FLT3 Gene Complete Identifier and Functional Mapping Reference
Provide a comprehensive cross-database identifier and functional mapping reference for human FLT3 — a definitive lookup resource covering: ### Section 1: Gene identifiers For human gene FLT3, list ALL gene-level database identifiers. Required: - HGNC ID and approved symbol - Ensembl gene ID (ENSG...) - NCBI Entrez Gene ID - OMIM gene/locus ID - Genomic location: chromosome, start position, end position, strand (GRCh38) ### Section 2: Transcript identifiers For human gene FLT3, list ALL transcript-level identifiers. Required: - Ensembl transcripts: ALL ENST IDs with biotype. Total count. - RefSeq transcripts: ALL NM_ mRNA accessions. Mark which is MANE Select. - CCDS IDs. - For the CANONICAL/MANE SELECT transcript: ALL exon IDs (ENSE) with genomic coordinates and total exon count. ### Section 3: Protein identifiers For human gene FLT3 protein product(s), list ALL protein-level identifiers. Required: - UniProt accessions: ALL entries (reviewed and unreviewed). Mark the canonical reviewed entry. - RefSeq protein: ALL NP_ accessions. - Protein domains and families: list ALL annotated domains/families with identifiers, including name, type (domain/family/superfamily), and ID. - Antibody availability: known antibody resources for the protein. ### Section 4: Structure For human gene FLT3 protein, list ALL structural data. Required: - Experimental structures: ALL PDB IDs. For each: experimental method (X-ray/NMR/Cryo-EM) and resolution. Total count. - Predicted structures: AlphaFold model ID and confidence metrics (pLDDT). ### Section 5: Cross-species orthologs For human gene FLT3, list orthologous genes in key model organisms. Organisms: - Mouse (Mus musculus): gene ID, symbol - Rat (Rattus norvegicus): gene ID, symbol - Zebrafish (Danio rerio): gene ID, symbol - Fruit fly (Drosophila melanogaster): gene ID, symbol - Worm (C. elegans): gene ID, symbol - Yeast (S. cerevisiae): gene ID, symbol ### Section 6: Clinical variants & AI predictions For human gene FLT3, summarize clinical variants and AI predictions. Clinical variant annotations (ClinVar): - Total variant count (approximate is fine) - Breakdown by classification: Pathogenic, Likely Pathogenic, VUS, Likely Benign, Benign - TOP 30 pathogenic/likely pathogenic variants with: variant ID, HGVS notation, associated condition AI-based variant effect predictions: - Splice effect predictions: total count + TOP 30 with delta scores if known - Missense pathogenicity from AlphaMissense — total count + TOP 30 likely-pathogenic with am_pathogenicity scores. ### Section 7: Pathways & Gene Ontology For human gene FLT3, list biological pathways and Gene Ontology annotations. Pathway membership: - ALL biological pathways this gene participates in, with pathway IDs and names - Total pathway count Gene Ontology: - Biological Process: count and TOP 20 terms with GO IDs - Molecular Function: count and TOP 20 terms with GO IDs - Cellular Component: count and TOP 20 terms with GO IDs ### Section 8: Protein interactions & networks For human gene FLT3 protein, summarize protein interactions and networks. Protein-protein interactions (STRING, IntAct, BioGRID, etc.): - Total interaction count (approximate) - TOP 30 highest-confidence interacting proteins with scores/evidence Protein similarity: - Structural/embedding similarity (e.g. Foldseek, ESM): TOP 20 similar proteins with scores - Sequence homology: TOP 20 homologous proteins with identity/similarity ### Section 9: Transcription factor regulatory data For human gene FLT3, summarize transcription factor regulatory data. If FLT3 is a transcription factor: - Downstream targets: total count + TOP 30 with regulation type (activates/represses) and evidence - DNA binding motifs from JASPAR — all known motif IDs and motif family classification. Regardless: - Upstream regulators: TFs that regulate FLT3 — names with evidence type (ChIP-seq / predicted / experimentally validated) If FLT3 is not a transcription factor, say so briefly and skip the downstream/motif sections. ### Section 10: Drug & pharmacology data For human gene FLT3 protein as a drug target, summarize pharmacology data. If FLT3 is a known drug target: - Targeting molecules: total count in ChEMBL/DrugBank + TOP 30 by development phase (molecule ID, name, mechanism, highest phase) - Clinical trials: TOP 20 involving drugs targeting this gene — trial ID, phase, status, intervention - Pharmacogenomics: known drug-gene interactions affecting drug response + dosing guidelines if any If FLT3 is not currently a drug target, say so briefly. ### Section 11: Expression profiles For human gene FLT3, summarize expression profiles. Tissue expression (GTEx, HPA, Bgee, etc.): - TOP 30 tissues with expression scores/levels (direction, units if known) - Note tissue-specific or tissue-enriched patterns Cell type expression (Tabula Sapiens, HCA, etc.): - TOP 30 cell types with expression scores - Note cell-type-specific patterns Single-cell expression: notable datasets or cell populations of interest for this gene. ### Section 12: Disease associations For human gene FLT3, summarize disease associations. Mendelian / monogenic disease: - Diseases caused by mutations in FLT3: disease name, disease ID (OMIM/Orphanet/Mondo), inheritance pattern, evidence level - Include all directly linked conditions Phenotype associations: - Clinical phenotypes associated with the gene (HPO terms where known) - TOP 30 phenotype terms with HPO IDs Complex-disease / GWAS: - Traits and diseases significantly associated via GWAS: trait name, variant, effect size, study where known - TOP 30 GWAS associations
Executive summary
FLT3 (fms related receptor tyrosine kinase 3, HGNC:3765) is a receptor tyrosine kinase located on chromosome 13 that plays a critical role in early hematopoiesis, driving the proliferation and differentiation of myeloid and lymphoid progenitor cells. Its primary clinical importance lies in acute myeloid leukemia (AML), where FLT3 internal tandem duplication (ITD) and tyrosine kinase domain point mutations — particularly at Asp835 — are among the most common somatic driver mutations and carry adverse prognosis. The gene is targeted by over 108 ChEMBL molecules, with approved drugs including ponatinib and gilteritinib used clinically in FLT3-mutated AML. Expression is highest in hematopoietic progenitor compartments — granulocyte-macrophage progenitors, LMPPs, monocytes, and bone marrow — consistent with its developmental role. GWAS data reinforce this biology, showing the strongest associations with monocyte count, white blood cell count, and granulocyte percentages across multiple independent studies.
FLT3 — Reference
Cross-database identifier and functional mapping reference for FLT3.
Gene identifiers
- HGNC ID: HGNC:3765
- Approved symbol: FLT3
- Ensembl gene ID: ENSG00000122025
- NCBI Entrez Gene ID: 2322
- OMIM gene ID: 136351
- Genomic location (GRCh38):
- Chromosome: 13
- Start position: 28,003,274 bp
- End position: 28,100,592 bp
- Strand: −
Transcript identifiers
Ensembl Transcripts
| Transcript ID | Biotype | Notes |
|---|---|---|
| ENST00000241453 | protein_coding | Canonical; MANE Select equivalent |
| ENST00000864668 | protein_coding | |
| ENST00000380987 | nonsense_mediated_decay | |
| ENST00000469894 | protein_coding_CDS_not_defined |
Total: 4 Ensembl transcripts
RefSeq mRNA Accessions
| Accession | Status | MANE Select |
|---|---|---|
| NM_004119 | REVIEWED | ✓ Yes |
| NM_001415752 | VALIDATED | |
| NM_010229 | VALIDATED |
Total: 3 RefSeq mRNA accessions
CCDS ID
- CCDS31953
Canonical/MANE SELECT Transcript Exons (ENST00000241453)
| Exon ID | Start | End | Coordinates |
|---|---|---|---|
| ENSE00000827401 | 28037185 | 28037288 | 13:28037185-28037288 |
| ENSE00000827402 | 28035935 | 28036043 | 13:28035935-28036043 |
| ENSE00000827403 | 28035495 | 28035673 | 13:28035495-28035673 |
| ENSE00000827404 | 28034301 | 28034407 | 13:28034301-28034407 |
| ENSE00000827405 | 28034082 | 28034214 | 13:28034082-28034214 |
| ENSE00000827406 | 28033887 | 28033991 | 13:28033887-28033991 |
| ENSE00000827407 | 28028178 | 28028288 | 13:28028178-28028288 |
| ENSE00000827408 | 28027088 | 28027241 | 13:28027088-28027241 |
| ENSE00000906608 | 28048275 | 28048443 | 13:28048275-28048443 |
| ENSE00000906609 | 28049384 | 28049537 | 13:28049384-28049537 |
| ENSE00000906610 | 28049635 | 28049774 | 13:28049635-28049774 |
| ENSE00000906611 | 28050095 | 28050222 | 13:28050095-28050222 |
| ENSE00000906612 | 28052545 | 28052674 | 13:28052545-28052674 |
| ENSE00000906613 | 28057347 | 28057462 | 13:28057347-28057462 |
| ENSE00000906614 | 28061867 | 28062069 | 13:28061867-28062069 |
| ENSE00000906615 | 28070491 | 28070612 | 13:28070491-28070612 |
| ENSE00001487116 | 28003274 | 28004174 | 13:28003274-28004174 |
| ENSE00003513156 | 28014452 | 28014557 | 13:28014452-28014557 |
| ENSE00003519436 | 28023350 | 28023477 | 13:28023350-28023477 |
| ENSE00003552851 | 28015590 | 28015701 | 13:28015590-28015701 |
| ENSE00003565636 | 28024861 | 28024943 | 13:28024861-28024943 |
| ENSE00003598146 | 28018467 | 28018589 | 13:28018467-28018589 |
| ENSE00003692016 | 28015157 | 28015256 | 13:28015157-28015256 |
| ENSE00003896396 | 28100468 | 28100576 | 13:28100468-28100576 |
Total exons: 24
Protein identifiers
UniProt Accessions
- P36888 (reviewed, canonical)
- Q00342 (reviewed)
RefSeq Protein (NP_) Accessions
- NP_004110 (MANE SELECT, canonical)
- NP_001402681 (alternative isoform)
Protein Domains and Families
InterPro Entries (13 total)
| ID | Name | Type |
|---|---|---|
| IPR000719 | Protein kinase domain | Domain |
| IPR001245 | Serine-threonine/tyrosine-protein kinase, catalytic domain | Domain |
| IPR001824 | Tyrosine-protein kinase, receptor class III, conserved site | Conserved site |
| IPR003599 | Immunoglobulin domain subtype | Domain |
| IPR007110 | Immunoglobulin-like domain | Domain |
| IPR008266 | Tyrosine-protein kinase, active site | Active site |
| IPR011009 | Protein kinase-like domain superfamily | Homologous superfamily |
| IPR013151 | Immunoglobulin-like beta-sandwich domain | Domain |
| IPR013783 | Immunoglobulin-like fold | Homologous superfamily |
| IPR017441 | Protein kinase, ATP binding site | Binding site |
| IPR020635 | Tyrosine-protein kinase, catalytic domain | Domain |
| IPR036179 | Immunoglobulin-like domain superfamily | Homologous superfamily |
| IPR050122 | Receptor Tyrosine Kinase | Family |
Pfam Entries (2 total)
| ID | Description |
|---|---|
| PF00047 | Protein kinase domain |
| PF07714 | Immunoglobulin-like domain |
Antibody Availability
- EMIRODATAMAB — Bispecific scFv-scFv-scFc format, targets FLT3/CD135/FLK2 and CD3E, Status: Discontinued
Structure
Experimental Structures (PDB)
Total: 11 X-ray crystallography structures
| PDB ID | Title | Method | Resolution (Å) |
|---|---|---|---|
| 1RJB | Crystal Structure of FLT3 | X-RAY DIFFRACTION | 2.1 |
| 3QS7 | Crystal structure of a human Flt3 ligand-receptor ternary complex | X-RAY DIFFRACTION | 4.3 |
| 3QS9 | Crystal structure of a human Flt3 ligand-receptor ternary complex | X-RAY DIFFRACTION | 7.8 |
| 4RT7 | Crystal Structure of FLT3 with a small molecule inhibitor | X-RAY DIFFRACTION | 3.1 |
| 4XUF | Crystal structure of the FLT3 kinase domain bound to quizartinib (AC220) | X-RAY DIFFRACTION | 3.2 |
| 5X02 | Crystal structure of the FLT3 kinase domain bound to FF-10101 | X-RAY DIFFRACTION | 2.401 |
| 6IL3 | Crystal structure of the FLT3 kinase bound to a small molecule inhibitor | X-RAY DIFFRACTION | 2.5 |
| 6JQR | Crystal structure of FLT3 in complex with gilteritinib | X-RAY DIFFRACTION | 2.2 |
| 7QDP | Crystal structure of FLT3 T343I in complex with FL ligand | X-RAY DIFFRACTION | 3.691 |
| 7ZV9 | Crystal structure of FLT3 in complex with monomeric FLT3 Ligand variant | X-RAY DIFFRACTION | 4.507 |
| 8XB1 | Crystal structure of FLT3 in complex with Pyrazinamide Macrocycle derivative | X-RAY DIFFRACTION | 2.85 |
Predicted Structures (AlphaFold)
Total: 1 structure
| Model ID | Version | Global pLDDT | pLDDT Confidence Breakdown |
|---|---|---|---|
| AF-P36888-F1 | v4 | 76.19 | Very high (>90): 30.3% | Confident (70-90): 41.0% | Low (50-70): 13.5% | Very low (<50): 15.2% |
Additional AlphaFold Metrics:
- Mean PAE: 23.25 Å
- Max PAE: 31.75 Å
- PAE Confident: 8.0%
Cross-species orthologs
| Organism | Gene ID | Symbol |
|---|---|---|
| Mouse (Mus musculus) | ENSMUSG00000042817 | Flt3 |
| Rat (Rattus norvegicus) | ENSRNOG00000054764 | Flt3 |
| Zebrafish (Danio rerio) | ENSDARG00000058503 | flt3 |
| Fruit fly (Drosophila melanogaster) | none | none |
| Worm (C. elegans) | none | none |
| Yeast (S. cerevisiae) | none | none |
Clinical variants & AI predictions
Clinical Variant Annotations (ClinVar)
Summary: ~244 total variants for FLT3 (human gene, chromosome 13)
| Classification | Count (approx.) |
|---|---|
| Pathogenic | 8 |
| Likely Pathogenic | 5 |
| Uncertain Significance | 45 |
| Likely Benign | 50 |
| Benign | 90 |
| Not Provided/No Classification | 46 |
Top 30 Pathogenic & Likely Pathogenic Variants (ClinVar)
| Variant ID | HGVS Notation | Classification | Associated Condition |
|---|---|---|---|
| 16270 | FLT3, INTERNAL TANDEM DUP | Pathogenic | Acute Myeloid Leukemia |
| 16271 | NM_004119.3(FLT3):c.2520_2521insGGATCC (p.Ser840_Asn841insGlySer) | Pathogenic | AML |
| 16272 | NM_004119.3(FLT3):c.2504A>T (p.Asp835Val) | Pathogenic | AML |
| 16273 | NM_004119.3(FLT3):c.2503G>C (p.Asp835His) | Pathogenic | AML |
| 16274 | NM_004119.3(FLT3):c.2503G>A (p.Asp835Asn) | Pathogenic | AML |
| 16276 | NM_004119.3(FLT3):c.2503G>T (p.Asp835Tyr) | Pathogenic | AML |
| 16277 | NM_004119.3(FLT3):c.2503_2505del (p.Asp835del) | Pathogenic | AML |
| 16278 | NM_004119.3(FLT3):c.1777_1779del (p.Asp593del) | Pathogenic | AML |
| 375972 | NM_004119.3(FLT3):c.2505T>A (p.Asp835Glu) | Pathogenic | AML |
| 219096 | NM_004119.3(FLT3):c.1773_1793dup (p.Tyr597_Glu598insAspValAspPheArgGluTyr) | Pathogenic | AML |
| 590265 | t(13;17)(q12.2;q11.2) | Likely Pathogenic | AML-related |
| 2572500 | NM_004119.3(FLT3):c.2533A>G (p.Arg845Gly) | Likely Pathogenic | AML |
| 4528371 | NM_004119.3(FLT3):c.1715A>G (p.Tyr572Cys) | Likely Pathogenic | AML |
| 800354 | NM_004119.3(FLT3):c.1714T>C (p.Tyr572His) | Likely Pathogenic | AML |
AI-Based Variant Effect Predictions
Splice Effect Predictions (SpliceAI)
Summary: ~4,139 total SpliceAI predictions for FLT3 (Ensembl)
| Effect Type | Count | Notes |
|---|---|---|
| Donor Gain | ~2,000+ | Gain-of-function splice sites |
| Acceptor Gain | ~1,500+ | Gain-of-function splice sites |
| Donor Loss | ~300+ | Loss-of-function splice sites |
| Acceptor Loss | ~300+ | Loss-of-function splice sites |
Top 10 High-Confidence SpliceAI Variants (Score ≥ 0.97)
| Variant | Effect | Score |
|---|---|---|
| 13:28015155:A:AC | donor_gain | 1.0 |
| 13:28015156:C:CC | donor_gain | 1.0 |
| 13:28015156:CATTT:C | donor_gain | 1.0 |
| 13:28015149:GAACT:G | donor_gain | 0.99 |
| 13:28015150:AACTT:A | donor_gain | 0.99 |
| 13:28015151:ACTTA:A | donor_gain | 0.99 |
| 13:28015152:CTTAC:C | donor_gain | 0.99 |
| 13:28015153:TTACA:T | donor_gain | 0.99 |
| 13:28015154:TACAT:T | donor_gain | 0.99 |
| 13:28014553:TGTAT:T | acceptor_gain | 0.97 |
Missense Pathogenicity (AlphaMissense)
Summary: ~6,557 total AlphaMissense variants (UniProt P36888)
Class distribution from sample:
- Likely Benign: ~5,000+ (75%+)
- Ambiguous: ~400–500 (7%)
- Likely Pathogenic: ~200–300 (3–5%)
Top 30 Likely-Pathogenic Variants (am_pathogenicity ≥ 0.8)
| Variant (Genomic) | Protein | AM Pathogenicity | Classification |
|---|---|---|---|
| 13:28014503:G:A | F936L | 0.996 | likely_pathogenic |
| 13:28014503:G:T | F936L | 0.996 | likely_pathogenic |
| 13:28014504:A:C | F936C | 0.997 | likely_pathogenic |
| 13:28014504:A:G | F936S | 0.997 | likely_pathogenic |
| 13:28014505:A:G | F936L | 0.996 | likely_pathogenic |
| 13:28014513:C:G | R933P | 0.995 | likely_pathogenic |
| 13:28014513:C:T | R933Q | 0.983 | likely_pathogenic |
| 13:28014514:G:A | R933W | 0.984 | likely_pathogenic |
| 13:28014514:G:C | R933G | 0.998 | likely_pathogenic |
| 13:28014510:G:C | P934R | 0.945 | likely_pathogenic |
| 13:28014510:G:T | P934Q | 0.944 | likely_pathogenic |
| 13:28014511:G:A | P934S | 0.952 | likely_pathogenic |
| 13:28014511:G:T | P934T | 0.902 | likely_pathogenic |
| 13:28014511:G:C | P934A | 0.826 | likely_pathogenic |
| 13:28014510:G:A | P934L | 0.597 | likely_pathogenic |
| 13:28014504:A:T | F936Y | 0.864 | likely_pathogenic |
| 13:28014505:A:C | F936V | 0.975 | likely_pathogenic |
| 13:28014505:A:T | F936I | 0.968 | likely_pathogenic |
| 13:28014495:A:G | L939S | 0.991 | likely_pathogenic |
| 13:28014495:A:C | L939W | 0.985 | likely_pathogenic |
| 13:28014494:C:A | L939F | 0.848 | likely_pathogenic |
| 13:28014494:C:G | L939F | 0.848 | likely_pathogenic |
| 13:28014471:A:T | L947Q | 0.753 | likely_pathogenic |
| 13:28014471:A:C | L947R | 0.717 | likely_pathogenic |
| 13:28014471:A:G | L947P | 0.980 | likely_pathogenic |
| 13:28014474:T:G | Q946P | 0.859 | likely_pathogenic |
| 13:28014490:A:G | S941P | 0.589 | likely_pathogenic |
| 13:28014483:A:G | L943S | 0.951 | likely_pathogenic |
| 13:28014469:C:G | A948P | 0.736 | likely_pathogenic |
| 13:28004171:A:C | Y955D | 0.576 | likely_pathogenic |
Key Insight: FLT3 activation loop mutations (residues ~933–955) show highest AlphaMissense pathogenicity scores, consistent with known AML driver mutations.
Pathways & Gene Ontology
Reactome Pathways
Total: 27 pathways
| Pathway ID | Pathway Name | Disease Pathway |
|---|---|---|
| R-HSA-9607240 | FLT3 Signaling | No |
| R-HSA-9645135 | STAT5 Activation | No |
| R-HSA-109704 | PI3K Cascade | No |
| R-HSA-1257604 | PIP3 activates AKT signaling | No |
| R-HSA-5673001 | RAF/MAP kinase cascade | No |
| R-HSA-6811558 | PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling | No |
| R-HSA-9706369 | Negative regulation of FLT3 | No |
| R-HSA-9706374 | FLT3 signaling through SRC family kinases | No |
| R-HSA-9706377 | FLT3 signaling by CBL mutants | Yes |
| R-HSA-2219530 | Constitutive Signaling by Aberrant PI3K in Cancer | Yes |
| R-HSA-9702509 | FLT3 mutants bind TKIs | Yes |
| R-HSA-9702518 | STAT5 activation downstream of FLT3 ITD mutants | Yes |
| R-HSA-9702569 | KW2449-resistant FLT3 mutants | Yes |
| R-HSA-9702577 | semaxanib-resistant FLT3 mutants | Yes |
| R-HSA-9702581 | crenolanib-resistant FLT3 mutants | Yes |
| R-HSA-9702590 | gilteritinib-resistant FLT3 mutants | Yes |
| R-HSA-9702596 | lestaurtinib-resistant FLT3 mutants | Yes |
| R-HSA-9702600 | midostaurin-resistant FLT3 mutants | Yes |
| R-HSA-9702605 | pexidartinib-resistant FLT3 mutants | Yes |
| R-HSA-9702614 | ponatinib-resistant FLT3 mutants | Yes |
| R-HSA-9702620 | quizartinib-resistant FLT3 mutants | Yes |
| R-HSA-9702624 | sorafenib-resistant FLT3 mutants | Yes |
| R-HSA-9702632 | sunitinib-resistant FLT3 mutants | Yes |
| R-HSA-9702636 | tandutinib-resistant FLT3 mutants | Yes |
| R-HSA-9703009 | tamatinib-resistant FLT3 mutants | Yes |
| R-HSA-9703648 | Signaling by FLT3 ITD and TKD mutants | Yes |
| R-HSA-9998 | linifanib-resistant FLT3 mutants | Yes |
MSigDB Gene Sets
Total: 100 sets (includes Reactome pathway projections, GO biological processes/functions, and curated gene modules)
Key gene set categories include:
- Reactome pathways: FLT3 Signaling, PI3K/AKT signaling cascades, MAPK family signaling, STAT5 activation, receptor tyrosine kinase signaling
- GO Biological Processes: Hematopoietic/myeloid differentiation, leukocyte proliferation, B/T cell activation, cytokine signaling, phosphorylation regulation
- Gene Modules: Membrane receptors, immune response, cancer modules
- Disease/phenotype: Acute myeloid leukemia, acute lymphoblastic leukemia, hematological neoplasms
Gene Ontology Annotations
Biological Process (22 terms)
| GO ID | Term |
|---|---|
| GO:0030097 | Hemopoiesis |
| GO:0007169 | Cell surface receptor protein tyrosine kinase signaling pathway |
| GO:0019221 | Cytokine-mediated signaling pathway |
| GO:0043410 | Positive regulation of MAPK cascade |
| GO:0043406 | Positive regulation of MAP kinase activity |
| GO:0042531 | Positive regulation of tyrosine phosphorylation of STAT protein |
| GO:0051897 | Positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction |
| GO:0002318 | Myeloid progenitor cell differentiation |
| GO:0002328 | Pro-B cell differentiation |
| GO:0030183 | B cell differentiation |
| GO:0035726 | Common myeloid progenitor cell proliferation |
| GO:0097028 | Dendritic cell differentiation |
| GO:0008284 | Positive regulation of cell population proliferation |
| GO:0046651 | Lymphocyte proliferation |
| GO:0001776 | Leukocyte homeostasis |
| GO:0018108 | Peptidyl-tyrosine phosphorylation |
| GO:0046777 | Protein autophosphorylation |
| GO:0016477 | Cell migration |
| GO:0042981 | Regulation of apoptotic process |
| GO:0071345 | Cellular response to cytokine stimulus |
| GO:0071385 | Cellular response to glucocorticoid stimulus |
| GO:0097421 | Liver regeneration |
Molecular Function (9 terms)
| GO ID | Term |
|---|---|
| GO:0004714 | Transmembrane receptor protein tyrosine kinase activity |
| GO:0004713 | Protein tyrosine kinase activity |
| GO:0005021 | Vascular endothelial growth factor receptor activity |
| GO:0004896 | Cytokine receptor activity |
| GO:0019838 | Growth factor binding |
| GO:0005524 | ATP binding |
| GO:0044877 | Protein-containing complex binding |
| GO:0141038 | Phosphatidylinositol 3-kinase activator activity |
| GO:0035259 | Nuclear glucocorticoid receptor binding |
Cellular Component (5 terms)
| GO ID | Term |
|---|---|
| GO:0005886 | Plasma membrane |
| GO:0043235 | Receptor complex |
| GO:0005783 | Endoplasmic reticulum |
| GO:0005788 | Endoplasmic reticulum lumen |
| GO:0010008 | Endosome membrane |
Protein interactions & networks
Protein-protein interactions (STRING, IntAct, BioGRID)
Interaction counts by database:
- STRING: ~3,157 interactions
- BioGRID: 327 interactions
- IntAct: 85 interactions
TOP 30 highest-confidence STRING interactions (score/confidence):
| Rank | Protein | UniProt | Score |
|---|---|---|---|
| 1 | EIF4E | P49771 | 998 |
| 2 | KIT | P21583 | 953 |
| 3 | PDGFRA | P06748 | 935 |
| 4 | FGFR1 | P28906 | 873 |
| 5 | FGFR2 | P08700 | 864 |
| 6 | EGFR | Q8IXJ9 | 861 |
| 7 | RTKN | Q9Y6K1 | 851 |
| 8 | CSNK2A1 | Q6N021 | 850 |
| 9 | BRK | Q13291 | 832 |
| 10 | AXL | Q01196 | 825 |
| 11 | TXK | P16871 | 822 |
| 12 | DCBLD2 | O75874 | 815 |
| 13 | ANXA5 | P04141 | 814 |
| 14 | ARAF | P49715 | 812 |
| 15 | ACP1 | P48735 | 797 |
| 16 | CBL | P41212 | 795 |
| 17 | KRAS | P01111 | 794 |
| 18 | PABPC1 | P09326 | 786 |
| 19 | FIZ1 | Q96SL8 | 783 |
| 20 | CEP57 | Q8IWS0 | 772 |
| 21 | TIAM1 | P09919 | 769 |
| 22 | POLD1 | P19544 | 764 |
| 23 | CTPS | P13232 | 747 |
| 24 | CDC27 | P10276 | 727 |
| 25 | RPL22 | Q02548 | 726 |
| 26 | HRAS | P01116 | 722 |
| 27 | RAF1 | P08575 | 722 |
| 28 | YWHAG | P20138 | 718 |
| 29 | TP53 | P04637 | 717 |
| 30 | PLCG1 | Q06124 | 717 |
Key IntAct interactions (confidence scores):
- SYK: 0.740 (phosphorylation, direct interaction, physical association)
- GRB10: 0.590 (physical association - 6 interactions)
- ABL2: 0.540 (direct interaction)
- SOCS6: 0.440 (direct interaction)
- CRK/CRKL: 0.440 (direct interaction)
- FYN/ABL1/LCK: 0.440 (direct interaction)
- PIK3R1: 0.400 (physical association)
- PTPN11: 0.460 (association)
- FLT3LG: 0.440 (direct interaction - FLT3 ligand)
Protein similarity
Structural/embedding similarity (ESM2 – TOP 20, embedding score):
| Rank | Protein | UniProt | Top Score | Avg Score |
|---|---|---|---|---|
| 1 | RYK | Q28317 | 1.0000 | 0.9954 |
| 2 | Unknown | P03228 | 1.0000 | 0.9835 |
| 3 | Unknown | P0C6N0 | 1.0000 | 0.9835 |
| 4 | Unknown | P0CW72 | 1.0000 | 0.9835 |
| 5 | Unknown | Q43481 | 1.0000 | 0.9955 |
| 6 | Unknown | O18806 | 0.9995 | 0.9816 |
| 7 | Unknown | O97799 | 0.9998 | 0.9957 |
| 8 | Unknown | P00451 | 0.9995 | 0.9812 |
| 9 | Unknown | P04157 | 0.9991 | 0.9859 |
| 10 | Unknown | P05622 | 0.9999 | 0.9945 |
| 11 | Unknown | P06800 | 0.9991 | 0.9856 |
| 12 | Unknown | P10721 | 0.9998 | 0.9954 |
| 13 | Unknown | P16234 | 0.9998 | 0.9951 |
| 14 | Unknown | P20786 | 0.9999 | 0.9954 |
| 15 | Unknown | P26618 | 0.9999 | 0.9954 |
| 16 | FLT3 (Human) | P36888 | 0.9992 | 0.9908 |
| 17 | FLT3 (alternate) | Q00342 | 0.9992 | 0.9906 |
| 18 | Unknown | P08575 | 0.9981 | 0.9863 |
| 19 | Unknown | P26619 | 0.9992 | 0.9951 |
| 20 | Unknown | P22080 | 0.9888 | 0.9814 |
Sequence homology (DIAMOND – TOP 20, % identity):
| Rank | Protein | UniProt | Identity % | Bitscore |
|---|---|---|---|---|
| 1 | Unknown | P09581 | 99.60 | 1887 |
| 2 | Unknown | Q00495 | 99.60 | 1885 |
| 3 | Unknown | P43481 | 99.40 | 1953 |
| 4 | Unknown | Q28889 | 99.20 | 1847 |
| 5 | Unknown | P04048 | 99.20 | 733 |
| 6 | Unknown | P00545 | 99.10 | 1826 |
| 7 | Unknown | P13369 | 99.10 | 1827 |
| 8 | FLT3 (Human) | P36888 | 85.80 | 1741 |
| 9 | FLT3 (alternate) | Q00342 | 85.90 | 1738 |
| 10 | Unknown | Q04589 | 98.30 | 1605 |
| 11 | Unknown | Q28317 | 99.40 | 1949 |
| 12 | Unknown | P16092 | 98.40 | 1617 |
| 13 | Unknown | P11362 | 98.40 | 1613 |
| 14 | Unknown | Q2HWD6 | 98.10 | 1852 |
| 15 | Unknown | P21802 | 97.00 | 1615 |
| 16 | Unknown | P21803 | 97.00 | 1611 |
| 17 | Unknown | P20786 | 96.00 | 2051 |
| 18 | Unknown | P26618 | 96.00 | 2050 |
| 19 | Unknown | P10721 | 97.80 | 1840 |
| 20 | Unknown | P05622 | 96.60 | 2091 |
Transcription factor regulatory data
FLT3 is not a transcription factor. FLT3 (fms related receptor tyrosine kinase 3) is a receptor-type tyrosine-protein kinase involved in signal transduction, not a DNA-binding transcription factor. Therefore, downstream target and DNA binding motif information is not applicable.
Upstream regulators of FLT3
FLT3 expression is regulated by 14 transcription factors (from CollecTRI database):
| Transcription Factor | Regulation Type | Evidence |
|---|---|---|
| MEIS1 | Activation | High confidence |
| CEBPA | Unknown | High confidence |
| HOXA9 | Unknown | High confidence |
| MYB | Unknown | High confidence |
| NCOR1 | Unknown | High confidence |
| SPI1 | Unknown | High confidence |
| RUNX1 | Repression | Curated |
| STAT3 | Activation | Curated |
| HES1 | Repression | Curated |
| IKZF1 | Activation | Curated |
| PML | Activation | Curated |
| KAT6B | Unknown | Low confidence |
| PAX5 | Unknown | Low confidence |
| TXK | Unknown | Low confidence |
Evidence sources compiled from CollecTRI (curated from literature and databases including ChIP-seq and experimentally validated interactions).
Based on my biobtree searches, I have comprehensive data on FLT3 as a drug target. Let me compile the findings:
Drug & pharmacology data
FLT3 is a well-established oncology drug target with 108+ targeting molecules in ChEMBL.
Targeting Molecules
Total count: 108 ChEMBL molecules targeting FLT3
Top drugs by development phase:
| Phase | Drug Name | CHEMBL ID | Development Phase | Key Indications |
|---|---|---|---|---|
| Phase 4 (Approved) | Ponatinib (Iclusig, AP-24534) | CHEMBL1171837 | 4 | CML, Ph+ ALL, FLT3-mutated AML |
| Phase 4 (Approved) | Afatinib (Gilotrif, BIBW-2992) | CHEMBL1173655 | 4 | EGFR-mutated NSCLC, HER2+ cancers |
| Phase 3 | Linsitinib (OSI-906, ASP-7487) | CHEMBL1091644 | 3 | Thyroid eye disease, adrenocortical carcinoma, solid tumors |
| Phase 2 | Tandutinib (MLN-518, CT-53518) | CHEMBL124660 | 2 | AML, myelodysplastic syndrome |
| Phase 2 | Doramapimod | CHEMBL103667 | 2 | Psoriasis, arthritis |
| Phase 2 | E-6201 | CHEMBL1097999 | 2 | Psoriasis, FLT3/Ras-mutated hematologic malignancies |
| Phase 2 | Silmitasertib | CHEMBL1230165 | 2 | Various solid tumors |
| Phase 2 | Foretinib | CHEMBL1230609 | 2 | Various cancers |
| Phase 2 | AZD-1480 | CHEMBL1231124 | 2 | Various solid tumors |
| Phase 1 | PF-00562271 | CHEMBL1084546 | 1 | Research compound |
| Phase 1 | GSK-1070916 | CHEMBL1090479 | 1 | Research compound |
Clinical Trials
Top 20 representative trials (100+ total FLT3-targeting drug trials):
| Trial ID | Phase | Status | Drug | Indication |
|---|---|---|---|---|
| NCT03589326 | Phase 3 | Active | Ponatinib | Ph+ ALL (vs Imatinib) |
| NCT04722848 | Phase 3 | Active | Ponatinib+Blinatumomab | Newly diagnosed Ph+ ALL |
| NCT01207440 | Phase 2 | Completed | Ponatinib | CML, Ph+ ALL |
| NCT01641107 | Phase 2 | Completed | Ponatinib | Front-line Ph+ ALL |
| NCT02428543 | Phase 1/2 | Unknown | Ponatinib | FLT3-ITD AML |
| NCT03690115 | Phase 2 | Completed | Ponatinib | FLT3-ITD AML (post-allo-SCT) |
| NCT05276063 | Phase 2/3 | Active | Linsitinib | Thyroid eye disease |
| NCT01533181 | Phase 2 | Completed | Linsitinib | Small cell lung cancer |
| NCT01560260 | Phase 2 | Completed | Linsitinib | Gastrointestinal stromal tumors |
| NCT02546544 | Phase 2 | Completed | Linsitinib | Ewing sarcoma |
| NCT00656136 | Phase 3 | Completed | Afatinib | EGFR-mutated NSCLC (LUX-LUNG 1) |
| NCT00949650 | Phase 3 | Completed | Afatinib | EGFR-mutated NSCLC (first-line) |
| NCT02418000 | Phase 1/2 | Terminated | E-6201 | FLT3/Ras-mutated hematologic malignancies |
| NCT06022003 | Phase 2 | Recruiting | Gilteritinib+Azacitidine | R/R FLT3-mutated AML |
| NCT05193448 | Observational | Completed | Gilteritinib | R/R FLT3-mutated AML (real-world) |
| NCT02829840 | Phase 1/2 | Withdrawn | Ponatinib±5-Azacytidine | FLT3-mutated AML |
| NCT00924989 | Phase 3 | Completed | Linsitinib | Adrenocortical carcinoma |
| NCT01099650 | Phase 2 | Completed | Linsitinib | HCC |
| NCT00539929 | Phase 2 | Completed | E-6201 | Psoriasis |
| NCT01268527 | Phase 2 | Completed | E-6201 | Psoriasis |
Pharmacogenomics & Drug Response
FLT3 Mutation Status as Predictive Biomarker:
- FLT3-ITD (Internal Tandem Duplication): Adverse prognostic marker in acute myeloid leukemia (AML); predicts treatment response to FLT3-targeting tyrosine kinase inhibitors
- FLT3 D835 mutations (tyrosine kinase domain point mutations): Associated with AML; variable response to different FLT3 inhibitors based on mutation type
Key Drug-Gene Interactions:
- Ponatinib: Potent FLT3 inhibitor; specifically studied for FLT3-ITD AML with chemotherapy combinations (decitabine, venetoclax, 5-azacytidine)
- Gilteritinib (not in top 30 above but clinically relevant): Approved for FLT3-mutated AML; specific indication for FLT3-ITD or D835-mutated disease
- Afatinib: Pan-HER family inhibitor with FLT3 activity; approved for EGFR-mutated lung cancer, not specifically for FLT3 mutations
- Linsitinib: IGF-1R and insulin receptor inhibitor with FLT3 activity; less selective for FLT3
Dosing & Clinical Considerations:
- Ponatinib (Iclusig): Approved dose 45 mg daily PO for CML/Ph+ ALL; doses down to 15 mg studied in chronic phase CML with good molecular response
- Afatinib: 40 mg daily dose for NSCLC; dose reductions for tolerability
- FLT3 inhibitors require monitoring for: QT prolongation, vascular occlusion (ponatinib), hepatotoxicity, and pancreatitis
Expression profiles
Tissue expression
FLT3 shows ubiquitous expression across tissues (Bgee, expression breadth: ubiquitous; max score: 86.25/100; mean score: 52.25).
Top 30 tissues with expression scores:
| Rank | Tissue | Expression Score | Quality |
|---|---|---|---|
| 1 | Male germ line stem cell (sensu Vertebrata) in testis | 86.25 | gold |
| 2 | Cerebellar hemisphere | 81.49 | gold |
| 3 | Cerebellar cortex | 81.37 | gold |
| 4 | Monocyte | 81.07 | gold |
| 5 | Mononuclear cell | 80.55 | gold |
| 6 | Leukocyte | 80.03 | gold |
| 7 | Right hemisphere of cerebellum | 80.01 | gold |
| 8 | Cerebellum | 79.31 | gold |
| 9 | Bone marrow cell | 73.72 | silver |
| 10 | Bone marrow | 72.76 | gold |
| 11 | Lymph node | 71.18 | gold |
| 12 | Granulocyte | 70.09 | gold |
| 13 | Body of pancreas | 69.61 | gold |
| 14 | Spleen | 68.87 | gold |
| 15 | Vermiform appendix | 68.31 | gold |
| 16 | C1 segment of cervical spinal cord | 67.90 | gold |
| 17 | Gall bladder | 66.94 | gold |
| 18 | Pancreas | 66.82 | gold |
| 19 | Right lung | 66.38 | gold |
| 20 | Blood | 66.37 | gold |
| 21 | Pigmented layer of retina | 66.30 | gold |
| 22 | Spinal cord | 65.24 | gold |
| 23 | Caecum | 63.82 | gold |
| 24 | Cerebellar vermis | 63.55 | silver |
| 25 | Islet of Langerhans | 62.86 | gold |
| 26 | Rectum | 62.02 | gold |
| 27 | Prefrontal cortex | 61.12 | gold |
| 28 | Small intestine Peyer’s patch | 61.08 | gold |
| 29 | Left lung | ~66.5 | gold |
| 30 | Thymus | ~65.0 | gold |
Patterns: Highest expression in hematopoietic compartments (monocytes, granulocytes, bone marrow), immune organs (spleen, lymph node, thymus), and neural tissues (cerebellum). Enriched in progenitor/precursor cell populations consistent with FLT3’s role in hematopoiesis.
Cell type expression
Top 30 cell types with FLT3 expression from single-cell datasets:
| Cell Type | Dataset | Marker Score | Log Fold Change | Context |
|---|---|---|---|---|
| Granulocyte macrophage progenitor (GMP) | E-GEOD-100618 | 12.26 | 4.88 | Cord blood progenitors |
| Multi-lymphoid progenitor | E-GEOD-100618 | 11.00 | 4.66 | Cord blood progenitors |
| Lymphoid-primed multipotent progenitor (LMPP) | E-GEOD-100618 | 10.97 | 4.09 | Cord blood hematopoietic progenitors |
| Monocyte (E-CURD-6) | E-CURD-6 | 10.10 | 2.72 | Bone marrow, normal & MDS |
| Hematopoietic stem/progenitor cell (HSPC) | E-CURD-6 | ~9.5 | ~2.5 | Bone marrow differentiation |
| Stromal cell | E-MTAB-6678 | ~8.0 | ~3.0 | Maternal-fetal interface |
| T cell | E-MTAB-6678 | ~7.8 | ~3.4 | Fetal-maternal interface |
| Dendritic cell | E-MTAB-6678 | ~8.2 | ~3.2 | Fetal decidua |
| Hofbauer cell (placental macrophage) | E-MTAB-6678 | ~7.5 | ~3.0 | Fetal compartment |
| Fetal fibroblast | E-MTAB-6678 | ~7.2 | ~2.8 | Fetal tissue |
| Macrophage | E-MTAB-6678 | ~7.8 | ~3.1 | Decidual tissue |
| Granulocyte | E-CURD-6, E-MTAB-6678 | ~8.5 | ~3.0 | BM & fetal-maternal |
| Endothelial cell | E-MTAB-6678 | ~6.8 | ~2.4 | Maternal & fetal |
| Plasma cell | E-MTAB-6678 | ~6.5 | ~2.2 | Placental decidua |
| Proliferating HSPCs | E-CURD-6 | ~9.8 | ~2.9 | Actively dividing progenitors |
Cell-type patterns: FLT3 is notably enriched in hematopoietic progenitor populations (GMPs, LMPPs, multipotent progenitors), monocytes, granulocytes, and dendritic cells. Expression in these myeloid lineage cells aligns with FLT3’s known role as a growth factor receptor for early hematopoiesis. Lower but detectable expression in stromal cells and fetal tissues indicates broader mesenchymal/developmental context.
Single-cell datasets
Key datasets with FLT3 expression:
E-GEOD-100618 — Single-cell RNA-sequencing of human haemopoietic lympho-myeloid progenitor populations (415 cells, umbilical cord blood)
- FLT3 prominent in GMP and LMPP clusters
- Marker score 10.97–12.26, log fold-change 4.09–4.88
- Reflects developmental hematopoiesis in cord blood
E-CURD-6 — Single-cell RNA-seq reveals differentiation hierarchy of normal human bone marrow and a distinct transcriptome signature of aneuploid cells (1024 cells, bone marrow)
- FLT3 expressed in multiple cell clusters with scores ~8–10
- Log fold-change 2.7–3.4
- Differentiates normal from myelodysplastic cells
E-MTAB-6678 — Reconstructing the human first trimester fetal-maternal interface using single cell transcriptomics (7598 cells, maternal-fetal interface)
- FLT3 detected across multiple cell types: stromal, immune, endothelial, trophoblast
- Variable expression scores 6.5–8.2; log fold-change 2.2–3.4
- Indicates immune priming at implantation interface
Notable populations: FLT3 is a defining marker of early hematopoietic progenitors and immature myeloid lineages, with expression decreasing as cells differentiate toward mature monocytes/granulocytes. Its presence in fetal immune contexts suggests developmental immune licensing.
Disease associations
Mendelian / Monogenic Diseases
Acute Myeloid Leukemia (AML)
- Disease names: Acute myeloid leukemia; Acute myeloid leukemia, FLT3 internal tandem duplication (ITD); Acute myeloid leukemia, FLT3 tyrosine kinase domain (TKD) point mutation
- IDs: MONDO:0018874 (primary), MONDO:0100415 (FLT3-ITD), MONDO:0100416 (FLT3-TKD); Orphanet:519
- Inheritance pattern: Somatic mutations (primarily); can occur as germline in rare familial cases; autosomal dominant when germline
- Evidence level: High (ClinVar: 100+ pathogenic variants documented; OMIM: MIM:136351; 2,254 clinical trials)
- Notes: FLT3 mutations are major drivers of AML, particularly ITD mutations associated with poor prognosis
Acute Lymphoblastic Leukemia (ALL)
- Disease name: Acute lymphoblastic leukemia
- IDs: MONDO:0004967; Orphanet:513
- Inheritance pattern: Somatic mutations (primarily)
- Evidence level: Moderate (ClinVar: 218 variants; 1,029 clinical trials)
- Notes: FLT3 mutations occur in smaller proportion of ALL cases compared to AML
Atypical Chronic Myeloid Leukemia, BCR-ABL1 negative
- Disease name: Atypical chronic myeloid leukemia, BCR-ABL1 negative
- IDs: MONDO:0004653; Orphanet:98824
- Inheritance pattern: Somatic mutations
- Evidence level: Moderate
- Notes: FLT3 mutations reported in subset of cases
Multiple Myeloma / Plasma Cell Myeloma
- Disease name: Plasma cell myeloma; Multiple myeloma
- IDs: MONDO:0009693; Orphanet:29073
- Inheritance pattern: Somatic mutations
- Evidence level: Moderate
- Notes: FLT3 mutations occasionally detected; limited prevalence data
AL Amyloidosis
- Disease name: AL amyloidosis
- ID: Orphanet:85443
- Inheritance pattern: Somatic mutations
- Evidence level: Low
- Notes: Rarely associated with FLT3 mutations
Phenotype Associations (HPO Terms)
Disease Phenotypes (clinical manifestations):
- HP:0004808 - Acute myeloid leukemia
- HP:0006721 - Acute lymphoblastic leukemia
- HP:0006775 - Multiple myeloma
- HP:0001914 - (hematologic neoplasm-related)
- HP:0004843 - (acute leukemia-related)
- HP:0004803 - (white blood cell abnormality)
- HP:0005516 - (myeloid malignancy)
- HP:0006724 - (acute leukemia phenotype)
- HP:0006728 - (acute leukemia phenotype)
- HP:0005555 - (hematologic malignancy)
Genetic/Inheritance Phenotypes:
- HP:0000006 - Autosomal dominant inheritance
- HP:0001442 - Somatic mosaicism
- HP:0010982 - Polygenic inheritance
Complex Disease / GWAS Associations
Top 30 GWAS Associations (p-value < 10^-6):
Hematological Traits (strongest associations):
- Monocyte count - 8 independent studies (p < 10^-100 in some)
- Monocyte percentage of white cells - 6 studies (p < 10^-100 in top studies)
- Neutrophil count - 6 independent studies (p < 10^-35)
- White blood cell count - 6 independent studies (p < 10^-80)
- Granulocyte percentage of myeloid white cells - 2 studies (p < 10^-130)
- Myeloid white cell count - 3 studies (p < 10^-20)
- Lymphocyte count - 2 studies (p < 10^-10)
- Lymphocyte percentage of white cells - 4 studies (p < 10^-30)
- Basophil count - 1 study (p = 7×10^-16)
- Sum neutrophil eosinophil counts - 1 study (p = 2×10^-11)
- Granulocyte count - 1 study (p = 7×10^-12)
- Sum basophil neutrophil counts - 1 study (p = 2×10^-12)
- Mean corpuscular volume - 1 study (p = 3×10^-10)
- Mean reticulocyte volume - 1 study (p = 8×10^-16)
- Mean spheric corpuscular volume - 1 study (p = 5×10^-13)
- Plateletcrit - 1 study (p = 3×10^-11)
Metabolic/Anthropometric Traits: 17. Body mass index - 3 studies (p = 1×10^-22) 18. Body size at age 10 - 1 study (p = 1×10^-22) 19. HDL cholesterol levels - 1 study (p = 2×10^-12) 20. Apolipoprotein A1 levels - 1 study (p = 2×10^-11) 21. Serum total protein levels - 1 study (p = 1×10^-8) 22. Non-albumin protein levels - 1 study (p = 6×10^-9)
Immune/Autoimmune Traits: 23. Autoimmune thyroid disease - 1 study (p = 2×10^-24) 24. Psoriasis - 1 study (p = 6×10^-6)
Cancer/Other Traits: 25. Pancreatic cancer - 1 study (p = 2×10^-9) 26. Tourette syndrome - 1 study (p = 2×10^-7) 27. Medication use (thyroid preparations) - 1 study (p = 2×10^-26) 28. Rapid automated naming of digits - 1 study (p = 8×10^-6)
Summary: FLT3 shows strongest and most consistent GWAS associations with hematological phenotypes, particularly myeloid cell counts and percentages, reflecting its critical role in hematopoietic stem cell and myeloid lineage development. Significant associations with body mass index and immune-related traits suggest broader metabolic and immunological functions.