relevant:

ENST00000241453(uc001urw.3 uc010aao.3 uc010tdn.2) ENST00000380987

ENST00000469894 ENST00000380982 ENST00000537084

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Additional mRNA sequence:

BC126350.1 BC144039.1 BC144040.1 L36162.1 U02687.1 Z26652.1

4 DOTS entries:

DT.120782229 DT.104253 DT.75174632 DT.91675080

17 AceView cDNA sequences:

BF589957 BC036028 BX279530 BU681356 L36162 AW059681 U02687 NM_004119

AV713950 Z26652 AW772610 AI150354 BI461248 AW057705 BF170536 BF176247

BF170584

GeneLoc Exon Structure

(RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, Protein expression images according to data from SPIRE ¹MOPED, ²PaxDb, and ³MaxQB, plus additional links to SOURCE, and/or BioGPS, and/or UniProtKB,
PCR Arrays from QIAGEN, Primers from OriGene, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
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FLT3 expression in normal human tissues (normalized intensities) FLT3 embryonic expression: see
See probesets specificity/sensitivity at GeneAnnot
About this imageBioGPS <intensity>^2/3
CGAP TAG: AGTGATTCCA

About this image

FLT3 expression in embryonic tissues and stem cells About this table

Data from LifeMap, the Embryonic Development and Stem Cells Database
selected tissues (see all 3) fully expand


Blood (Hematopoietic System) fully expand to see all 17 entries
Common Lymphoid Progenitor Cells Hematopoietic Bone Marrow
Bone Marrow CD133+ Cells
clps

Umbilical Cord (Extraembryonic Tissues)
stem cells (umbilical cord cd34+)

Bone (Muscoskeletal System)
BONE MARROW

FLT3 Protein expression data from MOPED¹, PaxDb² and MaxQB³:

About this image

FLT3 Protein Expression

SOURCE GeneReport for Unigene cluster: Hs.507590

UniProtKB/Swiss-Prot: FLT3_HUMAN, P36888

Tissue specificity: Detected in bone marrow, in hematopoietic stem cells, in myeloid progenitor cells and in

granulocyte/macrophage progenitor cells (at protein level). Detected in bone marrow, liver, thymus, spleen and

lymph node, and at low levels in kidney and pancreas. Highly expressed in T-cell leukemia

Pathway & Disease-focused RT² Profiler PCR Arrays including FLT3:

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T-cell & B-cell Activation in human mouse rat

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(Orthologs according to ^1,2HomoloGene (²older version, for species not in ¹newer version), ³euGenes, ⁴SGD , ⁵MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or ⁶Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
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This gene was present in the common ancestor of chordates.

Orthologs for FLT3 gene from Selected species (see all 11) About this table

Organism	Taxonomic classification	Gene	Description	Human Similarity	Orthology Type	Details
mouse (Mus musculus)	Mammalia	Flt3^{1 , 5}	FMS-like tyrosine kinase 3^{1, 5}	83.15(n)¹ 86.18(a)¹		5 (86.88 cM)⁵ 14255¹ NM_010229.2¹ NP_034359.2¹ 147330741⁵
chicken (Gallus gallus)	Aves	FLT3¹	fms-related tyrosine kinase 3	65.12(n) 57.13(a)		100858422 XM_003640612.2 XP_003640660.2
lizard (Anolis carolinensis)	Reptilia	FLT3⁶	fms-related tyrosine kinase 3	52(a)	1 ↔ 1	3(185864344-185941774)
tropical clawed frog (Xenopus tropicalis)	Amphibia	flt3¹	fms-related tyrosine kinase 3	59.73(n) 51.99(a)		101733150 XM_004912385.1 XP_004912442.1
zebrafish (Danio rerio)	Actinopterygii	flt3¹	fms-related tyrosine kinase 3	53.5(n) 45.67(a)		566708 XM_001921725.2 XP_001921760.2

ENSEMBL Gene Tree for FLT3 (if available)
TreeFam Gene Tree for FLT3 (if available)

(Paralogs according to ¹HomoloGene,
²Ensembl, and ³SIMAP, Pseudogenes according to ⁴Pseudogene.org Build 68)
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Paralogs for FLT3 gene

FLT4² FGFR4² PDGFRB² CSF1R² KIT² FGFR3² PDGFRA² RET²

KDR² FGFR1² FGFR2² FLT1²

16 SIMAP similar genes for FLT3 using alignment to 3 protein entries: FLT3_HUMAN (see all proteins):

STK-1 RET NIN/PDGFRB fusion ABL1 KIT FES

CSF1R FGR urf-ret EPHA2 DKFZp686M05208 CDK4

FGFR2 tec PDGFRA TIE1

FLT3 for paralogs About GeneDecksing

(SNPs/Variants according to the ¹NCBI SNP Database, ²Ensembl, ³PupaSUITE, ⁴UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD), the Human Cytochrome P450 Allele Nomenclature Database, and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers, Cancer Mutation PCR Arrays and Assays, and Copy Number PCR Arrays from QIAGEN)
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SNP ID	Valid	Clinical significance	Chr 13 pos	Sequence	#	AA Chg	Type	More	#	Allele freq	Pop	Total sample	More
Genomic Data					Transcription Related Data				Allele Frequencies
				--	--	--		--	--
VAR_065683⁴		Acute lymphoblastic leukemia patients⁴	--	see VAR_065683	2	D Y	mis⁴		0	--	--	--	--
VAR_065682⁴		Acute lymphoblastic leukemia patients⁴	--	see VAR_065682	2	D V	mis⁴		0	--	--	--	--
VAR_065684⁴		Acute lymphoblastic leukemia patients⁴	--	see VAR_065684	2	I M	mis⁴		0	--	--	--	--
VAR_065680⁴		Acute lymphoblastic leukemia patients⁴	--	see VAR_065680	2	D H	mis⁴		0	--	--	--	--
VAR_065681⁴		Acute lymphoblastic leukemia patients⁴	--	see VAR_065681	2	D N	mis⁴		0	--	--	--	--
VAR_065679⁴		Acute lymphoblastic leukemia patients⁴	--	see VAR_065679	2	D E	mis⁴		0	--	--	--	--
rs121909646^1,2	C	other¹	9547186(-)	`TCGAGA/TTATCA`	2	D V	mis¹		0	--	--	--	--
rs121913488^1,2	C	other¹	9547187(-)	`CTCGAA/C/G/T ATATC`	4	N H D Y	mis¹		0	--	--	--	--
rs181654932^1,2		--	9531466(+)	`GTTCCA/GGATCC`	1	--	ds500¹		0	--	--	--	--
rs187056138^1,2	C	--	9531491(+)	`CTACAC/TGCAAC`	1	--	ds500¹		0	--	--	--	--

HapMap Linkage Disequilibrium report for FLT3 (28577411 - 28674729 bp)

Structural Variations
Database of Genomic Variants (DGV) 8 variations for FLT3: About this table

Variant ID	Type	Subtype	PubMed ID
esv2674990	CNV	Deletion	23128226
esv2677792	CNV	Deletion	23128226
esv1336289	CNV	Insertion	17803354
nsv973	CNV	Insertion	18451855
esv269085	CNV	Insertion	20981092
esv275421	CNV	Loss	21479260
esv34052	CNV	Loss	18971310
nsv826599	CNV	Loss	20364138

Human Gene Mutation Database (HGMD): FLT3

Selected Site Specific Mutation Identification with PCR Assays for FLT3 (see all 20):

Cosmic Id	AA Change
27979	p.E596_Y597ins12
783	p.D835Y
28047	p.R834Q
19522	p.V592A
24531	p.M837P

Selected Site Specific Cancer Mutation PCR Panels containing FLT3 (see all 9):

Hematopoietic Neoplasms

FLT3 Pathway

Cancer Comprehensive Panel 384HT

Oncogene Panel 384HT

Receptor Tyrosine Kinase (RTK) (Panel I)

SeqTarget long-range PCR primers for resequencing FLT3

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(in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Conferences by KenesGroup, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
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OMIM gene information: 136351
OMIM disorders: 601626 613065
UniProtKB/Swiss-Prot: FLT3_HUMAN, P36888

Leukemia, acute myelogenous (AML) [MIM:601626]: A subtype of acute leukemia, a cancer of the white blood

cells. AML is a malignant disease of bone marrow characterized by maturational arrest of hematopoietic precursors

at an early stage of development. Clonal expansion of myeloid blasts occurs in bone marrow, blood, and other

tissue. Myelogenous leukemias develop from changes in cells that normally produce neutrophils, basophils,

eosinophils and monocytes. Note=The gene represented in this entry may be involved in disease pathogenesis.

Somatic mutations that lead to constitutive activation of FLT3 are frequent in AML patients. These mutations fall

into two classes, the most common being in-frame internal tandem duplications of variable length in the

juxtamembrane region that disrupt the normal regulation of the kinase activity. Likewise, point mutations in the

activation loop of the kinase domain can result in a constitutively activated kinase

Selected diseases for FLT3 (see all 71): About MalaCards

leukemia, acute lymphoblastic, somatic minimally differentiated acute myeloblastic leukemia leukemia, acute myeloid, reduced survival in acute myeloblastic leukemia without maturation

acute myeloid leukemia tetraploidy acute biphenotypic leukemia core binding factor acute myeloid leukemia

acute myeloblastic leukemia with maturation cytogenetically normal acute myeloid leukemia acute myelomonocytic leukemia lymphoblastic leukemia

8p11 myeloproliferative syndrome acute myeloid leukemia with abnormal bone marrow eosinophils inv(16)(p13q22) or t(16;16)(p13;q22) bone marrow cancer myeloid sarcoma

myeloid leukemia acute myeloid leukemia with t(8;21)(q22;q22) translocation chronic myeloproliferative disease acute leukemia

2 diseases from the University of Copenhagen DISEASES database for FLT3:

Leukemia Bone marrow cancer

FLT3 for disorders About GeneDecksing

Selected Novoseek inferred disease relationships for FLT3 gene (see all 73) About this table

Disease	-log (P-Val)	Hits	PubMed IDs for Articles with Shared Sentences (# sentences)
aml adult	85.2	22	12750701 (2), 15054042 (1), 15996732 (1), 10764154 (1) (see all 19)
leukemogenesis	81.6	32	17485549 (2), 12239147 (2), 14562119 (2), 10505320 (2) (see all 20)
aml childhood	80.8	29	15166029 (4), 20514303 (3), 15010072 (2), 17763464 (2) (see all 16)
leukemia	79.8	215	19541823 (6), 17330105 (5), 17332306 (5), 14555522 (4) (see all 99)
acute leukemia	73.4	56	17584026 (4), 15778081 (3), 17387224 (2), 18925699 (2) (see all 37)
lymphoblastic leukemia acute	68.2	35	16234090 (2), 18024407 (2), 19968062 (2), 12176867 (1) (see all 28)
leukemia promyelocytic acute	67.7	26	16105978 (2), 19176014 (2), 17939400 (2), 20096459 (2) (see all 18)
myelodysplastic syndromes	67.6	27	16902153 (2), 15036894 (2), 16787503 (2), 15257941 (2) (see all 23)
minimal residual disease	64	12	12239147 (3), 15645287 (2), 19176010 (1), 12854887 (1) (see all 6)
myeloproliferative disorders	63.8	8	16761019 (2), 16557239 (1), 16938665 (1), 17076649 (1) (see all 7)

Genetic Association Database (GAD): FLT3
Human Genome Epidemiology (HuGE) Navigator: FLT3 (128 documents)

Export disorders for FLT3 gene to outside databases

(in PubMed. Associations of this gene to articles via ¹Entrez Gene, ²UniProtKB/Swiss-Prot, ³HGNC, ⁴GAD, ⁵PharmGKB, ⁶HMDB, ⁷DrugBank, ⁸UniProtKB/TrEMBL, ⁹ Novoseek, and/or ¹⁰fRNAdb)
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PubMed articles for FLT3 gene, integrated from 10 sources (see all 1089):
(articles sorted by number of sources associating them with FLT3)

Utopia: connect your pdf to the dynamic
world of online information

Human FLT3/FLK2 gene: cDNA cloning and expression in hematopoietic cells. (PubMed id 8394751)^{1, 2, 3, 9} Rosnet O.... Birnbaum D. (Blood 1993)
[Correlation of FLT3 gene expression level and internal tandem duplication mutation in acute myeloid leukemia and its clinical significance]. (PubMed id 19176010)^{1, 4, 9} Wang Y.G....Jin J. (Zhonghua Xue Ye Xue Za Zhi 2008)
[Correlation of Fms-like tyrosine kinase 3 (FLT3) gene expression to FLT3/internal tandem duplication mutation in peripheral blood of acute myeloid leukemia.]. (PubMed id 19635202)^{1, 4, 9} Xu B....Zhou S.Y. (Ai Zheng 2009)
Mutations of the FLT3 gene in adult acute myeloid leukemia: determination of incidence and identification of a novel mutation in a Thai population. (PubMed id 16213360)^{1, 4, 9} Auewarakul C.U....Yenchitsomanus P.T. (Cancer Genet. Cytogenet. 2005)
An innovative phase I clinical study demonstrates inhibition of FLT3 phosphorylation by SU11248 in acute myeloid leukemia patients. (PubMed id 14654525)^{1, 7, 9} O'Farrell A.M....Cherrington J.M. (Clin. Cancer Res. 2003)
Structural and functional alterations of FLT3 in acute myeloid leukemia. (PubMed id 19549778)^{1, 2, 9} Meshinchi S. and Appelbaum F.R. (Clin. Cancer Res. 2009)
Human Flt3 is expressed at the hematopoietic stem cell and the granulocyte/macrophage progenitor stages to maintain cell survival. (PubMed id 18490735)^{1, 2, 9} Kikushige Y.... Akashi K. (J. Immunol. 2008)
Mutations of FLT3, NRAS, KRAS, and PTPN11 are frequent and possibly mutually exclusive in high hyperdiploid childhood acute lymphoblastic leukemia. (PubMed id 17910045)^{1, 4, 9} Paulsson K....Johansson B. (amp 2008)
Detection of FLT3 gene and FLT3/ITD mutation by polymerase chain reaction-single-strand conformation polymorphism in patients with acute lymphoblastic leukemia. (PubMed id 16234090)^{1, 4, 9} Xu B....Zhou S.Y. (Di Yi Jun Yi Da Xue Xue Bao 2005)
High transcript level of FLT3 associated with high risk of relapse in pediatric acute myeloid leukemia. (PubMed id 20514303)^{1, 4, 9} Kang H.J....Ahn H.S. (J. Korean Med. Sci. 2010)

(in PubMed, OMIM, and NCBI Bookshelf)
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		AND	OR
Aliases
Disorders
Free Text

Query String		PubMed OMIM NCBI Bookshelf
	(Note: In FireFox, select the above section and copy using Ctrl-C)

(According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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Entrez Gene: 2322	HGNC: 3765	AceView: FLT3	Ensembl:ENSG00000122025	euGenes: HUgn2322
ECgene: FLT3	Kegg: 2322	H-InvDB: FLT3

(According to HUGE)
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(According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, UniProtKB/TrEMBL, and/or others, e.g. Wikipedia and GeneReviews, via UniProtKB/Swiss-Prot)
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Name	Description
PharmGKB entry for FLT3	Pharmacogenomics, SNPs, Pathways
ATLAS Chromosomes in Cancer entry for FLT3	Genetics and Cytogenetics in Oncology and Haematology

Intellectual Property for FLT3 gene
(Patent information from GeneIP, Licensable technologies from WIS Yeda, Salk, Tufts, IP news from LifeMap Sciences, Inc.)

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Patent Information for FLT3 gene:
Search GeneIP for patents involving FLT3

GeneCards and IP:
Japan Patent Office Licenses GeneCards European Patent Office Licenses GeneCards Improving the IP Search

(Antibodies, recombinant proteins, and assays from EMD Millipore, R&D Systems, OriGene, QIAGEN, GenScript, Cell Signaling Technology, Novus Biologicals, Sino Biological, Enzo Life Sciences, Abcam, ProSpec, Cloud-Clone Corp., Thermo Fisher Scientific, LSBio, Gene Editing from DNA2.0. Clones from OriGene, GenScript, Sino Biological, DNA2.0, SwitchGear Genomics, Vector BioLabs, Cell lines from GenScript, and ESI BIO, PCR Arrays from QIAGEN, Drugs and/or compounds from EMD Millipore, Tocris Bioscience, Enzo Life Sciences, and/or ApexBio, In Situ Hybridization Assays from
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Fms-Related Tyrosine Kinase 3

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Fms-Related Tyrosine Kinase 3

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