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FLT3

gene
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Also known as STK1FLK2CD135

Summary

FLT3 (fms related receptor tyrosine kinase 3, HGNC:3765) is a protein-coding gene on chromosome 13q12.2, encoding Receptor-type tyrosine-protein kinase FLT3 (P36888). Tyrosine-protein kinase that acts as a cell-surface receptor for the cytokine FLT3LG and regulates differentiation, proliferation and survival of hematopoietic progenitor cells and of dendritic cells. In precision oncology, FLT3 ITD confers sensitivity to Gilteritinib in Acute Myeloid Leukemia (CIViC Level A); 80 further curated variant–drug associations are listed below.

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.

Source: NCBI Gene 2322 — RefSeq curated summary.

At a glance

  • Gene–disease (curated): leukemia, acute myeloid, susceptibility to (Limited, ClinGen)
  • GWAS associations: 63 (top 1% of genes corpus-wide)
  • Clinical variants (ClinVar): 247 total — 10 pathogenic, 4 likely-pathogenic
  • GTEx eGene: eQTL in 33 tissues, sQTL in 1 (q < 0.05)
  • Phenotypes (HPO): 5
  • Drug target: yes — 39 curated mechanism-of-action drugs; 143 molecules with ChEMBL bioactivity (top 1% of genes corpus-wide)
  • Approved drugs (ChEMBL mechanism of action): 8 — Fedratinib, Gilteritinib, Midostaurin, +5 more
  • Precision-oncology evidence (CIViC): 81 curated variant–drug associations
  • Cancer driver (intOGen): activating (oncogene-like) across 2 cancer types (inferred from mutation patterns)
  • Constraint (gnomAD): pLI 1.00 (loss-of-function intolerant), LOEUF 0.47 (moderately constrained)
  • Transcription factor: yes — 19 downstream targets (CollecTRI)
  • MANE Select transcript: NM_004119
  • Interaction hub: 2,904 STRING partners (top 3% of genes corpus-wide)

Identifiers

Gene identifiers

FieldValue
HGNC IDHGNC:3765
Approved symbolFLT3
Namefms related receptor tyrosine kinase 3
Location13q12.2
Locus typegene with protein product
StatusApproved
AliasesSTK1, FLK2, CD135
Ensembl geneENSG00000122025
Ensembl biotypeprotein_coding
OMIM136351
Entrez2322

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 3 protein_coding, 2 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

MANE Select: ENST00000241453

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 2, TSL 3: 1

ENST00000241453, ENST00000380987, ENST00000469894, ENST00000864668, ENST00001004561, ENST00001131816

RefSeq mRNA: 1 — MANE Select: NM_004119 NM_004119

CCDS: CCDS31953

Canonical transcript exons

ENST00000241453 — 24 exons

ExonStartEnd
ENSE000008274012803718528037288
ENSE000008274022803593528036043
ENSE000008274032803549528035673
ENSE000008274042803430128034407
ENSE000008274052803408228034214
ENSE000008274062803388728033991
ENSE000008274072802817828028288
ENSE000008274082802708828027241
ENSE000009066082804827528048443
ENSE000009066092804938428049537
ENSE000009066102804963528049774
ENSE000009066112805009528050222
ENSE000009066122805254528052674
ENSE000009066132805734728057462
ENSE000009066142806186728062069
ENSE000009066152807049128070612
ENSE000014871162800327428004174
ENSE000035131562801445228014557
ENSE000035194362802335028023477
ENSE000035528512801559028015701
ENSE000035656362802486128024943
ENSE000035981462801846728018589
ENSE000036920162801515728015256
ENSE000038963962810046828100576

Expression profiles

Bgee: expression breadth ubiquitous, 166 present calls, max score 86.25.

FANTOM5 (CAGE): breadth broad, TPM avg 2.7806 / max 577.0111, expressed in 297 samples.

Highest expression (Bgee): male germ line stem cell (sensu Vertebrata) in testis, cerebellar hemisphere, cerebellar cortex, monocyte, mononuclear cell.

Genetic regulation across tissues (GTEx eQTL / sQTL)

FLT3 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 33 tissues and its splicing (sQTL) in 1 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 34 significant tissue × QTL associations:

TissueQTLq-valueSlopeLead variant
Brain Cerebellumeqtl1.9e-71+1.2113:28027857:G:A
Brain Cerebellar Hemisphereeqtl4.6e-67+1.2113:28027514:T:C
Brain Cortexeqtl6.8e-51+1.0013:28027514:T:C
Brain Anterior cingulate cortex BA24eqtl2.6e-38+0.9413:28033573:G:C
Brain Frontal Cortex BA9eqtl2.1e-36+1.0013:28033573:G:C
Pancreaseqtl3.2e-25-0.7513:28086023:T:A
Skin Sun Exposed Lower legeqtl1.0e-22+0.3913:28028119:C:T
Brain Hypothalamuseqtl1.1e-20+0.6913:28028467:T:C
Skin Not Sun Exposed Suprapubiceqtl1.8e-13+0.3413:28028119:C:T
Nerve Tibialeqtl5.4e-11+0.3313:28033573:G:C
Brain Putamen basal gangliaeqtl6.0e-09+0.6313:28031877:G:A
Brain Caudate basal gangliaeqtl1.3e-08+0.6413:28032042:T:A
Lungeqtl1.5e-08+0.2913:28018990:G:A
Brain Nucleus accumbens basal gangliaeqtl2.1e-08+0.6213:28027857:G:A
Brain Hippocampuseqtl2.4e-08+0.5413:28027857:G:A
Brain Spinal cord cervical c-1eqtl4.2e-08+0.4613:28033380:T:C
Small Intestine Terminal Ileumeqtl6.4e-08+0.4013:28060647:T:C
Adipose Subcutaneouseqtl7.5e-08-0.2813:28037601:G:A
Esophagus Mucosaeqtl4.4e-07+0.2013:28020665:T:C
Spleeneqtl9.1e-07+0.4313:28027514:T:C

FANTOM5 promoters

2 alternative TSS:

Promoter IDTPM avgSamples expressed
1365272.7297296
1365260.050921

Top tissues by expression

showing 100 of 285 tissues by Bgee expression score (0-100, higher = more expressed):

TissueAnatomy IDExpression scoreQuality
male germ line stem cell (sensu Vertebrata) in testisCL:0000089 ∩ UBERON:000047386.25gold quality
cerebellar hemisphereUBERON:000224581.49gold quality
cerebellar cortexUBERON:000212981.37gold quality
monocyteCL:000057681.07gold quality
mononuclear cellCL:000084280.55gold quality
leukocyteCL:000073880.03gold quality
right hemisphere of cerebellumUBERON:001489080.01gold quality
cerebellumUBERON:000203779.31gold quality
bone marrow cellCL:000209273.72silver quality
bone marrowUBERON:000237172.76gold quality
lymph nodeUBERON:000002971.18gold quality
granulocyteCL:000009470.09gold quality
body of pancreasUBERON:000115069.61gold quality
spleenUBERON:000210668.87gold quality
vermiform appendixUBERON:000115468.31gold quality
C1 segment of cervical spinal cordUBERON:000646967.90gold quality
gall bladderUBERON:000211066.94gold quality
pancreasUBERON:000126466.82gold quality
right lungUBERON:000216766.38gold quality
bloodUBERON:000017866.37gold quality
pigmented layer of retinaUBERON:000178266.30gold quality
spinal cordUBERON:000224065.24gold quality
caecumUBERON:000115363.82gold quality
cerebellar vermisUBERON:000472063.55silver quality
tibialis anteriorUBERON:000138563.36silver quality
islet of LangerhansUBERON:000000662.86gold quality
rectumUBERON:000105262.02gold quality
prefrontal cortexUBERON:000045161.12gold quality
small intestine Peyer’s patchUBERON:000345461.08gold quality
epithelial cell of pancreasCL:000008359.89gold quality
upper leg skinUBERON:000426259.81gold quality
nephron tubuleUBERON:000123159.24gold quality
small intestineUBERON:000210859.09gold quality
smooth muscle tissueUBERON:000113558.93gold quality
secondary oocyteCL:000065558.77gold quality
right frontal lobeUBERON:000281058.72gold quality
cingulate cortexUBERON:000302758.32gold quality
anterior cingulate cortexUBERON:000983558.04gold quality
primary visual cortexUBERON:000243657.99gold quality
Brodmann (1909) area 9UBERON:001354057.98gold quality
neocortexUBERON:000195057.43gold quality
frontal cortexUBERON:000187057.42gold quality
colonic epitheliumUBERON:000039757.33silver quality
trabecular bone tissueUBERON:000248357.07gold quality
hypothalamusUBERON:000189856.70gold quality
deciduaUBERON:000245056.55gold quality
upper lobe of left lungUBERON:000895256.51gold quality
renal glomerulusUBERON:000007456.36silver quality
dorsolateral prefrontal cortexUBERON:000983456.04gold quality
superficial temporal arteryUBERON:000161455.91gold quality
kidney epitheliumUBERON:000481955.86silver quality
mucosa of stomachUBERON:000119955.85gold quality
ponsUBERON:000098855.84gold quality
tonsilUBERON:000237255.35gold quality
upper lobe of lungUBERON:000894855.12gold quality
paraflocculusUBERON:000535154.62silver quality
skin of hipUBERON:000155454.56gold quality
pancreatic ductal cellCL:000207954.34silver quality
left uterine tubeUBERON:000130354.04gold quality
cerebral cortexUBERON:000095653.92gold quality
cortical plateUBERON:000534353.80gold quality
right testisUBERON:000453453.72gold quality
left testisUBERON:000453353.69gold quality
pleuraUBERON:000097753.65silver quality
right coronary arteryUBERON:000162553.64gold quality
occipital lobeUBERON:000202153.62gold quality
transverse colonUBERON:000115753.48gold quality
parietal pleuraUBERON:000240053.34silver quality
deltoidUBERON:000147653.31gold quality
testisUBERON:000047353.20gold quality
hair follicleUBERON:000207353.13gold quality
intestineUBERON:000016052.80gold quality
lungUBERON:000204852.70gold quality
Brodmann (1909) area 46UBERON:000648352.20gold quality
central nervous systemUBERON:000101752.16gold quality
thymusUBERON:000237052.14silver quality
substantia nigraUBERON:000203852.08gold quality
brainUBERON:000095551.73gold quality
ileal mucosaUBERON:000033151.67silver quality
cortex of kidneyUBERON:000122551.20gold quality
midbrainUBERON:000189151.03gold quality
colonUBERON:000115550.99gold quality
visceral pleuraUBERON:000240150.90gold quality
muscle tissueUBERON:000238550.86gold quality
quadriceps femorisUBERON:000137750.82gold quality
large intestineUBERON:000005950.77gold quality
minor salivary glandUBERON:000183050.69gold quality
anatomical systemUBERON:000046750.66gold quality
material anatomical entityUBERON:000046550.49gold quality
multicellular organismUBERON:000046850.49gold quality
skin of legUBERON:000151150.47gold quality
frontal poleUBERON:000279550.41gold quality
zone of skinUBERON:000001450.33gold quality
middle frontal gyrusUBERON:000270250.30gold quality
mucosa of transverse colonUBERON:000499150.30gold quality
skin of abdomenUBERON:000141650.28gold quality
Brodmann (1909) area 10UBERON:001354150.18gold quality
left coronary arteryUBERON:000162649.87gold quality
male germ cellCL:000001549.86gold quality
esophagus mucosaUBERON:000246949.84gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 4.

ExperimentMarker?Max mean expression
E-MTAB-6678yes171.14
E-HCAD-6yes29.00
E-ANND-3yes10.72
E-MTAB-9801yes8.15
E-GEOD-99795no21.87

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 68 HPA tissues / cells by nTPM:

Tissue / cellAxisnTPM
Corpus callosumtissue14.0
Spinal cordtissue12.6
Ponstissue12.5
Midbraintissue12.5
Medulla oblongatatissue12.4
Thalamustissue11.0
Superior colliculitissue10.9
Cerebellumtissue10.1
Substantia nigratissue8.8
Periaqueductal graytissue7.7
Hypothalamustissue7.6
Lymph nodetissue6.1
Cerebral cortextissue5.7
Somatosensory cortextissue5.7
Occipital cortextissue5.6
Spleentissue5.3
Bone marrowtissue5.0
Thymustissue4.3
Septumtissue4.3
Ventral forebraintissue4.0
Retrosplenial cortextissue4.0
Hippocampal formationtissue3.9
Retrosplenial and cingulate cortextissue3.9
Motor cortextissue3.8
Prefrontal cortextissue3.5
Tonsiltissue3.4
Olfactory bulbtissue3.4
Entorhinal cortextissue3.3
Insular cortextissue3.3
Temporal cortextissue3.0
Amygdalatissue2.8
Appendixtissue2.8
Putamentissue2.7
Pancreastissue2.6
Postcentral gyrustissue2.0
Locus coeruleustissue1.8
Frontal cortextissue1.7
Gallbladdertissue1.5
Breasttissue1.4
Kidneytissue1.4
Urinary bladdertissue1.2
Basal gangliatissue1.2
Small intestinetissue0.9
Smooth muscletissue0.8
Caudate putamentissue0.8
Skin 1tissue0.7
Rectumtissue0.7
Colontissue0.7
Stomach 1tissue0.6
Esophagustissue0.6
Adipose tissuetissue0.5
Cervixtissue0.4
Testistissue0.4
Choroid plexustissue0.4
Lungtissue0.4
Livertissue0.4
Nucleus accumbenstissue0.3
Seminal vesicletissue0.2
Salivary glandtissue0.2
Endometrium 1tissue0.2

Brain sub-regions (HPA Brain Atlas): detected in 189; highest nTPM — White matter (14.0), Ventral spinal cord (12.6), Dorsal spinal cord (11.6), Cerebellar cortex (10.7), Flocculonodular lobe (9.6).

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

19 targets:

TargetRegulation
BCL2L1Activation
BCL2L11Repression
CDKN1AActivation
CDKN1BRepression
CEBPAUnknown
CEBPBRepression
CISHActivation
FZD4Unknown
ID1Activation
PARP1Activation
PIM1Activation
PIM2Activation
PTPN6Unknown
RAD51Activation
SOCS2Activation
SOCS3Activation
SPI1Unknown
USP22Activation
XRCC5Activation

Upstream regulators (CollecTRI, top): CEBPA, HES1, HOXA9, IKZF1, KAT6B, MEIS1, MYB, NCOR1, PAX5, PML, RUNX1, SPI1, STAT3, TXK

miRNA regulators (miRDB)

Targeting FLT3 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 56 miRNAs:

miRNAMax scoreAvg scoremiRNA target_count
HSA-MIR-4533100.0069.482758
HSA-MIR-518D-5P100.0067.51979
HSA-MIR-518E-5P100.0067.66954
HSA-MIR-518F-5P100.0067.51979
HSA-MIR-519A-5P100.0067.66954
HSA-MIR-519B-5P100.0067.66954
HSA-MIR-519C-5P100.0067.66954
HSA-MIR-520C-5P100.0067.51979
HSA-MIR-522-5P100.0067.66954
HSA-MIR-523-5P100.0067.66954
HSA-MIR-526A-5P100.0067.51979
HSA-MIR-3924100.0072.092394
HSA-MIR-3163100.0077.238605
HSA-MIR-1277-5P100.0073.955056
HSA-MIR-6798-5P100.0065.77699
HSA-MIR-548C-3P99.9974.017587
HSA-MIR-520G-5P99.9966.76658
HSA-MIR-548P99.9872.253784
HSA-MIR-570-3P99.9672.414910
HSA-MIR-497-5P99.9271.832674
HSA-MIR-15A-5P99.9072.802787
HSA-MIR-15B-5P99.9072.782798
HSA-MIR-16-5P99.9072.802780
HSA-MIR-195-5P99.9072.812805
HSA-MIR-449399.9066.48977
HSA-MIR-424-5P99.8971.902641
HSA-MIR-6838-5P99.8971.942690
HSA-MIR-3140-3P99.8868.472069
HSA-MIR-469899.8471.414303
HSA-MIR-139-5P99.8069.501399

Functional genomics

gnomAD constraint: pLI 0.997, LOEUF 0.468, missense Z 1.55 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000241453 — one region, missense o/e 0.90.

Literature-anchored findings (GeneRIF, showing 40)

  • First report of D835X mutations in human. Activating mutation of D835 within the activation loop of FLT3 in human hematologic malignancies. (PMID:11290608)
  • Flt3/Flk-2-ligand in synergy with thrombopoietin may slow down megakaryocyte development by causing increased proliferation of megakaryocyte progenitor cells. (PMID:11983110)
  • induces acute promyelocytic leukemia in a mouse model (PMID:12060771)
  • Analysis of FLT3 length mutations in 1003 patients with acute myeloid leukemia (PMID:12070009)
  • duplicated in relapsed acute myeloid leukemia (PMID:12239146)
  • mutations occur in paired presentation and relapse samples from patients with acute myeloid leukemia (PMID:12239147)
  • 767 of 6586 genes differed in expression between FLT3-WT- and FLT-ITD(internal tandem duplication)-expressing cell lines. ITD mutations of Flt3 activate transcriptional programs that partially mimic IL-3 activity. (PMID:12468433)
  • Internal tandem duplication of the Flt3 gene appearing or altering at time of AML relapse suggests Flt3-gene abnormalities are very important in the pathogenesis of chemotherapy-resistant AML (PMID:12481903)
  • The striking difference in flt3 and c-kit expression on hematopoietic stem cells translated into a corresponding difference in flt3 and c-kit function because FL was more efficient than SCF at supporting the survival of HSCs (PMID:12676789)
  • Intracellular signaling initiated by Flt3 ligation modulates the functional phenotype for native human AML blasts both with and without genetic Flt3 abnormalities. (PMID:12681969)
  • FLT3 mutations that lead to constitutive receptor activation and confer a poor prognosis in AML (PMID:12691136)
  • FLT3/ITD is less common in pediatric than in adult acute myeloid leukemia and FLT3/ITD is a strong and independent adverse prognostic factor, and high ratios between mutant and WT-FLT3 further compromise prognosis. (PMID:12816873)
  • antiapoptotic pathways from FLT3 with internal tandem duplication are more divergent than those from WtFLT3 (PMID:12842996)
  • Mutations in the FLT3 gene are common in AML, including tandem repeats or a mutation in the kinase domain. (PMID:12854887)
  • No significant correlation was found between FLT3 mutations and high levels of MDR1 in acute myeloid leukemia. (PMID:12926083)
  • REVIEW: The role of FLT3 mutations in APL and other AML (PMID:12935959)
  • wtFLT3 is often constitutively activated by FLT3 ligand in AML and thus, like its mutated form, might contribute to the altered signaling that characterizes leukemogenesis. (PMID:12969963)
  • FLT3-D835/I836 mutations are one of the second genetic events in infant ALL with MLL rearrangements or pediatric ALL with hyperdiploidy (PMID:14504097)
  • reduced AML1 activities predispose cells to the acquisition of the activating FLT3 mutation as a secondary event leading to full transformation in acute myeloblastic leukemia M0 (PMID:14562119)
  • distinct activating FLT3-TKD mutations at position D835 mediate primary resistance to FLT3 PTK inhibitors in FLT3-transformed cell lines (PMID:14604974)
  • FLT3 mutations are associated with molecular lesions in acute myeloid leukemias (PMID:14630076)
  • Phosphorylation is inhibited by SU11248 in acute myeloid leukemia. (PMID:14654525)
  • search for the presence of FLT3 mutations in leukemic blasts from 71 patients with childhood acute lymphoblastic leukemia discovered three novel in-frame deletions within a 7-amino acid region of the receptor juxtamembrane domain. (PMID:14670924)
  • FLT3 analysis shows the autoinhibitory conformation of its complete juxtamembrane domain (PMID:14759363)
  • FLT3 Asp(835) mutations may have a role in relapse of acute myeloid leukemia (PMID:14977832)
  • FLT3 can negatively regulate Foxo transcription factors, thereby promoting cell survival and proliferation. (PMID:14981546)
  • Mutations of Flt3 may disrupt transcriptional repressor function resulting in aberrant gene regulation and abnormal leukemia cell growth. (PMID:14982881)
  • Activating mutations in the FLT3 RTK gene were found in each of 3 CD117/KIT(+) cases that were analyzed, but not in 52 other adult T-acute lymphoblastic leukemia (PMID:15044257)
  • CXCR-4 expression was significantly higher in fetal liver tyrosine kinase-3 (Flt3)/internal tandem duplication (ITD) acute myeloid leukemia (PMID:15054042)
  • Internal tandem duplication of the juxtamembrane domain or by activating point mutations in the second tyrosine kinase domain in FLT3 are associated with leukocytosis and the monocytic FAB subtypes M4 and M5. (PMID:15059064)
  • Flt3 mutations identify patients at high risk of relapse (PMID:15061200)
  • FLT3/internal tandem duplication(ITD) mutations confer a particularly poor prognosis in pediatric acute myelogenous leukemia patients (PMID:15166029)
  • high frequency of FLT3 mutations in adult acute myelocytic leukemia without recurrent cytogenetic translocations. (PMID:15167911)
  • FLT3 autoinhibited structure showed that N841 is the key residue in a hydrogen-bonding network that likely stabilizes the activation loop (PMID:15178581)
  • Wild-type Flt3-overexpressing CD34+ cells exposed to high levels of its physiologic ligand did not produce early cobblestone areas (PMID:15242879)
  • FLT3 has roles in different signal transduction pathways that control proliferation, survival and other processes in hematopoietic cells [review] (PMID:15253381)
  • The loss of a clone with a mutation in the FLT3 gene at relapse did not improve the prognosis. (PMID:15289019)
  • Inspection of the FLT3 structure revealed that Y842 is the key residue in regulating the switch from the closed to the open (= active) conformation of the FLT3 activation loop (PMID:15345593)
  • mutations of specific residues located in the activation loop (D835X and 836-deletion in Flt-3; D816V in c-Kit) as well as a 6-base pair (6-bp) insertion at residue 840 in Flt-3 operate in a similar way (PMID:15363457)
  • transformation of TF-1 cells with FLT3/ITD mutations suppressed the activity of SHP-1 by approximately 3-fold (PMID:15574429)

Cross-species orthologs

2 orthologs

OrganismSymbolGene ID
mus_musculusFlt3ENSMUSG00000042817
rattus_norvegicusFlt3ENSRNOG00000054764

Paralogs (53): INSRR (ENSG00000027644), MUSK (ENSG00000030304), FLT4 (ENSG00000037280), EPHA3 (ENSG00000044524), ROS1 (ENSG00000047936), LTK (ENSG00000062524), ERBB3 (ENSG00000065361), TIE1 (ENSG00000066056), FGFR2 (ENSG00000066468), FGFR3 (ENSG00000068078), EPHA8 (ENSG00000070886), FGFR1 (ENSG00000077782), EPHA6 (ENSG00000080224), TYRO3 (ENSG00000092445), FLT1 (ENSG00000102755), MET (ENSG00000105976), EPHB6 (ENSG00000106123), PDGFRB (ENSG00000113721), EPHA4 (ENSG00000116106), TEK (ENSG00000120156), KDR (ENSG00000128052), EPHB2 (ENSG00000133216), PDGFRA (ENSG00000134853), EPHA7 (ENSG00000135333), IGF1R (ENSG00000140443), NTRK3 (ENSG00000140538), ERBB2 (ENSG00000141736), EPHA2 (ENSG00000142627), EPHA5 (ENSG00000145242), EGFR (ENSG00000146648), EPHA1 (ENSG00000146904), NTRK2 (ENSG00000148053), MERTK (ENSG00000153208), EPHB1 (ENSG00000154928), KIT (ENSG00000157404), FGFR4 (ENSG00000160867), DDR2 (ENSG00000162733), RYK (ENSG00000163785), MST1R (ENSG00000164078), LMTK2 (ENSG00000164715), RET (ENSG00000165731), AXL (ENSG00000167601), ROR2 (ENSG00000169071), ALK (ENSG00000171094), INSR (ENSG00000171105), ERBB4 (ENSG00000178568), CSF1R (ENSG00000182578), EPHB3 (ENSG00000182580), EPHA10 (ENSG00000183317), ROR1 (ENSG00000185483), EPHB4 (ENSG00000196411), NTRK1 (ENSG00000198400), DDR1 (ENSG00000204580)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:95559) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 79 distinct phenotype terms.

Mouse phenotype (MP)Records
increased leukocyte cell number3
enlarged spleen3
abnormal definitive hematopoiesis3
abnormal B cell differentiation3
increased monocyte cell number2
extramedullary hematopoiesis2
increased bone marrow cell number2
increased granulocyte number2
abnormal spleen morphology2
arrested B cell differentiation2
premature death2
decreased B cell number2
decreased NK cell number2
increased pro-B cell number2
decreased pre-B cell number2
intermingled spleen red and white pulp2
increased spleen white pulp amount2
abnormal bone marrow cell number1
increased neutrophil cell number1
decreased leukocyte cell number1
decreased neutrophil cell number1
abnormal heart morphology1
enlarged heart1
decreased bone marrow cell number1
abnormal skeletal muscle morphology1

+54 more (showing top 25).

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

OrganismUniProtIdentityMethod
Bos taurusP4348199.4%Diamond
Capra hircusQ2831799.4%Diamond
Felis catusQ2888999.2%Diamond
Canis lupus familiarisO9779998.4%Diamond
Sus scrofaQ2HWD698.1%Diamond
Callithrix jacchusQ76II094.6%Diamond
Gallus gallusP1846192.7%Diamond
Notophthalmus viridescensQ9114787.9%Diamond
Pleurodeles waltlQ9128587.8%Diamond
Danio rerioO7379181.5%Diamond
Coturnix coturnixQ9033081.0%Diamond
Xenopus laevisP2218280.6%Diamond
Takifugu rubripesQ8AXC773.2%Diamond
Coturnix japonicaP5258373.1%Diamond
Ciona intestinalisQ4H3K660.1%Diamond
Halocynthia roretziQ95YM959.9%Diamond
Drosophila melanogasterQ0914755.0%Diamond
Dugesia japonicaQ8MY8651.0%Diamond
Hydra vulgarisQ86PM450.2%Diamond
Caenorhabditis elegansQ2103849.5%Diamond
Strongylocentrotus purpuratusQ2661446.4%Diamond
Bombyx moriD2IYS244.0%Diamond
Feline sarcoma virus (STRAIN HARDY-ZUCKERMAN 4)P0404899.2%Diamond
Feline sarcoma virus (STRAIN MCDONOUGH)P0054599.1%Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

SymbolTypeEntrez
PAN3protein-coding255967
PAN3-AS1ncRNA100288730
URADprotein-coding646625
LINC00543ncRNA100132234
CDX2protein-coding1045
FLT1protein-coding2321

Protein

Protein identifiers

Receptor-type tyrosine-protein kinase FLT3 — P36888 (reviewed: P36888)

Alternative names: FL cytokine receptor, Fetal liver kinase-2, Fms-like tyrosine kinase 3, Stem cell tyrosine kinase 1

All UniProt accessions (2): E7ER61, P36888

UniProt curated annotations — full annotation on UniProt →

Function. Tyrosine-protein kinase that acts as a 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.

Subunit / interactions. Monomer in the absence of bound FLT3LG. Homodimer in the presence of bound FLT3LG. Interacts with FIZ1 following ligand activation. Interacts with FES, FER, LYN, FGR, HCK, SRC and GRB2. Interacts with PTPRJ/DEP-1 and PTPN11/SHP2. Interacts with RNF115 and RNF126. (Microbial infection) Interacts with human cytomegalovirus protein UL7.

Subcellular location. Membrane. Endoplasmic reticulum lumen.

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.

Post-translational modifications. N-glycosylated, contains complex N-glycans with sialic acid. 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 membrane. Rapidly ubiquitinated by UBE2L6 and the E3 ubiquitin-protein ligase SIAH1 after autophosphorylation, leading to its proteasomal degradation.

Disease relevance. 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. 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.

Activity regulation. Present in an inactive conformation in the absence of bound ligand. FLT3LG binding leads to dimerization and activation by autophosphorylation.

Domain organisation. 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.

Miscellaneous. Can be used as diagnostic tool to establish the exact cause of acute myeloid leukemia, and to determine the optimal therapy.

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

Isoforms (2)

UniProt IDNamesCanonical?
P36888-11yes
P36888-22

RefSeq proteins (1): NP_004110* (*=MANE)

Domains & families (InterPro)

IDNameType
IPR000719Prot_kinase_domDomain
IPR001245Ser-Thr/Tyr_kinase_cat_domDomain
IPR001824Tyr_kinase_rcpt_3_CSConserved_site
IPR007110Ig-like_domDomain
IPR008266Tyr_kinase_ASActive_site
IPR011009Kinase-like_dom_sfHomologous_superfamily
IPR013151Immunoglobulin_domDomain
IPR013783Ig-like_foldHomologous_superfamily
IPR017441Protein_kinase_ATP_BSBinding_site
IPR020635Tyr_kinase_cat_domDomain
IPR036179Ig-like_dom_sfHomologous_superfamily
IPR050122RTKFamily

Pfam: PF00047, PF07714

Enzyme classification (BRENDA)

  • EC 2.7.10.1 — receptor protein-tyrosine kinase (BRENDA: 44 organisms, 214 substrates, 574 inhibitors, 11 Km, 0 kcat entries)

Substrate kinetics (BRENDA)

4 substrates with measured Km, best-characterized 4. Km ranges are aggregated across organisms/conditions.

SubstrateKm (mM)Measurements
ATP0.0011–0.1294
AC-DYFE-6-CHLORO-W-NHME0.00511
AC-DYFGW-NHME0.071
YFEW0.2321

Catalyzed reactions (Rhea)

  • L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+) (RHEA:10596)

UniProt features (103 total): helix 18, strand 16, sequence variant 14, modified residue 13, glycosylation site 10, disulfide bond 7, sequence conflict 6, mutagenesis site 4, turn 3, binding site 2, topological domain 2, domain 2, signal peptide 1, chain 1, transmembrane region 1, splice variant 1, region of interest 1, active site 1

Structure

Experimental structures (PDB)

11 structures by resolution:

PDBTitleMethodResolution (Å)
1RJBCrystal Structure of FLT3X-RAY DIFFRACTION2.1
6JQRCrystal structure of FLT3 in complex with gilteritinibX-RAY DIFFRACTION2.2
5X02Crystal structure of the FLT3 kinase domain bound to the inhibitor FF-10101X-RAY DIFFRACTION2.4
6IL3Crystal structure of the FLT3 kinase bound to a small molecule inhibitorX-RAY DIFFRACTION2.5
8XB1Crystal structure of FLT3 in complex with a Pyrazinamide Macrocycle derivativeX-RAY DIFFRACTION2.85
4RT7Crystal Structure of FLT3 with a small molecule inhibitorX-RAY DIFFRACTION3.1
4XUFCrystal structure of the FLT3 kinase domain bound to the inhibitor quizartinib (AC220)X-RAY DIFFRACTION3.2
7QDPCrystal structure of FLT3 T343I in complex with the canonical ligand FLX-RAY DIFFRACTION3.69
3QS7Crystal structure of a human Flt3 ligand-receptor ternary complexX-RAY DIFFRACTION4.3
7ZV9Crystal structure of FLT3 in complex with a monomeric FLT3 Ligand variantX-RAY DIFFRACTION4.51
3QS9Crystal structure of a human Flt3 ligand-receptor ternary complexX-RAY DIFFRACTION7.8

Predicted structure (AlphaFold)

ModelpLDDTFraction very-high
AF-P36888-F176.190.30

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Transferases, Kinases, Tyr protein kinases, CD markers, Predicted membrane proteins, RAS pathway related proteins, Cancer-related genes, Mutated cancer genes, Mutational cancer driver genes, Disease related genes, FDA approved drug targets, Small molecule drugs, Human disease related genes

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): endoplasmic reticulum

Antibody reliability (HPA): IF approved

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1)

PositionRole
811proton acceptor

Ligand- & substrate-binding residues (2)

PositionRole
644ATP
616–624ATP

Post-translational modifications (13)

TypePositions
Phosphotyrosine572, 589, 591, 599, 726, 768, 793, 842, 955, 969
Phosphoserine574, 759, 993

Disulfide bonds (7)

TypePositions
Disulfide bond35–65, 103–114, 199–206, 232–241, 272–330, 368–407, 381–392

Glycosylation sites (10)

TypePositions
N-linked (glcnac…) asparagine43, 100, 151, 306, 323, 351, 354, 473, 502, 541

Mutagenesis-validated functional residues (4)

PositionPhenotype
589reduced phosphorylation of the wild-type kinase in response to ligand binding. no effect on the phosphorylation of the constitutively …
591no significant effect on tyrosine phosphorylation. abolishes activation of stat5a.
599abolishes interaction with ptpn11/shp2 and phosphorylation of ptpn11/shp2.
644abolishes kinase activity.

Function

Pathways and Gene Ontology

Reactome pathways

23 curated (TAS) of 46; 24 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

46 pathways:

IDPathwayEvidence
R-HSA-2219530Constitutive Signaling by Aberrant PI3K in Cancer ⚕curated
R-HSA-9702509FLT3 mutants bind TKIs ⚕curated
R-HSA-9706377FLT3 signaling by CBL mutants ⚕curated
R-HSA-9702569KW2449-resistant FLT3 mutants ⚕curated
R-HSA-9702518STAT5 activation downstream of FLT3 ITD mutants ⚕curated
R-HSA-9702581crenolanib-resistant FLT3 mutants ⚕curated
R-HSA-9702590gilteritinib-resistant FLT3 mutants ⚕curated
R-HSA-9702596lestaurtinib-resistant FLT3 mutants ⚕curated
R-HSA-9702998linifanib-resistant FLT3 mutants ⚕curated
R-HSA-9702600midostaurin-resistant FLT3 mutants ⚕curated
R-HSA-9702605pexidartinib-resistant FLT3 mutants ⚕curated
R-HSA-9702614ponatinib-resistant FLT3 mutants ⚕curated
R-HSA-9702620quizartinib-resistant FLT3 mutants ⚕curated
R-HSA-9702577semaxanib-resistant FLT3 mutants ⚕curated
R-HSA-9702624sorafenib-resistant FLT3 mutants ⚕curated
R-HSA-9702632sunitinib-resistant FLT3 mutants ⚕curated
R-HSA-9703009tamatinib-resistant FLT3 mutants ⚕curated
R-HSA-9702636tandutinib-resistant FLT3 mutants ⚕curated
R-HSA-9706369Negative regulation of FLT3curated
R-HSA-109704PI3K Cascadecurated
R-HSA-6811558PI5P, PP2A and IER3 Regulate PI3K/AKT Signalingcurated
R-HSA-1257604PIP3 activates AKT signalingcurated
R-HSA-5673001RAF/MAP kinase cascadecurated
R-HSA-1643685Disease ⚕—
R-HSA-5663202Diseases of signal transduction by growth factor receptors and second messengers ⚕—
R-HSA-9702506Drug resistance of FLT3 mutants ⚕—
R-HSA-9682385FLT3 signaling in disease ⚕—
R-HSA-2219528PI3K/AKT Signaling in Cancer ⚕—
R-HSA-9703648Signaling by FLT3 ITD and TKD mutants ⚕electronic
R-HSA-1280215Cytokine Signaling in Immune system—
R-HSA-9607240FLT3 Signalingelectronic
R-HSA-9706374FLT3 signaling through SRC family kinaseselectronic
R-HSA-2428924IGF1R signaling cascade—
R-HSA-112399IRS-mediated signalling—
R-HSA-2428928IRS-related events triggered by IGF1R—
R-HSA-168256Immune System—
R-HSA-74751Insulin receptor signalling cascade—
R-HSA-9006925Intracellular signaling by second messengers—
R-HSA-5683057MAPK family signaling cascades—
R-HSA-5684996MAPK1/MAPK3 signaling—
R-HSA-199418Negative regulation of the PI3K/AKT network—
R-HSA-9645135STAT5 Activationelectronic
R-HSA-162582Signal Transduction—
R-HSA-74752Signaling by Insulin receptor—
R-HSA-9006934Signaling by Receptor Tyrosine Kinases—
R-HSA-2404192Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R)—

MSigDB gene sets: 0 (showing top):

GO Biological Process (26): leukocyte homeostasis (GO:0001776), myeloid progenitor cell differentiation (GO:0002318), pro-B cell differentiation (GO:0002328), cell surface receptor protein tyrosine kinase signaling pathway (GO:0007169), positive regulation of cell population proliferation (GO:0008284), cell migration (GO:0016477), peptidyl-tyrosine phosphorylation (GO:0018108), cytokine-mediated signaling pathway (GO:0019221), hemopoiesis (GO:0030097), B cell differentiation (GO:0030183), common myeloid progenitor cell proliferation (GO:0035726), positive regulation of tyrosine phosphorylation of STAT protein (GO:0042531), regulation of apoptotic process (GO:0042981), positive regulation of MAP kinase activity (GO:0043406), positive regulation of MAPK cascade (GO:0043410), lymphocyte proliferation (GO:0046651), protein autophosphorylation (GO:0046777), positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0051897), cellular response to cytokine stimulus (GO:0071345), cellular response to glucocorticoid stimulus (GO:0071385), dendritic cell differentiation (GO:0097028), liver regeneration (GO:0097421), protein phosphorylation (GO:0006468), cell surface receptor signaling pathway (GO:0007166), positive regulation of macromolecule metabolic process (GO:0010604), vascular endothelial growth factor signaling pathway (GO:0038084)

GO Molecular Function (15): protein tyrosine kinase activity (GO:0004713), transmembrane receptor protein tyrosine kinase activity (GO:0004714), cytokine receptor activity (GO:0004896), vascular endothelial growth factor receptor activity (GO:0005021), ATP binding (GO:0005524), growth factor binding (GO:0019838), nuclear glucocorticoid receptor binding (GO:0035259), protein-containing complex binding (GO:0044877), phosphatidylinositol 3-kinase activator activity (GO:0141038), nucleotide binding (GO:0000166), protein kinase activity (GO:0004672), transmembrane signaling receptor activity (GO:0004888), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (6): endoplasmic reticulum lumen (GO:0005788), plasma membrane (GO:0005886), endosome membrane (GO:0010008), signaling receptor complex (GO:0043235), membrane (GO:0016020), protein-containing complex (GO:0032991)

Reactome top-level categories

10 top-level categories:

CategoryPathways
Drug resistance of FLT3 mutants11
IRS-mediated signalling1
Intracellular signaling by second messengers1
PI3K/AKT Signaling in Cancer1
MAPK1/MAPK3 signaling1
Negative regulation of the PI3K/AKT network1
Cytokine Signaling in Immune system1
FLT3 Signaling1
FLT3 signaling in disease1
Signaling by FLT3 ITD and TKD mutants1

GO top-level categories

showing 60 of 69 GO namespaces:

CategoryTerms
cell population proliferation2
protein phosphorylation2
positive regulation of intracellular signal transduction2
binding2
immune system process1
homeostasis of number of cells1
hematopoietic progenitor cell differentiation1
lymphoid progenitor cell differentiation1
enzyme-linked receptor protein signaling pathway1
regulation of cell population proliferation1
positive regulation of cellular process1
cell motility1
cell surface receptor signaling pathway1
cellular response to cytokine stimulus1
cell development1
lymphocyte differentiation1
B cell activation1
tyrosine phosphorylation of STAT protein1
regulation of tyrosine phosphorylation of STAT protein1
positive regulation of peptidyl-tyrosine phosphorylation1
apoptotic process1
regulation of programmed cell death1
MAP kinase activity1
regulation of MAP kinase activity1
positive regulation of MAPK cascade1
positive regulation of protein serine/threonine kinase activity1
MAPK cascade1
regulation of MAPK cascade1
mononuclear cell proliferation1
lymphocyte activation1
phosphatidylinositol 3-kinase/protein kinase B signal transduction1
regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction1
response to cytokine1
response to glucocorticoid1
cellular response to corticosteroid stimulus1
protein kinase activity1
protein tyrosine kinase activity1
transmembrane receptor protein kinase activity1
transmembrane signaling receptor activity1
cytokine-mediated signaling pathway1
cytokine binding1
immune receptor activity1
transmembrane receptor protein tyrosine kinase activity1
vascular endothelial growth factor signaling pathway1
vascular endothelial growth factor binding1
adenyl ribonucleotide binding1
purine ribonucleoside triphosphate binding1
anion binding1
protein binding1
nuclear receptor binding1
phosphatidylinositol 3-kinase regulator activity1
nucleoside phosphate binding1
heterocyclic compound binding1
kinase activity1
phosphotransferase activity, alcohol group as acceptor1
catalytic activity, acting on a protein1
signaling receptor activity1
transferase activity, transferring phosphorus-containing groups1
catalytic activity1
endoplasmic reticulum1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 1 of 47 annotations. The rest are phylogenetic / computational / electronic (IEA).

1 experimentally-supported GO terms:

GO termNSEvidence
hemopoiesisBPdirect assay

Protein interactions and networks

STRING

showing 15 of 2,904 interactions by confidence (×1000):

Protein AProtein BPartner UniProtScore
FLT3NPM1P06748930
FLT3CD34P28906865
FLT3FLT3LGP49771863
FLT3ASXL1Q8IXJ9862
FLT3DNMT3AQ9Y6K1844
FLT3TET2Q6N021840
FLT3IL7RP16871822
FLT3SLAMF1Q13291820
FLT3IDH1O75874800
FLT3CEBPAP49715800
FLT3RUNX1Q01196800
FLT3IL3P08700798
FLT3KITLGP21583792
FLT3IDH2P48735792
FLT3PHF6Q8IWS0780

IntAct

Human interaction partners of FLT3 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

22 partners by confidence:

PartnerInteraction typeMIscoreRecords
SYKdirect interaction0.74022
GRB10physical association0.5906
ABL2direct interaction0.5403
PTPN11association0.4602
ABL1direct interaction0.4402
CRKdirect interaction0.4402
CRKLdirect interaction0.4402
FYNdirect interaction0.4402
LCKdirect interaction0.4402
RASA1direct interaction0.4402
BLKdirect interaction0.4401
FLT3LGdirect interaction0.4401
SOCS6direct interaction0.4401
TNS1direct interaction0.4401
YES1direct interaction0.4401
PIK3R1physical association0.4002
MRPS28physical association0.4001
CLGNassociation0.3501
LANCL1association0.3501
PTPRJproximity0.2703
KIF2Aproximity0.2701
IKBKGdirect interaction0.0002

BioGRID (330 interactions; top human partners by supporting records): CBL (Affinity Capture-Western; 3 records), CTNNB1 (Affinity Capture-Western; 3 records), PTPN11 (Reconstituted Complex; 3 records), SLA (Affinity Capture-Western; 3 records), CALM3 (Affinity Capture-MS; 2 records), HSPA1B (Affinity Capture-MS; 2 records), PIK3R1 (Affinity Capture-Western; 2 records), PPAN (Positive Genetic; 2 records), SIAH1 (Reconstituted Complex; 2 records), SOCS1 (Affinity Capture-MS; 2 records), SOCS2 (Affinity Capture-Western; 2 records), UBE2L6 (Affinity Capture-Western; 2 records), ABCG5 (Positive Genetic), ADCK3 (Proximity Label-MS), AFG3L2 (Proximity Label-MS)

SIGNOR signaling

showing 50 of 115 signaling interactions:

AEffectBMechanism
FLT3up-regulatesFLT3phosphorylation
sunitinibdown-regulatesFLT3“chemical inhibition”
anthra[1,9-cd]pyrazol-6(2H)-onedown-regulatesFLT3“chemical inhibition”
CHIR-124down-regulatesFLT3“chemical inhibition”
4-amino-5-fluoro-3-[5-(4-methyl-1-piperazinyl)-1,3-dihydrobenzimidazol-2-ylidene]-2-quinolinonedown-regulatesFLT3“chemical inhibition”
“dovitinib; bis(lactic acid)”down-regulatesFLT3“chemical inhibition”
[4-[2-(1H-indazol-3-yl)ethenyl]phenyl]-(1-piperazinyl)methanonedown-regulatesFLT3“chemical inhibition”
MK-2461down-regulatesFLT3“chemical inhibition”
FLT3up-regulatesSkeletal_muscle_differentiation
quizartinibdown-regulatesFLT3“chemical inhibition”
tandutinibdown-regulatesFLT3“chemical inhibition”
TG101209down-regulatesFLT3“chemical inhibition”
FLT3“up-regulates activity”AKT
FLT3“down-regulates quantity by repression”CEBPA“transcriptional regulation”
FLT3“up-regulates activity”SHC1phosphorylation
FLT3“up-regulates activity”AKT1
FLT3“up-regulates activity”RUNX1
sunitinib“down-regulates activity”FLT3“chemical inhibition”
regorafenib“down-regulates activity”FLT3“chemical inhibition”
PIM1“up-regulates quantity”FLT3phosphorylation
FLT3“down-regulates quantity”PTPN6“transcriptional regulation”
FLT3“up-regulates activity”Glycolysis
FLT3“up-regulates activity”CTNNB1phosphorylation
FLT3“up-regulates activity”ERK1/2
FLT3“up-regulates activity”HK2
FLT3“down-regulates quantity by repression”PTPN6“transcriptional regulation”
FLT3“up-regulates quantity by stabilization”SIRT1“post transcriptional regulation”
FLT3“up-regulates quantity by expression”MYC
FLT3“up-regulates quantity by expression”USP22“transcriptional regulation”
cabozantinib“down-regulates activity”FLT3“chemical inhibition”
FLT3“up-regulates activity”ACAT1phosphorylation
FLT3“down-regulates activity”IDH2phosphorylation
FLT3“up-regulates activity”Hexokinase
FLT3“up-regulates activity”FLT3phosphorylation
PTPRJ“down-regulates activity”FLT3dephosphorylation
SYK“up-regulates activity”FLT3phosphorylation
FYN“up-regulates activity”FLT3phosphorylation
FLT3LGup-regulatesFLT3binding
FLT3“up-regulates activity”PTPN11binding
FLT3“up-regulates activity”GRB2binding
FLT3“up-regulates activity”STAT5Aphosphorylation
FLT3“up-regulates quantity by expression”ID1“transcriptional regulation”
CBL“down-regulates activity”FLT3binding
FLT3“up-regulates quantity by expression”miR-155“transcriptional regulation”
FLT3“up-regulates activity”GRB10binding
SLA2“down-regulates activity”FLT3binding
FLT3“up-regulates activity”PIK3R1
FLT3“up-regulates activity”PI3K
CBLB“down-regulates activity”FLT3ubiquitination
FLT3“up-regulates quantity by expression”FZD4“transcriptional regulation”

Protein complexes (CORUM) (5)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

5 complexes by size:

ComplexSubunitsMembers
★ FLT3-FLT3LG complex2FLT3LG, FLT3
★ FLT3-SET complex2FLT3, SET
★ CDKN1B-FLT3 complex2CDKN1B, FLT3
★ FES-FLT3 complex2FES, FLT3
★ FER-FLT3 complex2FER, FLT3

Ligand–receptor pairs (CellPhoneDB) (1)

Curated ligand–receptor partners (cell-cell communication), distinct from the protein–protein interactions above.

1 ligand–receptor pairs:

PartnerThis gene’s roleSignaling class
FLT3LGreceptor

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 22 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

PathwayPartnersFoldFDR
Regulation of signaling by CBL6156.8×1e-10
FLT3 Signaling8145.7×5e-14
Downstream signal transduction5100.2×7e-08
Signaling by SCF-KIT791.5×9e-11
GPVI-mediated activation cascade581.2×2e-07
FCGR3A-mediated phagocytosis549.3×1e-06
Constitutive Signaling by Aberrant PI3K in Cancer533.4×6e-06
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling525.5×2e-05

GO biological processes:

GO termPartnersFoldFDR
ephrin receptor signaling pathway693.8×1e-08
cellular response to transforming growth factor beta stimulus562.8×2e-06
T cell receptor signaling pathway641.4×1e-06
intracellular signal transduction813.9×4e-06

Disease & clinical

Cancer significance

From CIViC — curated cancer-variant interpretation:

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.

From intOGen — cancer-driver classification: activating (oncogene-like) across 2 cancer types — ALL, AML.

intOGen’s role is a computational inference from cohort mutation patterns and may diverge from the gene’s curated/literature role; read it alongside the evidence above.

Genetic variants

Variant evidence for FLT3: 247 ClinVar records (14 pathogenic / likely pathogenic); 20 CIViC cancer variants; 1 PharmGKB clinical annotation; 63 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

247 variants total. Per-class counts are floors (≥ shown; pagination cap):

ClassificationCount (floor)
Pathogenic10
Likely pathogenic4
Uncertain significance80
Likely benign40
Benign85

Top pathogenic / likely-pathogenic (14)

Showing all 14 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant IDHGVSClassificationReviewSubmitters
219096NM_004119.3(FLT3):c.1773_1793dup (p.Tyr597_Glu598insAspValAspPheArgGluTyr)Pathogeniccriteria provided, single submitter1
2572500NM_004119.3(FLT3):c.2533A>G (p.Arg845Gly)Likely pathogeniccriteria provided, single submitter1
4528371NM_004119.3(FLT3):c.1715A>G (p.Tyr572Cys)Likely pathogeniccriteria provided, single submitter1
16276NM_004119.3(FLT3):c.2503G>T (p.Asp835Tyr)Pathogenicno assertion criteria provided3
16272NM_004119.3(FLT3):c.2504A>T (p.Asp835Val)Pathogenicno assertion criteria provided2
16270FLT3, INTERNAL TANDEM DUPPathogenicno assertion criteria provided1
16271NM_004119.3(FLT3):c.2520_2521insGGATCC (p.Ser840_Asn841insGlySer)Pathogenicno assertion criteria provided1
16273NM_004119.3(FLT3):c.2503G>C (p.Asp835His)Pathogenicno assertion criteria provided1
16274NM_004119.3(FLT3):c.2503G>A (p.Asp835Asn)Pathogenicno assertion criteria provided1
16277NM_004119.3(FLT3):c.2503_2505del (p.Asp835del)Pathogenicno assertion criteria provided1
16278NM_004119.3(FLT3):c.1777_1779del (p.Asp593del)Pathogenicno assertion criteria provided1
375972NM_004119.3(FLT3):c.2505T>A (p.Asp835Glu)Pathogenicno assertion criteria provided1
590265t(13;17)(q12.2;q11.2)Likely pathogenicno assertion criteria provided1
800354NM_004119.3(FLT3):c.1714T>C (p.Tyr572His)Likely pathogenicno assertion criteria provided1

Per-variant reference — Sugi Variant

Explore FLT3’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 32 predictions of 2,456):

Position(s)EffectΔscoreSites
13:28015588–28015589donor_loss1.00005
13:28015702–28015703acceptor_loss1.00005
13:28015714–28015715acceptor_gain1.00002
13:28023374donor_gain1.0000
13:28028176–28028177donor_loss1.00005
13:28034080–28034081donor_loss1.00005
13:28034085donor_gain1.0000
13:28037293acceptor_gain1.0000
13:28062070–28062071acceptor_loss1.00002
13:28070489–28070490donor_loss1.00005

AlphaMissense

1,717 missense substitutions predicted likely pathogenic (of 6,557 scored), across 404 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

ResidueLikely-pathogenic substitutionsMean am_pathogenicityMax am_pathogenicity
M90890.9540.997
M85590.9510.995
M79990.9310.995
M64590.8580.957
M92290.8530.994
N81680.9980.999
D82980.9981.000
D81180.9971.000
H80980.9940.998
D87080.9940.998
F62180.9891.000
F83080.9850.998
D69880.9780.996
F88280.9750.998
F93680.9740.997
F89880.9700.998
D78780.9620.989
F60580.9560.999
S86980.9551.000
D83580.9340.975

HPA cancer prognostics

RNA cancer specificity: Cancer enhanced (Breast Invasive Carcinoma)

Disease associations

OMIM: gene MIM:136351 | disease phenotypes: MIM:601626, MIM:254500

GenCC curated gene-disease

1 curated gene-disease records:

DiseaseClassificationInheritanceRecords
leukemia, acute myeloid, susceptibility toLimitedAutosomal dominant

ClinGen Gene-Disease Validity

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

1 validity classifications:

DiseaseClassificationInheritance
leukemia, acute myeloid, susceptibility toLimitedAD

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (1 panels, 0 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

1 panels:

PanelRating
Cytopenias and congenital anaemiasamber

Mondo (5): acute myeloid leukemia (MONDO:0018874), acute lymphoblastic leukemia (MONDO:0004967), atypical chronic myeloid leukemia, BCR-ABL1 negative (MONDO:0004653), plasma cell myeloma (MONDO:0009693), leukemia, acute myeloid, susceptibility to (MONDO:0100173)

Orphanet (5): Acute myeloid leukemia (Orphanet:519), Acute lymphoblastic leukemia (Orphanet:513), Atypical chronic myeloid leukemia (Orphanet:98824), Multiple myeloma (Orphanet:29073), AL amyloidosis (Orphanet:85443)

HPO phenotypes

5 phenotypes (HPO-id order):

HPOTerm
HP:0000006Autosomal dominant inheritance
HP:0001442Typified by somatic mosaicism
HP:0004808Acute myeloid leukemia
HP:0006721Acute lymphoblastic leukemia
HP:0010982Polygenic inheritance

GWAS associations

showing 30 of 63 associations:

StudyTraitp-value
GCST90002393_231Monocyte count0.000000e+00
GCST90002394_159Monocyte percentage of white cells0.000000e+00
GCST004625_31Monocyte count3e-240
GCST004609_180Monocyte percentage of white cells4e-188
GCST004608_125Granulocyte percentage of myeloid white cells2e-136
GCST90002393_236Monocyte count4e-117
GCST90002394_160Monocyte percentage of white cells1e-109
GCST90002393_232Monocyte count5e-92
GCST90002407_445White blood cell count4e-83
GCST90002394_164Monocyte percentage of white cells4e-68
GCST004625_32Monocyte count2e-41
GCST90002393_234Monocyte count2e-40
GCST90002407_446White blood cell count9e-40
GCST90002398_346Neutrophil count3e-38
GCST90002398_347Neutrophil count9e-35
GCST90002389_423Lymphocyte percentage of white cells2e-33
GCST007932_49Medication use (thyroid preparations)2e-26
GCST90002393_233Monocyte count3e-25
GCST004609_179Monocyte percentage of white cells5e-25
GCST010571_59Autoimmune thyroid disease2e-24
GCST90002407_447White blood cell count1e-23
GCST010989_154Body size at age 101e-22
GCST90002389_422Lymphocyte percentage of white cells2e-22
GCST004626_61Myeloid white cell count8e-21
GCST004610_79White blood cell count2e-19
GCST90002394_161Monocyte percentage of white cells4e-19
GCST90002394_163Monocyte percentage of white cells8e-19
GCST008129_11Body mass index1e-18
GCST90002393_235Monocyte count1e-18
GCST90002394_162Monocyte percentage of white cells4e-18

EFO canonical traits (from GWAS)

18 canonical traits:

EFO IDTrait name
EFO:0004340body mass index
EFO:0005091monocyte count
EFO:0007997granulocyte percentage of myeloid white cells
EFO:0007989monocyte percentage of leukocytes
EFO:0004833neutrophil count
EFO:0004842eosinophil count
EFO:0007987granulocyte count
EFO:0005090basophil count
EFO:0007993lymphocyte percentage of leukocytes
EFO:0005301reading and spelling ability
EFO:0009933Thyroid preparation use measurement
EFO:0004614apolipoprotein A 1 measurement
EFO:0004612high density lipoprotein cholesterol measurement
EFO:0009819comparative body size at age 10, self-reported
EFO:0004587lymphocyte count
EFO:0010701mean reticulocyte volume
EFO:0007990neutrophil percentage of leukocytes
EFO:0007985platelet crit

MeSH disease descriptors

2 disease descriptors:

DescriptorNameTree numbers
D015470Leukemia, Myeloid, AcuteC04.557.337.539.275; C15.378.508.539.275
D009101Multiple MyelomaC04.557.595.500; C14.907.454.460; C15.378.147.780.650; C15.378.463.515.460; C20.683.515.845; C20.683.780.650

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (4): CHEMBL1974 (SINGLE PROTEIN), CHEMBL3430908 (SELECTIVITY GROUP), CHEMBL4523735 (PROTEIN-PROTEIN INTERACTION), CHEMBL4630730 (PROTEIN-PROTEIN INTERACTION)

Drugs by curated mechanism of action (ChEMBL)

Drugs whose curated ChEMBL mechanism of action targets the FLT3 protein itself — single-protein targets only (drugs acting on a protein family or complex that merely includes it are excluded). Includes antibodies and oligonucleotides that bioactivity screening does not capture.

39 curated-mechanism drugs:

DrugModalityMax phase
FEDRATINIBSmall molecule4
GILTERITINIBSmall molecule4
MIDOSTAURINSmall molecule4
PACRITINIBSmall molecule4
PEXIDARTINIBSmall molecule4
QUIZARTINIBSmall molecule4
SORAFENIB TOSYLATESmall molecule4
SUNITINIBSmall molecule4
CM-082Unknown3
CRENOLANIBSmall molecule3
DOVITINIBSmall molecule3
FAMITINIBSmall molecule3
LESTAURTINIBSmall molecule3
LINIFANIBSmall molecule3
RUSERONTINIBSmall molecule3
AKN-028Small molecule2
AMUVATINIBSmall molecule2
AT-9283Small molecule2
C-1311Small molecule2
CDX-301Unknown2
ENMD-2076Small molecule2
ENMD-981693Small molecule2
FORETINIBSmall molecule2
NINGETINIBSmall molecule2
SU-014813Small molecule2
TANDUTINIBSmall molecule2
XL-999Small molecule2
ZOTIRACICLIBSmall molecule2
4SC-203Small molecule1
AMG553Unknown1
AS-602868Small molecule1
AST-487Small molecule1
CEP-2563 DIHYDROCHLORIDESmall molecule1
CT-1578Small molecule1
FF-10101Small molecule1
FLYSYNUnknown1
IMC-EB10Unknown1
KW-2449Small molecule1
RG-1530Small molecule1

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 402,854 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

showing 60 of 143 molecules by phase:

MoleculeNamePhasePatents
CHEMBL1287853FEDRATINIB43,770
CHEMBL3301622GILTERITINIB42,542
CHEMBL608533MIDOSTAURIN47,641
CHEMBL2035187PACRITINIB43,544
CHEMBL3813873PEXIDARTINIB43,751
CHEMBL576982QUIZARTINIB44,647
CHEMBL2105709QUIZARTINIB DIHYDROCHLORIDE4304
CHEMBL1336SORAFENIB487,476
CHEMBL535SUNITINIB480,232
CHEMBL3301610ABEMACICLIB47,497
CHEMBL1173655AFATINIB415,878
CHEMBL1289926AXITINIB416,510
CHEMBL288441BOSUTINIB412,869
CHEMBL3545311BRIGATINIB45,988
CHEMBL2105717CABOZANTINIB411,799
CHEMBL2403108CERITINIB49,002
CHEMBL601719CRIZOTINIB415,133
CHEMBL5416410DASATINIB4674
CHEMBL1983268ENTRECTINIB43,737
CHEMBL553ERLOTINIB4109,860
CHEMBL3301607FILGOTINIB4
CHEMBL2103830FOSTAMATINIB4
CHEMBL939GEFITINIB4
CHEMBL1873475IBRUTINIB4
CHEMBL941IMATINIB4
CHEMBL1852688INFIGRATINIB4
CHEMBL1834657INFIGRATINIB PHOSPHATE4
CHEMBL180022NERATINIB4
CHEMBL255863NILOTINIB4
CHEMBL502835NINTEDANIB4
CHEMBL189963PALBOCICLIB4
CHEMBL477772PAZOPANIB4
CHEMBL1171837PONATINIB4
CHEMBL4582651PRALSETINIB4
CHEMBL1946170REGORAFENIB4
CHEMBL1289494TIVOZANIB4
CHEMBL24828VANDETANIB4
CHEMBL2105728CRENOLANIB3
CHEMBL522892DOVITINIB3
CHEMBL603469LESTAURTINIB3
CHEMBL223360LINIFANIB3
CHEMBL428690ALVOCIDIB3
CHEMBL415049BARASERTIB3
CHEMBL31965CANERTINIB3
CHEMBL491473CEDIRANIB3
CHEMBL3137331DEFACTINIB3
CHEMBL3265032ENTOSPLETINIB3
CHEMBL300138ENZASTAURIN3
CHEMBL3904602LEROCICLIB3
CHEMBL1091644LINSITINIB3
CHEMBL572881MOTESANIB3
CHEMBL2316582OLVEREMBATINIB3
CHEMBL274654ORANTINIB3
CHEMBL50QUERCETIN3
CHEMBL165RESVERATROL3
CHEMBL91829RUBOXISTAURIN3
CHEMBL217092SARACATINIB3
CHEMBL276711SEMAXANIB3
CHEMBL3989926SITRAVATINIB3
CHEMBL4297190SURUFATINIB3

Clinical evidence (CIViC)

Drug × variant × indication, from 99 curated evidence items; also 25 prognostic, 10 oncogenic, 5 diagnostic, 1 functional. CIViC evidence level: A (validated) → B (clinical) → C (case study) → D (preclinical) → E (inferential).

showing 30 of 81 predictive associations by evidence level:

VariantTherapyIndicationEffectLevelCIViC
FLT3 ITDGilteritinibAcute Myeloid LeukemiaSensitivity/ResponseCIViC AEID12621 +2
FLT3 ITD OR FLT3 D835 OR FLT3 I836Midostaurin + ChemotherapyAcute Myeloid LeukemiaSensitivity/ResponseCIViC AEID11261
FLT3 ITD OR FLT3 D835 OR FLT3 I836GilteritinibAcute Myeloid LeukemiaSensitivity/ResponseCIViC AEID7728
FLT3 MutationMidostaurinAcute Myeloid LeukemiaSensitivity/ResponseCIViC AEID5261
FLT3 ITDSorafenibAcute Myeloid LeukemiaSensitivity/ResponseCIViC BEID1040 +2
FLT3 F691LPexidartinibAcute Myeloid LeukemiaSensitivity/ResponseCIViC BEID8674 +1
FLT3 ITDMidostaurinAcute Myeloid LeukemiaSensitivity/ResponseCIViC BEID7061 +1
FLT3 MutationNilotinibAcute Myeloid LeukemiaSensitivity/ResponseCIViC BEID5575 +1
FLT3 AmplificationSunitinibColorectal CancerSensitivity/ResponseCIViC BEID11667
FLT3 ITDLestaurtinibAcute Myeloid LeukemiaSensitivity/ResponseCIViC BEID297
FLT3 ITDHematopoietic Cell Transplantation + SorafenibAcute Myeloid LeukemiaSensitivity/ResponseCIViC BEID9069
FLT3 ITDSorafenib + Hematopoietic Cell TransplantationAcute Myeloid LeukemiaSensitivity/ResponseCIViC BEID9070
FLT3 ITDPacritinibAcute Myeloid LeukemiaSensitivity/ResponseCIViC BEID9217
FLT3 MutationGilteritinibAcute Myeloid LeukemiaSensitivity/ResponseCIViC BEID7283
FLT3 TKD MUTATIONMidostaurinAcute Myeloid LeukemiaSensitivity/ResponseCIViC BEID1295
FLT3 F691LQuizartinibAcute Myeloid LeukemiaResistanceCIViC BEID9718 +1
FLT3 D835Quizartinib + SorafenibAcute Myeloid LeukemiaResistanceCIViC BEID1038
FLT3 D835SorafenibAcute Myeloid LeukemiaResistanceCIViC BEID1039
FLT3 F691LPexidartinibAcute Myeloid LeukemiaResistanceCIViC BEID9717
FLT3 ITDAnthracycline Antineoplastic Antibiotic + TretinoinAcute Promyelocytic LeukemiaResistanceCIViC BEID1112
FLT3 ITDSelumetinibAcute Myeloid LeukemiaResistanceCIViC BEID1137
FLT3 ITDTretinoinAcute Myeloid LeukemiaResistanceCIViC BEID127
FLT3 TKD MUTATIONSorafenibAcute Myeloid LeukemiaResistanceCIViC BEID248
FLT3 T227MSunitinibRenal Cell CarcinomaAdverse ResponseCIViC BEID1317
FLT3 D835SunitinibAcute Myeloid LeukemiaSensitivity/ResponseCIViC CEID4024 +2
FLT3 D835VSunitinibAcute Myeloid LeukemiaSensitivity/ResponseCIViC CEID4022 +2
FLT3 D835YSorafenibAcute Myeloid LeukemiaSensitivity/ResponseCIViC CEID12625 +2
FLT3 D835HSunitinibAcute Myeloid LeukemiaSensitivity/ResponseCIViC CEID4027 +1
FLT3 D835YGilteritinibAcute Myeloid LeukemiaSensitivity/ResponseCIViC CEID12620 +1
FLT3 AmplificationRegorafenib AnhydrousColorectal CancerSensitivity/ResponseCIViC CEID7102

CIViC column: a representative evidence item (EID); +N = additional CIViC items supporting the same association.

Clinical-actionability assertions (CIViC AMP/ASCO/CAP)

Curated AMP/ASCO/CAP tier assertions — the clinical-actionability classification (Tier I highest) for this gene’s variants, distilling the CIViC evidence above into a tiered call.

5 CIViC assertions:

Molecular profileDiseaseTherapyTypeAMP tierSignificance
FLT3 D835YAcute Myeloid LeukemiaGilteritinib †PredictiveTier I - Level ASensitivity/Response
FLT3 D835Acute Myeloid LeukemiaGilteritinib †PredictiveTier I - Level ASensitivity/Response
FLT3 ITDAcute Myeloid LeukemiaGilteritinib †PredictiveTier I - Level ASensitivity/Response
FLT3 N841IAcute Myeloid LeukemiaOncogenicOncogenic
FLT3 D835YAcute Myeloid LeukemiaOncogenicOncogenic

† an FDA-approved companion diagnostic exists for this assertion.

CIViC curated variants (20)

Named clinical variants curated in CIViC for this gene (the catalogue beneath the predictive evidence above):

D835V (missense variant), Amplification, D835Y (missense variant), Y842C, F691L, D835I, N841I (missense variant), I836, I836S, I836T, D593del, D835 (protein altering variant), Mutation (gain of function variant,transcript variant), T227M (missense variant,SNP), M737I, ITD (inframe insertion), TKD MUTATION, Overexpression, D835H (missense variant), D835H/Y (missense variant).

PharmGKB: 1 entry (CPIC guideline: no)

PharmGKB clinical annotations

1 annotations by evidence level (1 strongest → 4):

VariantAssociationLevelDrugsPhenotypes
rs1933437Toxicity3sunitinibLeukopenia;Myelosuppression;Neutropenia;Thrombocytopenia

PharmGKB variants

1 variants:

VariantGenesLevelScore#Clin annotsDrugs
rs1933437FLT336.501sunitinib

PharmGKB variant annotations

Per-publication pharmacogenomic findings for this gene (significant associations).

3 published findings:

VariantDrug(s)CategoryFindingPMID
rs1933437sunitinibToxicityGenotype AA is associated with increased risk of Leukopenia and Neutropenia when treated with sunitinib in people with Carcinoma, Renal Cell as compared to genotypes AG + GG.PMID:26244574
rs1933437sunitinibToxicityGenotypes AG + GG is associated with decreased likelihood of Leukopenia when treated with sunitinib in people with Carcinoma, Renal Cell or Gastrointestinal Stromal Tumors as compared to genotype AA.PMID:19667267
rs1933437sunitinibToxicityGenotypes AG + GG is associated with decreased likelihood of Thrombocytopenia when treated with sunitinib in people with Carcinoma, Renal Cell or Gastrointestinal Stromal Tumors as compared to genotype AA.PMID:20683446

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: catalytic receptor — Type III RTKs: PDGFR, CSFR, Kit, FLT3 receptor family

Most potent curated ligand interactions (68 total), top 25:

LigandActionAffinityParameter
faldoritinibIrreversible inhibition10.0pIC50
gilteritinibInhibition9.52pIC50
nefextinibInhibition9.47pIC50
denfivontinibInhibition9.4pIC50
AC710Inhibition9.3pKd
Gö 6976Inhibition9.15pIC50
TTT-3002Inhibition9.14pIC50
crenolanibInhibition9.13pKd
compound 8i [PMID: 22765894]Inhibition9.1pIC50
compound 8h [PMID: 22765894]Inhibition9.07pIC50
dorsomorphinInhibition9.0pIC50
dovitinibInhibition9.0pIC50
RGB-286638Inhibition9.0pIC50
ilorasertibInhibition9.0pIC50
tuspetinibInhibition8.96pIC50
compound 2c [PMID: 24900538]Inhibition8.68pIC50
compound 6li [Chan et al., 2022]Inhibition8.6pKd
ENMD-2076Inhibition8.52pIC50
compound 5e [PMID: 28580438]Inhibition8.44pKd
faronoltinibInhibition8.4pIC50
compound 34f [PMID: 37535845]Inhibition8.4pIC50
linifanibInhibition8.4pIC50
URMC-099Inhibition8.4pIC50
quizartinibInhibition8.38pIC50
mivavotinibInhibition8.34pIC50

Binding affinities (BindingDB)

3824 measured of 4881 human assays (4965 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

LigandMeasureValuePatent
[6-cyclopropyl-3-[6-[[(3S,4S)-4-fluoropyrrolidin-3-yl]amino]-2-pyridinyl]imidazo[1,2-a]pyridin-7-yl]methanolKD0.007 nMUS-20230303563: MULTI-CYCLIC IRAK AND FLT3 INHIBITING COMPOUNDS AND USES THEREOF
6-[6-(difluoromethyl)imidazo[1,2-a]pyridin-3-yl]-N-[(3S,4S)-4-fluoropyrrolidin-3-yl]pyridin-2-amineKD0.007 nMUS-20230303563: MULTI-CYCLIC IRAK AND FLT3 INHIBITING COMPOUNDS AND USES THEREOF
Exemplary Synthetic Procedure #38KD0.008 nMUS-20230303563: MULTI-CYCLIC IRAK AND FLT3 INHIBITING COMPOUNDS AND USES THEREOF
2-(3-(6-(((3S,4S)-4- fluoropyrrolidin-3- yl)amino)pyridin-2-yl)-7- methoxyimidazo[1,2- a]pyridin-6-yl)propan-2-olKD0.009 nMUS-20230303563: MULTI-CYCLIC IRAK AND FLT3 INHIBITING COMPOUNDS AND USES THEREOF
6-(6- (difluoromethyl)imidazo[1,2- a]pyridin-3-yl)-N-((3R,4S)-4- (trifluoromethyl)pyrrolidin-3- yl)pyridin-2-amineKD0.009 nMUS-20230303563: MULTI-CYCLIC IRAK AND FLT3 INHIBITING COMPOUNDS AND USES THEREOF
6-(6- (difluoromethyl)imidazo[1,2- a]pyridin-3-yl)-N-(2,2- dimethylpyrrolidin-3- yl)pyridin-2-amineKD0.009 nMUS-20230303563: MULTI-CYCLIC IRAK AND FLT3 INHIBITING COMPOUNDS AND USES THEREOF
N-(6-(6- (difluoromethyl)imidazo[1,2- a]pyridin-3-yl)pyridin-2-yl)-2- azaspiro[3.4]octan-6-amineKD0.01 nMUS-20230303563: MULTI-CYCLIC IRAK AND FLT3 INHIBITING COMPOUNDS AND USES THEREOF
6-(6-(difluorometh- oxy)imidazo[1,2-a]- pyridin-3-yl)-N-((3S, 4S)-4-fluoropyrrolidin- 3-yl)pyridin-2-amineKD0.011 nMUS-20230303563: MULTI-CYCLIC IRAK AND FLT3 INHIBITING COMPOUNDS AND USES THEREOF
6-(6-(1-cyclopropyl-1H- pyrazol-4-yl)imidazo- [1,2-a]pyridin-3-yl)-N- ((3S,4S)-4-fluoro- pyrrolidin-3-yl)pyridin- 2-amineKD0.011 nMUS-20230303563: MULTI-CYCLIC IRAK AND FLT3 INHIBITING COMPOUNDS AND USES THEREOF
N-((3S,4S)-4-fluoro- pyrrolidin-3-yl)-6-(6-(1- methyl-1H-pyrazol-4- yl)imidazo[1,2-a]pyridin- 3-yl)pyridin-2-amineKD0.012 nMUS-20230303563: MULTI-CYCLIC IRAK AND FLT3 INHIBITING COMPOUNDS AND USES THEREOF
CHEMBL4744130IC500.015 nM
1-(4-(3-(6-(((3S,4S)-4- fluoropyrrolidin-3-yl)- amino)pyridin-2-yl)- imidazo[1,2-a]pyridin-6- yl)-1H-pyrazol-1-yl)-2- methylpropan-2-olKD0.016 nMUS-20230303563: MULTI-CYCLIC IRAK AND FLT3 INHIBITING COMPOUNDS AND USES THEREOF
2-(3-(6-(((3S,4S)-4- fluoropiperidin-3- yl)amino)pyridin-2-yl)-7- methoxyimidazo[1,2- a]pyridin-6-yl)propan-2-olKD0.017 nMUS-20230303563: MULTI-CYCLIC IRAK AND FLT3 INHIBITING COMPOUNDS AND USES THEREOF
N-((3S,4S)-4- fluoropyrrolidin-3-yl)-6-(7- isopropoxyimidazo[1,2- a]pyridin-3-yl)pyridin-2- amineKD0.018 nMUS-20230303563: MULTI-CYCLIC IRAK AND FLT3 INHIBITING COMPOUNDS AND USES THEREOF
(R)-N-(6-(6- (difluoromethyl)imidazo[1,2- a]pyridin-3-yl)pyridin-2-yl)-5- azaspiro[2.4]heptan-7-amineKD0.02 nMUS-20230303563: MULTI-CYCLIC IRAK AND FLT3 INHIBITING COMPOUNDS AND USES THEREOF
CHEMBL5440655IC500.024 nM
3,5-difluoro-N-((3S,4S)-4- fluoropiperidin-3-yl)-6-(7- isopropoxyimidazo[1,2- a]pyridin-3-yl)pyridin-2- amineKD0.025 nMUS-20230303563: MULTI-CYCLIC IRAK AND FLT3 INHIBITING COMPOUNDS AND USES THEREOF
N-(6-(6-(1-methyl- cyclopropyl)imidazo- [1,2-a]pyridin-3-yl)- pyridin-2-yl)-2- azaspiro[3.4]octan-6- amineKD0.034 nMUS-20230303563: MULTI-CYCLIC IRAK AND FLT3 INHIBITING COMPOUNDS AND USES THEREOF
CHEMBL4519741IC500.038 nM
3,5-difluoro-N-((3S,4S)-4- fluoropyrrolidin-3-yl)-6- (7- isopropoxyimidazo[1,2- a]pyridin-3-yl)pyridin-2- amineKD0.049 nMUS-20230303563: MULTI-CYCLIC IRAK AND FLT3 INHIBITING COMPOUNDS AND USES THEREOF
3-[2-(Imidazo[1,2-b]pyridazin-3-yl)ethynyl]-4-methyl-N-{4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl}benzamideEC500.05 nM
CHEMBL6191359IC500.05 nM
CHEMBL6191849IC500.05 nM
CHEMBL6192901IC500.05 nM
CHEMBL6189235IC500.05 nM
(17E)-16-ethyl-8,12,14-trimethyl- 2,11,12,14-tetrahydro-8H-3,5- ethenotripyrazolo[3,4-f:3’,4’-j:4″,3″- n][1,4]oxazacyclopentadecin-13(10H)- oneKD0.058 nMUS-20260070924: INDAZOLE MACROCYCLES AND THEIR USE
CHEMBL6192930IC500.06 nM
CHEMBL5641913IC500.061 nM
CHEMBL5641673IC500.061 nM
CHEMBL5639694IC500.063 nM
CHEMBL5639591IC500.063 nM
CHEMBL4790915IC500.072 nM
CHEMBL6188781IC500.08 nM
CHEMBL6189029IC500.08 nM
CHEMBL6192679IC500.08 nM
CHEMBL6191366IC500.09 nM
CHEMBL5639373IC500.102 nM
CHEMBL5593388IC500.11 nM
CHEMBL5646935IC500.117 nM
CHEMBL5647067IC500.118 nM
CHEMBL5646820IC500.119 nM
CHEMBL5639601IC500.132 nM
CHEMBL6190161IC500.14 nM
CHEMBL5618643IC500.142 nM
CHEMBL5639222IC500.147 nM
CHEMBL5639369IC500.147 nM
CHEMBL4790597IC500.15 nM
CHEMBL6189611IC500.15 nM
CHEMBL6192249IC500.16 nM
CHEMBL5640024IC500.168 nM

ChEMBL bioactivities

6100 potent at pChembl≥5 of 6100 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChemblTypeValueUnitMolecule
11.00Kd0.01nMCHEMBL5176837
11.00Kd0.01nMCHEMBL5927784
10.92Kd0.012nMCHEMBL5176837
10.82IC500.015nMCHEMBL4744130
10.81Kd0.0154nMCHEMBL5195819
10.80Kd0.016nMCRENOLANIB
10.77Kd0.017nMCHEMBL6078253
10.68Kd0.021nMCHEMBL6002371
10.62IC500.024nMCHEMBL5440655
10.60Kd0.025nMCHEMBL5927784
10.47Kd0.034nMCHEMBL6078253
10.42IC500.038nMCHEMBL4519741
10.30IC500.05nMCHEMBL6191359
10.30IC500.05nMCHEMBL6191849
10.30IC500.05nMCHEMBL6192901
10.30IC500.05nMCHEMBL6189235
10.25Kd0.056nMCHEMBL6078253
10.22IC500.06nMCRENOLANIB
10.22IC500.06nMCHEMBL6192930
10.21IC500.061nMCHEMBL5641913
10.21IC500.061nMCHEMBL5641673
10.20IC500.063nMCHEMBL5639694
10.20IC500.063nMCHEMBL5639591
10.19Kd0.065nMCHEMBL6002371
10.14IC500.072nMCHEMBL4790915
10.13Kd0.074nMCHEMBL6078253
10.10IC500.08nMCHEMBL6188781
10.10IC500.08nMCHEMBL6189029
10.10IC500.08nMCHEMBL6192679
10.05IC500.09nMCHEMBL6191366
10.03Kd0.093nMCHEMBL256961
10.00IC500.101nMCHEMBL4086149
10.00IC500.1nMCHEMBL4513768
10.00Ki0.1nMCHEMBL4864449
10.00Ki0.1nMCHEMBL4870188
10.00IC500.1nMCHEMBL5268237
10.00Kd0.1nMCHEMBL6078253
10.00Ki0.1nMCHEMBL273187
9.99IC500.102nMCHEMBL5639373
9.96IC500.11nMCHEMBL5593388
9.96Kd0.11nMCHEMBL6002371
9.93IC500.118nMCHEMBL5647067
9.93IC500.117nMCHEMBL5646935
9.92IC500.121nMCHEMBL5440655
9.92IC500.119nMCHEMBL5646820
9.92Kd0.12nMCHEMBL6002371
9.91IC500.123nMCHEMBL3612622
9.89IC500.13nMCHEMBL4092761
9.88IC500.132nMCHEMBL5639601
9.85IC500.14nMCHEMBL6190161

PubChem BioAssay actives

3025 with measured affinity, of 6100 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

CompoundAssayTypeValueUnit
6-[7-methoxy-6-(1-methylpyrazol-4-yl)imidazo[1,2-a]pyridin-3-yl]-N-pyrrolidin-3-ylpyridin-2-amine1894563: Binding affinity to FLT3-ITD-D835V mutant (unknown origin) assessed as dissociation constantkd<0.0001uM
1-(5-tert-butyl-1,2-oxazol-3-yl)-3-[3-fluoro-4-(1H-imidazo[4,5-b]pyridin-7-yloxy)phenyl]urea1696916: Inhibition of FLT3 ITD mutant (unknown origin) expressed in mouse BaF3 cellsic50<0.0001uM
2-[3-[6-[[(3S,4S)-4-fluoropiperidin-3-yl]amino]-2-pyridinyl]-7-methoxyimidazo[1,2-a]pyridin-6-yl]propan-2-ol2205385: Binding affinity to FLT3 D835V mutant (unknown origin) expressed in Escherichia coli BL21 assessed as dissociation constant by DiscoverX KINOMEscan assaykd<0.0001uM
6-(6-cyclopropyl-7-methoxyimidazo[1,2-a]pyridin-3-yl)-N-[(3S,4S)-4-fluoropyrrolidin-3-yl]pyridin-2-amine2205370: Inhibition of NanoLuc-fused FLT3 ITD/D835Y mutant (unknown origin) transfected in HEK293 cells incubated for 1 hr by NanoBRET assayic50<0.0001uM
2-[(E)-[2-(2-hydroxy-1H-indol-3-yl)indol-3-ylidene]amino]oxy-1-piperazin-1-ylethanone;hydrochloride1868178: Binding affinity to FLT3 ITD/F691L double mutant (unknown origin) by KINOMEscan assaykd<0.0001uM
N-[(5-methyl-1H-imidazol-2-yl)methyl]-4-(8,9,10,11-tetrahydro-3H-pyrazolo[4,5-a]phenanthridin-7-yl)benzamide2003941: Inhibition of FLT3 D835Y mutant (unknown origin)ic50<0.0001uM
1-[2-[5-[(3-methyloxetan-3-yl)methoxy]benzimidazol-1-yl]quinolin-8-yl]piperidin-4-amine1562814: Inhibition of FLT3 D835Y mutant (unknown origin)ic500.0001uM
5-chloro-3-[1-(2-methyl-5-nitrophenyl)sulfonylpyrrol-3-yl]pyrazolo[1,5-a]pyrimidine1245695: Inhibition of FLT3 (unknown origin) using biotin-Glu-Gly-Pro-Trp-Leu-Glu-Glu-Glu-Glu-Glu-Ala-Tyr-Gly-Trp-Met-Asp-Phe-NH2 as substrate after 90 mins by luminescence assayic500.0001uM
1-(5-tert-butyl-1,2-oxazol-3-yl)-3-[4-(6,7-dimethoxyquinolin-4-yl)oxy-3-fluorophenyl]urea1696916: Inhibition of FLT3 ITD mutant (unknown origin) expressed in mouse BaF3 cellsic500.0001uM
N-[6-(4-ethylpiperazin-1-yl)-2-methylpyrimidin-4-yl]-5-pyridin-4-yl-1,3-thiazol-2-amine;hydrochloride1581288: Inhibition of wild type FLT3 (unknown origin) expressed in HEK293T cells assessed as decrease in FLT3 phosphorylation at 0.1 to 1000 nM after 1 hr by Western blot analysisic500.0001uM
4-[(6-ethylthieno[2,3-d]pyrimidin-4-yl)amino]-N-[4-[(4-methylpiperazin-1-yl)methyl]phenyl]-1H-pyrazole-5-carboxamide1489804: Inhibition of human FLT3 using EAIYAAPFAKKK as substrate preincubated for 20 mins followed by [gamma-33P]-ATP addition measure after 120 mins by filter binding methodic500.0001uM
N-[4-(diethylaminomethyl)phenyl]-4-(7H-pyrrolo[2,3-d]pyrimidin-4-ylamino)-1H-pyrazole-5-carboxamide1489804: Inhibition of human FLT3 using EAIYAAPFAKKK as substrate preincubated for 20 mins followed by [gamma-33P]-ATP addition measure after 120 mins by filter binding methodic500.0001uM
4-[3-[(E)-2-[3-fluoro-4-(morpholin-4-ylmethyl)phenyl]ethenyl]-1H-indazol-6-yl]pyrimidin-2-amine2279207: Inhibition of His-tagged human recombinant FLT3 catalytic domain (564 to 958 residues) expressed in insect cells using ATP as substrate incubated for 60 mins by LanthaScreen analysisic500.0001uM
4-[3-[(E)-2-(4-morpholin-4-ylphenyl)ethenyl]-1H-indazol-6-yl]pyridin-2-amine2279207: Inhibition of His-tagged human recombinant FLT3 catalytic domain (564 to 958 residues) expressed in insect cells using ATP as substrate incubated for 60 mins by LanthaScreen analysisic500.0001uM
4-[3-[(E)-2-[4-(4-methylpiperazin-1-yl)phenyl]ethenyl]-1H-indazol-6-yl]pyridin-2-amine2279207: Inhibition of His-tagged human recombinant FLT3 catalytic domain (564 to 958 residues) expressed in insect cells using ATP as substrate incubated for 60 mins by LanthaScreen analysisic500.0001uM
4-[3-[(E)-2-[4-[(4-methylpiperazin-1-yl)methyl]phenyl]ethenyl]-1H-indazol-6-yl]pyridin-2-amine2279207: Inhibition of His-tagged human recombinant FLT3 catalytic domain (564 to 958 residues) expressed in insect cells using ATP as substrate incubated for 60 mins by LanthaScreen analysisic500.0001uM
4-[3-[(E)-2-[3-fluoro-4-(morpholin-4-ylmethyl)phenyl]ethenyl]-1H-indazol-6-yl]pyridin-2-amine2279207: Inhibition of His-tagged human recombinant FLT3 catalytic domain (564 to 958 residues) expressed in insect cells using ATP as substrate incubated for 60 mins by LanthaScreen analysisic500.0001uM
N-[(2S,4S,6R)-2,6-dimethyl-16-oxo-29-oxa-1,7,17-triazaoctacyclo[12.12.2.12,6.07,28.08,13.015,19.020,27.021,26]nonacosa-8,10,12,14,19,21,23,25,27-nonaen-4-yl]-N-methylbenzamide1691299: Inhibition of human FLT3 D835Y mutant EAIYAAPFAKKK peptide as substrate in presence of 33P-gamma ATP by hotspot kinase assayic500.0001uM
1-[4-[3-[[4-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-2-yl]amino]phenyl]-1,4-diazepan-1-yl]ethanone1756404: Inhibition of FLT3 ITD mutant (unknown origin) using Glu/Tyr peptide substrate incubated for 120 mins measured after 40 mins incubation under dark by ADP-glo based luminescence assayki0.0001uM
1-[4-[4-[[4-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-2-yl]amino]phenyl]piperazin-1-yl]ethanone1756404: Inhibition of FLT3 ITD mutant (unknown origin) using Glu/Tyr peptide substrate incubated for 120 mins measured after 40 mins incubation under dark by ADP-glo based luminescence assayki0.0001uM
3-(6-morpholin-4-yl-1H-benzimidazol-2-yl)-N-[(3R)-pyrrolidin-3-yl]-1H-indazole-5-carboxamide2143345: Inhibition of recombinant wild type FLT3 kinase domain (unknown origin) using peptide substrate incubated for for 30 mins by HTRF assayic500.0001uM
(4-aminopiperidin-1-yl)-[3-(6-morpholin-4-yl-1H-benzimidazol-2-yl)-1H-indazol-5-yl]methanone2143345: Inhibition of recombinant wild type FLT3 kinase domain (unknown origin) using peptide substrate incubated for for 30 mins by HTRF assayic500.0001uM
N-(3-aminopropyl)-3-(6-morpholin-4-yl-1H-benzimidazol-2-yl)-1H-indazole-5-carboxamide2143345: Inhibition of recombinant wild type FLT3 kinase domain (unknown origin) using peptide substrate incubated for for 30 mins by HTRF assayic500.0001uM
N-[(1S,3S)-3-aminocyclopentyl]-3-(6-morpholin-4-yl-1H-benzimidazol-2-yl)-1H-indazole-5-carboxamide2143345: Inhibition of recombinant wild type FLT3 kinase domain (unknown origin) using peptide substrate incubated for for 30 mins by HTRF assayic500.0001uM
N-(3-aminopropyl)-3-(6-piperidin-1-yl-1H-benzimidazol-2-yl)-1H-indazole-5-carboxamide2143345: Inhibition of recombinant wild type FLT3 kinase domain (unknown origin) using peptide substrate incubated for for 30 mins by HTRF assayic500.0001uM
N-[(1S,3R)-3-aminocyclopentyl]-3-(6-morpholin-4-yl-1H-benzimidazol-2-yl)-1H-indazole-5-carboxamide2143345: Inhibition of recombinant wild type FLT3 kinase domain (unknown origin) using peptide substrate incubated for for 30 mins by HTRF assayic500.0001uM
N-[(1S,3S)-3-aminocyclopentyl]-3-(6-methoxy-1H-benzimidazol-2-yl)-1H-indazole-5-carboxamide2143349: Inhibition of recombinant FLT3 D835Y mutant (unknown origin) using peptide substrate incubated for for 30 mins by HTRF assayic500.0001uM
3-(6-morpholin-4-yl-1H-benzimidazol-2-yl)-N-[[(3S)-pyrrolidin-3-yl]methyl]-1H-indazole-5-carboxamide2143345: Inhibition of recombinant wild type FLT3 kinase domain (unknown origin) using peptide substrate incubated for for 30 mins by HTRF assayic500.0001uM
N-[3-(dimethylamino)propyl]-3-(6-morpholin-4-yl-1H-benzimidazol-2-yl)-1H-indazole-5-carboxamide2143345: Inhibition of recombinant wild type FLT3 kinase domain (unknown origin) using peptide substrate incubated for for 30 mins by HTRF assayic500.0001uM
3-(6-morpholin-4-yl-1H-benzimidazol-2-yl)-N-[[(3R)-pyrrolidin-3-yl]methyl]-1H-indazole-5-carboxamide2143345: Inhibition of recombinant wild type FLT3 kinase domain (unknown origin) using peptide substrate incubated for for 30 mins by HTRF assayic500.0001uM
N-(4-aminocyclohexyl)-3-(6-morpholin-4-yl-1H-benzimidazol-2-yl)-1H-indazole-5-carboxamide2143345: Inhibition of recombinant wild type FLT3 kinase domain (unknown origin) using peptide substrate incubated for for 30 mins by HTRF assayic500.0001uM
piperazin-1-yl-[4-[(E)-2-(6-pyridin-4-yl-1H-indazol-3-yl)ethenyl]phenyl]methanone2279207: Inhibition of His-tagged human recombinant FLT3 catalytic domain (564 to 958 residues) expressed in insect cells using ATP as substrate incubated for 60 mins by LanthaScreen analysisic500.0001uM
[4-[(E)-2-[6-(2-amino-4-pyridinyl)-1H-indazol-3-yl]ethenyl]phenyl]-morpholin-4-ylmethanone2279207: Inhibition of His-tagged human recombinant FLT3 catalytic domain (564 to 958 residues) expressed in insect cells using ATP as substrate incubated for 60 mins by LanthaScreen analysisic500.0001uM
3-N-[4-(4-morpholin-4-ylcyclohexyl)phenyl]-1-pyridin-2-yl-1,2,4-triazole-3,5-diamine649408: Inhibition of human recombinant FLT3 by radiometric assayki0.0002uM
N-[(E)-(5-cyanopyrazolo[1,5-a]pyrimidin-3-yl)methylideneamino]-N,2-dimethyl-5-nitrobenzenesulfonamide1245695: Inhibition of FLT3 (unknown origin) using biotin-Glu-Gly-Pro-Trp-Leu-Glu-Glu-Glu-Glu-Glu-Ala-Tyr-Gly-Trp-Met-Asp-Phe-NH2 as substrate after 90 mins by luminescence assayic500.0002uM
N-[2-(5-chloropyrazolo[1,5-a]pyrimidin-3-yl)ethyl]-2-methyl-5-nitrobenzenesulfonamide1245695: Inhibition of FLT3 (unknown origin) using biotin-Glu-Gly-Pro-Trp-Leu-Glu-Glu-Glu-Glu-Glu-Ala-Tyr-Gly-Trp-Met-Asp-Phe-NH2 as substrate after 90 mins by luminescence assayic500.0002uM
N-[2-(5-chloropyrazolo[1,5-a]pyrimidin-3-yl)ethyl]-5-cyano-N,2-dimethylbenzenesulfonamide1245695: Inhibition of FLT3 (unknown origin) using biotin-Glu-Gly-Pro-Trp-Leu-Glu-Glu-Glu-Glu-Glu-Ala-Tyr-Gly-Trp-Met-Asp-Phe-NH2 as substrate after 90 mins by luminescence assayic500.0002uM
4-[3-[(E)-2-[4-(morpholin-4-ylmethyl)phenyl]ethenyl]-1H-indazol-6-yl]pyridin-2-amine2279207: Inhibition of His-tagged human recombinant FLT3 catalytic domain (564 to 958 residues) expressed in insect cells using ATP as substrate incubated for 60 mins by LanthaScreen analysisic500.0002uM
4-[(2-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)amino]-N-(4-piperazin-1-ylphenyl)-1H-pyrazole-5-carboxamide1360758: Inhibition of human FLT3 by Hotspot assayic500.0002uM
2-[4-(4-acetylpiperazin-1-yl)anilino]-4-(1H-indazol-3-yl)pyrimidine-5-carbonitrile1756404: Inhibition of FLT3 ITD mutant (unknown origin) using Glu/Tyr peptide substrate incubated for 120 mins measured after 40 mins incubation under dark by ADP-glo based luminescence assayki0.0002uM
2-[(E)-[2-(2-hydroxy-1H-indol-3-yl)indol-3-ylidene]amino]oxy-N-[(3S)-pyrrolidin-3-yl]acetamide;hydrochloride1868174: Inhibition of human recombinant His-tagged FLT3/D835Y mutant expressed in baculovirus expression system incubated for 30 mins in presence of ATP by HTRF analysisic500.0002uM
2-[(E)-[2-(5-chloro-2-hydroxy-1H-indol-3-yl)indol-3-ylidene]amino]oxy-1-piperazin-1-ylethanone;hydrochloride1868174: Inhibition of human recombinant His-tagged FLT3/D835Y mutant expressed in baculovirus expression system incubated for 30 mins in presence of ATP by HTRF analysisic500.0002uM
2-[(E)-[2-(2-hydroxy-1H-indol-3-yl)indol-3-ylidene]amino]oxy-N-[(3R)-pyrrolidin-3-yl]acetamide;hydrochloride1868174: Inhibition of human recombinant His-tagged FLT3/D835Y mutant expressed in baculovirus expression system incubated for 30 mins in presence of ATP by HTRF analysisic500.0002uM
2-[(E)-[2-(5-fluoro-2-hydroxy-1H-indol-3-yl)indol-3-ylidene]amino]oxy-1-piperazin-1-ylethanone;hydrochloride1868174: Inhibition of human recombinant His-tagged FLT3/D835Y mutant expressed in baculovirus expression system incubated for 30 mins in presence of ATP by HTRF analysisic500.0002uM
2-[(E)-[2-(5-bromo-2-hydroxy-1H-indol-3-yl)indol-3-ylidene]amino]oxy-1-piperazin-1-ylethanone;hydrochloride1868174: Inhibition of human recombinant His-tagged FLT3/D835Y mutant expressed in baculovirus expression system incubated for 30 mins in presence of ATP by HTRF analysisic500.0002uM
N-[(1S,3S)-3-aminocyclopentyl]-3-[6-(furan-3-yl)-1H-benzimidazol-2-yl]-1H-indazole-5-carboxamide2143349: Inhibition of recombinant FLT3 D835Y mutant (unknown origin) using peptide substrate incubated for for 30 mins by HTRF assayic500.0002uM
2-[7-methoxy-3-[6-[[(3R)-piperidin-3-yl]amino]-2-pyridinyl]imidazo[1,2-a]pyridin-6-yl]propan-2-ol2205383: Binding affinity to FLT3 (unknown origin) expressed in Escherichia coli BL21 assessed as dissociation constant by DiscoverX KINOMEscan assaykd0.0002uM
3-(6-morpholin-4-yl-1H-benzimidazol-2-yl)-N-(piperidin-3-ylmethyl)-1H-indazole-5-carboxamide2143345: Inhibition of recombinant wild type FLT3 kinase domain (unknown origin) using peptide substrate incubated for for 30 mins by HTRF assayic500.0002uM
N-(3-aminopropyl)-3-(6-pyrrolidin-1-yl-1H-benzimidazol-2-yl)-1H-indazole-5-carboxamide2143345: Inhibition of recombinant wild type FLT3 kinase domain (unknown origin) using peptide substrate incubated for for 30 mins by HTRF assayic500.0002uM
N-(3-amino-2-methylpropyl)-3-(6-morpholin-4-yl-1H-benzimidazol-2-yl)-1H-indazole-5-carboxamide2143345: Inhibition of recombinant wild type FLT3 kinase domain (unknown origin) using peptide substrate incubated for for 30 mins by HTRF assayic500.0002uM

CTD chemical–gene interactions

58 total (human), top 30 by PubMed support.

ChemicalActions (top 5)PubMed papers
Sorafenibincreases response to substance, decreases reaction, increases phosphorylation, decreases activity, decreases phosphorylation5
ponatinibdecreases activity, decreases reaction, increases phosphorylation, decreases phosphorylation4
Arsenic Trioxideincreases expression, affects binding, increases reaction, decreases phosphorylation, increases degradation (+1 more)3
Benzo(a)pyreneaffects methylation, decreases expression, increases methylation3
sodium arseniteincreases expression, increases phosphorylation2
Semaxinibdecreases activity2
Tretinoinaffects cotreatment, decreases expression, increases reaction, increases response to substance2
2-hydroxy-1-(2-((9-(4-methylcyclohexyl)-9H-pyrido(4’,3’-4,5)pyrrolo(2,3-d)pyrimidin-2-yl)amino)-7,8-dihydro-1,6-naphthyridin-6(5H)-yl)ethanonedecreases phosphorylation1
pexidartinibdecreases activity1
RGFP966affects reaction, decreases expression, decreases phosphorylation1
bisphenol Faffects cotreatment, increases methylation1
S63845decreases expression, increases reaction1
parthenolidedecreases expression, increases reaction1
fulvic acidaffects cotreatment, decreases reaction, increases expression1
bisphenol Aincreases expression1
ethyl-p-hydroxybenzoatedecreases expression1
terbufosincreases methylation1
benzo(e)pyreneincreases methylation1
celastroldecreases expression1
bafilomycin Aincreases expression, increases degradation, decreases reaction1
midostaurindecreases response to substance, decreases activity1
romidepsindecreases phosphorylation, increases reaction1
gedunindecreases expression1
tanespimycindecreases expression1
SU 5614decreases activity1
D-65476affects cotreatment, decreases expression, increases reaction1
THRX 165724decreases phosphorylation1
NSC 23766affects response to substance1
palbociclibaffects response to substance, decreases expression, decreases phosphorylation1
5-((5-fluoro-2-oxo-1,2-dihydro-3H-indol-3-ylidene)methyl)-N-(2-hydroxy-3-morpholin-4-ylpropyl)-2,4-dimethyl-1H-pyrrole-3-carboxamidedecreases phosphorylation1

ChEMBL screening assays

3132 unique, capped per target: 3096 binding, 24 functional, 8 admet, 4 toxicity

Representative assays (with source publication via chembl_document):

Assay IDTypeDescriptionSource paper
CHEMBL1003890BindingInhibition of Flt3Discovery of pyrrolopyridine-pyridone based inhibitors of Met kinase: synthesis, X-ray crystallographic analysis, and biological activities. — *J Med Chem*
CHEMBL1963779FunctionalPUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: FLT3PubChem BioAssay data set
CHEMBL3826089ADMETInhibition of FLT3 (unknown origin)Discovery of a potent and highly selective transforming growth factor β receptor-associated kinase 1 (TAK1) inhibitor by structure based drug design (SBDD). — *Bioorg Med Chem*

Cellosaurus cell lines

194 cell lines: 148 cancer cell line, 39 factor-dependent cell line, 4 embryonic stem cell, 2 spontaneously immortalized cell line, 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

CellosaurusNameCategorySex
CVCL_0064MV4-11Cancer cell lineMale
CVCL_0138ACH-2Cancer cell lineFemale
CVCL_0207CCRF-CEMCancer cell lineFemale
CVCL_0614Kasumi-6Cancer cell lineMale
CVCL_0R18CEM-TART clone 1A2Cancer cell lineFemale
CVCL_0U11CEM/MX1Cancer cell lineFemale
CVCL_1150CTV-1Cancer cell lineMale
CVCL_1B35CEM/VM-1Cancer cell lineFemale
CVCL_1E04Rev-CEMCancer cell lineFemale
CVCL_1G53CEM-GFPCancer cell lineFemale

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

showing 60 of 300 trials:

NCTPhaseStatusTitle
NCT00199147Phase 4UNKNOWNEfficacy of G-CSF-Priming in Elderly AML Patients
NCT00304447Phase 4COMPLETEDStudy Evaluating the Effect of Corticosteroids on Mylotarg® Infusion-Related Adverse Events in Patients With Leukemia
NCT00464217Phase 4COMPLETEDTreatment of the Acute Myeloblastic Leukaemia in Patients Over 65 Years
NCT00487448Phase 4COMPLETEDSMD_FLAG-IDA_98: FLAG-IDA in Induction Treatment of High Risk Myelodysplastic Syndromes or Secondary Acute Myeloblastic Leukemia
NCT00488709Phase 4COMPLETEDFludarabine, Cytarabine, Topotecan in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia
NCT00686543Phase 4COMPLETEDOral Posaconazole in High Risk Patients With Gastrointestinal Dysfunction (Study P05115)
NCT01041040Phase 4COMPLETEDLAM07: Study to Analyze the Efficacy of a Risk Adapted Treatment Strategy, Including Gemtuzumab Ozogamicin (GO) During Consolidation, for Patients With Acute Myeloid Leukemia (AML)
NCT01198054Phase 4TERMINATEDLENA-LMA-5:Lenalidomide in Acute Myeloid Leukemia (AML)
NCT01200355Phase 4COMPLETEDPosaconazole Versus Micafungin for Prophylaxis Against Invasive Fungal Infections During Neutropenia in Patients Undergoing Chemotherapy for Acute Myelogenous Leukemia, Acute Lymphocytic Leukemia or Myelodysplastic Syndrome
NCT01347996Phase 4COMPLETEDMaintenance Therapy With Ceplene® (Histamine) and IL-2 on Immune Response and MRD in Acute Myeloid Leukemia
NCT01587430Phase 4UNKNOWN3 Anthracyclines, 2 Types of Consolidation With Different ARA-C Doses and Maintenance in Adult Acute Myeloid Leukemia
NCT01819792Phase 4COMPLETEDRespiratory Viral Infections During Acute Myeloid Leukemia (AML)Chemotherapy Related Aplasia
NCT02024308Phase 4UNKNOWNAML1-ETO Acute Myeloid Leukemia With Fludarabine and Cytarabine Chemotherapy
NCT02027064Phase 4UNKNOWNInterferon for the Intervention of Molecular Relapse in t (8; 21) AML After Allo-HSCT
NCT02277847Phase 4UNKNOWNIdarubicin at Different Dosages as Induction Therapy for Newly Diagnosed Acute Myeloid Leukaemia
NCT02386800Phase 4ACTIVE_NOT_RECRUITINGCINC424A2X01B Rollover Protocol
NCT02926586Phase 4COMPLETEDFludarabine and Cytarabine Versus High-dose Cytarabine for CBF-AML
NCT02933333Phase 4UNKNOWNG-CSF Alone or Combination With GM-CSF on Prevention and Treatment of Infection in Children With Malignant Tumor
NCT03026842Phase 4UNKNOWNDecitabine Versus Conventional Chemotherapy for Maintenance Therapy of Acute Myeloid Leukemia With t(8;21)
NCT03150134Phase 4UNKNOWNEarly Tapering of Immunosuppressive Agents to Immunomodulation to Improve Survival of AML Patients
NCT05144243Phase 4ACTIVE_NOT_RECRUITINGStudy to Assess Adverse Events and Change in Disease State of Oral Venetoclax in Combination With Subcutaneous (SC) Azacitidine in Newly Diagnosed Adult Participants With Acute Myeloid Leukemia (AML) Who Are Ineligible for Intensive Chemotherapy in China
NCT06370000Phase 4RECRUITINGOral Azacitidine in Transplant-Eligible Patients With Acute Myeloid Leukemia (AML) Suffering From Health-Inequality
NCT06571825Phase 4RECRUITINGRIC Allo-HSCT vs. Venetoclax-Based Consolidation in Elderly AML Patients After First CR
NCT07016165Phase 4RECRUITINGCiprofloxacin vs Ceftazidime for Empirical Treatment of High-Risk Neutropenic Fever in Children With Hematologic Malignancies
NCT07044687Phase 4RECRUITINGStudy to Assess Adverse Events and Change in Disease Activity of Oral Venetoclax in Combination With Subcutaneous (SC) or Intravenous (IV) Azacitidine in Newly Diagnosed Adult Participants With Acute Myeloid Leukemia (AML) Who Are Ineligible for Standard Induction Therapy in India
NCT07486713Phase 4RECRUITINGOlutasidenib DDI Study in Patients With IDH1 Mutation Positive Malignancies
NCT07561892Phase 4RECRUITINGStudy of the Effectiveness and Safety of Daunorubicin /Idarubicin ± Silibinin in Treating Newly Diagnosed AML (Non-M3).
NCT07773909Phase 4COMPLETEDVenetoclax With Hypomethylating Agents in Newly Diagnosed AML Unfit for Intensive Chemotherapy
NCT00000589Phase 3COMPLETEDTrial to Reduce Alloimmunization to Platelets (TRAP)
NCT00044486Phase 3COMPLETEDProphylaxis Trial of Posaconazole Versus Standard Azole Therapy for Neutropenic Patients (Study P01899)
NCT00093990Phase 3COMPLETEDTipifarnib Versus Best Supportive Care in the Treatment of Newly Diagnosed Acute Myeloid Leukemia (AML)
NCT00125606Phase 3TERMINATEDPhase 3 Trial for AML Patients in CR2 Comparing 8Gy TBI /Fludarabine to Conditioning With TBI 12Gy/Cyclophosphamide
NCT00136084Phase 3COMPLETEDTreatment of Patients With Newly Diagnosed Acute Myeloid Leukemia or Myelodysplasia
NCT00146120Phase 3COMPLETEDRisk-Adapted Therapy of Acute Myeloid Leukemia of Adults (18-60 Years) According to the Cytogenetic Result
NCT00150878Phase 3TERMINATEDStandard vs. Reduced-Intensity Conditioning in Patients With Acute Myeloid Leukemia in First Remission
NCT00151255Phase 3COMPLETEDAll-Trans Retinoic Acid in Combination With Standard Induction and Consolidation Therapy in Older Patients With Newly Diagnosed Acute Myeloid Leukemia
NCT00152139Phase 3COMPLETEDStem Cell Transplantation for Patients With Hematologic Malignancies
NCT00152594Phase 3TERMINATEDVoriconazole or Placebo in the Prophylaxis of Lung Infiltrates in Patients Undergoing Induction Chemotherapy for Acute Myelogenous Leukemia
NCT00186966Phase 3COMPLETEDTreatment of Children and Adolescents With Refractory or Relapsed Acute Myeloid Leukemia
NCT00226512Phase 3WITHDRAWNTo Determine the Role of Adding Campath-1H or ATG Given In-vivo in Addition to Fludarabine and Low Dose Busulfex on Outcome in Patients Treated With Reduced Intensity Conditioning
NCT00260832Phase 3COMPLETEDTrial of Decitabine in Patients With Acute Myeloid Leukemia
NCT00266136Phase 3COMPLETEDBiology and Treatment Strategy of AML in Its Subgroups: Multicenter Randomized Trial by the German Acute Myeloid Leukemia Cooperative Group (AMLCG)
NCT00317642Phase 3COMPLETEDA Study of Clofarabine and Cytarabine for Older Patients With Relapsed or Refractory Acute Myelogenous Leukemia (AML)(CLASSIC I)
NCT00322101Phase 3COMPLETEDLow-Dose or High-Dose Conditioning Followed by Peripheral Blood Stem Cell Transplant in Treating Patients With Myelodysplastic Syndrome or Acute Myelogenous Leukemia
NCT00363025Phase 3TERMINATEDA Randomized Study of Post-Remission Therapy in Elderly Patients With Acute Myelogenous Leukemia.
NCT00406393Phase 3COMPLETEDSirolimus/Tacrolimus Versus Tacrolimus/Methotrexate for Preventing Graft-Versus-Host Disease (GVHD) (BMT CTN 0402)
NCT00412360Phase 3COMPLETEDSingle vs Double Umbilical Cord Blood Transplants in Children With High Risk Leukemia and Myelodysplasia (BMT CTN 0501)
NCT00428558Phase 3COMPLETEDTimed-Sequential Induction in CBF-AML
NCT00469144Phase 3COMPLETEDIV Busulfan With Allo-BMT: Study for Patients With Acute Myelogenous Leukemia and Myelodysplastic Syndrome
NCT00474006Phase 3COMPLETEDHigh Dose Daunorubicin Vs. Standard Dose Daunorubicin in Induction Treatment of AML
NCT00476541Phase 3COMPLETEDNOPHO-AML 2004 Study for Children With Acute Myeloid Leukemia
NCT00480064Phase 3COMPLETEDLomustine and Intermediate Dose Cytarabine in Older Patients With AML
NCT00495287Phase 3COMPLETEDA Remission Induction Therapy and Risk-oriented Postremission Strategy for Adult Acute Myelogenous Leukemia (AML)
NCT00513305Phase 3TERMINATEDCytarabine in Combination With Arsenic Trioxide vs. Cytarabine Alone in Elderly Patients With Acute Myeloid Leukemia
NCT00568633Phase 3TERMINATEDAllogeneic HCT Using Nonmyeloablative Host Conditioning With TLI & ATG vs SOC in AML
NCT00589082Phase 3COMPLETEDDaunoXome + Ara-C vs Daunorubicin + Ara-C in Elderly AML
NCT00590837Phase 3COMPLETEDAdding Lomustine to Chemotherapy in Older Patients With Acute Myelogenous Leukemia (AML), and Allogeneic Transplantation for Patients From 60 to 65 Years Old
NCT00606723Phase 3COMPLETEDAllogenic Stem Cell Transplantation for Children, Adolescents and Young Adults With Relapsed or Refractory AML
NCT00656448Phase 3COMPLETEDA Randomized Trial of Procrit vs. No Procrit in AML and High Risk MDS
NCT00678275Phase 3COMPLETEDChronic Graft-versus-host Disease (cGvHD) Prophylaxis With or Without ATG Prior to Stem Cell Transplantation (SCT) From HLA-identical Siblings in Patients With Acute Leukemia

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for FLT3 across ~30M SureChEMBL compounds — explore on Sugi Predict.