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25 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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AXL
AXL receptor tyrosine kinase
Chromosome 19 · 19q13.2
NCBI Gene: 558Ensembl: ENSG00000167601.12HGNC: HGNC:905UniProt: M0R0W6
411PubMed Papers
20Diseases
6Drugs
1Pathogenic Variants
FUNCTIONAL ROLE
KinaseOncogeneReceptor
RESEARCH IMPACT
Highly StudiedTrending
CLINICAL
FDA Approved Target
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
virus receptor activityphosphatidylserine bindingprotein tyrosine kinase activityprotein bindingacute myeloid leukemianeurodegenerative diseaseAlzheimer diseasemultiple sclerosis
✦AI Summary

AXL is a receptor tyrosine kinase belonging to the TAM family that functions as a critical regulator of immune responses, viral infection, and cancer progression. Mechanistically, AXL binds ligands GAS6 and Protein S to activate downstream signaling through PI3K and RAC1, triggering actin remodeling, macropinocytosis, and cellular invasion 1. In viral infections, AXL promotes Zika virus entry in glial cells and astrocytes 23, though ZIKV subsequently downregulates AXL expression via autophagy to sustain persistent infection 4. In cancer, AXL overexpression drives proliferation, epithelial-mesenchymal transition, metastasis, and acquired drug resistance 56. AXL signaling on macrophages promotes M2-like polarization and efferocytosis, skewing the tumor microenvironment toward immunosuppression 7. In pulmonary fibrosis, AXL expression in monocytes drives pathogenic M2 macrophage differentiation, and AXL inhibition ameliorates disease progression 8. In rheumatoid arthritis, AXL expression inversely correlates with pro-inflammatory markers and is modulated by IL-6 inhibition 9. Clinically, AXL represents a promising therapeutic target through small-molecule kinase inhibitors, monoclonal antibodies, and antibody-drug conjugates in cancer and fibrotic diseases 5106.

Sources cited
1
AXL promotes Zika virus entry and infection
PMID: 28076778
2
AXL promotes Zika virus entry via SOCS1-dependent mechanism
PMID: 29379210
3
ZIKV downregulates AXL via autophagy to sustain infection
PMID: 40408405
4
GAS6-AXL signaling triggers actin remodeling, macropinocytosis, and cancer cell invasion via PI3K/RAC1
PMID: 34244439
5
AXL overexpression in cancer promotes drug resistance and poor prognosis
PMID: 37328828
6
AXL drives cancer proliferation, EMT, metastasis, and therapeutic resistance; facilitates viral infections
PMID: 39924521
7
AXL on tumor-associated macrophages promotes M2 polarization and efferocytosis
PMID: 31088471
8
AXL in monocytes drives M2 macrophage differentiation and pulmonary fibrosis progression; inhibition ameliorates disease
PMID: 39788632
9
Dual AXL/HDAC2 inhibitors show potent anti-proliferative and antitumor efficacy in colorectal cancer
PMID: 38134358
10
AXL expression inversely correlates with pro-inflammatory markers in rheumatoid arthritis synovium
PMID: 38493215
Disease Associationsⓘ20
acute myeloid leukemiaOpen Targets
0.59Moderate
neurodegenerative diseaseOpen Targets
0.57Moderate
Alzheimer diseaseOpen Targets
0.53Moderate
multiple sclerosisOpen Targets
0.53Moderate
Parkinson diseaseOpen Targets
0.53Moderate
lysosomal storage diseaseOpen Targets
0.53Moderate
dengue diseaseOpen Targets
0.51Moderate
myeloid leukemiaOpen Targets
0.44Moderate
neoplasmOpen Targets
0.42Moderate
childhood acute myeloid leukemiaOpen Targets
0.39Weak
acute myeloid leukemia by FAB classificationOpen Targets
0.39Weak
NK-cell enteropathyOpen Targets
0.26Weak
cardiovascular diseaseOpen Targets
0.20Weak
skin diseaseOpen Targets
0.16Weak
non-small cell lung carcinomaOpen Targets
0.14Weak
amenorrheaOpen Targets
0.14Weak
breast cancerOpen Targets
0.13Weak
triple-negative breast cancerOpen Targets
0.13Weak
hepatocellular carcinomaOpen Targets
0.12Weak
cancerOpen Targets
0.11Weak
Pathogenic Variants1
NM_021913.5(AXL):c.2161C>G (p.Leu721Val)Likely pathogenic
NK-cell enteropathy
☆☆☆☆2019→ Residue 721
View on ClinVar ↗
Drug Targets6
BEMCENTINIBPhase II
Tyrosine-protein kinase receptor UFO inhibitor
myelodysplastic syndrome
BPI-9016Phase I
Tyrosine-protein kinase receptor UFO inhibitor
ENAPOTAMAB VEDOTINPhase I/II
Tyrosine-protein kinase receptor UFO binding agent
GILTERITINIBApproved
Tyrosine-protein kinase receptor FLT3 inhibitor
acute myeloid leukemia by FAB classification
GILTERITINIB FUMARATEApproved
Tyrosine-protein kinase receptor FLT3 inhibitor
acute myeloid leukemia
MECBOTAMAB VEDOTINPhase II
Tyrosine-protein kinase receptor UFO binding agent
ovarian cancer
Related Genes
PIK3R1Protein interaction100%PIK3CAProtein interaction100%PROS1Protein interaction100%HSP90AA1Protein interaction99%EGFRProtein interaction99%ERBB3Protein interaction99%
Tissue Expression6 tissues
Ovary
100%
Lung
83%
Heart
78%
Brain
47%
Liver
20%
Bone Marrow
13%
Gene Interaction Network
Click a node to explore
AXLPIK3R1PIK3CAPROS1HSP90AA1EGFRERBB3
PROTEIN STRUCTURE
Preparing viewer…
PDB5VXZ · 2.30 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.63LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.50 [0.40–0.63]
RankingsWhere AXL stands among ~20K protein-coding genes
  • #701of 20,598
    Most Researched411 · top 5%
  • #517of 1,025
    FDA-Approved Drug Targets2
  • #4,635of 5,498
    Most Pathogenic Variants1
  • #4,391of 17,882
    Most Constrained (LOEUF)0.63 · top quartile
Genes detectedAXL
Sources retrieved25 papers
Response time—
📄 Sources
25▼
1
Inhibition of AXL ameliorates pulmonary fibrosis
PMID: 39788632
Eur Respir J · 2025
1.00
2
AXL in cancer: a modulator of drug resistance and therapeutic target.
PMID: 37328828
J Exp Clin Cancer Res · 2023
0.90
3
Targeting Tyro3, Axl and MerTK (TAM receptors): implications for macrophages in the tumor microenvironment.
PMID: 31088471
Mol Cancer · 2019
0.80
4
Discovery of novel and potent dual-targeting AXL/HDAC2 inhibitors for colorectal cancer treatment via structure-based pharmacophore modelling, virtual screening, and molecular docking, molecular dynamics simulation studies, and biological evaluation.
PMID: 38134358
J Enzyme Inhib Med Chem · 2024
0.70
5
Research Progress of Axl Inhibitors.
PMID: 31218961
Curr Top Med Chem · 2019
0.64