KIT
Chr 4ADIsolated casesKIT proto-oncogene, receptor tyrosine kinase
Also known as: C-Kit, CD117, MASTC, PBT, SCFR
This gene encodes a receptor tyrosine kinase. This gene was initially identified as a homolog of the feline sarcoma viral oncogene v-kit and is often referred to as proto-oncogene c-Kit. The canonical form of this glycosylated transmembrane protein has an N-terminal extracellular region with five immunoglobulin-like domains, a transmembrane region, and an intracellular tyrosine kinase domain at the C-terminus. Upon activation by its cytokine ligand, stem cell factor (SCF), this protein phosphorylates multiple intracellular proteins that play a role in in the proliferation, differentiation, migration and apoptosis of many cell types and thereby plays an important role in hematopoiesis, stem cell maintenance, gametogenesis, melanogenesis, and in mast cell development, migration and function. This protein can be a membrane-bound or soluble protein. Mutations in this gene are associated with gastrointestinal stromal tumors, mast cell disease, acute myelogenous leukemia, and piebaldism. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2020]
Primary Disease Associations & Inheritance
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly LoF-intolerant (top ~10% of genes)
Moderately missense-constrained (top ~2.5%)
This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function, loss-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
KIT · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
Gene2Phenotype Curations
Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
A New Treatment of Newly Diagnosed KIT Mutation CBF-Acute Myeloid Leukemia
RECRUITINGDietary Strategy to Tackle Cognitive and Locomotor Abilities in Early Elderly Subjects
RECRUITINGSpanish Study for Molecular Characterization of Thyroid Carcinoma
ACTIVE NOT RECRUITINGA Study Providing Genetic Testing to Find Those Who May Have Primary Ciliary Dyskinesia for Potential Clinical Trials
ACTIVE NOT RECRUITINGGenetic Investigations in Spontaneous Coronary Artery Dissection (SCAD)
ENROLLING BY INVITATIONVaginal CO2 Laser Therapy for Genitourinary Syndrome in Breast Cancer Survivors
RECRUITINGIntern Health Study
ENROLLING BY INVITATIONPMPR and Chlorhexidine on Periodontal Disease and Vascular Function
NOT YET RECRUITINGPrecision Physical Exercise for Personalized Onco-Hematology.
NOT YET RECRUITINGThe Texas Interprofessional Pharmacogenomics (IPGx)
RECRUITINGCARE-CRC: Microbiome Insights and Correlations for Risk and Outcomes in Colorectal Cancer
NOT YET RECRUITINGMRI Functional Imaging Characteristics and Fat Quantification of CT-fat-free Renal Neoplasms: Relationships With Histological Classifications and Molecular Markers
ACTIVE NOT RECRUITINGExternal Resources
Links to major genomics databases and tools