FLT3

Chr 13

fms related receptor tyrosine kinase 3

Also known as: CD135, FLK-2, FLK2, STK1

NCBI Gene: 2322 ENSG00000122025 UniProt: P36888

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.

ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a class III receptor tyrosine kinase that regulates hematopoiesis. This receptor is activated by binding of the fms-related tyrosine kinase 3 ligand to the extracellular domain, which induces homodimer formation in the plasma membrane leading to autophosphorylation of the receptor. The activated receptor kinase subsequently phosphorylates and activates multiple cytoplasmic effector molecules in pathways involved in apoptosis, proliferation, and differentiation of hematopoietic cells in bone marrow. Mutations that result in the constitutive activation of this receptor result in acute myeloid leukemia and acute lymphoblastic leukemia. [provided by RefSeq, Jan 2015]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtLeukemia, acute myelogenous

Clinical highlights

Gene–disease validity (ClinGen)

Limited · leukemia, acute myeloid, susceptibility to · AD · ClinGen 2025

not for standalone diagnostic reporting

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

1052

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.35

LOEUF· LoF intol.

Multiple*

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.35LOEUF

pLI 0.608

Z-score 5.42

OE 0.22 (0.14–0.35)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

0.98Z-score

OE missense 0.88 (0.81–0.95)

461 obs / 524.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.22 (0.14–0.35)

0≤0.351.4

Missense OE?0.88 (0.81–0.95)

0≤0.61.4

Synonymous OE?1.01

0≤1.21.6

LoF obs/exp: 12 / 55.6Missense obs/exp: 461 / 524.3Syn Z: -0.10

Background carrier burden — how many people carry a rare variant somewhere in FLT3?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 45

1,132 rare PASS variants

Rare truncating (LoF)

1 in 2,600

106 rare PASS variants

Rare synonymous (reference)

1 in 76

433 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for FLT3. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 73	1 in 2,800
South Asian	~43k	1 in 40	1 in 2,400
Remaining (unassigned)	~30k	1 in 45	1 in 4,300
European (Finnish)	~27k	1 in 290	1 in 2,700
Admixed American	~22k	1 in 51	1 in 1,100
African / African American	~21k	1 in 53	1 in 1,600
East Asian	~20k	1 in 55	1 in 2,800
Ashkenazi Jewish	~13k	1 in 330	1 in 1,200
Middle Eastern	~2,884	1 in 82	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 18 of 24 coding exons well covered in gnomAD exomes; exons 1, 2, 4, 10, 16, 22 marginal. Genomes: all 24.? see exons ↓

ClinVar Variant Classifications

0 submitted variants in ClinVar

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.

External Resources

Links to major genomics databases and tools

Franklin by Genoox

AI-powered variant curation and clinical analysis

DECIPHER

Genomic variants and phenotypes in rare disease patients

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

FLT3 Gene MutationAML

The Efficacy of Triple Regimen in Newly Diagnosed AML Patients With FLT3 Mutation

RECRUITING

NCT06561880Phase PHASE1, PHASE2Institute of Hematology & Blood Diseases Hospital, ChinaStarted 2024-10-08

VenetoclaxCytarabineGilteritinib

Acute Myeloid Leukemia With t(9;11)(p22.3;q23.3); MLLT3-KMT2AFibroblast Growth Factor Basic Form MeasurementFLT3 Internal Tandem Duplication

Nintedanib and Azacitidine in Treating Participants With HOX Gene Overexpression Relapsed or Refractory Acute Myeloid Leukemia

ACTIVE NOT RECRUITING

NCT03513484Phase PHASE1Northwestern UniversityStarted 2018-11-14

AzacitidineLaboratory Biomarker AnalysisNintedanib

Acute Myeloid LeukemiaFLT3 Gene MutationAdult AML

Efficacy of Gilteritinib in Combination With FLAI as Induction Therapy of FLT3-positive Acute Myeloid Leukemia

NOT YET RECRUITING

NCT06667973Phase PHASE2Gruppo Italiano Malattie EMatologiche dell'AdultoStarted 2025-06

Gilteritinib

Acute Myeloid Leukemia

Combination of Midostaurin and Gemtuzumab Ozogamicin in First-line Standard Therapy for Acute Myeloid Leukemia (MOSAIC)

RECRUITING

NCT04385290Phase PHASE1, PHASE2Technische Universität DresdenStarted 2020-09-04

MODULE: conventional chemotherapy (Cytarabine+Daunorubicin) in combination with midostaurin+GOMAGNOLIA-trial: Midostaurin associated with conventional chemotherapy (AraC+DNR)+GOMAGNOLIA-trial: conventional chemotherapy (AraC+DNR)+GO

Acute Myeloid Leukemia (AML)

A Study of Gilteritinib in Combination With Ivosidenib or Enasidenib in People With Acute Myeloid Leukemia (AML)

ACTIVE NOT RECRUITING

NCT05756777Phase PHASE1Memorial Sloan Kettering Cancer CenterStarted 2023-10-25

GilteritinibIvosidenibEnasidenib

Acute Myeloid Leukemia (AML)FLT3-mutated Acute Myeloid Leukemia

A Study of Gilteritinib, Venetoclax and Azacitidine as a Combined Treatment for People Newly Diagnosed With Acute Myeloid Leukemia

ACTIVE NOT RECRUITING

NCT05520567Phase PHASE1, PHASE2Astellas Pharma Global Development, Inc.Started 2023-01-31

GilteritinibVenetoclaxAzacitidine

Acute Myeloid Leukemia

A Study to Compare Standard Chemotherapy to Therapy With CPX-351 and/or Gilteritinib for Patients With Newly Diagnosed AML With or Without FLT3 Mutations

RECRUITING

NCT04293562Phase PHASE3Children's Oncology GroupStarted 2020-07-21

Allogeneic Hematopoietic Stem Cell TransplantationAsparaginase Erwinia chrysanthemiBiospecimen Collection

AML With Gene Mutations

Dose Escalation and Expansion Study to Evaluate the Safety, PK, PD and Efficacy of ZE46-0134 in Adults With FLT3 Mutated or Spliceosome Mutated Relapsed or Refractory Acute Myeloid Leukemia

RECRUITING

NCT06366789Phase PHASE1Lomond Therapeutics Holdings, Inc.Started 2024-05-29

ZE46-0134

Acute Myeloid Leukemia With FLT3/ITD MutationAcute Myeloid Leukemia With KMT2A RearrangementAcute Myeloid Leukemia With NPM1 Mutation

SNDX-5613 and Gilteritinib for the Treatment of Relapsed or Refractory FLT3-Mutated Acute Myeloid Leukemia and Concurrent MLL-Rearrangement or NPM1 Mutation

RECRUITING

NCT06222580Phase PHASE1Uma BorateStarted 2024-02-20

Biospecimen CollectionBone Marrow Aspiration and BiopsyGilteritinib

Clinical Literature

Open Research Assistant →

Landmark / reviewRecent case evidence

Full-Text Mentions

NLP-detected gene mentions in article bodies · via PubTator3

PubTator3

Targeting FLT3 for treating diseases: FLT3 inhibitors.

Rong QY et al.·Drug Discov Today

2025