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

2015-11-01   Lars Rönnstrand , Johan Lennartsson 


Atlas Image
KIT (4q12) - Courtesy Mariano Rocchi



The KIT gene located on human chromsome 4q11 and contains 21 exons. Exon1 encodes the initation codon, exon 2-9 encodes the extracellular domain, exon 10 the transmembrane region and exons 11-21 the intracellular part.


The 5.23 kb mRNA is alternatively spliced into two isoforms differing in the presence or absence of exon 9. This splicing gives rise to KIT variants that differ by the presence or absence of the amino acid sequence GNNK (denoted KIT and KITA, respectively). In addition there is alterative splicing occurring in humans, but not in mice, giving rise of isoforms that differ by the presence or absence of a serine residue in the kinase insert region. In postmeiotic germ cells a shorter KIT transcript is expressed that gives rise to a truncated version of KIT (tr-KIT) containing part of the kinase domain and the C-terminal tail.



976 aa; 145 kDa; type III receptor tyrosine kinase; glycoprotein; contains an extracellular domains with 5 Ig-like loops, a highly hydrophobic transmembrane 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. Tr-KIT does not contain the whole kinase domain and is therefore kinase inactive.


Hematopoietic stem cells, mast cells, melanocytes, germ-cell lineages and ICCs (Interstitial cells of Cajal). Expression pattern in the mouse suggest that KIT may play a role in tissues such as nervous system, placenta, heart, lung and midgestational kidneys.


Plasma membrane. The truncated tr-KIT lacks the transmembrane domain and is hence not present at the plasma membrane.


KIT is a cell surface receptor with tyrosine kinase activity; binding of ligand KITLG (also denoted MGF or SCF) induces receptor dimerization, autophosphorylation and signal transduction via molecules containing SH2- domains. KIT signaling leads to cell proliferation, survival, migration and differentiation.


with CSF-1R, PDGFRB, PDGFRA, and FLT3.
Atlas Image
Loss-of-function mutations.
Atlas Image
Gain-of-function mutations.



See figures Loss-of-function mutations and Gain-of-function mutations.

Implicated in

Entity name
Autosomal dominant disorder of pigmentation; loss of function abnormalities of the KIT gene have been demonstrated in 59% of the typical patients.
Entity name
Familial Gastrointestinal Stromal Tumors and sporadic gastrointestinal stromal tumors (GISTs)
GISTs are the most common mesenchymal tumors in the human digestive tract; they originate from KIT-expressing cells (ICCs). All GISTs express KIT which is frequently (80-85% of the cases) mutated in exon 11 encoding the juxtamembrane domain. However, also mutations in exon 9 (encoding the extracellular region) and 17 (encoding a region around the activation loop in the kinase domain) have been found. Most GIST cells produce SCF thus establishing autocrine stimulation.
Mast cell hyperplasia in the bone marrow, liver, spleen, lymph nodes, gastrointestinal tract and skin; gain of function mutations are detected in most patients. About 90% of patients with systemic mastocytosis have mutation in exon 17 in KIT, often Asp-816 is replaced with Val. In children with systemic mastocytosis the frequency of KIT mutations in exon 17 is lower (about 40%), but mutations in other KIT regions are found in 40% of the children, for example mutation in exon 8 and 9 (encoding Ig-like domain 5 in the extracellular region of KIT).
The prognosis depends 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
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 name
Small Cell Lung cancer (SCLC)
KIT overexpression is found in 70% of SCLC patients. Co-expression ofKIT and SCF has been found to create an autocrine loop. The prognostic value of KIT expression is not clear.
Entity name
Testicular Carcinoma
Activating mutations in KIT exon 17 is found in about 25% of seminomas. Often Asp-816 is replaced with a Val or His residue.
Entity name
KIT is important for the development of melanocytes. The about 80% of melanomas contain BRAF mutations, but a subset contain activating KITmutations. Interestingly in acral melanomas (affecting foot soles or palms) there is a higher frequency of tumors with activating KIT mutations (20-25% of cases). Examples of KIT mutations found in melanoma are L576P (in exon 11) and K642E (in exon 13). Mutation in position 816 (in exon 17) has also been observed but is not so frequent occurring.
Entity name
Acute Myeloid Leukemia
KIT expression can be found in about 85% of AML cells. KIT activation can occur by different mechanisms: 1) co-expression of SCF causing an autocrine loop 2) activating mutations in exon 17 affecting Asp-816 or Asn-822. Interestingly, KIT mutations occurs primarily in a subset of leukemias containing inv(16) or t(8;21), so-called core factor binding AML. Apart from exon 17 mutations, also internal tandem duplications in exon 11 have been described.
Presence of D816V mutation in KIT is a poor prognostic factor.


Pubmed IDLast YearTitleAuthors
90275091997Sequence analysis of two genomic regions containing the KIT and the FMS receptor tyrosine kinase genes.Andre C et al
106603212000C-kit mutations in core binding factor leukemias.Beghini A et al
169089312006Somatic activation of KIT in distinct subtypes of melanoma.Curtin JA et al
75299641995Novel mutations and deletions of the KIT (steel factor receptor) gene in human piebaldism.Ezoe K et al
105547981999c-kit proto-oncogene exon 8 in-frame deletion plus insertion mutations in acute myeloid leukaemia.Gari M et al
94388541998Gain-of-function mutations of c-kit in human gastrointestinal stromal tumors.Hirota S et al
230736282012Stem cell factor receptor/c-Kit: from basic science to clinical implications.Lennartsson J et al
99900721999Activating and dominant inactivating c-KIT catalytic domain mutations in distinct clinical forms of human mastocytosis.Longley BJ Jr et al
85897241996Somatic c-KIT activating mutation in urticaria pigmentosa and aggressive mastocytosis: establishment of clonality in a human mast cell neoplasm.Longley BJ et al
107023942000KIT extracellular and kinase domain mutations in gastrointestinal stromal tumors.Lux ML et al
106656491999C-kit gene abnormalities in gastrointestinal stromal tumors (tumors of interstitial cells of Cajal.Sakurai S et al
103627881999Activating c-kit gene mutations in human germ cell tumors.Tian Q et al
13778101992Cloning and structural analysis of the human c-kit gene.Vandenbark GR et al
159481152005Human malignant melanoma: detection of BRAF- and c-kit-activating mutations by high-resolution amplicon melting analysis.Willmore-Payne C et al
204571362010Targeting KIT in melanoma: a paradigm of molecular medicine and targeted therapeutics.Woodman SE et al

Other Information

Locus ID:

NCBI: 3815
MIM: 164920
HGNC: 6342
Ensembl: ENSG00000157404


dbSNP: 3815
ClinVar: 3815
TCGA: ENSG00000157404


Gene IDTranscript IDUniprot

Expression (GTEx)



PathwaySourceExternal ID
Cytokine-cytokine receptor interactionKEGGko04060
Hematopoietic cell lineageKEGGko04640
Acute myeloid leukemiaKEGGko05221
Cytokine-cytokine receptor interactionKEGGhsa04060
Hematopoietic cell lineageKEGGhsa04640
Pathways in cancerKEGGhsa05200
Acute myeloid leukemiaKEGGhsa05221
PI3K-Akt signaling pathwayKEGGhsa04151
PI3K-Akt signaling pathwayKEGGko04151
Ras signaling pathwayKEGGhsa04014
Rap1 signaling pathwayKEGGhsa04015
Rap1 signaling pathwayKEGGko04015
Central carbon metabolism in cancerKEGGhsa05230
Central carbon metabolism in cancerKEGGko05230
Diseases of signal transductionREACTOMER-HSA-5663202
PI3K/AKT Signaling in CancerREACTOMER-HSA-2219528
Constitutive Signaling by Aberrant PI3K in CancerREACTOMER-HSA-2219530
Immune SystemREACTOMER-HSA-168256
Adaptive Immune SystemREACTOMER-HSA-1280218
Signaling by the B Cell Receptor (BCR)REACTOMER-HSA-983705
Downstream signaling events of B Cell Receptor (BCR)REACTOMER-HSA-1168372
PIP3 activates AKT signalingREACTOMER-HSA-1257604
Negative regulation of the PI3K/AKT networkREACTOMER-HSA-199418
Innate Immune SystemREACTOMER-HSA-168249
DAP12 interactionsREACTOMER-HSA-2172127
DAP12 signalingREACTOMER-HSA-2424491
RAF/MAP kinase cascadeREACTOMER-HSA-5673001
Fc epsilon receptor (FCERI) signalingREACTOMER-HSA-2454202
FCERI mediated MAPK activationREACTOMER-HSA-2871796
Role of LAT2/NTAL/LAB on calcium mobilizationREACTOMER-HSA-2730905
Cytokine Signaling in Immune systemREACTOMER-HSA-1280215
Signaling by InterleukinsREACTOMER-HSA-449147
Interleukin-2 signalingREACTOMER-HSA-451927
Interleukin receptor SHC signalingREACTOMER-HSA-912526
Interleukin-3, 5 and GM-CSF signalingREACTOMER-HSA-512988
Signal TransductionREACTOMER-HSA-162582
Signaling by EGFRREACTOMER-HSA-177929
GRB2 events in EGFR signalingREACTOMER-HSA-179812
SHC1 events in EGFR signalingREACTOMER-HSA-180336
GAB1 signalosomeREACTOMER-HSA-180292
Signaling by Insulin receptorREACTOMER-HSA-74752
Insulin receptor signalling cascadeREACTOMER-HSA-74751
IRS-mediated signallingREACTOMER-HSA-112399
SOS-mediated signallingREACTOMER-HSA-112412
Signalling by NGFREACTOMER-HSA-166520
NGF signalling via TRKA from the plasma membraneREACTOMER-HSA-187037
Signalling to ERKsREACTOMER-HSA-187687
Signalling to RASREACTOMER-HSA-167044
Signalling to p38 via RIT and RINREACTOMER-HSA-187706
Prolonged ERK activation eventsREACTOMER-HSA-169893
Frs2-mediated activationREACTOMER-HSA-170968
ARMS-mediated activationREACTOMER-HSA-170984
PI3K/AKT activationREACTOMER-HSA-198203
Signaling by PDGFREACTOMER-HSA-186797
Downstream signal transductionREACTOMER-HSA-186763
Signaling by VEGFREACTOMER-HSA-194138
VEGFR2 mediated cell proliferationREACTOMER-HSA-5218921
Signaling by SCF-KITREACTOMER-HSA-1433557
Regulation of KIT signalingREACTOMER-HSA-1433559
MAPK family signaling cascadesREACTOMER-HSA-5683057
MAPK1/MAPK3 signalingREACTOMER-HSA-5684996
Signaling by GPCRREACTOMER-HSA-372790
Gastrin-CREB signalling pathway via PKC and MAPKREACTOMER-HSA-881907
Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R)REACTOMER-HSA-2404192
IGF1R signaling cascadeREACTOMER-HSA-2428924
IRS-related events triggered by IGF1RREACTOMER-HSA-2428928
Signaling by LeptinREACTOMER-HSA-2586552
Gene ExpressionREACTOMER-HSA-74160
Generic Transcription PathwayREACTOMER-HSA-212436
Developmental BiologyREACTOMER-HSA-1266738
Axon guidanceREACTOMER-HSA-422475
NCAM signaling for neurite out-growthREACTOMER-HSA-375165
Phospholipase D signaling pathwayKEGGko04072
Phospholipase D signaling pathwayKEGGhsa04072
PI5P, PP2A and IER3 Regulate PI3K/AKT SignalingREACTOMER-HSA-6811558
Transcriptional regulation by the AP-2 (TFAP2) family of transcription factorsREACTOMER-HSA-8864260
TFAP2 (AP-2) family regulates transcription of growth factors and their receptorsREACTOMER-HSA-8866910
RET signalingREACTOMER-HSA-8853659
Breast cancerKEGGko05224
Breast cancerKEGGhsa05224

Protein levels (Protein atlas)

Not detected


Entity IDNameTypeEvidenceAssociationPKPDPMIDs
PA10804imatinibChemicalLabelAnnotation, VariantAnnotation, VipGeneassociatedPD11526490
PA151958383Gastrointestinal Stromal TumorsDiseaseMultilinkAnnotation, VipGeneassociated19248971


Pubmed IDYearTitleCitations
125222572003PDGFRA activating mutations in gastrointestinal stromal tumors.502
163652912005The role of microRNA genes in papillary thyroid carcinoma.382
189554582008Primary and secondary kinase genotypes correlate with the biological and clinical activity of sunitinib in imatinib-resistant gastrointestinal stromal tumor.172
189554512008Correlation of kinase genotype and clinical outcome in the North American Intergroup Phase III Trial of imatinib mesylate for treatment of advanced gastrointestinal stromal tumor: CALGB 150105 Study by Cancer and Leukemia Group B and Southwest Oncology Group.164
189809762008KIT gene mutations and copy number in melanoma subtypes.148
189809762008KIT gene mutations and copy number in melanoma subtypes.148
160768672005Nucleophosmin gene mutations are predictors of favorable prognosis in acute myelogenous leukemia with a normal karyotype.143
216904682011Phase II, open-label, single-arm trial of imatinib mesylate in patients with metastatic melanoma harboring c-Kit mutation or amplification.139
190880792009Induction of microRNA-221 by platelet-derived growth factor signaling is critical for modulation of vascular smooth muscle phenotype.133
167842372006A conserved quadruplex motif located in a transcription activation site of the human c-kit oncogene.123


Lars Rönnstrand ; Johan Lennartsson

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

Atlas Genet Cytogenet Oncol Haematol. 2015-11-01

Online version:

Historical Card

2000-06-01 KIT (v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog) by  Lidia Larizza,Alessandro Beghini 

Division of Translational Cancer Research and, Lund Stem Cell Center, Lund University, Lund, Sweden., Ludwig Institute for Cancer Research, Uppsala, Sweden

1998-09-01 KIT (v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog) by  Lidia Larizza,Alessandro Beghini 

Division of Translational Cancer Research and, Lund Stem Cell Center, Lund University, Lund, Sweden., Ludwig Institute for Cancer Research, Uppsala, Sweden