FLT1
Chr 13fms related receptor tyrosine kinase 1
Also known as: FLT, FLT-1, VEGFR-1, VEGFR1
This gene encodes VEGFR-1, a receptor tyrosine kinase that binds VEGF-A, VEGF-B, and placental growth factor to regulate angiogenesis, vasculogenesis, and endothelial cell survival during embryonic development and in adulthood. Mutations cause autosomal dominant retinal arterial macroaneurysm with supravalvular pulmonic stenosis, a condition affecting the cardiovascular and ocular systems. The gene is highly constrained against loss-of-function variants (pLI = 1.0, LOEUF = 0.25), indicating that most loss-of-function mutations are likely pathogenic.
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 (loss-of-function and gain-of-function). The Badonyi & Marsh model scores gain-of-function highest among its predictions, but genomic evidence (constraint, ClinVar variant spectrum, and literature) most strongly supports loss-of-function (haploinsufficiency). 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. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
FLT1 · 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
Testing Oral Decitabine and Cedazuridine (ASTX727) in Combination With Venetoclax for Higher-Risk Acute Myeloid Leukemia Patients
ACTIVE NOT RECRUITINGA Single Center, Single Arm Clinical Study on the Treatment of Advanced Non-small Cell Lung Cancer With Positive EGFR Sensitive Mutations and Failed EGFR TKIs With the Combination of Enrotinib and Paclitaxel Monoclonal Antibody
NOT YET RECRUITINGStatin Intervention for Severe Early-Onset Placental Insufficiency. (STATIN-PRE Trial)
RECRUITINGRevumenib in Combination With 7+3 + Midostaurin in AML
RECRUITINGTAPUR: Testing the Use of Food and Drug Administration (FDA) Approved Drugs That Target a Specific Abnormality in a Tumor Gene in People With Advanced Stage Cancer
RECRUITINGAutophagy/Apoptosis Balance in Placental Vascular Pathologies
RECRUITINGSafety of Recombinant Human IL-21-expressing Oncolytic Vaccinia Virus Injection (hV01) in Advanced Tumors
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 RECRUITINGCombination of Midostaurin and Gemtuzumab Ozogamicin in First-line Standard Therapy for Acute Myeloid Leukemia (MOSAIC)
RECRUITINGCanadian Profiling and Targeted Agent Utilization Trial (CAPTUR)
RECRUITINGExternal Resources
Links to major genomics databases and tools