FLT3 | GeneID:2322 | Homo sapiens

Gene Summary

[ - ] NCBI Entrez Gene

Gene ID 2322 Official Symbol FLT3
Locus RP11-153M24.3 Gene Type protein-coding
Synonyms CD135; FLK2; STK1
Full Name fms-related tyrosine kinase 3
Description fms-related tyrosine kinase 3
Chromosome 13q12
Also Known As CD135 antigen; FL cytokine receptor; FLT3 receptor tyrosine kinase; OTTHUMP00000042340; fetal liver kinase 2; growth factor receptor tyrosine kinase type III; stem cell tyrosine kinase 1; tyrosine-protein kinase receptor FLT3
Summary This gene encodes a class III receptor tyrosine kinase that regulates hematopoiesis. The receptor consists of an extracellular domain composed of five immunoglobulin-like domains, one transmembrane region, and a cytoplasmic kinase domain split into two parts by a kinase-insert domain. The receptor is activated by binding of the fms-related tyrosine kinase 3 ligand to the extracellular domain, which induces homodimer formation in the plasma membrane leading to autophosphorylation of the receptor. The activated receptor kinase subsequently phosphorylates and activates multiple cytoplasmic effector molecules in pathways involved in apoptosis, proliferation, and differentiation of hematopoietic cells in bone marrow. Mutations that result in the constitutive activation of this receptor result in acute myeloid leukemia and acute lymphoblastic leukemia. [provided by RefSeq]

Orthologs and Paralogs

[ - ] Homologs - NCBI's HomoloGene Group: 3040

ID Symbol Protein Species
GeneID:2322 FLT3 NP_004110.2 Homo sapiens
GeneID:14255 Flt3 NP_034359.2 Mus musculus
GeneID:140635 Flt3 XP_221874.4 Rattus norvegicus
GeneID:452508 FLT3 XP_509601.2 Pan troglodytes
GeneID:486025 FLT3 NP_001018647.1 Canis lupus familiaris
GeneID:512700 FLT3 XP_590263.3 Bos taurus
GeneID:566708 LOC566708 XP_001921760.1 Danio rerio

Antibodies

[ - ] Monoclonal and Polyclonal Antibodies

No. Provider Product No. Description
1 abcam ab23895 Flt3 / CD135 antibody [BV10A4H2] (Phycoerythrin) (ab23895); Mouse monoclonal [BV10A4H2] to Flt3 / CD135 (Phycoerythrin)
2 abcam ab33085 Flt3 / CD135 antibody (ab33085); Rabbit polyclonal to Flt3 / CD135
3 abcam ab33092 Flt3 / CD135 antibody (ab33092); Rabbit polyclonal to Flt3 / CD135
4 abcam ab18370 Flt3 / CD135 antibody [BV10A4H2] (ab18370); Mouse monoclonal [BV10A4H2] to Flt3 / CD135
5 abcam ab37847 Flt3 / CD135 antibody - Aminoterminal end (ab37847); Rabbit polyclonal to Flt3 / CD135 - Aminoterminal end
6 abgent AP7644a FLT3 Antibody (N-term); Purified Rabbit Polyclonal Antibody (Pab)
7 abgent AP7644b FLT3 Antibody (C-term); Purified Rabbit Polyclonal Antibody (Pab)
8 abnova H00002322-M01A FLT3 monoclonal antibody (M01A), clone 1A11; Mouse monoclonal antibody raised against a partial recombinant FLT3.
9 acris AP09468PU-N CD135 / FLT3; antibody Ab
10 acris SM1207R CD135 / FLT3; antibody Ab
11 acris AP09468PU-S CD135 / FLT3; antibody Ab
12 acris SM1207P CD135 / FLT3; antibody Ab
13 acris AP14352PU-N CD135 / FLT3 (N-term); antibody Ab
14 acris AP14353PU-N CD135 / FLT3 (C-term); antibody Ab
15 acris AP07015PU-N CD135 / FLT3; antibody Ab
16 acris BM2462 CD135 / FLT3; antibody Ab
17 scbt FLT3 FLT3 Antibody / FLT3 Antibodies;
18 sigma F0550 Anti-Flt-3 antibody produced in goat ;

Exon, Intron and UTRs

Exon, Intron and UTRs of FLT3 Gene Transcript Isoforms

CpG near TSS

CpG dinucleotides near Transcription Start Site of FLT3 Gene

Gene Classification

[ - ] Gene Ontology

IDCategoryGO Term
GO:0005887 Component integral to plasma membrane
GO:0016020 Component membrane
GO:0005524 Function ATP binding
GO:0000166 Function nucleotide binding
GO:0004872 Function receptor activity
GO:0016740 Function transferase activity
GO:0005021 Function vascular endothelial growth factor receptor activity
GO:0030097 Process hemopoiesis
GO:0008284 Process positive regulation of cell proliferation
GO:0006468 Process protein amino acid phosphorylation
GO:0007169 Process transmembrane receptor protein tyrosine kinase signaling pathway

RefSeq Isoforms

[ - ] RefSeq Annotation and UniProt Database

No. RefSeq RNA RefSeq Protein UniProt Equivalent
1 NM_004119  UCSC Browser NP_004110

Transcript Sequences

[ - ] Transcript Accession Number Cloud [ GenBank ]

AW057705   BC036028   BC126350   BC144039   BC144040   BI461248   L36162   NM_004119   U02687   Z26652  

Protein Sequences

[ - ] Protein Accession Number Cloud [ GenPept ]

Mutations and SNPs

[ - ] NCBI's dbSNP

[ - ] Somatic Mutations in Cancer - Sanger's COSMIC

The mutation data was obtained from the Sanger Institute Catalogue Of Somatic Mutations In Cancer web site, http://www.sanger.ac.uk/cosmic Bamford et al (2004) The COSMIC (Catalogue of Somatic Mutations in Cancer) database and website. Br J Cancer, 91,355-358.
Mutation (top 10)Total Observations
c.?_?ins?3761
c.?395
c.2503G>T120
c.2504A>T35
c.2503_2505GAT>?23
c.2503G>C20
c.2506_2508delATC9
c.2508C>G5
c.2503G>A4
c.1800_1801ins214
Primary Site / Histology (Top 10)Mutations (sites * observations)
haematopoietic and lymphoid tissue / haematopoietic neoplasm4472
haematopoietic and lymphoid tissue / lymphoid neoplasm48
lung / carcinoma1

Phenotypes

[ - ] Genes and Diseases - MIM at NCBI

Chemicals and Drugs

[ - ] Comparative Toxicogenomics Database from MDI Biological Lab

Curated [chemical–gene interactions|chemical–disease|gene–disease] data were retrieved from the Comparative Toxicogenomics Database (CTD), Mount Desert Island Biological Laboratory, Salisbury Cove, Maine. World Wide Web (URL: http://ctd.mdibl.org/). [Jan. 2009].
Chemical and Interaction
17-(allylamino)-17-demethoxygeldanamycin
  • 17-(allylamino)-17-demethoxygeldanamycin results in decreased expression of FLT3 protein
17010675
2-Acetylaminofluorene
  • 2-Acetylaminofluorene affects the expression of FLT3 mRNA
18031378
Acetaminophen
  • Acetaminophen affects the expression of FLT3 mRNA
17562736
D-65476
  • FLT3 gene mutant form promotes the reaction [[D-65476 co-treated with Tretinoin] results in decreased expression of BIRC5 mRNA]
  • FLT3 gene mutant form promotes the reaction [[D-65476 co-treated with Tretinoin] results in decreased expression of BIRC5 protein]
16473406
gedunin
  • gedunin results in decreased expression of FLT3 protein
17010675
SU 11657
  • SU 11657 results in decreased activity of FLT3 protein
17184839
SU 5614
  • SU 5614 results in decreased activity of FLT3 protein
16038735
Tretinoin
  • FLT3 gene mutant form promotes the reaction [[D-65476 co-treated with Tretinoin] results in decreased expression of BIRC5 mRNA]
  • FLT3 gene mutant form promotes the reaction [[D-65476 co-treated with Tretinoin] results in decreased expression of BIRC5 protein]
16473406
tripterine
  • tripterine results in decreased expression of FLT3 protein
17010675

Gene and Diseases

[ - ] Gene and Diseases [Data source: CTD]

Curated [chemical–gene interactions|chemical–disease|gene–disease] data were retrieved from the Comparative Toxicogenomics Database (CTD), Mount Desert Island Biological Laboratory, Salisbury Cove, Maine. World Wide Web (URL: http://ctd.mdibl.org/). [Jan. 2009].
Disease Name Relationship PubMed
Leukemia, Myeloid, Acute marker 17050201, 17184839
Leukemia, Promyelocytic, Acute marker 17454189
Alopecia inferred via Tretinoin 15955085
Arthritis, Experimental inferred via Tretinoin 16412693
Arthritis, Rheumatoid inferred via Tretinoin 16292516
Asthma inferred via Tretinoin 16456186
Barrett Esophagus inferred via Tretinoin 16935849
Blood Coagulation Disorders inferred via Tretinoin 16197459, 16206674
Breast Neoplasms inferred via Tretinoin 16873071, 16166294, 16443354
Bronchopulmonary Dysplasia inferred via Tretinoin 16813970
Carcinoma, Embryonal inferred via Tretinoin 16168501
Carcinoma, Squamous Cell inferred via Tretinoin 16096774, 16051514
Cataract inferred via Tretinoin 17460283
Cervical Intraepithelial Neoplasia inferred via Tretinoin 16129372
Choriocarcinoma inferred via Tretinoin 16461808
Colitis inferred via Tretinoin 17035595
Craniofacial Abnormalities inferred via Tretinoin 16925845
Endometrial Neoplasms inferred via Tretinoin 16569247
Eye Abnormalities inferred via Tretinoin 16938888
Glioblastoma inferred via Tretinoin 17312396
Head and Neck Neoplasms inferred via Tretinoin 16096774
Hearing Loss, Noise-Induced inferred via Tretinoin 16084493
Hyperalgesia inferred via Tretinoin 16870215
Hypereosinophilic Syndrome inferred via Tretinoin 16778211
Leukemia inferred via Tretinoin 17143497
Leukemia, Myeloid inferred via Tretinoin 16932348, 16482212
Leukemia, Myeloid, Acute inferred via Tretinoin 16294345
Leukemia, Promyelocytic, Acute inferred via Tretinoin 16891316, 16823087, 15748426, 17107899, 16788101, 16935935, 12679006, 16766008, 16140955, 16331271, 17294898, 17361223, 17368321, 17301526, 17339181, 17506722, 17217047
Liver Cirrhosis, Experimental inferred via Tretinoin 16248980, 18397230
Medulloblastoma inferred via Tretinoin 17453147
Melanoma inferred via Tretinoin 16752155
Meningomyelocele inferred via Tretinoin 16940565
Neoplasms inferred via Tretinoin 16946489, 16594593
Ovarian Neoplasms inferred via Tretinoin 16936753
Pain inferred via Tretinoin 16870215
Pancreatic Neoplasms inferred via Tretinoin 15976015
Pterygium inferred via Tretinoin 16723453
Rhabdomyosarcoma inferred via Tretinoin 16116481, 16283617
Skin Neoplasms inferred via Tretinoin 16467112
Stomach Neoplasms inferred via Tretinoin 17261132
Thyroid Neoplasms inferred via Tretinoin 17045167, 16026305
Tongue Neoplasms inferred via Tretinoin 16051514
Tuberculosis inferred via Tretinoin 16040207
Uterine Cervical Neoplasms inferred via Tretinoin 16129372
Uveal Neoplasms inferred via Tretinoin 16752155
Vitiligo inferred via Tretinoin 16761959
Wilms Tumor inferred via Tretinoin 16287080
Leukemia, Myeloid, Acute inferred via SU 5614 16038735
Leukemia, Promyelocytic, Acute inferred via SU 11657 17184839
Hepatitis, Toxic inferred via Acetaminophen 2444490, 16081117, 17562736, 16177239, 15968718, 16227642, 14986274, 17522070
Hyperalgesia inferred via Acetaminophen 16870215
Liver Failure, Acute inferred via Acetaminophen 16871587, 17185352
Pain inferred via Acetaminophen 16870215
Adenoma inferred via 2-Acetylaminofluorene 10737359
Carcinoma, Hepatocellular inferred via 2-Acetylaminofluorene 10737359
Liver Neoplasms inferred via 2-Acetylaminofluorene 10737359, 18001218, 14678523, 10672840, 11376686, 16273603
Lung Neoplasms inferred via 2-Acetylaminofluorene 11376686
Urinary Bladder Neoplasms inferred via 2-Acetylaminofluorene 15867355, 15289314
Colonic Neoplasms inferred via 17-(allylamino)-17-demethoxygeldanamycin 15993848
Lymphoma, Large-Cell, Anaplastic inferred via 17-(allylamino)-17-demethoxygeldanamycin 17157164

Gene Interactions

[ - ] BioGRID Gene Product Interaction Database

Symbol Interaction Binary Experiment Source
GRB2 GRB2 / FLT3 Affinity Capture-Western Zhang S (1999)
SOCS1 SOCS1 / FLT3 Affinity Capture-Western De Sepulveda P (1999)

Transcript Cluster

[ - ] NCBI's UniGene

Selected Publications

[ - ] Gene-related publications indexed at PubMed

  1. [ + ] Schneider F, et al. (2009) "NPM1 but not FLT3-ITD mutations predict early blast cell clearance and CR rate in patients with normal karyotype AML (NK-AML) or high-risk myelodysplastic syndrome (MDS)." Blood. 113(21):5250-5253. PMID:19279329
  2. [ + ] Blackford A, et al. (2009) "Genetic mutations associated with cigarette smoking in pancreatic cancer." Cancer Res. 69(8):3681-3688. PMID:19351817
  3. [ + ] Kreil S, et al. (2009) "A high-throughput candidate gene mutation screen in lymphoproliferative and myeloproliferative neoplasias." Leuk Res. 33(9):e168-e169. PMID:19464057
  4. [ + ] Vu HA, et al. (2009) "The juxtamembrane domain in ETV6/FLT3 is critical for PIM-1 up-regulation and cell proliferation." Biochem Biophys Res Commun. 383(3):308-313. PMID:19345670
  5. [ + ] Akagi T, et al. (2009) "Frequent genomic abnormalities in acute myeloid leukemia/myelodysplastic syndrome with normal karyotype." Haematologica. 94(2):213-223. PMID:19144660
  6. [ + ] Schlenk RF, et al. (2009) "Gene mutations and response to treatment with all-trans retinoic acid in elderly patients with acute myeloid leukemia. Results from the AMLSG Trial AML HD98B." Haematologica. 94(1):54-60. PMID:19059939
  7. [ + ] Seifert H, et al. (2009) "The prognostic impact of 17p (p53) deletion in 2272 adults with acute myeloid leukemia." Leukemia. 23(4):656-663. PMID:19151774
  8. [ + ] Gaidzik VI, et al. (2009) "Prognostic impact of WT1 mutations in cytogenetically normal acute myeloid leukemia: a study of the German-Austrian AML Study Group." Blood. 113(19):4505-4511. PMID:19221039
  9. [ + ] Iwanaga E, et al. (2009) "A JAK2-V617F activating mutation in addition to KIT and FLT3 mutations is associated with clinical outcome in patients with t(8;21)(q22;q22) acute myeloid leukemia." Haematologica. 94(3):433-435. PMID:19181784
  10. [ + ] Schmidt-Arras D, et al. (2009) "Anchoring of FLT3 in the endoplasmic reticulum alters signaling quality." Blood. 113(15):3568-3576. PMID:19204327
  11. [ + ] Kim DH, et al. (2009) "Genetic variants in the candidate genes of the apoptosis pathway and susceptibility to chronic myeloid leukemia." Blood. 113(11):2517-2525. PMID:19141860
  12. [ + ] Weisel KC, et al. (2009) "Regulation of FLT3 and its ligand in normal hematopoietic progenitor cells." Ann Hematol. 88(3):203-211. PMID:18797870
  13. [ + ] Breitenbuecher F, et al. (2009) "Identification of a novel type of ITD mutations located in nonjuxtamembrane domains of the FLT3 tyrosine kinase receptor." Blood. 113(17):4074-4077. PMID:18483393
  14. [ + ] Paulsson K, et al. (2008) "Mutations of FLT3, NRAS, KRAS, and PTPN11 are frequent and possibly mutually exclusive in high hyperdiploid childhood acute lymphoblastic leukemia." Genes Chromosomes Cancer. 47(1):26-33. PMID:17910045
  15. [ + ] Sallmyr A, et al. (2008) "Internal tandem duplication of FLT3 (FLT3/ITD) induces increased ROS production, DNA damage, and misrepair: implications for poor prognosis in AML." Blood. 111(6):3173-3182. PMID:18192505
  16. [ + ] Whitman SP, et al. (2008) "FLT3 D835/I836 mutations are associated with poor disease-free survival and a distinct gene-expression signature among younger adults with de novo cytogenetically normal acute myeloid leukemia lacking FLT3 internal tandem duplications." Blood. 111(3):1552-1559. PMID:17940205
  17. [ + ] Weisberg E, et al. (2008) "Potentiation of antileukemic therapies by the dual PI3K/PDK-1 inhibitor, BAG956: effects on BCR-ABL- and mutant FLT3-expressing cells." Blood. 111(7):3723-3734. PMID:18184863
  18. [ + ] Scholl S, et al. (2008) "Clinical impact of nucleophosmin mutations and Flt3 internal tandem duplications in patients older than 60 yr with acute myeloid leukaemia." Eur J Haematol. 80(3):208-215. PMID:18081718
  19. [ + ] Andersson A, et al. (2008) "FLT3 mutations in a 10 year consecutive series of 177 childhood acute leukemias and their impact on global gene expression patterns." Genes Chromosomes Cancer. 47(1):64-70. PMID:17943971
  20. [ + ] Xue MX, et al. (2008) "[Prevalence and clinical significance of FLT3 mutations in acute promyelocytic leukemia]" Zhonghua Xue Ye Xue Za Zhi. 29(11):757-761. PMID:19176014
  21. [ + ] De Lourdes Chauffaille M, et al. (2008) "Acute promyelocytic leukemia with t(15;17): frequency of additional clonal chromosome abnormalities and FLT3 mutations." Leuk Lymphoma. 49(12):2387-2389. PMID:19052993
  22. [ + ] Nishioka C, et al. (2008) "Blockade of MEK/ERK signaling enhances sunitinib-induced growth inhibition and apoptosis of leukemia cells possessing activating mutations of the FLT3 gene." Leuk Res. 32(6):865-872. PMID:17983653
  23. [ + ] Wang YG, et al. (2008) "[Correlation of FLT3 gene expression level and internal tandem duplication mutation in acute myeloid leukemia and its clinical significance]" Zhonghua Xue Ye Xue Za Zhi. 29(11):741-745. PMID:19176010
  24. [ + ] Stubbs MC, et al. (2008) "MLL-AF9 and FLT3 cooperation in acute myelogenous leukemia: development of a model for rapid therapeutic assessment." Leukemia. 22(1):66-77. PMID:17851551
  25. [ + ] Shimada A, et al. (2008) "Tandem duplications of MLL and FLT3 are correlated with poor prognoses in pediatric acute myeloid leukemia: a study of the Japanese childhood AML Cooperative Study Group." Pediatr Blood Cancer. 50(2):264-269. PMID:17763464
  26. [ + ] Sritana N, et al. (2008) "KIT and FLT3 receptor tyrosine kinase mutations in acute myeloid leukemia with favorable cytogenetics: two novel mutations and selective occurrence in leukemia subtypes and age groups." Exp Mol Pathol. 85(3):227-231. PMID:18977345
  27. [ + ] Grosjean-Raillard J, et al. (2008) "Flt3 receptor inhibition reduces constitutive NFkappaB activation in high-risk myelodysplastic syndrome and acute myeloid leukemia." Apoptosis. 13(9):1148-1161. PMID:18670883
  28. [ + ] Boonthimat C, et al. (2008) "Nucleophosmin mutation in Southeast Asian acute myeloid leukemia: eight novel variants, FLT3 coexistence and prognostic impact of NPM1/FLT3 mutations." Haematologica. 93(10):1565-1569. PMID:18641025
  29. [ + ] Peng HL, et al. (2008) "Fms-like tyrosine kinase (FLT) 3 and FLT3 internal tandem duplication in different types of adult leukemia: analysis of 147 patients." Croat Med J. 49(5):650-669. PMID:18925699
  30. [ + ] Schlenk RF, et al. (2008) "Mutations and treatment outcome in cytogenetically normal acute myeloid leukemia." N Engl J Med. 358(18):1909-1918. PMID:18450602
  31. [ + ] Rausei-Mills V, et al. (2008) "Aberrant expression of CD7 in myeloblasts is highly associated with de novo acute myeloid leukemias with FLT3/ITD mutation." Am J Clin Pathol. 129(4):624-629. PMID:18343790
  32. [ + ] Al-Tonbary Y, et al. (2008) "Prognostic significance of foetal-like tyrosine kinase 3 mutation in Egyptian children with acute leukaemia." Int J Lab Hematol. ():. PMID:18336585
  33. [ + ] Nishioka C, et al. (2008) "MS-275, a novel histone deacetylase inhibitor with selectivity against HDAC1, induces degradation of FLT3 via inhibition of chaperone function of heat shock protein 90 in AML cells." Leuk Res. 32(9):1382-1392. PMID:18394702
  34. [ + ] Kikushige Y, et al. (2008) "Human Flt3 is expressed at the hematopoietic stem cell and the granulocyte/macrophage progenitor stages to maintain cell survival." J Immunol. 180(11):7358-7367. PMID:18490735
  35. [ + ] Koch S, et al. (2008) "Abnormal localization and accumulation of FLT3-ITD, a mutant receptor tyrosine kinase involved in leukemogenesis." Cells Tissues Organs. 188(1-2):225-235. PMID:18303245
  36. [ + ] Breccia M, et al. (2008) "Negative impact of FLT3 abnormalities in elderly acute myeloid leukemia patients." Leuk Lymphoma. 49(5):994-997. PMID:18464120
  37. [ + ] Hou HA, et al. (2008) "Characterization of acute myeloid leukemia with PTPN11 mutation: the mutation is closely associated with NPM1 mutation but inversely related to FLT3/ITD." Leukemia. 22(5):1075-1078. PMID:17972951
  38. [ + ] Paschka P, et al. (2008) "Wilms' tumor 1 gene mutations independently predict poor outcome in adults with cytogenetically normal acute myeloid leukemia: a cancer and leukemia group B study." J Clin Oncol. 26(28):4595-4602. PMID:18559874
  39. [ + ] Tomasson MH, et al. (2008) "Somatic mutations and germline sequence variants in the expressed tyrosine kinase genes of patients with de novo acute myeloid leukemia." Blood. 111(9):4797-4808. PMID:18270328
  40. [ + ] Malinge S, et al. (2008) "Activating mutations in human acute megakaryoblastic leukemia." Blood. 112(10):4220-4226. PMID:18755984
  41. [ + ] Meshinchi S, et al. (2008) "Structural and numerical variation of FLT3/ITD in pediatric AML." Blood. 111(10):4930-4933. PMID:18305215
  42. [ + ] Bang SM, et al. (2008) "Low frequency and variability of FLT3 mutations in Korean patients with acute myeloid leukemia." J Korean Med Sci. 23(5):833-837. PMID:18955790
  43. [ + ] Saito T, et al. (2008) "Combined mobilization and stimulation of tumor-infiltrating dendritic cells and natural killer cells with Flt3 ligand and IL-18 in vivo induces systemic antitumor immunity." Cancer Sci. 99(10):2028-2036. PMID:19016763
  44. [ + ] Emerenciano M, et al. (2008) "Clinical relevance of FLT3 gene abnormalities in Brazilian patients with infant leukemia." Leuk Lymphoma. 49(12):2291-2297. PMID:19052976
  45. [ + ] Bacher U, et al. (2008) "Prognostic relevance of FLT3-TKD mutations in AML: the combination matters--an analysis of 3082 patients." Blood. 111(5):2527-2537. PMID:17965322
  46. [ + ] Gale RE, et al. (2008) "The impact of FLT3 internal tandem duplication mutant level, number, size, and interaction with NPM1 mutations in a large cohort of young adult patients with acute myeloid leukemia." Blood. 111(5):2776-2784. PMID:17957027
  47. [ + ] Odgerel T, et al. (2008) "The FLT3 inhibitor PKC412 exerts differential cell cycle effects on leukemic cells depending on the presence of FLT3 mutations." Oncogene. 27(22):3102-3110. PMID:18071308
  48. [ + ] Bullinger L, et al. (2008) "An FLT3 gene-expression signature predicts clinical outcome in normal karyotype AML." Blood. 111(9):4490-4495. PMID:18309032