KIT Gene (CD117): Structure, Function, and Clinical Significance
A comprehensive overview of the KIT proto-oncogene, its role in normal physiology and disease, including cancer and developmental disorders.
Gene Information Card
| Symbol | KIT |
|---|---|
| Full Name | KIT proto-oncogene, receptor tyrosine kinase |
| Gene Type | Protein coding |
| Chromosomal Location | 4q12 |
| NCBI Gene ID | 3815 ncbi.nlm.nih.gov/gene/3815 |
| Ensembl ID | ENSG00000157404 |
| UniProt ID | P10721 |
| OMIM ID | 164920 |
| HGNC ID | 6342 |
| Aliases | CD117, C-Kit, SCFR, PBT |
Description
The KIT gene encodes the KIT receptor tyrosine kinase (CD117), a type III receptor for stem cell factor (SCF). KIT plays a critical role in hematopoiesis, melanogenesis, and gametogenesis. Mutations in KIT are associated with various cancers, including gastrointestinal stromal tumors (GISTs), mastocytosis, and acute myeloid leukemia, as well as developmental disorders like piebaldism.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Gastrointestinal stromal tumor (GIST) | Activating mutations in KIT lead to constitutive kinase activity, promoting tumor cell proliferation and survival. | COSMIC, ClinVar, OMIM |
| Mastocytosis | Somatic activating mutations (e.g., D816V) cause uncontrolled mast cell growth and accumulation. | ClinVar, OMIM |
| Piebaldism | Loss-of-function mutations in KIT impair melanocyte development, leading to depigmentation patches. | OMIM, ClinVar |
| Acute myeloid leukemia (AML) | KIT mutations, particularly in core-binding factor AML, are associated with poor prognosis and increased relapse risk. | COSMIC, ClinVar |
| Testicular germ cell tumors | KIT mutations and overexpression are implicated in tumorigenesis, especially in seminomas. | COSMIC, PubMed (via NCBI) |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Bone Marrow | High | High |
| Small Intestine | High | High |
| Skin | Medium | Medium |
| Stomach | Medium | Medium |
| Lung | Low | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| GIST cell lines (e.g., GIST-T1) | High | Constitutively active KIT due to mutations |
| Mast cell lines (e.g., HMC-1) | High | Activating mutations (e.g., D816V) |
| Melanoma cell lines | Variable | Expression varies; some have KIT mutations |
| Leukemia cell lines (e.g., Kasumi-1) | High | KIT mutations in AML |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| D816V | Missense | Common in mastocytosis and AML | Constitutive activation of kinase domain |
| V559D | Missense | Common in GIST | Constitutive activation of juxtamembrane domain |
| W557_K558del | Deletion | GIST | Constitutive activation |
| L576P | Missense | GIST | Constitutive activation |
| N822K | Missense | AML | Constitutive activation |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations (e.g., frameshift, nonsense) impair KIT receptor signaling, leading to developmental defects like piebaldism due to reduced melanocyte survival.
Gain of Function (GOF)
Gain-of-function mutations (e.g., D816V, V559D) cause ligand-independent activation of the kinase, driving oncogenic signaling in GIST, mastocytosis, and AML.
Dominant Negative (DN)
Some KIT mutations may exert dominant-negative effects by forming inactive heterodimers with wild-type receptors, reducing overall signaling, though this is less common than gain-of-function.
View complete mutation data：
Gene Ontology (GO)
| • protein tyrosine kinase activity | • transmembrane receptor protein tyrosine kinase signaling pathway |
| • stem cell factor receptor activity | • cell surface receptor signaling pathway |
| • positive regulation of cell population proliferation | • mast cell differentiation |
| • melanocyte differentiation | • hematopoiesis |
Pathways
• KIT receptor signaling pathway
• MAPK/ERK signaling pathway
• PI3K/AKT signaling pathway
• JAK/STAT signaling pathway
• SCF/KIT signaling in hematopoiesis
Protein Summary
The KIT protein (CD117) is a 145 kDa transmembrane receptor tyrosine kinase. It consists of five extracellular immunoglobulin-like domains, a single transmembrane region, and a cytoplasmic kinase domain split by a kinase insert. Binding of stem cell factor (SCF) induces receptor dimerization and autophosphorylation, activating downstream pathways such as MAPK, PI3K, and JAK/STAT. KIT is essential for the development of hematopoietic stem cells, melanocytes, and germ cells. Aberrant KIT signaling due to mutations contributes to tumorigenesis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| KITLG Knockout HEK293 Cell Line | EDJ-KQ680 | Human | 4254 | Details Get a Quote |
| KIT Knockout HEK293 Cell Line | EDJ-KQ17830 | Human | 3815 | Details Get a Quote |
| KITLG Knockout A-549 Cell Line | EDJ-KQ19221 | Human | 4254 | Details Get a Quote |
| KITLG Knockout HCT 116 Cell Line | EDJ-KQ19222 | Human | 4254 | Details Get a Quote |
| KITLG Knockout HeLa Cell Line | EDJ-KQ19223 | Human | 4254 | Details Get a Quote |
| KIT Knockout HeLa Cell Line | EDJ-KQ53741 | Human | 3815 | Details Get a Quote |
| KIT Knockout A-549 Cell Line | EDJ-KQ62216 | Human | 3815 | Details Get a Quote |
| KIT Knockout HCT 116 Cell Line | EDJ-KQ70702 | Human | 3815 | Details Get a Quote |
| KIT (p.V559A) Point Mutation in HCT 116 Cell Line | EDC03176 | Human | 3815 | Details Get a Quote |
| KIT (p.V560D) Point Mutation in HCT 116 Cell Line | EDC03120 | Human | 3815 | Details Get a Quote |
| KIT (p.L862=) Point Mutation in HAP1 Cell Line | EDC03525 | Human | 3815 | Details Get a Quote |
| KIT (p.S967=) Point Mutation in HAP1 Cell Line | EDC03526 | Human | 3815 | Details Get a Quote |
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