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KIT (v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog)

Identity

Other namesSCFR (Stem Cell Factor Receptor)
CD117
HGNC (Hugo) KIT
LocusID (NCBI) 3815
Location 4q12
Location_base_pair Starts at 55524095 and ends at 55606881 bp from pter ( according to hg19-Feb_2009)  [Mapping]
Local_order centromere-PDGFRA -KIT-KDR-telomere
 
  KIT (4q12) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics.

DNA/RNA

Description spans 89 kb; 21 exons; size of intron 1 : 37,4 kb
Transcription 5,23 kb mRNA; alternative splicing of exon 9 gives rise to two isoforms, KitA and Kit, that differ by the presence or absence of four aminoacids.

Protein

Description 976 aa; 145 kDa; type III receptor tyrosine kinase; contains an extracellular domains with 5 Ig-like loops, a highly hydrophobic transmenbrane domain (23 aa), and an intracellular domain with tyrosine kinase activity split by a kinase insert (KI) in an ATP-binding region and in the phosphotransferase domain
Expression hematopoietic stem cells, mast cells, melanocytes, germ-cell lineages and ICCs (Interstitial cells of Cajal).
Localisation plasma membrane
Function SCF/MGF receptor with tyrosine kinase activity; binding of ligand (SCF) induces receptor dimerization, autophosphorylation and signal transduction via molecules containing SH2- domains.
 
Homology with CSF-1R, PDGFRb, PDGFRa, and FLT3.

Mutations

Note see diagrams: Loss-of-function mutations, and Gain-of-function mutations
 
Germinal in piebaldism, and in familial gastrointestinal stromal tumours (see below).
Somatic in aggressive mastocytosis, mast cell leukemia, ANLL with/without mast cell involvement, myeloproliferative disorders, colon carcinoma and gastrointestinal stromal tumours and germ cell tumors (GCCs)

Implicated in

Entity Piebaldism.
Disease autosomal dominant disorder of pigmentation; loss of function abnormalities of the c-kit gene have been demonstrated in 59% of the typical patients.
  
Entity Familial gastrointestinal stromal tumours and sporadic gastrointestinal stromal tumours (GISTs).
Disease GISTs are the most common mesenchymal tumors in the human digestive tract; they originate from kit-expressing cells (ICCs), and often have activating c-kit mutations clustered in the juxtamembrane domain.
  
Entity systemic mast cell disease (SMCD)
Disease mast cell hyperplasia in the bone marrow, liver, spleen, lymph nodes, gastrointestinal tract and skin; gain of function mutations are detected in most patients
Prognosis depending on the four clinical entities recognized: indolent form, form associated with hematologic disorder, aggressive SMCD and mast cell leukemia; leukemic transformation with mast cell involvement is characterized by rapid progression of disease with a survival time less than 1 year
Oncogenesis clinical features of malignant hematopoietic cell growth are influenced by the time, the location of c-kit mutative events, and the number of associated lesions.
  
Entity Core binding factor leukemias (ANLL-M2 with t(8;21) (link), (ANLL-M4Eo with inv(16))
Disease characterized by disruption and loss of CBFa2/AML1 - CBFb/PEBP2b function. Myelomonoblastic leukemia cells are marked by combined positivity for the stem cell antigens CD34, CD117 and high frequency of c-kit mutations ( see Figure on CBF leukemia and KIT mutations)
  

To be noted

loss of expression of c-KIT appears to be associated with progression of some tumors (melanoma) and autocrine/paracrine stimulation of the c-kit/SCF system may participate in human solid tumors such as lung, breast, testicular and gynecological malignancies.

Other Leukemias implicated (Data extracted from papers in the Atlas)

Leukemias 11q23ChildAMLID1615 11q23ID1030 11q23secondLeukID1131 t1119ELLID1029

Other Solid tumors implicated (Data extracted from papers in the Atlas)

Solid Tumors AmeloblastomID5945 MedulloblastomaID5065 rhab5004 rhabID5004

External links

Nomenclature
HGNC (Hugo)KIT   6342
Cards
AtlasKITID127
Entrez_Gene (NCBI)KIT  3815  v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog
GeneCards (Weizmann)KIT
Ensembl (Hinxton)ENSG00000157404 [Gene_View]  chr4:55524095-55606881 [Contig_View]  KIT [Vega]
ICGC DataPortalENSG00000157404
AceView (NCBI)KIT
Genatlas (Paris)KIT
WikiGenes3815
SOURCE (Princeton)NM_000222 NM_001093772
Genomic and cartography
GoldenPath (UCSC)KIT  -  4q12   chr4:55524095-55606881 +  4q11-q12   [Description]    (hg19-Feb_2009)
EnsemblKIT - 4q11-q12 [CytoView]
Mapping of homologs : NCBIKIT [Mapview]
OMIM154800   164920   172800   273300   606764   
Gene and transcription
Genbank (Entrez)AJ438313 AK304031 BC071593 CN414753 DC376760
RefSeq transcript (Entrez)NM_000222 NM_001093772
RefSeq genomic (Entrez)AC_000136 NC_000004 NC_018915 NG_007456 NT_022853 NW_001838913 NW_004929319
Consensus coding sequences : CCDS (NCBI)KIT
Cluster EST : UnigeneHs.479754 [ NCBI ]
CGAP (NCI)Hs.479754
Alternative Splicing : Fast-db (Paris)GSHG0022597
Alternative Splicing GalleryENSG00000157404
Gene ExpressionKIT [ NCBI-GEO ]     KIT [ SEEK ]   KIT [ MEM ]
Protein : pattern, domain, 3D structure
UniProt/SwissProtP10721 (Uniprot)
NextProtP10721  [Medical]
With graphics : InterProP10721
Splice isoforms : SwissVarP10721 (Swissvar)
Catalytic activity : Enzyme2.7.10.1 [ Enzyme-Expasy ]   2.7.10.12.7.10.1 [ IntEnz-EBI ]   2.7.10.1 [ BRENDA ]   2.7.10.1 [ KEGG ]   
Domaine pattern : Prosite (Expaxy)IG_LIKE (PS50835)    PROTEIN_KINASE_ATP (PS00107)    PROTEIN_KINASE_DOM (PS50011)    PROTEIN_KINASE_TYR (PS00109)    RECEPTOR_TYR_KIN_III (PS00240)   
Domains : Interpro (EBI)Ig-like_dom    Ig-like_fold    Ig_sub    Ig_sub2    Immunoglobulin    Kinase-like_dom    Prot_kinase_dom    Protein_kinase_ATP_BS    SCGF_receptor    Ser-Thr/Tyr_kinase_cat_dom    Tyr_kinase_AS    Tyr_kinase_cat_dom    Tyr_kinase_CSF1/PDGF_rcpt    Tyr_kinase_rcpt_3_CS   
Related proteins : CluSTrP10721
Domain families : Pfam (Sanger)ig (PF00047)    Pkinase_Tyr (PF07714)   
Domain families : Pfam (NCBI)pfam00047    pfam07714   
Domain families : Smart (EMBL)IG (SM00409)  IGc2 (SM00408)  TyrKc (SM00219)  
DMDM Disease mutations3815
Blocks (Seattle)P10721
PDB (SRS)1PKG    1QZJ    1QZK    1R01    1T45    1T46    2E9W    2EC8    2VIF    3G0E    3G0F    4HVS    4K94    4K9E   
PDB (PDBSum)1PKG    1QZJ    1QZK    1R01    1T45    1T46    2E9W    2EC8    2VIF    3G0E    3G0F    4HVS    4K94    4K9E   
PDB (IMB)1PKG    1QZJ    1QZK    1R01    1T45    1T46    2E9W    2EC8    2VIF    3G0E    3G0F    4HVS    4K94    4K9E   
PDB (RSDB)1PKG    1QZJ    1QZK    1R01    1T45    1T46    2E9W    2EC8    2VIF    3G0E    3G0F    4HVS    4K94    4K9E   
Human Protein AtlasENSG00000157404
Peptide AtlasP10721
HPRD01287
IPIIPI00022296   IPI00848233   IPI01013771   
Protein Interaction databases
DIP (DOE-UCLA)P10721
IntAct (EBI)P10721
FunCoupENSG00000157404
BioGRIDKIT
IntegromeDBKIT
STRING (EMBL)KIT
Ontologies - Pathways
QuickGOP10721
Ontology : AmiGOactivation of MAPK activity  ovarian follicle development  acrosomal vesicle  protease binding  myeloid progenitor cell differentiation  lymphoid progenitor cell differentiation  immature B cell differentiation  dendritic cell cytokine production  mast cell chemotaxis  protein tyrosine kinase activity  transmembrane receptor protein tyrosine kinase activity  receptor signaling protein tyrosine kinase activity  stem cell factor receptor activity  protein binding  ATP binding  extracellular space  plasma membrane  glycosphingolipid metabolic process  inflammatory response  signal transduction  epidermal growth factor receptor signaling pathway  spermatogenesis  spermatogenesis  spermatid development  positive regulation of cell proliferation  germ cell migration  regulation of cell shape  visual learning  fibroblast growth factor receptor signaling pathway  male gonad development  external side of plasma membrane  cytoplasmic side of plasma membrane  positive regulation of gene expression  positive regulation of phospholipase C activity  positive regulation of phosphatidylinositol 3-kinase signaling  integral component of membrane  peptidyl-tyrosine phosphorylation  cytokine-mediated signaling pathway  stem cell maintenance  cytokine binding  signal transduction by phosphorylation  signal transduction by phosphorylation  lamellipodium assembly  hemopoiesis  T cell differentiation  erythrocyte differentiation  melanocyte differentiation  melanocyte differentiation  positive regulation of cell migration  positive regulation of pseudopodium assembly  actin cytoskeleton reorganization  mast cell cytokine production  somatic stem cell maintenance  embryonic hemopoiesis  ectopic germ cell programmed cell death  megakaryocyte development  Fc receptor signaling pathway  Fc-epsilon receptor signaling pathway  Kit signaling pathway  erythropoietin-mediated signaling pathway  regulation of cell proliferation  positive regulation of tyrosine phosphorylation of Stat1 protein  positive regulation of tyrosine phosphorylation of Stat3 protein  positive regulation of tyrosine phosphorylation of Stat5 protein  mast cell granule  protein homodimerization activity  negative regulation of programmed cell death  mast cell degranulation  positive regulation of MAPK cascade  pigmentation  positive regulation of phosphatidylinositol 3-kinase activity  innate immune response  positive regulation of Notch signaling pathway  positive regulation of JAK-STAT cascade  protein autophosphorylation  metal ion binding  neurotrophin TRK receptor signaling pathway  phosphatidylinositol-mediated signaling  regulation of developmental pigmentation  somatic stem cell division  positive regulation of long-term neuronal synaptic plasticity  digestive tract development  stem cell differentiation  epithelial cell proliferation  detection of mechanical stimulus involved in sensory perception of sound  positive regulation of sequence-specific DNA binding transcription factor activity  cell chemotaxis  mast cell differentiation  mast cell differentiation  mast cell proliferation  cellular response to thyroid hormone stimulus  melanocyte migration  melanocyte adhesion  
Ontology : EGO-EBIactivation of MAPK activity  ovarian follicle development  acrosomal vesicle  protease binding  myeloid progenitor cell differentiation  lymphoid progenitor cell differentiation  immature B cell differentiation  dendritic cell cytokine production  mast cell chemotaxis  protein tyrosine kinase activity  transmembrane receptor protein tyrosine kinase activity  receptor signaling protein tyrosine kinase activity  stem cell factor receptor activity  protein binding  ATP binding  extracellular space  plasma membrane  glycosphingolipid metabolic process  inflammatory response  signal transduction  epidermal growth factor receptor signaling pathway  spermatogenesis  spermatogenesis  spermatid development  positive regulation of cell proliferation  germ cell migration  regulation of cell shape  visual learning  fibroblast growth factor receptor signaling pathway  male gonad development  external side of plasma membrane  cytoplasmic side of plasma membrane  positive regulation of gene expression  positive regulation of phospholipase C activity  positive regulation of phosphatidylinositol 3-kinase signaling  integral component of membrane  peptidyl-tyrosine phosphorylation  cytokine-mediated signaling pathway  stem cell maintenance  cytokine binding  signal transduction by phosphorylation  signal transduction by phosphorylation  lamellipodium assembly  hemopoiesis  T cell differentiation  erythrocyte differentiation  melanocyte differentiation  melanocyte differentiation  positive regulation of cell migration  positive regulation of pseudopodium assembly  actin cytoskeleton reorganization  mast cell cytokine production  somatic stem cell maintenance  embryonic hemopoiesis  ectopic germ cell programmed cell death  megakaryocyte development  Fc receptor signaling pathway  Fc-epsilon receptor signaling pathway  Kit signaling pathway  erythropoietin-mediated signaling pathway  regulation of cell proliferation  positive regulation of tyrosine phosphorylation of Stat1 protein  positive regulation of tyrosine phosphorylation of Stat3 protein  positive regulation of tyrosine phosphorylation of Stat5 protein  mast cell granule  protein homodimerization activity  negative regulation of programmed cell death  mast cell degranulation  positive regulation of MAPK cascade  pigmentation  positive regulation of phosphatidylinositol 3-kinase activity  innate immune response  positive regulation of Notch signaling pathway  positive regulation of JAK-STAT cascade  protein autophosphorylation  metal ion binding  neurotrophin TRK receptor signaling pathway  phosphatidylinositol-mediated signaling  regulation of developmental pigmentation  somatic stem cell division  positive regulation of long-term neuronal synaptic plasticity  digestive tract development  stem cell differentiation  epithelial cell proliferation  detection of mechanical stimulus involved in sensory perception of sound  positive regulation of sequence-specific DNA binding transcription factor activity  cell chemotaxis  mast cell differentiation  mast cell differentiation  mast cell proliferation  cellular response to thyroid hormone stimulus  melanocyte migration  melanocyte adhesion  
Pathways : BIOCARTARegulation of BAD phosphorylation [Genes]    Melanocyte Development and Pigmentation [Genes]   
Pathways : KEGGRas signaling pathway    Rap1 signaling pathway    Cytokine-cytokine receptor interaction    Endocytosis    PI3K-Akt signaling pathway    Hematopoietic cell lineage    Melanogenesis    Pathways in cancer    Acute myeloid leukemia   
REACTOMEP10721 [protein]
REACTOME PathwaysREACT_116125 Disease [pathway]
REACTOME PathwaysREACT_6900 Immune System [pathway]
REACTOME PathwaysREACT_111102 Signal Transduction [pathway]
Protein Interaction DatabaseKIT
Wikipedia pathwaysKIT
Gene fusion - rearrangments
Rearrangement : TICdbCNTRL [9q33.2]  -  KIT [12q13.3]
Polymorphisms : SNP, mutations, diseases
SNP Single Nucleotide Polymorphism (NCBI)KIT
SNP (GeneSNP Utah)KIT
SNP : HGBaseKIT
Genetic variants : HAPMAPKIT
1000_GenomesKIT 
ICGC programENSG00000157404 
Cancer Gene: CensusKIT 
CONAN: Copy Number AnalysisKIT 
Somatic Mutations in Cancer : COSMICKIT 
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
LOVD (Leiden Open Variation Database)Zhejiang University Center for Genetic and Genomic Medicine (ZJU-CGGM)
DECIPHER (Syndromes)4:55524095-55606881
Mutations and Diseases : HGMDKIT
OMIM154800    164920    172800    273300    606764   
MedgenKIT
GENETestsKIT
Disease Genetic AssociationKIT
Huge Navigator KIT [HugePedia]  KIT [HugeCancerGEM]
Genomic VariantsKIT  KIT [DGVbeta]
Exome VariantKIT
dbVarKIT
ClinVarKIT
snp3D : Map Gene to Disease3815
General knowledge
Homologs : HomoloGeneKIT
Homology/Alignments : Family Browser (UCSC)KIT
Phylogenetic Trees/Animal Genes : TreeFamKIT
Chemical/Protein Interactions : CTD3815
Chemical/Pharm GKB GenePA30128
Drug Sensitivity KIT
Clinical trialKIT
Cancer Resource (Charite)ENSG00000157404
Other databases
Other databasehttp://cancergenome.broadinstitute.org/index.php?tgene=KIT
Probes
ProbeCancer Cytogenetics (Bari)
Litterature
PubMed499 Pubmed reference(s) in Entrez
CoreMineKIT
GoPubMedKIT
iHOPKIT

Bibliography

Cloning and structural analysis of the human c-kit gene.
Vandenbark GR, deCastro CM, Taylor H, Dew-Knight S, Kaufman RE
Oncogene. 1992 ; 7 (7) : 1259-1266.
PMID 1377810
 
Novel mutations and deletions of the KIT (steel factor receptor) gene in human piebaldism.
Ezoe K, Holmes SA, Ho L, Bennett CP, Bolognia JL, Brueton L, Burn J, Falabella R, Gatto EM, Ishii N
American journal of human genetics. 1995 ; 56 (1) : 58-66.
PMID 7529964
 
Somatic c-KIT activating mutation in urticaria pigmentosa and aggressive mastocytosis: establishment of clonality in a human mast cell neoplasm.
Longley BJ, Tyrrell L, Lu SZ, Ma YS, Langley K, Ding TG, Duffy T, Jacobs P, Tang LH, Modlin I
Nature genetics. 1996 ; 12 (3) : 312-314.
PMID 8589724
 
Sequence analysis of two genomic regions containing the KIT and the FMS receptor tyrosine kinase genes.
Andre C, Hampe A, Lachaume P, Martin E, Wang XP, Manus V, Hu WX, Galibert F
Genomics. 1997 ; 39 (2) : 216-226.
PMID 9027509
 
Gain-of-function mutations of c-kit in human gastrointestinal stromal tumors.
Hirota S, Isozaki K, Moriyama Y, Hashimoto K, Nishida T, Ishiguro S, Kawano K, Hanada M, Kurata A, Takeda M, Muhammad Tunio G, Matsuzawa Y, Kanakura Y, Shinomura Y, Kitamura Y
Science (New York, N.Y.). 1998 ; 279 (5350) : 577-580.
PMID 9438854
 
C-kit gene abnormalities in gastrointestinal stromal tumors (tumors of interstitial cells of Cajal.
Sakurai S, Fukasawa T, Chong JM, Tanaka A, Fukayama M
Japanese journal of cancer research : Gann. 1999 ; 90 (12) : 1321-1328.
PMID 10665649
 
c-kit proto-oncogene exon 8 in-frame deletion plus insertion mutations in acute myeloid leukaemia.
Gari M, Goodeve A, Wilson G, Winship P, Langabeer S, Linch D, Vandenberghe E, Peake I, Reilly J
British journal of haematology. 1999 ; 105 (4) : 894-900.
PMID 10554798
 
Activating c-kit gene mutations in human germ cell tumors.
Tian Q, Frierson HF Jr, Krystal GW, Moskaluk CA
The American journal of pathology. 1999 ; 154 (6) : 1643-1647.
PMID 10362788
 
Activating and dominant inactivating c-KIT catalytic domain mutations in distinct clinical forms of human mastocytosis.
Longley BJ Jr, Metcalfe DD, Tharp M, Wang X, Tyrrell L, Lu SZ, Heitjan D, Ma Y
Proceedings of the National Academy of Sciences of the United States of America. 1999 ; 96 (4) : 1609-1614.
PMID 9990072
 
KIT extracellular and kinase domain mutations in gastrointestinal stromal tumors.
Lux ML, Rubin BP, Biase TL, Chen CJ, Maclure T, Demetri G, Xiao S, Singer S, Fletcher CD, Fletcher JA
The American journal of pathology. 2000 ; 156 (3) : 791-795.
PMID 10702394
 
C-kit mutations in core binding factor leukemias.
Beghini A, Peterlongo P, Ripamonti CB, Larizza L, Cairoli R, Morra E, Mecucci C
Blood. 2000 ; 95 (2) : 726-727.
PMID 10660321
 
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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Contributor(s)

Written09-1998Lidia Larizza and Alessandro Beghini
Updated06-2000Lidia Larizza and Alessandro Beghini

Citation

This paper should be referenced as such :
Larizza, L ; Beghini, A
KIT (v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog)
Atlas Genet Cytogenet Oncol Haematol. 2000;4(3):96-98.
Free online version   Free pdf version   [Bibliographic record ]
History of this paper:
Larizza, L ; Beghini, A. KIT (v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog). Atlas Genet Cytogenet Oncol Haematol. 2000;4(3):96-98.
http://documents.irevues.inist.fr/bitstream/2042/37632/1/06-2000-KITID127.pdf
URL : http://AtlasGeneticsOncology.org/Genes/KITID127.html

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indexed on : Sat Nov 8 16:47:40 CET 2014

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