FLT3
Chr 13fms related receptor tyrosine kinase 3
Also known as: CD135, FLK-2, FLK2, STK1
This gene encodes FMS-like tyrosine kinase 3, a receptor tyrosine kinase that regulates hematopoietic cell differentiation, proliferation, and survival by binding FLT3 ligand and activating downstream signaling pathways including RAS, MTOR, and STAT5. Somatic mutations causing constitutive kinase activation result in acute lymphoblastic leukemia and acute myeloid leukemia. The gene shows high constraint against loss-of-function variants (LOEUF 0.35), and germline mutations causing pediatric neurologic disease have not been established.
Limited evidence — not for standalone diagnostic reporting
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly LoF-intolerant (top ~10% of genes)
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (gain-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.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
FLT3 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
Tolerability and Efficacy of Midostaurin to 10-day Decitabine in Unfit Adult AML and High Risk MDS Patients
ACTIVE NOT RECRUITINGVenetoclax and HMA Treatment of Older and Unfit Adults With FLT3 Mutated Acute Myeloid Leukemia (AML) (A MyeloMATCH Treatment Trial)
RECRUITINGRevumenib in Combination With 7+3 + Midostaurin in AML
RECRUITINGMulticenter, Platform-type Clinical Study of Refractory/Recurrent Acute Myeloid Leukemia
RECRUITINGMRD-positive AML Clinical Study
RECRUITINGNintedanib and Azacitidine in Treating Participants With HOX Gene Overexpression Relapsed or Refractory Acute Myeloid Leukemia
ACTIVE NOT RECRUITINGCombination of Midostaurin and Gemtuzumab Ozogamicin in First-line Standard Therapy for Acute Myeloid Leukemia (MOSAIC)
RECRUITINGA Study of BN104 in the Treatment of Acute Leukemia
ACTIVE NOT RECRUITINGThe Prognostic Significance of Platelet to White Blood Cell Ratio (PWR) in Patients With Acute Myeloid Leukemia
NOT YET RECRUITINGTesting Oral Decitabine and Cedazuridine (ASTX727) in Combination With Venetoclax for Higher-Risk Acute Myeloid Leukemia Patients
ACTIVE NOT RECRUITINGA Study of Gilteritinib, Venetoclax and Azacitidine as a Combined Treatment for People Newly Diagnosed With Acute Myeloid Leukemia
ACTIVE NOT RECRUITINGA Study of Gilteritinib Versus Midostaurin in Combination With Induction and Consolidation Therapy Followed by One-year Maintenance in Patients With Newly Diagnosed Acute Myeloid Leukemia or Myelodysplastic Syndromes With Excess Blasts-2 With FLT3 Mutations Eligible for Intensive Chemotherapy
ACTIVE NOT RECRUITINGExternal Resources
Links to major genomics databases and tools