Free for academic non-profit institutions. Other users need a Commercial license
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. [provided by RefSeq, Jan 2015]
FLT3 is an important cytokine receptor involved in normal hematopoiesis. Mutations in this gene are common in acute myeloid leukemia (AML) and screening for mutations in this gene has been recommended by the World Health Organization in patients with AML, particularly in cases of cytogenetically normal AML (CN-AML). FLT3 mutations commonly co-occur with mutations such as NPM1 that are associated with CN-AML and likely modulate prognostic impact. While FLT3-ITD mutations have been associated with poorer prognosis in AML, the prognostic impact of FLT3-TKD mutations are still up for debate.
FLT3 (Fms Related Receptor Tyrosine Kinase 3) is a Protein Coding gene. Diseases associated with FLT3 include Leukemia, Acute Myeloid and Acute Myeloblastic Leukemia Without Maturation. Among its related pathways are Transcriptional misregulation in cancer and Activation of cAMP-Dependent PKA. Gene Ontology (GO) annotations related to this gene include protein homodimerization activity and protein kinase activity. An important paralog of this gene is PDGFRA.
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. Its expression in these cells means that FLT3 has an important role in the pathogenesis of AML.
GeneHancer (GH) Identifier | GH Type | GH Score |
GH Sources | Gene Association Score | Total Score | TSS distance (kb) | Number of Genes Away | Size (kb) | Transcription Factor Binding Sites |
Gene Targets |
---|---|---|---|---|---|---|---|---|---|---|
GH13J028099 | Promoter/Enhancer | 1.8 | EPDnew Ensembl ENCODE CraniofacialAtlas | 600.7 | +0.2 | 191 | 2 | RNF2 PRDM10 ZNF692 ZIC2 POLR2A PATZ1 EZH2 ZFX ZNF561 ZBTB44 | FLT3 HSALNG0095991 PAN3-AS1 URAD | |
GH13J028102 | Promoter | 0.5 | Ensembl | 600.7 | -1.4 | -1409 | 0.4 | HLF EZH2 | FLT3 HSALNG0095991 CHCHD2P8 PAN3 | |
GH13J028098 | Enhancer | 0.4 | FANTOM5 | 617.3 | +1.7 | 1675 | 0.2 | RNF2 ZNF133 EZH2 | FLT3 HSALNG0095991 MN298114-049 URAD | |
GH13J028031 | Enhancer | 0.7 | ENCODE | 30.4 | +68.9 | 68882 | 0.9 | BACH1 IKZF2 CEBPA EED DPF2 RELB RUNX3 GATAD2B BCL11A ELF1 | FLT3 PAN3 piR-43107-080 MN309627 URAD | |
GH13J028022 | Enhancer | 0.7 | Ensembl ENCODE | 30.4 | +77.4 | 77392 | 1.6 | HNRNPL TEAD4 SOX13 POLR2A SMAD4 BCL6 HNF4A NR2F6 XRCC5 | lnc-URAD-2-002 FLT3 lnc-URAD-2-001 URAD |
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0000166 | nucleotide binding | IEA | -- |
GO:0004672 | protein kinase activity | IEA | -- |
GO:0004713 | protein tyrosine kinase activity | IEA | -- |
GO:0004714 | transmembrane receptor protein tyrosine kinase activity | IEA,TAS | 19549778 |
GO:0004896 | cytokine receptor activity | ISS | -- |
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0005634 | nucleus | IEA | -- |
GO:0005737 | cytoplasm | IEA | -- |
GO:0005783 | endoplasmic reticulum | IEA,IDA | -- |
GO:0005788 | endoplasmic reticulum lumen | IEA | -- |
GO:0005829 | cytosol | IEA | -- |
SuperPathway | Contained pathways | ||
---|---|---|---|
1 | GPCR Pathway |
Paxillin Interactions
.73
Ras Pathway
.73
GPCR Pathway
.62
Pancreatic Adenocarcinoma
.59
|
Breast Cancer Regulation by Stathmin1
.58
NFAT in Immune Response
.58
Estrogen Pathway
.55
P2Y Receptor Signaling
.38
|
2 | ERK Signaling |
ERK Signaling
.61
Rho Family GTPases
.61
MAPK Signaling
.58
|
Molecular Mechanisms of Cancer
.51
ILK Signaling
.49
|
3 | Nanog in Mammalian ESC Pluripotency |
GSK3 Signaling
.62
Nanog in Mammalian ESC Pluripotency
.62
|
14-3-3 Induced Intracellular Signaling
.59
eNOS Signaling
.48
|
4 | Actin Nucleation by ARP-WASP Complex |
Actin Nucleation and Branching
.66
Actin Nucleation by ARP-WASP Complex
.66
|
CDC42 Pathway
.41
|
5 | Activation of cAMP-Dependent PKA |
Activation of cAMP-Dependent PKA
.77
|
Activation of PKA through GPCR
.71
|
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0000165 | MAPK cascade | TAS | -- |
GO:0001776 | leukocyte homeostasis | ISS | -- |
GO:0002244 | hematopoietic progenitor cell differentiation | IBA | -- |
GO:0002318 | myeloid progenitor cell differentiation | ISS | -- |
GO:0002328 | pro-B cell differentiation | ISS | -- |
Name | Status | Disease Links | Group | Role | Mechanism of Action | Clinical Trials |
---|---|---|---|---|---|---|
Sunitinib | Approved, Investigational | Pharma | Target, inhibitor | VEGFR/PDGFRβ/ KIT/ FLT3/RET/CSF-1R inhibitor, RTK inhibitor, Potent VEGFR, PDGFRbeta and KIT inhibitor, Kinase Inhibitors, Vascular endothelial growth factor (VEGF) and VEGF receptor (VEGFR) inhibitors | 552 | |
Sorafenib | Approved, Investigational | Pharma | Target, antagonist, inhibitors, inhibitor | Raf kinases and tyrosine kinases inhibitor, RAF, VEGFR2, and PDGFR-beta inhibitors, Kinase Inhibitors, Vascular endothelial growth factor (VEGF) and VEGF receptor (VEGFR) inhibitors | 779 | |
midostaurin | Approved, Investigational | Pharma | Target, antagonist, inhibitor | Kinase Inhibitors | 47 | |
Idarubicin | Approved | Pharma | inhibitor | 258 | ||
gilteritinib | Approved, Investigational | Pharma | Target, inhibitor | 0 |
Name | Synonyms | Role | CAS Number | PubChem IDs | PubMed IDs | |
---|---|---|---|---|---|---|
ADP |
|
Agonist, Full agonist, Partial agonist, Gating inhibitor, Antagonist | 58-64-0 |
|
||
CHMFL-FLT3-122 |
|
1839150-56-9 |
|
|
Compound | Action | Cas Number |
---|---|---|
5'-Fluoroindirubinoxime | FLT3 inhibitor; displays antiproliferative activity | 861214-33-7 |
CHMFL-FLT3-122 | Potent and selective FLT3 inhibitor | 1839150-56-9 |
TCS 359 | Potent FLT3 inhibitor | 301305-73-7 |
Compound | Action | Cas Number |
---|---|---|
5'-Fluoroindirubinoxime | 861214-33-7 | |
AMG 925 | FLT3/CDK4 inhibitor,potent and selective | 1401033-86-0 |
Amuvatinib (MP-470, HPK 56) | Tyrosine kinase inhibitor | 850879-09-3 |
AZD2932 | inhibitor of VEGFR-2, PDGFRβ, Flt-3, and c-Kit | 883986-34-3 |
CHIR-124 | Chk1 inhibitor,novel and potent | 405168-58-3 |
Dovitinib (TKI-258, CHIR-258) | Multitargeted RTK inhibitor | 405169-16-6 |
Dovitinib Dilactic acid | 852433-84-2 | |
ENMD-2076 | Selective Aurora A/Flt3 inhibitor | 934353-76-1 |
G-749 | FLT3 inhibitor | 1457983-28-6 |
KW 2449 | Multikinase inhibitor | 1000669-72-6 |
Lestaurtinib | JAK2/FLT3/TrkA inhibitor | 111358-88-4 |
Linifanib (ABT-869) | VEGFR/PDGFR inhibitor | 796967-16-3 |
Pacritinib (SB1518) | JAK2/FLT3 inhibitor | 937272-79-2 |
Quizartinib (AC220) | FLT3 inhibitor,potent and selective | 950769-58-1 |
SB1317 | CDK,JAK and FLT inhibitor | 937270-47-8 |
Silvestrol | Antineoplastic | 697235-38-4 |
Sorafenib | Raf kinases and tyrosine kinases inhibitor | 284461-73-0 |
SU14813 maleate | VEGFR/PDGFR/Kit/FLT-3 inhibitor | 849643-15-8 |
SU5416 | VEGF receptor inhibitor and AHR agonist | 204005-46-9 |
Sunitinib malate | VEGFR/PDGFRβ/ KIT/ FLT3/RET/CSF-1R inhibitor | 341031-54-7 |
Tandutinib (MLN518) | FLT3 inhibitor,potent and selective | 387867-13-2 |
TCS 359 | Potent FLT3 inhibitor | 301305-73-7 |
TG 100801 | Multi-kinase inhibitor | 867331-82-6 |
TG101209 | JAK2/3 inhibitor | 936091-14-4 |
UNC2025 | 1429881-91-3 | |
VX-680 (MK-0457,Tozasertib) | Aurora kinase inhibitor | 639089-54-6 |
This gene was present in the common ancestor of chordates.
Organism | Taxonomy | Gene | Similarity | Type | Details |
---|---|---|---|---|---|
Chimpanzee (Pan troglodytes) |
Mammalia | FLT3 30 31 |
|
OneToOne | |
Dog (Canis familiaris) |
Mammalia | FLT3 30 31 |
|
OneToOne | |
Cow (Bos Taurus) |
Mammalia | FLT3 30 31 |
|
OneToOne | |
Mouse (Mus musculus) |
Mammalia | Flt3 30 17 31 |
|
OneToOne | |
Rat (Rattus norvegicus) |
Mammalia | Flt3 30 |
|
||
Oppossum (Monodelphis domestica) |
Mammalia | FLT3 31 |
|
OneToOne | |
Platypus (Ornithorhynchus anatinus) |
Mammalia | FLT3 31 |
|
OneToOne | |
Chicken (Gallus gallus) |
Aves | FLT3 30 31 |
|
OneToOne | |
Lizard (Anolis carolinensis) |
Reptilia | FLT3 31 |
|
OneToOne | |
Tropical Clawed Frog (Silurana tropicalis) |
Amphibia | flt3 30 |
|
||
Zebrafish (Danio rerio) |
Actinopterygii | flt3 30 31 |
|
OneToOne |
SNP ID | Clinical significance and condition | Chr 13 pos | Variation | AA Info | Type |
---|---|---|---|---|---|
710610 | Likely Benign: not provided | 28,014,488(-) | C/T | NON_CODING_TRANSCRIPT_VARIANT,SYNONYMOUS_VARIANT | |
720701 | Benign: not provided | 28,049,783(-) | T/C | INTRON_VARIANT | |
725869 | Likely Benign: not provided | 28,018,560(-) | G/A | NON_CODING_TRANSCRIPT_VARIANT,SYNONYMOUS_VARIANT | |
725922 | Benign: not provided | 28,057,339(-) | G/A | INTRON_VARIANT | |
727593 | Benign: not provided | 28,023,353(-) | C/T | NON_CODING_TRANSCRIPT_VARIANT,SYNONYMOUS_VARIANT |
Variant ID | Type | Subtype | PubMed ID |
---|---|---|---|
esv1336289 | CNV | insertion | 17803354 |
esv2674990 | CNV | deletion | 23128226 |
esv2677792 | CNV | deletion | 23128226 |
esv275421 | CNV | loss | 21479260 |
esv3349981 | CNV | insertion | 20981092 |
esv34052 | CNV | loss | 18971310 |
esv3550234 | CNV | deletion | 23714750 |
esv3550235 | CNV | deletion | 23714750 |
esv3580585 | CNV | loss | 25503493 |
esv3631627 | CNV | loss | 21293372 |
esv3631628 | CNV | loss | 21293372 |
esv3631630 | CNV | loss | 21293372 |
esv3631631 | CNV | loss | 21293372 |
esv3631632 | CNV | loss | 21293372 |
nsv1070579 | CNV | deletion | 25765185 |
nsv826599 | CNV | loss | 20364138 |
nsv973 | CNV | insertion | 18451855 |
Disorder | Aliases | PubMed IDs |
---|---|---|
leukemia, acute myeloid |
|
|
acute myeloblastic leukemia without maturation |
|
|
acute myeloid leukemia with minimal differentiation |
|
|
acute myeloblastic leukemia with maturation |
|
|
leukemia, acute lymphoblastic |
|