AXL

Summary

AXL (AXL receptor tyrosine kinase, HGNC:905) is a protein-coding gene on chromosome 19q13.2, encoding Tyrosine-protein kinase receptor UFO (P30530). Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding growth factor GAS6 and which is thus regulating many physiological processes including cell survival, cell proliferation, migration and differentiation.

The protein encoded by this gene is a member of the Tyro3-Axl-Mer (TAM) receptor tyrosine kinase subfamily. The encoded protein possesses an extracellular domain which is composed of two immunoglobulin-like motifs at the N-terminal, followed by two fibronectin type-III motifs. It transduces signals from the extracellular matrix into the cytoplasm by binding to the vitamin K-dependent protein growth arrest-specific 6 (Gas6). This gene may be involved in several cellular functions including growth, migration, aggregation and anti-inflammation in multiple cell types. The encoded protein acts as a host cell receptor for multiple viruses, including Marburg, Ebola and Lassa viruses and is a candidate receptor for the SARS-CoV2 virus.

Source: NCBI Gene 558 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Kallmann syndrome (Limited, GenCC)
• GWAS associations: 10
• Clinical variants (ClinVar): 305 total — 1 likely-pathogenic
• Regional missense constraint (gnomAD): 1 of 5 regions constrained (≈1% of expected missense variation)
• Expression (HPA): Low tissue specificity — highest in blood vessel, area postrema, nucleus gracilis
• GTEx eGene: eQTL in 31 tissues, sQTL in 20 (q < 0.05)
• Phenotypes (HPO): 12
• Drug target: yes — 6 curated mechanism-of-action drugs; 59 molecules with ChEMBL bioactivity (top 1% of genes corpus-wide)
• Approved drugs (ChEMBL mechanism of action): 1 — Gilteritinib
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 0.62 (unconstrained)
• MANE Select transcript: NM_021913
• Interaction hub: 2,928 STRING partners (top 3% of genes corpus-wide)
• Notable: 305 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:905
Approved symbol	AXL
Name	AXL receptor tyrosine kinase
Location	19q13.2
Locus type	gene with protein product
Status	Approved
Aliases	UFO, JTK11, Tyro7, ARK
Ensembl gene	ENSG00000167601
Ensembl biotype	protein_coding
OMIM	109135
Entrez	558

Gene structure

Transcript identifiers

Ensembl transcripts: 23 — 18 protein_coding, 3 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined, 1 retained_intron

MANE Select: ENST00000301178

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 4, TSL 4: 1

ENST00000301178, ENST00000359092, ENST00000593513, ENST00000594880, ENST00000599659, ENST00000898512, ENST00000915596, ENST00000915597, ENST00000915598, ENST00000915599, ENST00000915600, ENST00001002647, ENST00001090409, ENST00001090410, ENST00001090411, ENST00001090412, ENST00001115281, ENST00001115282, ENST00001126106, ENST00001128477, ENST00001128478, ENST00001128479, ENST00001143165

RefSeq mRNA: 3 — MANE Select: NM_021913 NM_001278599, NM_001699, NM_021913

CCDS: CCDS12574, CCDS12575, CCDS62677

Canonical transcript exons

ENST00000301178 — 20 exons

Exon	Start	End
ENSE00001114774	41243616	41243707
ENSE00001114775	41256452	41256611
ENSE00001114780	41248514	41248609
ENSE00001114784	41253599	41253708
ENSE00001114792	41252846	41252967
ENSE00001114794	41257493	41257629
ENSE00001114797	41248743	41248820
ENSE00001114801	41252351	41252443
ENSE00001361520	41259553	41261766
ENSE00001361543	41219223	41219477
ENSE00003518744	41237944	41238154
ENSE00003533736	41239164	41239314
ENSE00003547478	41221146	41221246
ENSE00003548162	41231183	41231298
ENSE00003565990	41221880	41222056
ENSE00003576856	41242883	41243015
ENSE00003638151	41239694	41239720
ENSE00003650369	41220636	41220858
ENSE00003657173	41230967	41231047
ENSE00003676850	41238470	41238609

Expression profiles

Bgee: expression breadth ubiquitous, 290 present calls, max score 99.00.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 62.8572 / max 810.3034, expressed in 1417 samples.

Highest expression (Bgee): synovial joint, saphenous vein, stromal cell of endometrium, cartilage tissue, vein.

Genetic regulation across tissues (GTEx eQTL / sQTL)

AXL is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 31 tissues and its splicing (sQTL) in 20 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 51 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Lung	sqtl	8.0e-51	-1.24	19:41256620:A:G
Cells Cultured fibroblasts	sqtl	1.9e-37	+0.63	19:41242848:T:C
Artery Coronary	sqtl	1.2e-29	-1.36	19:41256620:A:G
Colon Sigmoid	sqtl	1.7e-27	-1.08	19:41256620:A:G
Heart Atrial Appendage	sqtl	8.6e-25	-1.09	19:41256620:A:G
Nerve Tibial	sqtl	1.2e-19	+0.58	19:41226518:T:C
Artery Tibial	eqtl	1.2e-17	+0.22	19:41250133:T:G
Brain Caudate basal ganglia	sqtl	2.0e-09	-1.00	19:41256620:A:G
Nerve Tibial	eqtl	2.5e-09	+0.20	19:41247010:T:TCAA
Adrenal Gland	sqtl	2.9e-09	-0.89	19:41256620:A:G
Muscle Skeletal	eqtl	7.6e-09	+0.18	19:41250133:T:G
Artery Tibial	sqtl	1.7e-08	+0.35	19:41242848:T:C
Adipose Subcutaneous	eqtl	3.5e-08	+0.18	19:41248312:G:T
Cells Cultured fibroblasts	eqtl	8.0e-08	+0.13	19:41250133:T:G
Skin Sun Exposed Lower leg	eqtl	6.7e-07	+0.11	19:41250133:T:G
Brain Nucleus accumbens basal ganglia	eqtl	1.5e-06	+0.19	19:41246489:G:GC
Skin Sun Exposed Lower leg	sqtl	4.5e-06	+0.34	19:41226518:T:C
Brain Cerebellum	eqtl	7.1e-06	+0.17	19:41250133:T:G
Breast Mammary Tissue	eqtl	1.7e-05	+0.15	19:41247010:T:TCAA
Prostate	sqtl	1.7e-05	-0.81	19:41250598:A:G

FANTOM5 promoters

showing 10 of 15 alternative TSS:

Promoter ID	TPM avg	Samples expressed
175931	43.2852	1374
175930	6.2763	1231
175933	4.2395	955
175932	3.9721	919
208821	1.1640	591
175950	0.6917	362
175946	0.6666	382
175951	0.6013	192
175947	0.4623	270
208822	0.3925	227

Top tissues by expression

showing 100 of 300 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
synovial joint	UBERON:0002217	99.00	gold quality
saphenous vein	UBERON:0007318	98.27	gold quality
stromal cell of endometrium	CL:0002255	97.81	gold quality
cartilage tissue	UBERON:0002418	97.39	gold quality
vein	UBERON:0001638	97.24	gold quality
layer of synovial tissue	UBERON:0007616	97.24	gold quality
urethra	UBERON:0000057	97.22	gold quality
pericardium	UBERON:0002407	96.57	gold quality
decidua	UBERON:0002450	96.21	gold quality
popliteal artery	UBERON:0002250	96.02	gold quality
tibial artery	UBERON:0007610	96.01	gold quality
tendon of biceps brachii	UBERON:0008188	95.61	gold quality
right coronary artery	UBERON:0001625	95.26	gold quality
aorta	UBERON:0000947	94.83	gold quality
coronary artery	UBERON:0001621	94.70	gold quality
left coronary artery	UBERON:0001626	94.61	gold quality
descending thoracic aorta	UBERON:0002345	94.55	gold quality
vena cava	UBERON:0004087	94.25	gold quality
mucosa of stomach	UBERON:0001199	94.23	gold quality
blood vessel layer	UBERON:0004797	94.02	gold quality
nipple	UBERON:0002030	93.51	gold quality
tendon	UBERON:0000043	93.32	gold quality
smooth muscle tissue	UBERON:0001135	93.32	gold quality
thoracic aorta	UBERON:0001515	93.25	gold quality
penis	UBERON:0000989	93.24	gold quality
endocervix	UBERON:0000458	93.22	gold quality
skin of hip	UBERON:0001554	93.20	gold quality
ascending aorta	UBERON:0001496	93.16	gold quality
calcaneal tendon	UBERON:0003701	92.88	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	92.52	gold quality
mammalian vulva	UBERON:0000997	92.48	gold quality
cauda epididymis	UBERON:0004360	92.47	gold quality
subcutaneous adipose tissue	UBERON:0002190	92.42	gold quality
lower esophagus muscularis layer	UBERON:0035833	92.32	gold quality
lower esophagus	UBERON:0013473	92.24	gold quality
muscle layer of sigmoid colon	UBERON:0035805	92.23	gold quality
myometrium	UBERON:0001296	92.12	gold quality
periodontal ligament	UBERON:0008266	91.62	gold quality
connective tissue	UBERON:0002384	91.61	gold quality
colonic epithelium	UBERON:0000397	91.60	gold quality
adipose tissue	UBERON:0001013	91.53	gold quality
sural nerve	UBERON:0015488	91.16	gold quality
sigmoid colon	UBERON:0001159	90.97	gold quality
tibial nerve	UBERON:0001323	90.86	gold quality
adult organism	UBERON:0007023	90.84	gold quality
left uterine tube	UBERON:0001303	90.74	gold quality
urinary bladder	UBERON:0001255	90.68	gold quality
visceral pleura	UBERON:0002401	90.51	gold quality
adipose tissue of abdominal region	UBERON:0007808	90.40	gold quality
body of uterus	UBERON:0009853	90.39	gold quality
trabecular bone tissue	UBERON:0002483	90.32	gold quality
peritoneum	UBERON:0002358	90.21	gold quality
omental fat pad	UBERON:0010414	90.21	gold quality
parietal pleura	UBERON:0002400	89.54	gold quality
pleura	UBERON:0000977	89.39	gold quality
gall bladder	UBERON:0002110	89.35	gold quality
ectocervix	UBERON:0012249	89.31	gold quality
upper leg skin	UBERON:0004262	89.24	gold quality
mucosa of urinary bladder	UBERON:0001259	89.17	gold quality
trachea	UBERON:0003126	89.03	gold quality
seminal vesicle	UBERON:0000998	88.64	gold quality
mammary duct	UBERON:0001765	88.58	gold quality
type B pancreatic cell	CL:0000169	88.51	gold quality
thoracic mammary gland	UBERON:0005200	88.48	gold quality
adrenal tissue	UBERON:0018303	88.35	gold quality
mammary gland	UBERON:0001911	88.28	gold quality
ventricular zone	UBERON:0003053	88.22	gold quality
cardiac atrium	UBERON:0002081	88.21	gold quality
dorsal root ganglion	UBERON:0000044	88.19	gold quality
uterus	UBERON:0000995	88.19	gold quality
right atrium auricular region	UBERON:0006631	88.19	gold quality
olfactory bulb	UBERON:0002264	88.11	silver quality
placenta	UBERON:0001987	88.10	gold quality
lung	UBERON:0002048	88.08	gold quality
fundus of stomach	UBERON:0001160	88.05	gold quality
superficial temporal artery	UBERON:0001614	87.81	gold quality
female reproductive system	UBERON:0000474	87.77	gold quality
lower lobe of lung	UBERON:0008949	87.76	gold quality
lateral globus pallidus	UBERON:0002476	87.74	gold quality
epithelium of mammary gland	UBERON:0003244	87.58	gold quality
vagina	UBERON:0000996	87.43	gold quality
right ovary	UBERON:0002118	87.38	gold quality
ovary	UBERON:0000992	87.28	gold quality
trigeminal ganglion	UBERON:0001675	87.19	gold quality
upper arm skin	UBERON:0004263	87.14	gold quality
colon	UBERON:0001155	87.08	gold quality
large intestine	UBERON:0000059	86.94	gold quality
upper lobe of lung	UBERON:0008948	86.88	gold quality
upper lobe of left lung	UBERON:0008952	86.83	gold quality
left ovary	UBERON:0002119	86.77	gold quality
right lung	UBERON:0002167	86.56	gold quality
heart right ventricle	UBERON:0002080	86.42	gold quality
cardiac muscle of right atrium	UBERON:0003379	86.31	gold quality
uterine cervix	UBERON:0000002	86.30	gold quality
skin of leg	UBERON:0001511	86.18	gold quality
apex of heart	UBERON:0002098	86.16	gold quality
intestine	UBERON:0000160	86.11	gold quality
cardia of stomach	UBERON:0001162	86.01	gold quality
prostate gland	UBERON:0002367	85.93	gold quality
globus pallidus	UBERON:0001875	85.90	gold quality

Single-cell (SCXA)

Detected in 16 experiment(s), a significant marker in 15.

Experiment	Marker?	Max mean expression
E-GEOD-81383	yes	19843.77
E-GEOD-86618	yes	2971.95
E-CURD-11	yes	2485.90
E-GEOD-109979	yes	1509.26
E-MTAB-7008	yes	666.47
E-MTAB-8205	yes	305.96
E-MTAB-8142	yes	104.41
E-MTAB-6701	yes	42.51
E-GEOD-135922	yes	33.51
E-MTAB-6678	yes	26.78
E-MTAB-10553	yes	24.78
E-HCAD-9	yes	15.66
E-GEOD-81547	yes	9.73
E-CURD-112	yes	5.74
E-MTAB-7381	no	1216.76

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 77 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Spinal cord	tissue	44.2
Superior colliculi	tissue	40.5
Substantia nigra	tissue	39.4
Medulla oblongata	tissue	35.8
Thalamus	tissue	35.4
Spleen	tissue	35.4	not detected
Smooth muscle	tissue	34.7	low
Hypothalamus	tissue	34.2
Midbrain	tissue	32.5
Pons	tissue	32.4
Periaqueductal gray	tissue	32.4
Caudate putamen	tissue	32.4
Placenta	tissue	32.0	low
Adipose tissue	tissue	31.8	not detected
Frontal cortex	tissue	31.6
Putamen	tissue	30.9
Nucleus accumbens	tissue	30.7
Septum	tissue	30.5
Cervix	tissue	28.6	low
Hippocampus	tissue	28.2	not detected
Cerebral cortex	tissue	27.6	low
Motor cortex	tissue	27.6
Ventral forebrain	tissue	27.2
Amygdala	tissue	27.1
Hippocampal formation	tissue	27.1
Somatosensory cortex	tissue	26.7
Locus coeruleus	tissue	25.8
Entorhinal cortex	tissue	25.7
Basal ganglia	tissue	25.4	not detected
Occipital cortex	tissue	25.0
Insular cortex	tissue	24.9
Temporal cortex	tissue	24.8
Prefrontal cortex	tissue	24.7
Lung	tissue	24.4	medium
Postcentral gyrus	tissue	24.0
Vagina	tissue	23.9	not detected
Seminal vesicle	tissue	23.1	not detected
Retrosplenial cortex	tissue	23.0
Endometrium 1	tissue	22.9	medium
Corpus callosum	tissue	22.8
Retrosplenial and cingulate cortex	tissue	22.1
Olfactory bulb	tissue	21.8
Urinary bladder	tissue	21.0	low
Gallbladder	tissue	20.9	medium
Ovary	tissue	20.5	not detected
Choroid plexus	tissue	19.5
Fallopian tube	tissue	19.4	not detected
Adrenal gland	tissue	17.7	not detected
Testis	tissue	17.4	high
Esophagus	tissue	16.4	not detected
Appendix	tissue	14.6	medium
Colon	tissue	14.2	medium
Liver	tissue	14.0	low
Small intestine	tissue	13.8	medium
Heart muscle	tissue	13.0	low
Prostate	tissue	12.2	not detected
Breast	tissue	11.8	not detected
Rectum	tissue	11.8	medium
Stomach 1	tissue	11.6	not detected
Cerebellum	tissue	11.2	not detected

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Blood vessel (72.4), Area postrema (50.8), Nucleus gracilis (50.0), Nucleus rhomboideus (44.2), Ventral spinal cord (44.2).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, EZH2, FOXC1, GAS6, KLF9, MEF2B, MZF1, NFKBIA, PAX3, SP1, SP3, TFAP2A, TP53, TP63

miRNA regulators (miRDB)

Targeting AXL by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 114 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-518D-5P	100.00	67.51	979
HSA-MIR-518E-5P	100.00	67.66	954
HSA-MIR-518F-5P	100.00	67.51	979
HSA-MIR-519A-5P	100.00	67.66	954
HSA-MIR-519B-5P	100.00	67.66	954
HSA-MIR-519C-5P	100.00	67.66	954
HSA-MIR-520C-5P	100.00	67.51	979
HSA-MIR-522-5P	100.00	67.66	954
HSA-MIR-523-5P	100.00	67.66	954
HSA-MIR-526A-5P	100.00	67.51	979
HSA-MIR-574-5P	100.00	66.01	989
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-33A-5P	99.99	68.62	1055
HSA-MIR-33B-5P	99.99	68.58	1062
HSA-MIR-520G-5P	99.99	66.76	658
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-6825-5P	99.96	69.81	3431

Functional genomics

gnomAD constraint: pLI 2.53e-06, LOEUF 0.625, missense Z 2.17 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000301178 splits into 5 regions with different missense tolerance; 1 is missense-constrained (≈1% of the expected missense variation). Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
19:41,219,393–41,220,792	124 / 115.5	1.07	no
19:41,220,793–41,221,904	41 / 76.2	0.54	no
19:41,221,905–41,239,231	332 / 343.9	0.97	no
19:41,239,232–41,239,273	4 / 16.9	0.24	yes (p 1.7e-03)
19:41,239,274–41,259,901	523 / 636.0	0.82	no

Literature-anchored findings (GeneRIF, showing 40)

• Data suggest that Gas6 and Axl signal transduction is aberrantly stimulated in endometriotic endometria, and is plausibly related to its growth potential. (PMID:12029073)
• Acidification prevents vascular endothelial cell apoptosis by Axl activation (PMID:12364394)
• Interaction of Axl receptor tyrosine kinase with C1-TEN (C1 domain-containing phosphatase and TENsin homologue). (PMID:12470648)
• Axl and Gas6 expression might be involved in childhood thyroid tumorigenesis around Chernobyl. (PMID:12490074)
• Gas6 receptors were not upregulated in any of the allograft groups, except for the Axl receptor, which increased only in acute tubular necrosis. (PMID:12768229)
• We found that there was a significant increase in the steady-state levels of Axl mRNA in the RCC compared with the normal kidney pair (PMID:14565870)
• Axl pathway mediates increased survival of uveal melanoma cells (PMID:14729616)
• GAS6/Axl signaling is involved in human renal disease. (PMID:14750094)
• Gas6-Axl interactions can rescue endothelial cells from apoptosis. (PMID:15130893)
• Axl stimulation by GAS6 results in inhibition of the ligand-dependent activation of vascular endothelial growth factor (VEGF) receptor 2 and the consequent activation of an angiogenic program in vascular endothelial cells (PMID:15507525)
• Axl overexpression and activation by Gas6 could be involved in progression of prostate neoplastic disease (PMID:15605394)
• Axl, Sky and Mer are Gas6 receptors that enhance platelet activation and regulate thrombotic responses (PMID:15733062)
• This report demonstrates that Gas6-induced downregulation of Axl is blocked by inhibitors of endocytosis and lysosomal degradation, but not by inhibitors of proteosomal activity. (PMID:15958209)
• Results identify and characterise a novel interaction between RanBPM and the related receptor tyrosine kinases, Axl and Sky. (PMID:15964779)
• Over-expression of axl is associated with lung adenocarcinoma and with tumor progression (PMID:16354588)
• The crystal structure at 3.3 A resolution of a minimal human Gas6/Axl complex reveals an assembly of 2:2 stoichiometry. (PMID:16362042)
• Suppression of Gas6 using small interfering RNA and the Axl-extracellular domain abolished the preventive effect of statins on Pi-induced apoptosis and calcification. (PMID:16556867)
• Identification, functional manipulation, in vitro and in vivo validation, and preclinical therapeutic inhibition of a target receptor tyrosine kinase mediating glioma growth and invasion. (PMID:16585512)
• Overexpression of the Axl tyrosine kinase receptor is associated with the development of squamous cell skin cancers (PMID:16641895)
• These results implicate Twist proteins in regulation of TNFalpha production by antiinflammatory factors and pathways, and provide a mechanism by which type I IFNs and Axl receptors suppress inflammatory cytokine production. (PMID:16831897)
• Here we show the involvement of members of the Tyro3 receptor tyrosine kinase family-Axl, Dtk, and Mer-in cell entry of filoviruses. (PMID:17005688)
• Signaling through Axl inhibits vascular calcification in vitro. (PMID:17255529)
• Axl and Gas6 are frequently overexpressed in both glioma and vascular cells and predict poor prognosis in GBM patients. (PMID:18172262)
• coordination of ERK signaling and NF-kappaB and Brg-1 activation are indispensable to regulation of Axl-dependent MMP-9 gene transcription (PMID:18345028)
• Axl gene expression in cancer cells is constitutively driven by Sp1/Sp3 bound to five core promoter motifs, and restricted by methylation within/around Sp-binding sites. (PMID:18522535)
• Possible strategies for targeted inhibition of the TAM family in the treatment of human cancer. (PMID:18620092)
• Activation of Axl may be a protective mechanism against hypertonicity-induced apoptosis. Our results identify Axl as an important element of osmotic stress-induced signalling. (PMID:18673450)
• The Axl/Gas6 pathway contributes to normal human NK-cell development via an effect on the master regulatory transcription factor T-BET. (PMID:18840707)
• In human endometriosis, the PI3K-Akt and MAPK signaling pathways may be activated via overexpression of AXL and SHC1, respectively. (PMID:19055724)
• there was a negative correlation between Gas6 and soluble Axl and Mer in established multiple sclerosis lesions. In addition, increased levels of soluble Axl and Mer were associated with increased levels of mature ADAM17, mature ADAM10, and Furin (PMID:19541935)
• Data show that Axl and Gas6 expression in RCC are associated with tumor advancement and patient survival. (PMID:19567592)
• Data demonstrates that Axl plays multiple roles in tumorigenesis. (PMID:19633687)
• Results identify several receptor tyrosine kinases, including Axl, that can bind to the ACK1/MIG6 homology region. (PMID:19815557)
• Axl and its ligand Gas6, the vitamin-K dependent protein product of the growth arrest-specific gene 6, have a role in progression of clear cell RCC (ccRCC) derived cells (PMID:19888345)
• findings suggest that Axl is a downstream effector of the tumor cell EMT that is required for breast cancer metastasis. Thus, the detection and targeted treatment of Axl-expressing tumors represents an important new therapeutic strategy for breast cancer (PMID:20080645)
• Gas6 in circulation is bound to sAxl suggesting circulating Gas6 to be inhibited and incapable of stimulating the TAM receptors. (PMID:20088931)
• Taken together, this is the first study to show that MZF1 induces invasion and in vivo metastasis in colorectal and cervical cancer, at least in part by regulating Axl gene expression. (PMID:20145042)
• Gas6 and soluble Axl have a role in critical limb ischemia, presumably connected to the inflammatory process (PMID:20417630)
• Axl has a potential role in Kaposi sarcoma pathogenesis (PMID:20442363)
• Gas6 and Tyro3, Axl and Mer (TAM) receptors have roles in human and murine platelet activation and thrombus stabilization (PMID:20546121)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	axl	ENSDARG00000112045
mus_musculus	Axl	ENSMUSG00000002602
rattus_norvegicus	Axl	ENSRNOG00000020716

Paralogs (53): INSRR (ENSG00000027644), MUSK (ENSG00000030304), FLT4 (ENSG00000037280), EPHA3 (ENSG00000044524), ROS1 (ENSG00000047936), LTK (ENSG00000062524), ERBB3 (ENSG00000065361), TIE1 (ENSG00000066056), FGFR2 (ENSG00000066468), FGFR3 (ENSG00000068078), EPHA8 (ENSG00000070886), FGFR1 (ENSG00000077782), EPHA6 (ENSG00000080224), TYRO3 (ENSG00000092445), FLT1 (ENSG00000102755), MET (ENSG00000105976), EPHB6 (ENSG00000106123), PDGFRB (ENSG00000113721), EPHA4 (ENSG00000116106), TEK (ENSG00000120156), FLT3 (ENSG00000122025), KDR (ENSG00000128052), EPHB2 (ENSG00000133216), PDGFRA (ENSG00000134853), EPHA7 (ENSG00000135333), IGF1R (ENSG00000140443), NTRK3 (ENSG00000140538), ERBB2 (ENSG00000141736), EPHA2 (ENSG00000142627), EPHA5 (ENSG00000145242), EGFR (ENSG00000146648), EPHA1 (ENSG00000146904), NTRK2 (ENSG00000148053), MERTK (ENSG00000153208), EPHB1 (ENSG00000154928), KIT (ENSG00000157404), FGFR4 (ENSG00000160867), DDR2 (ENSG00000162733), RYK (ENSG00000163785), MST1R (ENSG00000164078), LMTK2 (ENSG00000164715), RET (ENSG00000165731), ROR2 (ENSG00000169071), ALK (ENSG00000171094), INSR (ENSG00000171105), ERBB4 (ENSG00000178568), CSF1R (ENSG00000182578), EPHB3 (ENSG00000182580), EPHA10 (ENSG00000183317), ROR1 (ENSG00000185483), EPHB4 (ENSG00000196411), NTRK1 (ENSG00000198400), DDR1 (ENSG00000204580)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1347244) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 1 distinct phenotype terms.

Mouse phenotype (MP)	Records
increased vascular permeability	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Felis catus	A0M8S8	100.0%	Diamond
Neofelis nebulosa	Q07E37	100.0%	Diamond
Pan troglodytes	Q2QLF1	99.8%	Diamond
Gorilla gorilla gorilla	Q2IBF2	99.7%	Diamond
Pongo abelii	Q2IBD8	99.5%	Diamond
Papio anubis	A0M8R7	99.3%	Diamond
Colobus guereza	Q07DZ1	99.3%	Diamond
Chlorocebus aethiops	Q2IBA6	99.3%	Diamond
Aotus nancymaae	Q07DV8	99.1%	Diamond
Nomascus leucogenys	Q07DY1	99.1%	Diamond
Ateles geoffroyi	Q09YL1	99.1%	Diamond
Saimiri boliviensis boliviensis	Q09YH7	99.0%	Diamond
Gallus gallus	P08941	98.7%	Diamond
Plecturocebus moloch	Q2QLC0	98.6%	Diamond
Bos taurus	Q05688	97.7%	Diamond
Callithrix jacchus	Q2QLG5	97.7%	Diamond
Ovis aries	Q09YI9	97.5%	Diamond
Muntiacus muntjak	Q09YK0	97.4%	Diamond
Eulemur macaco macaco	Q2IBG7	97.4%	Diamond
Microcebus murinus	Q2QL89	97.4%	Diamond
Mustela putorius furo	Q07E24	96.4%	Diamond
Canis lupus familiaris	Q75ZY9	96.4%	Diamond
Xenopus tropicalis	A0JM20	95.5%	Diamond
Xenopus laevis	Q8QFP9	95.5%	Diamond
Equus caballus	Q2QLA9	94.9%	Diamond
Sus scrofa	Q2QLE0	94.9%	Diamond
Otolemur garnettii	Q2QLH6	94.0%	Diamond
Atelerix albiventris	Q00PJ8	92.0%	Diamond
Loxodonta africana	Q108U6	91.8%	Diamond
Dasypus novemcinctus	Q07E48	91.4%	Diamond
Oryctolagus cuniculus	Q09YN5	91.2%	Diamond
Rhinolophus ferrumequinum	Q2IBC0	90.1%	Diamond
Echinops telfairi	A1X150	87.8%	Diamond
Ornithorhynchus anatinus	Q07E01	79.2%	Diamond
Drosophila melanogaster	P13368	62.3%	Diamond
Lymnaea stagnalis	O76997	54.2%	Diamond
Hydra vulgaris	Q25197	50.8%	Diamond
Aedes aegypti	Q93105	49.8%	Diamond
Caenorhabditis elegans	Q21038	49.5%	Diamond
Avian retrovirus RPL30	P33497	67.7%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
HNRNPUL1	protein-coding	11100
CYP2S1	protein-coding	29785
TGFB1	protein-coding	7040
CCDC97	protein-coding	90324
CYP2A13	protein-coding	1553
CYP2F1	protein-coding	1572

Protein

Protein identifiers

Tyrosine-protein kinase receptor UFO — P30530 (reviewed: P30530)

Alternative names: AXL oncogene

All UniProt accessions (2): P30530, M0R0W6

UniProt curated annotations — full annotation on UniProt →

Function. Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding growth factor GAS6 and which is thus regulating many physiological processes including cell survival, cell proliferation, migration and differentiation. Ligand binding at the cell surface induces dimerization and autophosphorylation of AXL. Following activation by ligand, AXL binds and induces tyrosine phosphorylation of PI3-kinase subunits PIK3R1, PIK3R2 and PIK3R3; but also GRB2, PLCG1, LCK and PTPN11. Other downstream substrate candidates for AXL are CBL, NCK2, SOCS1 and TNS2. Recruitment of GRB2 and phosphatidylinositol 3 kinase regulatory subunits by AXL leads to the downstream activation of the AKT kinase. GAS6/AXL signaling plays a role in various processes such as endothelial cell survival during acidification by preventing apoptosis, optimal cytokine signaling during human natural killer cell development, hepatic regeneration, gonadotropin-releasing hormone neuron survival and migration, platelet activation, or regulation of thrombotic responses. Also plays an important role in inhibition of Toll-like receptors (TLRs)-mediated innate immune response. (Microbial infection) Acts as a receptor for lassa virus and lymphocytic choriomeningitis virus, possibly through GAS6 binding to phosphatidyl-serine at the surface of virion envelope. (Microbial infection) Acts as a receptor for Ebolavirus, possibly through GAS6 binding to phosphatidyl-serine at the surface of virion envelope. (Microbial infection) Promotes Zika virus entry in glial cells, Sertoli cells and astrocytes. Additionally, Zika virus potentiates AXL kinase activity to antagonize type I interferon signaling and thereby promotes infection. Interferon signaling inhibition occurs via an SOCS1-dependent mechanism.

Subunit / interactions. Heterodimer and heterotetramer with ligand GAS6. Interacts with CBL, GRB2, LCK, NCK2, PIK3R1, PIK3R2, PIK3R3, PLCG1, SOCS1 and TNS2. Part of a complex including AXL, TNK2 and GRB2, in which GRB2 promotes AXL recruitment by TNK2.

Subcellular location. Cell membrane.

Tissue specificity. Highly expressed in metastatic colon tumors. Expressed in primary colon tumors. Weakly expressed in normal colon tissue.

Post-translational modifications. Monoubiquitinated upon GAS6-binding. A very small proportion of the receptor could be subjected to polyubiquitination in a very transient fashion. Phosphorylated at tyrosine residues by autocatalysis, which activates kinase activity.

Disease relevance. AXL and its ligand GAS6 are highly expressed in thyroid carcinoma tissues, and might thus be involved in thyroid tumorigenesis. Overexpression of AXL and its ligand was also detected in many other cancers such as myeloproliferative disorders, prostatic carcinoma cells, or breast cancer.

Activity regulation. Activated by GAS6-binding and subsequent autophosphorylation.

Induction. (Microbial infection) Up-regulated by Aedes aegypti lymphotoxin beta receptor inhibitor during Zika virus infection.

Similarity. Belongs to the protein kinase superfamily. Tyr protein kinase family. AXL/UFO subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
P30530-1	Long	yes
P30530-2	Short

RefSeq proteins (3): NP_001265528, NP_001690, NP_068713* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000719	Prot_kinase_dom	Domain
IPR001245	Ser-Thr/Tyr_kinase_cat_dom	Domain
IPR003599	Ig_sub	Domain
IPR003961	FN3_dom	Domain
IPR007110	Ig-like_dom	Domain
IPR008266	Tyr_kinase_AS	Active_site
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR013783	Ig-like_fold	Homologous_superfamily
IPR017441	Protein_kinase_ATP_BS	Binding_site
IPR020635	Tyr_kinase_cat_dom	Domain
IPR036116	FN3_sf	Homologous_superfamily
IPR036179	Ig-like_dom_sf	Homologous_superfamily
IPR050122	RTK	Family

Pfam: PF00041, PF07714, PF13927

Enzyme classification (BRENDA)

• EC 2.7.10.1 — receptor protein-tyrosine kinase (BRENDA: 44 organisms, 214 substrates, 574 inhibitors, 11 Km, 0 kcat entries)

Substrate kinetics (BRENDA)

4 substrates with measured Km, best-characterized 4. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ATP	0.0011–0.129	4
AC-DYFE-6-CHLORO-W-NHME	0.0051	1
AC-DYFGW-NHME	0.07	1
YFEW	0.232	1

Catalyzed reactions (Rhea)

• L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+) (RHEA:10596)

UniProt features (96 total): strand 31, helix 20, glycosylation site 6, sequence conflict 6, modified residue 5, sequence variant 5, domain 5, mutagenesis site 4, region of interest 3, binding site 2, topological domain 2, disulfide bond 2, signal peptide 1, chain 1, active site 1, splice variant 1, transmembrane region 1

Structure

Experimental structures (PDB)

4 structures by resolution:

PDB	Title	Method	Resolution (Å)
5VXZ	High-affinity AXL decoy receptor	X-RAY DIFFRACTION	2.3
5U6B	Structure of the Axl kinase domain in complex with a macrocyclic inhibitor	X-RAY DIFFRACTION	2.84
4RA0	An engineered Axl ‘decoy receptor’ effectively silences the Gas6-Axl signaling axis	X-RAY DIFFRACTION	3.07
2C5D	Structure of a minimal Gas6-Axl complex	X-RAY DIFFRACTION	3.3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P30530-F1	75.57	0.39

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Transferases, Kinases, Tyr protein kinases, Predicted membrane proteins, Plasma proteins, Disease related genes, FDA approved drug targets, Small molecule drugs

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): plasma membrane; actin filaments; vesicles

Antibody reliability (HPA): IH uncertain · IF supported

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1)

Position	Role
672	proton acceptor

Ligand- & substrate-binding residues (2)

Position	Role
542–550	ATP
567	ATP

Post-translational modifications (5)

Type	Positions
Phosphotyrosine	703, 779, 821, 866
Phosphoserine	884

Disulfide bonds (2)

Type	Positions
Disulfide bond	56–117, 160–205

Glycosylation sites (6)

Type	Positions
N-linked (glcnac…) asparagine	43, 157, 198, 339, 345, 401

Mutagenesis-validated functional residues (4)

Position	Phenotype
63	slightly reduced affinity for gas6.
66	reduced affinity for gas6.
84	reduced affinity for gas6.
567	catalytically inactive mutant.

Function

Pathways and Gene Ontology

Reactome pathways

2 curated (TAS) of 5; 1 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

5 pathways:

ID	Pathway	Evidence
R-HSA-9918485	Dengue Virus Attachment and Entry ⚕	curated
R-HSA-4420097	VEGFA-VEGFR2 Pathway	curated
R-HSA-162582	Signal Transduction	—
R-HSA-9006934	Signaling by Receptor Tyrosine Kinases	—
R-HSA-194138	Signaling by VEGF	—

MSigDB gene sets: 485 (showing top): BROWNE_HCMV_INFECTION_30MIN_DN, GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_NEGATIVE_REGULATION_OF_NEURON_APOPTOTIC_PROCESS, FREAC2_01, GOBP_PINOCYTOSIS, JI_RESPONSE_TO_FSH_UP, GOBP_DENDRITIC_CELL_DIFFERENTIATION, GOBP_NATURAL_KILLER_CELL_DIFFERENTIATION, MYOGENIN_Q6, GOBP_POSITIVE_REGULATION_OF_ENDOCYTOSIS, GOBP_POSITIVE_REGULATION_OF_HEMOPOIESIS, GOBP_MYELOID_CELL_HOMEOSTASIS, GOBP_INFLAMMATORY_RESPONSE, GOBP_RESPONSE_TO_PEPTIDE, GOBP_REGULATION_OF_LEUKOCYTE_APOPTOTIC_PROCESS

GO Biological Process (30): natural killer cell differentiation (GO:0001779), positive regulation of cytokine-mediated signaling pathway (GO:0001961), phagocytosis (GO:0006909), signal transduction (GO:0007165), cell surface receptor protein tyrosine kinase signaling pathway (GO:0007169), nervous system development (GO:0007399), cell migration (GO:0016477), platelet activation (GO:0030168), negative regulation of type II interferon production (GO:0032689), positive regulation of natural killer cell differentiation (GO:0032825), cellular response to interferon-alpha (GO:0035457), negative regulation of apoptotic process (GO:0043066), innate immune response (GO:0045087), symbiont entry into host cell (GO:0046718), vascular endothelial growth factor receptor signaling pathway (GO:0048010), cell maturation (GO:0048469), positive regulation of pinocytosis (GO:0048549), positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0051897), cellular response to lipopolysaccharide (GO:0071222), dendritic cell differentiation (GO:0097028), positive regulation of viral life cycle (GO:1903902), negative regulation of dendritic cell apoptotic process (GO:2000669), negative regulation of cytokine production (GO:0001818), immune system process (GO:0002376), protein phosphorylation (GO:0006468), enzyme-linked receptor protein signaling pathway (GO:0007167), positive regulation of signal transduction (GO:0009967), cell differentiation (GO:0030154), regulation of lymphocyte activation (GO:0051249), mononuclear cell differentiation (GO:1903131)

GO Molecular Function (10): virus receptor activity (GO:0001618), phosphatidylserine binding (GO:0001786), protein tyrosine kinase activity (GO:0004713), transmembrane receptor protein tyrosine kinase activity (GO:0004714), ATP binding (GO:0005524), nucleotide binding (GO:0000166), protein kinase activity (GO:0004672), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (5): plasma membrane (GO:0005886), cell surface (GO:0009986), signaling receptor complex (GO:0043235), extracellular exosome (GO:0070062), membrane (GO:0016020)

Reactome top-level categories

4 top-level categories:

Category	Pathways
Signaling by VEGF	1
Dengue Virus Infection	1
Signaling by Receptor Tyrosine Kinases	1
Signal Transduction	1

GO top-level categories

showing 60 of 72 GO namespaces:

Category	Terms
anion binding	2
cellular anatomical structure	2
lymphocyte differentiation	1
natural killer cell activation	1
regulation of cytokine-mediated signaling pathway	1
positive regulation of signal transduction	1
cytokine-mediated signaling pathway	1
positive regulation of response to cytokine stimulus	1
endocytosis	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
enzyme-linked receptor protein signaling pathway	1
system development	1
animal gross anatomical part developmental process	1
cell motility	1
cell activation	1
blood coagulation	1
negative regulation of cytokine production	1
type II interferon production	1
regulation of type II interferon production	1
natural killer cell differentiation	1
positive regulation of natural killer cell activation	1
regulation of natural killer cell differentiation	1
positive regulation of lymphocyte differentiation	1
response to interferon-alpha	1
cellular response to cytokine stimulus	1
apoptotic process	1
regulation of apoptotic process	1
negative regulation of programmed cell death	1
immune response	1
defense response to symbiont	1
viral life cycle	1
symbiont entry into host	1
cell surface receptor protein tyrosine kinase signaling pathway	1
cell development	1
cellular developmental process	1
anatomical structure maturation	1
pinocytosis	1
positive regulation of endocytosis	1
regulation of pinocytosis	1
phosphatidylinositol 3-kinase/protein kinase B signal transduction	1
regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	1
positive regulation of intracellular signal transduction	1
response to lipopolysaccharide	1
cellular response to molecule of bacterial origin	1
cellular response to lipid	1
cellular response to oxygen-containing compound	1
mononuclear cell differentiation	1
symbiont entry into host cell	1
exogenous protein binding	1
phospholipid binding	1
modified amino acid binding	1
protein kinase activity	1
protein tyrosine kinase activity	1
transmembrane receptor protein kinase activity	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 18 of 46 annotations. The rest are phylogenetic / computational / electronic (IEA).

18 experimentally-supported GO terms:

GO term	NS	Evidence
cell maturation	BP	expression pattern
cellular response to interferon-alpha	BP	direct assay
cellular response to lipopolysaccharide	BP	direct assay
dendritic cell differentiation	BP	expression pattern
negative regulation of dendritic cell apoptotic process	BP	direct assay
negative regulation of type II interferon production	BP	direct assay
phagocytosis	BP	direct assay
positive regulation of cytokine-mediated signaling pathway	BP	direct assay
positive regulation of natural killer cell differentiation	BP	direct assay
positive regulation of pinocytosis	BP	mutant phenotype
positive regulation of viral life cycle	BP	mutant phenotype
symbiont entry into host cell	BP	mutant phenotype
cell surface	CC	direct assay
extracellular exosome	CC	high-throughput assay
plasma membrane	CC	direct assay
phosphatidylserine binding	MF	direct assay
protein tyrosine kinase activity	MF	experiment
virus receptor activity	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 2,928 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
AXL	GAS6	Q14393	970
AXL	PROS1	P07225	924
AXL	PIK3CA	P42336	782
AXL	SOCS1	O15524	782
AXL	PIK3CD	O00329	765
AXL	PIK3CB	P42338	765
AXL	PIK3CG	P48736	761
AXL	IFNAR1	P17181	707
AXL	TREM2	Q9NZC2	702
AXL	SOCS3	O14543	692
AXL	TNS2	Q63HR2	670
AXL	TMEM119	Q4V9L6	648
AXL	P2RY12	Q9H244	648
AXL	APOE	P02649	628
AXL	STAT1	P42224	627

IntAct

Human interaction partners of AXL in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

26 partners by confidence:

Partner	Interaction type	MIscore	Records
GRB2	association	0.600	3
PIK3R1	association	0.600	2
EGFR	physical association	0.580	5
HSP90AB1	physical association	0.560	1
EPHA2	physical association	0.500	1
PLCG1	association	0.460	2
SPOP	physical association	0.450	5
GAS6	direct interaction	0.440	8
IL1RL1	physical association	0.400	2
H2BC12L	physical association	0.400	1
IL6R	physical association	0.400	1
KIR2DL5A	physical association	0.400	1
KIR3DL1	physical association	0.400	1
MXRA5	physical association	0.400	1
PILRA	physical association	0.400	1
PILRB	physical association	0.400	1
PSG9	physical association	0.400	1
PTPRF	physical association	0.400	1
SRC	physical association	0.400	1
FBXW7	proximity	0.270	4
SMAD4	proximity	0.270	4
SMARCA4	proximity	0.270	4
AKT1	proximity	0.270	1
BRAF	proximity	0.270	1
PTEN	proximity	0.270	1
TP53	proximity	0.270	1

BioGRID (407 interactions; top human partners by supporting records): EGFR (Biochemical Activity; 5 records), GRB2 (Affinity Capture-Western; 5 records), HSP90AA1 (Affinity Capture-MS; 4 records), CANX (Affinity Capture-MS; 3 records), EPHA2 (Proximity Label-MS; 3 records), GAS6 (Reconstituted Complex; 3 records), PIK3R1 (Affinity Capture-Western; 3 records), RANBP9 (Affinity Capture-Western; 3 records), CBL (PCA; 2 records), CDC37 (Affinity Capture-MS; 2 records), EMD (Proximity Label-MS; 2 records), ERBB2IP (Proximity Label-MS; 2 records), HSPA1A (Affinity Capture-MS; 2 records), HSPA1B (Proximity Label-MS; 2 records), INSRR (Affinity Capture-MS; 2 records)

SIGNOR signaling

showing 16 of 19 signaling interactions:

A	Effect	B	Mechanism
GAS6	up-regulates	AXL	binding
N-[4-[(2-amino-3-chloro-4-pyridinyl)oxy]-3-fluorophenyl]-4-ethoxy-1-(4-fluorophenyl)-2-oxo-3-pyridinecarboxamide	down-regulates	AXL	“chemical inhibition”
cabozantinib	“down-regulates activity”	AXL	“chemical inhibition”
AXL	“up-regulates quantity by stabilization”	MLKL	phosphorylation
AXL	“up-regulates activity”	YES1	phosphorylation
GAS6	“up-regulates activity”	AXL	binding
AXL	“up-regulates activity”	Epithelial-mesenchymal_transition	binding
AXL	up-regulates	Metastasis
AXL	“up-regulates quantity”	TNS2	phosphorylation
AXL	“up-regulates activity”	NEDD9	phosphorylation
AXL	“up-regulates activity”	EGFR	phosphorylation
EGFR	“up-regulates activity”	AXL	phosphorylation
AXL	“down-regulates activity”	ERBB2	phosphorylation
PROS1	up-regulates	AXL	binding
AXL	“up-regulates activity”	AXL	phosphorylation
N1’-[3-fluoro-4-[[6-methoxy-7-[3-(4-morpholinyl)propoxy]-4-quinolinyl]oxy]phenyl]-N1-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide	“down-regulates activity”	AXL	“chemical inhibition”

Protein complexes (CORUM) (4)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

4 complexes by size:

Complex	Subunits	Members
★ AXL-DOCK1-ELMO2-MET complex	4	AXL, DOCK1, ELMO2, MET
★ AXL-GBR2-TNK2 complex	3	AXL, GRB2, TNK2
AXL-ERRFI1-GRB2 complex	3	AXL, ERRFI1, GRB2
AXL homodimer	1	AXL

Ligand–receptor pairs (CellPhoneDB) (1)

Curated ligand–receptor partners (cell-cell communication), distinct from the protein–protein interactions above.

1 ligand–receptor pairs:

Partner	This gene’s role	Signaling class
GAS6	receptor	Signaling by Growth arrest

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 26 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	6	24.2×	1e-05
PIP3 activates AKT signaling	6	16.7×	7e-05
RAF/MAP kinase cascade	5	12.7×	9e-04

GO biological processes:

GO term	Partners	Fold	FDR
epidermal growth factor receptor signaling pathway	6	57.2×	5e-07
positive regulation of ERK1 and ERK2 cascade	5	16.4×	1e-03
protein stabilization	5	12.9×	2e-03
negative regulation of apoptotic process	8	10.7×	2e-04

Disease & clinical

Genetic variants

Variant evidence for AXL: 305 ClinVar records (1 pathogenic / likely pathogenic); 1 CIViC cancer variant; 10 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

305 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	139
Likely benign	81
Benign	62

Top pathogenic / likely-pathogenic (1)

Showing all 1 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
638632	NM_021913.5(AXL):c.2161C>G (p.Leu721Val)	Likely pathogenic	no assertion criteria provided	1

Per-variant reference — Sugi Variant

Explore AXL’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 30 predictions of 1,428):

Position(s)	Effect	Δscore	Sites
19:41220634–41220635	acceptor_loss	1.0000	6
19:41222057–41222058	donor_loss	1.0000	4
19:41231299–41231300	donor_loss	1.0000	5
19:41248446	acceptor_gain	1.0000
19:41248509	acceptor_gain	1.0000
19:41248512–41248513	acceptor_loss	1.0000	5
19:41248822	donor_loss	1.0000
19:41248826	donor_gain	1.0000
19:41252349	acceptor_gain	1.0000
19:41252349–41252350	acceptor_loss	1.0000	5

AlphaMissense

1,937 missense substitutions predicted likely pathogenic (of 5,784 scored), across 444 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M589	9	0.992	1.000
M679	9	0.992	1.000
M660	9	0.990	0.999
M623	9	0.983	1.000
M782	9	0.942	0.997
M711	9	0.923	0.998
M653	9	0.912	0.995
M598	9	0.899	0.998
M569	9	0.892	0.996
D672	8	1.000	1.000
N677	8	1.000	1.000
D690	8	1.000	1.000
F691	8	0.999	1.000
D731	8	0.999	1.000
H670	8	0.998	1.000
F547	8	0.997	1.000
D627	8	0.997	0.999
F582	8	0.993	0.999
F592	8	0.990	0.999
H594	8	0.987	0.998

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

1 prognostic cancer types:

Cancer	Prognostic	p-value
Ovary Serous Cystadenocarcinoma (validation)	unfavorable	1.07e-05

Disease associations

OMIM: gene MIM:109135 | disease phenotypes:

GenCC curated gene-disease

1 curated gene-disease records:

Disease	Classification	Inheritance	Records
Kallmann syndrome	Limited	Autosomal dominant

Mondo (1): Kallmann syndrome (MONDO:0018800)

HPO phenotypes

12 phenotypes (HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000028	Cryptorchidism
HP:0000044	Hypogonadotropic hypogonadism
HP:0000054	Micropenis
HP:0000771	Gynecomastia
HP:0000786	Primary amenorrhea
HP:0000789	Infertility
HP:0002215	Sparse axillary hair
HP:0002225	Sparse pubic hair
HP:0003621	Juvenile onset
HP:0004408	Abnormality of the sense of smell
HP:0008734	Decreased testicular size

GWAS associations

10 associations:

Study	Trait	p-value
GCST006979_550	Heel bone mineral density	9e-30
GCST006979_501	Heel bone mineral density	1e-21
GCST90002390_14	Mean corpuscular hemoglobin	4e-16
GCST90002392_141	Mean corpuscular volume	4e-14
GCST90002397_382	Mean spheric corpuscular volume	2e-10
GCST010244_234	Triglyceride levels	1e-9
GCST90002403_700	Red blood cell count	1e-9
GCST010796_3343	Electrocardiogram morphology (amplitude at temporal datapoints)	7e-9
GCST010173_147	Triglyceride levels	4e-8
GCST008141_6	HDL cholesterol	1e-6

EFO canonical traits (from GWAS)

6 canonical traits:

EFO ID	Trait name
EFO:0009270	heel bone mineral density
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004530	triglyceride measurement
EFO:0004327	electrocardiography
EFO:0004527	mean corpuscular hemoglobin
EFO:0004305	erythrocyte count

MeSH disease descriptors

1 disease descriptors:

Descriptor	Name	Tree numbers
D017436	Kallmann Syndrome	C12.050.351.875.253.096.750; C12.200.706.316.096.750; C12.800.316.096.750; C16.131.939.316.096.750; C16.320.467; C19.391.119.096.750; C19.391.482.600

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (5): CHEMBL4523666 (CHIMERIC PROTEIN), CHEMBL4895 (SINGLE PROTEIN), CHEMBL5169079 (PROTEIN-PROTEIN INTERACTION), CHEMBL5465244 (PROTEIN-PROTEIN INTERACTION), CHEMBL6066566 (PROTEIN FAMILY)

Drugs by curated mechanism of action (ChEMBL)

Drugs whose curated ChEMBL mechanism of action targets the AXL protein itself — single-protein targets only (drugs acting on a protein family or complex that merely includes it are excluded). Includes antibodies and oligonucleotides that bioactivity screening does not capture.

6 curated-mechanism drugs:

Drug	Modality	Max phase
GILTERITINIB	Small molecule	4
BEMCENTINIB	Small molecule	2
ENAPOTAMAB VEDOTIN	Antibody drug conjugate	2
MECBOTAMAB VEDOTIN	Antibody drug conjugate	2
NINGETINIB	Small molecule	2
BPI-9016	Unknown	1

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 590,804 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

59 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL3301622	GILTERITINIB	4	2,542
CHEMBL1173655	AFATINIB	4	15,878
CHEMBL1289926	AXITINIB	4	16,510
CHEMBL288441	BOSUTINIB	4	12,869
CHEMBL2105717	CABOZANTINIB	4	11,799
CHEMBL601719	CRIZOTINIB	4	15,133
CHEMBL5416410	DASATINIB	4	674
CHEMBL1983268	ENTRECTINIB	4	3,737
CHEMBL553	ERLOTINIB	4	109,860
CHEMBL1287853	FEDRATINIB	4	3,770
CHEMBL939	GEFITINIB	4	119,425
CHEMBL608533	MIDOSTAURIN	4	7,641
CHEMBL180022	NERATINIB	4	9,891
CHEMBL502835	NINTEDANIB	4	8,978
CHEMBL576982	QUIZARTINIB	4	4,647
CHEMBL1336	SORAFENIB	4	87,476
CHEMBL535	SUNITINIB	4	80,232
CHEMBL24828	VANDETANIB	4	43,290
CHEMBL428690	ALVOCIDIB	3	28,145
CHEMBL31965	CANERTINIB	3	8,307
CHEMBL491473	CEDIRANIB	3
CHEMBL522892	DOVITINIB	3
CHEMBL300138	ENZASTAURIN	3
CHEMBL3622820	ITACITINIB	3
CHEMBL603469	LESTAURTINIB	3
CHEMBL223360	LINIFANIB	3
CHEMBL5095079	POVORCITINIB	3
CHEMBL50	QUERCETIN	3
CHEMBL3989926	SITRAVATINIB	3
CHEMBL5314428	ZANZALINTINIB	3
CHEMBL3809489	BEMCENTINIB	2
CHEMBL3984441	NINGETINIB	2
CHEMBL575448	BMS-754807	2
CHEMBL460702	BMS-777607	2
CHEMBL1967878	CENISERTIB	2
CHEMBL3818247	DALMELITINIB	2
CHEMBL215152	DEFOSBARASERTIB	2
CHEMBL4544478	DENFIVONTINIB	2
CHEMBL2216863	DEZAPELISIB	2
CHEMBL2022968	DUBERMATINIB	2
CHEMBL1230609	FORETINIB	2
CHEMBL3989914	GLESATINIB	2
CHEMBL1980297	ILORASERTIB	2
CHEMBL3545307	MERESTINIB	2
CHEMBL253969	OSI-632	2
CHEMBL607707	PELITINIB	2
CHEMBL475251	R-406	2
CHEMBL1738757	REBASTINIB	2
CHEMBL565612	SOTRASTAURIN	2
CHEMBL1721885	SU-014813	2
CHEMBL5314429	TAMNORZATINIB	2
CHEMBL124660	TANDUTINIB	2
CHEMBL572878	TOZASERTIB	2
CHEMBL574738	AST-487	1
CHEMBL1908397	KW-2449	1
CHEMBL259084	MLN-8054	1
CHEMBL1084546	PF-00562271	1
CHEMBL6060997	PF-07265807	1
CHEMBL3764045	TAS-115	1

CIViC curated variants (1)

Named clinical variants curated in CIViC for this gene (the catalogue beneath the predictive evidence above):

EXPRESSION.

PharmGKB: 1 entry (CPIC guideline: no)

PharmGKB variants

1 variant:

Variant	Genes	Level	Score	#Clin annots	Drugs
rs12459996	AXL	3	0.00	1	glatiramer acetate

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: catalytic receptor — Type XI RTKs: TAM (TYRO3-, AXL- and MER-TK) receptor family

Most potent curated ligand interactions (22 total), top 22:

Ligand	Action	Affinity	Parameter
canlitinib	Inhibition	9.62	pIC50
gilteritinib	Inhibition	9.1	pIC50
BMS-777607	Inhibition	8.96	pIC50
sitravatinib	Inhibition	8.82	pIC50
compound 6li [Chan et al., 2022]	Inhibition	8.8	pIC50
ligritinib	Inhibition	8.74	pIC50
compound 8i [PMID: 22765894]	Inhibition	8.34	pIC50
UNC8969	Inhibition	8.28	pIC50
A-910	Inhibition	8.09	pIC50
zanzalintinib	Inhibition	8.0	pIC50
ningetinib	Inhibition	7.96	pIC50
merestinib	Inhibition	7.96	pIC50
bemcentinib	Inhibition	7.85	pIC50
dubermatinib	Inhibition	7.57	pIC50
belizatinib	Inhibition	7.54	pKd
LDC1267	Inhibition	7.54	pIC50
RIPK1 inhibitor 22b	Inhibition	7.46	pIC50
UNC4203	Inhibition	7.4	pKi
compound 19a [PMID: 30503936]	Inhibition	7.28	pIC50
adrixetinib	Inhibition	7.0	pKd
SLC-391	Inhibition	6.3	pIC50
compound 1 [Cruz-López et al., 2019]	Inhibition	4.89	pIC50

Binding affinities (BindingDB)

3513 measured of 5565 human assays (5568 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
4-[4-({[2-amino-5- (1-methyl-1H- imidazol-4- yl)pyridin-3- yl]oxy}methyl) piperidin-1-yl]-N- (bicyclo[1.1.1]pent- 1-yl)-6-[(1- cyanocyclopropyl) methoxy]-1,3,5- triazine-2- carboxamide	KI	0.01 nM	US-9593097: Axl inhibitors
4-[4-[[2-amino-5-(1-methylimidazol-4-yl)-3-pyridinyl]oxymethyl]piperidin-1-yl]-N-[(2R)-1-hydroxypropan-2-yl]-6-[[(2R)-oxolan-2-yl]methoxy]-1,3,5-triazine-2-carboxamide	KI	0.012 nM	US-9593097: Axl inhibitors
4-[4-({[2-amino-5- (1-methyl-1H- imidazol-4- yl)pyridin-3- yl]oxy}methyl) piperidin-1- yl]-6-[(1- cyanocyclopropyl) methoxy]-N-(1- methylcyclobutyl)- 1,3,5-triazine-2- carboxamide	KI	0.012 nM	US-9593097: Axl inhibitors
N-[(2R)-1- hydroxypropan-2- yl]-2-[(2R)-2- methoxypropoxy]- 6-[4-(4-methoxy- 1H-pyrrolo[2,3- b]pyridin-3- yl)piperidin-1- yl]pyrimidine-4- carboxamide	KI	0.014 nM	US-9593097: Axl inhibitors
4-[4-({[2-amino-5- (1-methyl-1H- imidazol-4- yl)pyridin-3- yl]oxy}methyl) piperidin-1-yl]-6- {[(1R)-2,2- difluoro- cyclopropyl] methoxy}-N- (propan-2-yl)- 1,3,5-triazine-2- carboxamide	KI	0.015 nM	US-9593097: Axl inhibitors
N-[(2R)-1- hydroxypropan-2- yl]-6-[4-(4- methoxy-1H- pyrazolo[3,4- b]pyridin-3- yl)piperidin-1-yl]- 2-[{2R)- tetrahydrofuran-2- ylmethoxy] pyrimidine- 4-carboxamide	KI	0.015 nM	US-9593097: Axl inhibitors
4-[4-({[2-amino-5- (1-methyl-1H- imidazol-4- yl)pyridin-3- yl]oxy}methyl) piperidin-1- yl]-6-[(1- cyanocyclopropyl) methoxy]-N- cyclobutyl-1,3,5- triazine-2- carboxamide	KI	0.016 nM	US-9593097: Axl inhibitors
4-[4-({[2-amino-5- (1-methyl-1H- imidazol-4- yl)pyridin-3- yl]oxy}methyl) piperidin-1-yl]- 6-[(2R)- tetrahydrofuran-2- ylmethoxy]-N- [(2S)-1,1,1- trifluoropropan-2- yl]-1,3,5-triazine- 2-carboxamide	KI	0.016 nM	US-9593097: Axl inhibitors
N-(2- methoxyethyl)-6- [4-(4-methoxy-1H- pyrrolo[2,3- b]pyridin-3- yl)piperidin-1-yl]-2- [(2R)- tetrahydrofuran-2- ylmethoxy] pyrimidine- 4-carboxamide	KI	0.016 nM	US-9593097: Axl inhibitors
(3,3- difluoroazetidin-1- yl)(2-{[(2R)-1- methoxypropan-2- yl]oxy}-6-[4-(4- methoxy-1H- pyrrolo[2,3- b]pyridin-3- yl)piperidin-1- yl]pyrimidin-4- yl)methanone	KI	0.018 nM	US-9593097: Axl inhibitors
4-[4-({[2-amino-5- (1-methyl-1H- imidazol-4- yl)pyridin-3- yl]oxy}methyl) piperidin-1- yl]-6-[(1- cyanocyclopropyl) methoxy]-N-[(1R)- 1-cyclopropylethyl]- 1,3,5-triazine-2- carboxamide	KI	0.019 nM	US-9593097: Axl inhibitors
4-[4-({[2-amino-5- (1-methyl-1H- imidazol-4- yl)pyridin-3- yl]oxy}methyl) piperidin-1-yl]-N- tert-butyl-6-[(1- cyanocyclopropyl) methoxy]-1,3,5- triazine-2- carboxamide	KI	0.02 nM	US-9593097: Axl inhibitors
N-[(2R)-3- hydroxy-3- methylbutan-2-yl]- 4-[4-(4-methoxy- 1H-pyrrolo[2,3- b]pyridin-3- yl)piperidin-1-yl]-6- [(2R)- tetrahydrofuran-2- ylmethoxy]-1,3,5- triazine-2- carboxamide	KI	0.02 nM	US-9593097: Axl inhibitors
N-[(2R)-1- hydroxypropan-2- yl]-2-[(2S)-2- methoxypropoxy]- 6-[4-(4-methoxy- 1H-pyrrolo[2,3- b]pyridin-3- yl)piperidin-1- yl]pyrimidine-4- carboxamide	KI	0.02 nM	US-9593097: Axl inhibitors
4-[4-({[2-amino-5- (1-methyl-1H- imidazol-4- yl)pyridin-3- yl]oxy}methyl) piperidin-1- yl]-N-tert- butyl-6-{[(1S,2R)- 2- cyanocyclopropyl] methoxy}-1,3,5- triazine-2- carboxamide	KI	0.021 nM	US-9593097: Axl inhibitors
4-[(1- cyanocyclopropyl) methoxy]-6-[4-(4- methoxy-1H- pyrrolo[2,3- b]pyridin-3- yl)piperidin-1-yl]- N-[(2S)-1,1,1- trifluoropropan-2- yl]-1,3,5-triazine- 2-carboxamide	KI	0.021 nM	US-9593097: Axl inhibitors
N-cyclobutyl-4- {[(2R)-1- methoxypropan-2- yl]oxy}-6-[4-(4- methoxy-1H- pyrazolo[3,4- b]pyridin-3- yl)piperidin-1-yl]- 1,3,5-triazine-2- carboxamide	KI	0.021 nM	US-9593097: Axl inhibitors
4-(benzyloxy)-N- [(2R)-1- hydroxypropan-2- yl]-6-[4-(4- methoxy-1H- pyrrolo[2,3- b]pyridin-3- yl)piperidin-1-yl]- 1,3,5-triazine-2- carboxamide	KI	0.025 nM	US-9593097: Axl inhibitors
4-[4-({[2-amino-5- (1-methyl-1H- imidazol-4- yl)pyridin-3- yl]oxy}methyl) piperidin-1-yl]-N- [(2R)- butan-2-yl]-6-[(1- cyanocyclopropyl) methoxy]-1,3,5- triazine-2- carboxamide	KI	0.026 nM	US-9593097: Axl inhibitors
4-[4-({[2-amino-5- (1-methyl-1H- imidazol-4- yl)pyridin-3- yl]oxy}methyl) piperidin-1-yl]-N- (bicyclo[1.1.1]pent- 1-yl)-6-{[(1S,2R)- 2- cyanocyclopropyl] methoxy}-1,3,5- triazine-2- carboxamide	KI	0.028 nM	US-9593097: Axl inhibitors
4-[4-({[2-amino-5- (1-methyl-1H- imidazol-4- yl)pyridin-3- yl]oxy}methyl) piperidin-1- yl]-6-[(1- cyanocyclopropyl) methoxy]-N-(2,2- dimethylpropyl)- 1,3,5-triazine-2- carboxamide	KI	0.028 nM	US-9593097: Axl inhibitors
N-[(2R)-1- hydroxypropan-2- yl]-4-{[(2R)-1- methoxypropan-2- yl]oxy}-6-[4-(4- methoxy-1H- pyrrolo[2,3- b]pyridin-3- yl)piperidin-1-yl]- 1,3,5-triazine-2- carboxamide	KI	0.028 nM	US-9593097: Axl inhibitors
4-[4-({[2-amino-5- (1-methyl-1H- imidazol-4- yl)pyridin-3- yl]oxy}methyl) piperidin-1-yl]-6- {[(1R)-2,2- difluoro- cyclopropyl] methoxy}-N- [(2R)-1- hydroxypropan-2- yl]-1,3,5-triazine- 2-carboxamide	KI	0.029 nM	US-9593097: Axl inhibitors
N- (bicyclo[1.1.1]pent- 1-yl)-4-{[(1S,2R)- 2- cyanocyclopropyl] methoxy}-6-[4-(4- methoxy-1H- pyrazolo[3,4- b]pyridin-3- yl)piperidin-1-yl]- 1,3,5-triazine-2- carboxamide	KI	0.03 nM	US-9593097: Axl inhibitors
N-[(2R)-1- hydroxypropan-2- yl]-4-[4-(4- methoxy-1H- pyrrolo[2,3- b]pyridin-3- yl)piperidin-1-yl]-6- [(2R)- tetrahydrofuran-2- ylmethoxy]-1,3,5- triazine-2- carboxamide	KI	0.03 nM	US-9593097: Axl inhibitors
4-[(1- cyanocyclopropyl) methoxy]-N-[(2R)- 1-hydroxypropan- 2-yl]-6-[4-(4- methoxy-1H- pyrrolo[2,3- b]pyridin-3- yl)piperidin-1-yl]- 1,3,5-triazine-2- carboxamide	KI	0.03 nM	US-9593097: Axl inhibitors
4-[4-({[2-amino-5- (1-methyl-1H- imidazol-4- yl)pyridin-3- yl]oxy}methyl) piperidin-1-yl]-6-[(1- cyanocyclopropyl) methoxy]-N- (cyclo- propylmethyl)- 1,3,5-triazine-2- carboxamide	KI	0.032 nM	US-9593097: Axl inhibitors
4-{[(1S,2R)-2- cyanocyclopropyl] methoxy}-N-[(2R)- 3-hydroxy-3- methylbutan-2-yl]- 6-[4-(4-methoxy- 1H-pyrrolo[2,3- b]pyridin-3- yl)piperidin-1-yl]- 1,3,5-triazine-2- carboxamide	KI	0.032 nM	US-9593097: Axl inhibitors
6-[4-({[2-amino-5- (1-methyl-1H- imidazol-4- yl)pyridin-3- yl]oxy}methyl) piperidin-1-yl]-2- {[(1S)-2,2- difluoro- cyclopropyl] methoxy}-N- [(2R)-1- hydroxypropan-2- yl]pyrimidine-4- carboxamide	KI	0.033 nM	US-9593097: Axl inhibitors
4-[4-({[2-amino-5- (1-methyl-1H- imidazol-4- yl)pyridin-3- yl]oxy}methyl) piperidin-1-yl]-N- [(2R)-3-hydroxy-3- methylbutan-2-yl]- 6-[(2R)- tetrahydrofuran-2- ylmethoxy]-1,3,5- triazine-2- carboxamide	KI	0.034 nM	US-9593097: Axl inhibitors
N-(3-amino-3-methylbutan-2-yl)-2-[(2R)-1-methoxypropan-2-yl]oxy-6-[4-(4-methoxy-1H-pyrrolo[2,3-b]pyridin-3-yl)piperidin-1-yl]pyrimidine-4-carboxamide	KI	0.034 nM	US-9593097: Axl inhibitors
N-[(1R,2R)-2- hydroxy- cyclobutyl]- 6-[4-(4-methoxy- 1H-pyrazolo[3,4- b]pyridin-3- yl)piperidin-1-yl]-2- [(2R)- tetrahydrofuran-2- ylmethoxy] pyrimidine- 4-carboxamide	KI	0.034 nM	US-9593097: Axl inhibitors
4-{[(1S,2R)-2- cyanocyclopropyl] methoxy}-N-[(2R)- 1-hydroxypropan- 2-yl]-6-[4-(4- methoxy-1H- pyrrolo[2,3- b]pyridin-3- yl)piperidin-1-yl]- 1,3,5-triazine-2- carboxamide	KI	0.035 nM	US-9593097: Axl inhibitors
4-(benzyloxy)-N- [(2R)-1- hydroxypropan-2- yl]-6-[4-(4- methoxy-1H- pyrazolo[3,4- b]pyridin-3- yl)piperidin-1-yl]- 1,3,5-triazine-2- carboxamide	KI	0.037 nM	US-9593097: Axl inhibitors
N-[(2R)-3- hydroxy-3- methylbutan-2-yl]- 4-{[(2R)-1- methoxypropan-2- yl]oxy}-6-[4-(4- methoxy-1H- pyrrolo[2,3- b]pyridin-3- yl)piperidin-1-yl]- 1,3,5-triazine-2- carboxamide	KI	0.038 nM	US-9593097: Axl inhibitors
4-[(1- cyanocyclopropyl) methoxy]-N-[(2R)- 3-hydroxy-3- methylbutan-2-yl]- 6-[4-(4-methoxy- 1H-pyrrolo[2,3- b]pyridin-3- yl)piperidin-1-yl]- 1,3,5-triazine-2- carboxamide	KI	0.038 nM	US-9593097: Axl inhibitors
4-[4-({[2-amino-5- (1-methyl-1H- imidazol-4- yl)pyridin-3- yl]oxy}methyl) piperidin-1- yl]-6-[(1- cyanocyclopropyl) methoxy]-N- (2,2,2- trifluoroethyl)- 1,3,5-triazine-2- carboxamide	KI	0.039 nM	US-9593097: Axl inhibitors
4-[4-({[2-amino-5- (1-methyl-1H- imidazol-4- yl)pyridin-3- yl]oxy}methyl) piperidin-1- yl]-6-[(1- cyanocyclopropyl) methoxy]-N-(3,3- difluorobutan-2- yl)-1,3,5-triazine- 2-carboxamide	KI	0.04 nM	US-9593097: Axl inhibitors
N-(3-amino-3- methylbutan-2-yl)- 2-[(1- cyanocyclopropyl) methoxy]-6-[4-(4- methoxy-1H- pyrrolo[2,3- b]pyridin-3- yl)piperidin-1- yl]pyrimidine-4- carboxamide	KI	0.04 nM	US-9593097: Axl inhibitors
N-(2-hydroxycyclobutyl)-2-[(2R)-1-methoxypropan-2-yl]oxy-6-[4-(4-methoxy-2H-pyrazolo[3,4-b]pyridin-3-yl)piperidin-1-yl]pyrimidine-4-carboxamide	KI	0.041 nM	US-9593097: Axl inhibitors
4-[4-({[2-amino-5- (1-methyl-1H- imidazol-4- yl)pyridin-3- yl]oxy}methyl) piperidin-1- yl]-6-[(1- cyanocyclopropyl) methoxy]-N- (propan-2-yl)- 1,3,5-triazine-2- carboxamide	KI	0.042 nM	US-9593097: Axl inhibitors
N-[(1R,2S)-2- hydroxycyclobutyl]- 6-[4-(4-methoxy- 1H-pyrazolo[3,4- b]pyridin-3- yl)piperidin- 1-yl]-2-[(2R- tetrahydrofuran-2- ylmethoxy] pyrimidine- 4-carboxamide	KI	0.042 nM	US-9593097: Axl inhibitors
4-[(1- cyanocyclopropyl) methoxy]-6-[4-(4- methoxy-1H- pyrrolo[2,3- b]pyridin-3- yl)piperidin-1-yl]- N-(2,2,2- trifluoroethyl)- 1,3,5-triazine-2- carboxamide	KI	0.048 nM	US-9593097: Axl inhibitors
N-[(3R,4S)-4- hydroxytetrahydro- furan-3-yl]-2- {[(2R)-1- methoxypropan-2- yl]oxy}-6-[4-(4- methoxy-1H- pyrrolo[2,3- b]pyridin-3- yl)piperidin-1- yl]pyrimidine-4- carboxamide	KI	0.048 nM	US-9593097: Axl inhibitors
2-[(1- cyanocyclopropyl) methoxy]-N-[(2R)- 1-hydroxypropan- 2-yl]-6-[4-(4- methoxy-1H- pyrazolo[3,4- b]pyridin-3- yl)piperidin-1- yl]pyrimidine-4- carboxamide	KI	0.049 nM	US-9593097: Axl inhibitors
N-[(2R)-3- hydroxy-3- methylbutan-2-yl]- 6-[4-(4-methoxy- 1H-pyrazolo[3,4- b]pyridin-3- yl)piperidin-1-yl]-2- [(2R)- tetrahydrofuran-2- ylmethoxy] pyrimidine- 4-carboxamide	KI	0.05 nM	US-9593097: Axl inhibitors
N-(2- methoxyethyl)-4- [4-(4-methoxy-1H- pyrrolo[2,3- b]pyridin-3- yl)piperidin-1-yl]-6- [(2R)- tetrahydrofuran-2- ylmethoxy]-1,3,5- triazine-2- carboxamide	KI	0.051 nM	US-9593097: Axl inhibitors
4-[4-({[2-amino-5- (1-methyl-1H- imidazol-4- yl)pyridin-3- yl]oxy}methyl) piperidin-1-yl]-6- {[(1S,2R)-2- cyanocyclopropyl] methoxy}-N- cyclobutyl-1,3,5- triazine-2- carboxamide	KI	0.053 nM	US-9593097: Axl inhibitors
4- (cyclo- propylmethoxy)- N-[(2R)-3- hydroxy-3- methylbutan-2-yl]- 6-[4-(4-methoxy- 1H-pyrazolo[3,4- b]pyridin-3- yl)piperidin-1-yl]- 1,3,5-triazine-2- carboxamide	KI	0.053 nM	US-9593097: Axl inhibitors
6-[4-(4-ethoxy-1H- pyrazolo[3,4- b]pyridin-3- yl)piperidin-1-yl]- N-[(2R)-1- hydroxypropan-2- yl]-2-{[(2R)-1- methoxypropan-2- yl]oxy}pyrimidine- 4-carboxamide	KI	0.054 nM	US-9593097: Axl inhibitors

ChEMBL bioactivities

3511 potent at pChembl≥5 of 3609 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
11.00	Ki	0.01	nM	CHEMBL5758853
10.92	Ki	0.012	nM	CHEMBL5935453
10.92	Ki	0.012	nM	CHEMBL5932919
10.85	Ki	0.014	nM	CHEMBL5792035
10.82	Ki	0.015	nM	CHEMBL5923596
10.82	Ki	0.015	nM	CHEMBL5930737
10.80	Ki	0.016	nM	CHEMBL5906788
10.80	Ki	0.016	nM	CHEMBL6041852
10.80	Ki	0.016	nM	CHEMBL5931969
10.74	Ki	0.018	nM	CHEMBL5819606
10.72	Ki	0.019	nM	CHEMBL5912055
10.70	Ki	0.02	nM	CHEMBL5964033
10.70	Ki	0.02	nM	CHEMBL5880806
10.70	Ki	0.02	nM	CHEMBL5972896
10.68	Ki	0.021	nM	CHEMBL5851400
10.68	Ki	0.021	nM	CHEMBL5820622
10.68	Ki	0.021	nM	CHEMBL5804857
10.60	Ki	0.025	nM	CHEMBL5813796
10.59	Ki	0.026	nM	CHEMBL5911851
10.55	Ki	0.028	nM	CHEMBL5990089
10.55	Ki	0.028	nM	CHEMBL5934471
10.55	Ki	0.028	nM	CHEMBL5952989
10.54	Ki	0.029	nM	CHEMBL6019578
10.52	Ki	0.03	nM	CHEMBL5952495
10.52	Ki	0.03	nM	CHEMBL5913877
10.52	Ki	0.03	nM	CHEMBL6028906
10.49	Ki	0.032	nM	CHEMBL5929819
10.49	Ki	0.032	nM	CHEMBL6039322
10.48	Ki	0.033	nM	CHEMBL5851291
10.47	Ki	0.034	nM	CHEMBL5855090
10.47	Ki	0.034	nM	CHEMBL5866479
10.47	Ki	0.034	nM	CHEMBL5907610
10.46	Ki	0.035	nM	CHEMBL5914736
10.43	Ki	0.037	nM	CHEMBL5814025
10.42	Ki	0.038	nM	CHEMBL5844227
10.42	Ki	0.038	nM	CHEMBL5865745
10.41	Ki	0.039	nM	CHEMBL5809410
10.40	Ki	0.04	nM	CHEMBL5886143
10.40	Ki	0.04	nM	CHEMBL5831618
10.39	Ki	0.041	nM	CHEMBL5803601
10.38	Ki	0.042	nM	CHEMBL5900027
10.38	Ki	0.042	nM	CHEMBL5941635
10.32	Ki	0.048	nM	CHEMBL6019416
10.32	Ki	0.048	nM	CHEMBL5822798
10.31	Ki	0.049	nM	CHEMBL5781623
10.31	Ki	0.049	nM	CHEMBL5803601
10.30	Ki	0.05	nM	CHEMBL5783301
10.29	Ki	0.051	nM	CHEMBL5966426
10.28	Ki	0.053	nM	CHEMBL5987998
10.28	Ki	0.053	nM	CHEMBL5993500

PubChem BioAssay actives

1347 with measured affinity, of 3273 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
N-[4-(4-amino-7-methylpyrrolo[2,3-d]pyrimidin-5-yl)phenyl]-5-(4-fluorophenyl)-1-(oxan-4-ylmethyl)-4-oxopyridine-3-carboxamide	1778599: Inhibition of AXL (unknown origin) by ELISA	ic50	0.0001	uM
1-N’-[3-fluoro-4-[6-methoxy-7-(3-morpholin-4-ylpropoxy)quinolin-4-yl]oxyphenyl]-1-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide	624840: Binding constant for AXL kinase domain	kd	0.0001	uM
(16R)-19-amino-14-chloro-13-fluoro-5-(2-hydroxyethyl)-3,8,16-trimethyl-17-oxa-4,5,8,20,22-pentazatetracyclo[16.3.1.02,6.010,15]docosa-1(21),2(6),3,10(15),11,13,18(22),19-octaen-9-one	2265085: Binding affinity to His-tagged Axl intracellular domain (473 to 894 residues) (unknown origin) extracted from Sf21 cells assessed as inhibition constant using Glu-Ala-Ile-Tyr-Ala-Ala-Pro-Phe-Ala-Lys-Lys-Lys, as substrate incubated for 30 mins in presence of ATP by ITC analysis	ki	0.0001	uM
N-[4-(4-amino-7-methylpyrrolo[2,3-d]pyrimidin-5-yl)-2-fluorophenyl]-5-(4-fluorophenyl)-1-(oxan-4-ylmethyl)-4-oxopyridine-3-carboxamide	1778599: Inhibition of AXL (unknown origin) by ELISA	ic50	0.0002	uM
N-[4-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-5-yl)phenyl]-5-(4-fluorophenyl)-1-(oxan-4-ylmethyl)-4-oxopyridine-3-carboxamide	1778599: Inhibition of AXL (unknown origin) by ELISA	ic50	0.0002	uM
N-[4-(4-amino-7-methylpyrrolo[2,3-d]pyrimidin-5-yl)phenyl]-5-(4-chlorophenyl)-1-(oxan-4-ylmethyl)-4-oxopyridine-3-carboxamide	1778599: Inhibition of AXL (unknown origin) by ELISA	ic50	0.0002	uM
N-[4-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-2,5-difluorophenyl]-5-(4-fluorophenyl)-4-oxo-1-propan-2-ylpyridine-3-carboxamide	1778599: Inhibition of AXL (unknown origin) by ELISA	ic50	0.0002	uM
N-cyclohexyl-3-[3-fluoro-4-[6-methoxy-7-(3-morpholin-4-ylpropoxy)quinolin-4-yl]oxyanilino]-1-methylpyrazole-4-carboxamide	1849343: Binding affinity to AXL (unknown origin) assessed as dissociation constant by competition binding assay	kd	0.0003	uM
3-[(3-cyclopentyl-1,2,4,5-tetrahydro-3-benzazepin-7-yl)amino]-6-ethyl-5-(oxan-4-ylamino)pyrazine-2-carboxamide	1624310: Inhibition of TEL/AXL (unknown origin) expressed in mouse BA/F3 cells assessed as growth inhibition after 72 hrs by SRB assay	ic50	0.0003	uM
N-[4-(4-amino-7-methylpyrrolo[2,3-d]pyrimidin-5-yl)phenyl]-1-(oxan-4-ylmethyl)-4-oxo-5-[4-(trifluoromethyl)phenyl]pyridine-3-carboxamide	1778599: Inhibition of AXL (unknown origin) by ELISA	ic50	0.0004	uM
N-[4-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-2,5-difluorophenyl]-5-(4-fluorophenyl)-1-(oxan-4-ylmethyl)-4-oxopyridine-3-carboxamide	1778599: Inhibition of AXL (unknown origin) by ELISA	ic50	0.0004	uM
N-[4-(4-amino-7-methylpyrrolo[2,3-d]pyrimidin-5-yl)phenyl]-5-(4-fluorophenyl)-4-oxo-1-propan-2-ylpyridine-3-carboxamide	1778599: Inhibition of AXL (unknown origin) by ELISA	ic50	0.0004	uM
N-[4-(4-amino-7-methylpyrrolo[2,3-d]pyrimidin-5-yl)phenyl]-1-[2-(dimethylamino)-2-oxoethyl]-5-(4-fluorophenyl)-4-oxopyridine-3-carboxamide	1778599: Inhibition of AXL (unknown origin) by ELISA	ic50	0.0005	uM
N-[4-(4-amino-7-methylpyrrolo[2,3-d]pyrimidin-5-yl)-2,5-difluorophenyl]-5-(4-fluorophenyl)-1-(oxan-4-ylmethyl)-4-oxopyridine-3-carboxamide	1778599: Inhibition of AXL (unknown origin) by ELISA	ic50	0.0005	uM
N-[2-[2-[4-(4-acetylpiperazin-1-yl)anilino]-5-(trifluoromethyl)pyrimidin-4-yl]-1,3-dihydroisoindol-4-yl]-N-methylmethanesulfonamide	1529866: Inhibition of N-terminal His-tagged recombinant human AXL (473 to end amino acids) expressed by baculovirus in Sf9 cells using axltide substrate and ATP by ADP-Glo luminescence assay	ic50	0.0005	uM
2-(2,3,4-trihydroxyphenyl)-2,3-dihydrochromen-4-one	1915844: Inhibition of AXL (unknown origin) by biochemical assay	ic50	0.0005	uM
Cabozantinib	2280101: Inhibition of AXL (unknown origin) by fluorescence-based microfluidic mobility shift assay	ic50	0.0005	uM
N-[[3-fluoro-4-[2-[5-[(2-methoxyethylamino)methyl]-2-pyridinyl]thieno[3,2-b]pyridin-7-yl]oxyphenyl]carbamothioyl]-2-(4-fluorophenyl)acetamide	2280101: Inhibition of AXL (unknown origin) by fluorescence-based microfluidic mobility shift assay	ic50	0.0005	uM
N-[3-fluoro-4-[1-methyl-6-(1H-pyrazol-4-yl)indazol-5-yl]oxyphenyl]-1-(4-fluorophenyl)-6-methyl-2-oxopyridine-3-carboxamide	2280101: Inhibition of AXL (unknown origin) by fluorescence-based microfluidic mobility shift assay	ic50	0.0005	uM
3-(4-fluorophenyl)-N-[4-[[2-[[2-(1-methylpiperidin-4-yl)acetyl]amino]-4-pyridinyl]oxy]phenyl]-2,4-dioxo-1-propan-2-ylpyrimidine-5-carboxamide	1763427: Inhibition of recombinant human GST-tagged Axl incubated for 1 hr by ADP-glo based luminometry analysis	ic50	0.0006	uM
6-[(7S)-3-[3-[4-(1-methylimidazol-2-yl)phenyl]-2H-pyrazolo[3,4-b]pyridin-5-yl]-6,7,8,9-tetrahydro-5H-benzo[7]annulen-7-yl]-3-oxa-6-azabicyclo[3.1.1]heptane	2264936: Inhibition of human AXL measured after 150 mins by ATP-competitive HTRF based biochemical assay	ic50	0.0006	uM
2-amino-N-[(1S,2S)-2-[[4-[4-[2-[4-(2,3-dihydroxypropyl)piperazin-1-yl]propan-2-yl]phenyl]phenyl]methoxy]cyclopentyl]-5-(1-methylpyrazol-4-yl)pyridine-3-carboxamide	2247346: Inhibition of N-terminal His-tagged recombinant human Axl (473 to end residues) expressed in baculovirus-infected Sf9 cells using biotin-labeled TK and ATP as substrate preincubated with enzyme for 30 mins followed by substrate addition and measured after 1 hr by HTRF assay	ic50	0.0006	uM
6-ethyl-3-[[3-(3-ethylcyclopentyl)-1,2,4,5-tetrahydro-3-benzazepin-7-yl]amino]-5-(oxan-4-ylamino)pyrazine-2-carboxamide	1624309: Inhibition of AXL (unknown origin) using poly (Glu, Tyr) as substrate after 60 mins by ELISA	ic50	0.0007	uM
6-[(7S)-3-[3-[4-(3-methyl-2-pyridinyl)phenyl]-1H-pyrrolo[2,3-b]pyridin-5-yl]-6,7,8,9-tetrahydro-5H-benzo[7]annulen-7-yl]-3-oxa-6-azabicyclo[3.1.1]heptane	2264936: Inhibition of human AXL measured after 150 mins by ATP-competitive HTRF based biochemical assay	ic50	0.0007	uM
1-(3,4-diazatricyclo[9.4.0.02,7]pentadeca-1(15),2,4,6,11,13-hexaen-5-yl)-3-N-[(7S)-7-pyrrolidin-1-yl-6,7,8,9-tetrahydro-5H-benzo[7]annulen-3-yl]-1,2,4-triazole-3,5-diamine	1374805: Inhibition of wild-type human partial length AXL (R497 to Y821 residues) expressed in bacterial expression system using poly [Glu, Try] 4:1 as substrate in presence of [gamma-33P]ATP	ic50	0.0007	uM
Gilteritinib	1562831: Inhibition of N-terminal GST-tagged human AXL (464 to 885 residues) cytoplasmic domain expressed in baculovirus expression system by ELISA	ic50	0.0007	uM
N-[5-(6,7-dimethoxyquinolin-4-yl)oxy-2-pyridinyl]-2,5-dioxo-1-phenyl-7,8-dihydro-6H-quinoline-3-carboxamide	2064258: Inhibition of AXL (unknown origin) by HTRF kinase assay	ic50	0.0007	uM
2-amino-N-[(1S,2S)-2-[[4-[4-[2-[4-(2-hydroxyethyl)piperazin-1-yl]propan-2-yl]phenyl]phenyl]methoxy]cyclopentyl]-5-(1-methylpyrazol-4-yl)pyridine-3-carboxamide	2247346: Inhibition of N-terminal His-tagged recombinant human Axl (473 to end residues) expressed in baculovirus-infected Sf9 cells using biotin-labeled TK and ATP as substrate preincubated with enzyme for 30 mins followed by substrate addition and measured after 1 hr by HTRF assay	ic50	0.0008	uM
N-[4-(4-amino-7-methylpyrrolo[2,3-d]pyrimidin-5-yl)phenyl]-5-(2,4-difluorophenyl)-1-(oxan-4-ylmethyl)-4-oxopyridine-3-carboxamide	1778599: Inhibition of AXL (unknown origin) by ELISA	ic50	0.0008	uM
N-[4-(4-amino-7-methylpyrrolo[2,3-d]pyrimidin-5-yl)-3-fluorophenyl]-5-(4-fluorophenyl)-1-(oxan-4-ylmethyl)-4-oxopyridine-3-carboxamide	1778599: Inhibition of AXL (unknown origin) by ELISA	ic50	0.0008	uM
N-[3-fluoro-4-(1H-imidazo[4,5-b]pyridin-7-yloxy)phenyl]-1-(4-fluorophenyl)-2-oxopyridine-3-carboxamide	1418401: Inhibition of recombinant His-tagged human Axl (473 to end residues) cytoplasmic domain expressed in insect system using poly (Glu-Ala-Tyr) peptide as substrate after 5 mins in presence of ADP by fluorescence analysis	ic50	0.0008	uM
N-[3-fluoro-4-[[2-(1-methylpyrazol-4-yl)-4-pyridinyl]oxy]phenyl]-3-(4-fluorophenyl)-2,4-dioxo-1-propan-2-ylpyrimidine-5-carboxamide	1764488: Inhibition of AXL (unknown origin) using poly [Glu, Tyr] 4:1 as substrate incubated for 60 mins in presence of ATP by ELISA	ic50	0.0008	uM
N-[4-[6-(cyclopropanecarbonylamino)pyrimidin-4-yl]oxyphenyl]-3-(4-fluorophenyl)-2,4-dioxo-1-propan-2-ylpyrimidine-5-carboxamide	1763427: Inhibition of recombinant human GST-tagged Axl incubated for 1 hr by ADP-glo based luminometry analysis	ic50	0.0008	uM
N-[2,5-difluoro-4-[[2-[[4-(4-methylpiperazin-1-yl)piperidine-1-carbonyl]amino]-4-pyridinyl]oxy]phenyl]-3-(4-fluorophenyl)-2,4-dioxo-1-propan-2-ylpyrimidine-5-carboxamide	1763427: Inhibition of recombinant human GST-tagged Axl incubated for 1 hr by ADP-glo based luminometry analysis	ic50	0.0008	uM
N-[2-fluoro-4-[[2-[[2-(1-methylpiperidin-4-yl)acetyl]amino]-4-pyridinyl]oxy]phenyl]-3-(4-fluorophenyl)-2,4-dioxo-1-propan-2-ylpyrimidine-5-carboxamide	1763427: Inhibition of recombinant human GST-tagged Axl incubated for 1 hr by ADP-glo based luminometry analysis	ic50	0.0008	uM
5-[(7S)-7-methyl-7-[(2R)-2-methylpyrrolidin-1-yl]-5,6,8,9-tetrahydrobenzo[7]annulen-3-yl]-3-[4-(3-methyl-2-pyridinyl)phenyl]-2H-pyrazolo[3,4-b]pyridine	2264936: Inhibition of human AXL measured after 150 mins by ATP-competitive HTRF based biochemical assay	ic50	0.0008	uM
2-amino-N-[(1S,2S)-2-[[4-[(5S)-5-[4-(2-hydroxyethyl)piperazin-1-yl]-5,6,7,8-tetrahydronaphthalen-2-yl]phenyl]methoxy]cyclopentyl]-5-(1-methylpyrazol-4-yl)pyridine-3-carboxamide	2247346: Inhibition of N-terminal His-tagged recombinant human Axl (473 to end residues) expressed in baculovirus-infected Sf9 cells using biotin-labeled TK and ATP as substrate preincubated with enzyme for 30 mins followed by substrate addition and measured after 1 hr by HTRF assay	ic50	0.0008	uM
2-amino-N-[(1S,2S)-2-[[4-[(1S)-1-[4-(2-hydroxyethyl)piperazin-1-yl]-2,3-dihydro-1H-inden-5-yl]phenyl]methoxy]cyclopentyl]-5-(1-methylpyrazol-4-yl)pyridine-3-carboxamide	2247346: Inhibition of N-terminal His-tagged recombinant human Axl (473 to end residues) expressed in baculovirus-infected Sf9 cells using biotin-labeled TK and ATP as substrate preincubated with enzyme for 30 mins followed by substrate addition and measured after 1 hr by HTRF assay	ic50	0.0008	uM
2-amino-N-[(1S,2S)-2-[[4-[4-[[1-(2-hydroxyethyl)piperidin-4-yl]-methylamino]phenyl]phenyl]methoxy]cyclopentyl]-5-(1-methylpyrazol-4-yl)pyridine-3-carboxamide	2247346: Inhibition of N-terminal His-tagged recombinant human Axl (473 to end residues) expressed in baculovirus-infected Sf9 cells using biotin-labeled TK and ATP as substrate preincubated with enzyme for 30 mins followed by substrate addition and measured after 1 hr by HTRF assay	ic50	0.0008	uM
N-methyl-N-[2-[2-(4-morpholin-4-ylanilino)-5-(trifluoromethyl)pyrimidin-4-yl]-1,3-dihydroisoindol-4-yl]methanesulfonamide	1529866: Inhibition of N-terminal His-tagged recombinant human AXL (473 to end amino acids) expressed by baculovirus in Sf9 cells using axltide substrate and ATP by ADP-Glo luminescence assay	ic50	0.0009	uM
N-[4-[[2-(cyclopropanecarbonylamino)-4-pyridinyl]oxy]-3-fluorophenyl]-3-(4-fluorophenyl)-2,4-dioxo-1-propan-2-ylpyrimidine-5-carboxamide	1764488: Inhibition of AXL (unknown origin) using poly [Glu, Tyr] 4:1 as substrate incubated for 60 mins in presence of ATP by ELISA	ic50	0.0009	uM
Crizotinib	617240: Inhibition of AXL	ic50	0.0010	uM
2-amino-N-[(1S,2S)-2-[[4-[4-[2-(4-methylpiperazin-1-yl)propan-2-yl]phenyl]phenyl]methoxy]cyclopentyl]-5-(1-methylpyrazol-4-yl)pyridine-3-carboxamide	2247346: Inhibition of N-terminal His-tagged recombinant human Axl (473 to end residues) expressed in baculovirus-infected Sf9 cells using biotin-labeled TK and ATP as substrate preincubated with enzyme for 30 mins followed by substrate addition and measured after 1 hr by HTRF assay	ic50	0.0010	uM
N-[4-(4-amino-7-methylpyrrolo[2,3-d]pyrimidin-5-yl)phenyl]-1-(oxan-4-ylmethyl)-4-oxo-5-phenylpyridine-3-carboxamide	1778599: Inhibition of AXL (unknown origin) by ELISA	ic50	0.0010	uM
N-[2-[4-[(3S)-1-methylsulfonylpiperidin-3-yl]-1,3-thiazol-2-yl]-4-piperazin-1-ylphenyl]-1H-imidazole-2-carboxamide	1434708: Inhibition of Axl (unknown origin)	ic50	0.0010	uM
2-amino-N-[(1S,2S)-2-[[4-[4-[2-[4-(1H-imidazol-2-ylmethyl)piperazin-1-yl]propan-2-yl]phenyl]phenyl]methoxy]cyclopentyl]-5-(1-methylpyrazol-4-yl)pyridine-3-carboxamide	2247346: Inhibition of N-terminal His-tagged recombinant human Axl (473 to end residues) expressed in baculovirus-infected Sf9 cells using biotin-labeled TK and ATP as substrate preincubated with enzyme for 30 mins followed by substrate addition and measured after 1 hr by HTRF assay	ic50	0.0010	uM
2-amino-5-(2-fluoro-3-pyridinyl)-N-[(1S,2S)-2-[[4-[4-[2-[4-(2-hydroxyethyl)piperazin-1-yl]propan-2-yl]phenyl]phenyl]methoxy]cyclopentyl]pyridine-3-carboxamide	2247346: Inhibition of N-terminal His-tagged recombinant human Axl (473 to end residues) expressed in baculovirus-infected Sf9 cells using biotin-labeled TK and ATP as substrate preincubated with enzyme for 30 mins followed by substrate addition and measured after 1 hr by HTRF assay	ic50	0.0010	uM
N-[3-fluoro-4-[7-(2-hydroxy-2-methylpropoxy)quinolin-4-yl]oxyphenyl]-1,5-dimethyl-3-oxo-2-phenylpyrazole-4-carboxamide	2100797: Inhibition of AXL (unknown origin)	ic50	0.0010	uM
N-[4-(4-amino-7-methylpyrrolo[2,3-d]pyrimidin-5-yl)phenyl]-5-(4-fluorophenyl)-1-(oxan-4-yl)-4-oxopyridine-3-carboxamide	1778599: Inhibition of AXL (unknown origin) by ELISA	ic50	0.0011	uM
N-[4-[(2-amino-3-chloro-4-pyridinyl)oxy]-3-fluorophenyl]-1-(4-fluorophenyl)-4-methoxy-2-oxopyridine-3-carboxamide	1691581: Inhibition of Axl (unknown origin)	ic50	0.0011	uM

CTD chemical–gene interactions

91 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases methylation, increases expression	6
Valproic Acid	affects cotreatment, decreases expression	5
Cisplatin	increases expression, affects expression	3
Cyclosporine	decreases expression, increases expression	3
Aflatoxin B1	increases expression, increases methylation	3
bisphenol A	decreases expression	2
sodium arsenite	increases expression	2
cobaltous chloride	decreases expression, increases expression	2
Decitabine	affects expression, decreases methylation, increases expression	2
Zoledronic Acid	decreases expression	2
Air Pollutants	decreases expression, increases abundance, increases expression	2
Doxorubicin	affects response to substance, increases expression	2
Lipopolysaccharides	affects expression, affects response to substance, increases expression	2
Methyl Methanesulfonate	increases expression	2
Tobacco Smoke Pollution	decreases expression	2
Cadmium Chloride	increases expression	2
aristolochic acid I	increases expression	1
napabucasin	decreases expression	1
chloroacetaldehyde	affects expression	1
2,2’-methylenebis(4-methyl-6-tert-butylphenol)	affects expression, affects response to substance	1
sodium arsenate	increases abundance, increases expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
3,4-dichloroaniline	decreases expression	1
arsenite	affects binding, decreases reaction	1
methylparaben	decreases expression	1
mono-(2-ethylhexyl)phthalate	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
doxifluridine	decreases response to substance	1
benzo(e)pyrene	decreases methylation	1
aflatoxin B2	decreases methylation	1

ChEMBL screening assays

701 unique, capped per target: 698 binding, 3 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4424133	Binding	Inhibition of TEL/AXL (unknown origin) expressed in mouse BA/F3 cells assessed as growth inhibition after 72 hrs by SRB assay	Discovery of a potent tyrosine kinase AXL inhibitor bearing the 3-((2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-yl)amino)pyrazine core. — *Bioorg Med Chem Lett*
CHEMBL1964114	Functional	PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: AXL	PubChem BioAssay data set

Cellosaurus cell lines

8 cell lines: 7 cancer cell line, 1 factor-dependent cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B1KS	Abcam HeLa AXL KO 1	Cancer cell line	Female
CVCL_B1KT	Abcam HeLa AXL KO 2	Cancer cell line	Female
CVCL_D8HT	Ubigene HCT 116 AXL KO	Cancer cell line	Male
CVCL_D9YC	Ubigene HeLa AXL KO	Cancer cell line	Female
CVCL_F5AV	EDITGENE AXL Knockout A549 Cell Line	Cancer cell line	Male
CVCL_HG04	HCT 116 AXL KO Tet-inducible	Cancer cell line	Male
CVCL_SE39	HAP1 AXL (-)	Cancer cell line	Male
CVCL_UE62	Ba/F3 AXL	Factor-dependent cell line

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

51 trials:

NCT	Phase	Status	Title
NCT01403532	Phase 4	COMPLETED	Sequential Therapy for Hypogonadotropic Hypogonadism
NCT02880280	Phase 4	UNKNOWN	Human Menopausal Gonadotropin Combining With Human Chorionic Gonadotropin Treat Congenital Hypogonadotropic Hypogonadism
NCT03687606	Phase 4	UNKNOWN	Efficacy and Safety of Long Term Use of hCG or hCG Plus hMG in Males With Isolated Hypogonadotropic Hypogonadism (IHH)
NCT01103518	Phase 4	UNKNOWN	Ethinyl Estradiol and Cyproterone Acetate in Irregular Menstruation
NCT01206153	Phase 4	COMPLETED	Metformin for Treatment Antipsychotic Induced Amenorrhea in Female Schizophrenic Patients
NCT02393482	Phase 4	UNKNOWN	Psychological Impact of Amenorrhea in Women With Endometriosis
NCT00827151	Phase 3	WITHDRAWN	Bone Mass Accrual in Adolescent Athletes
NCT00064987	Phase 2	TERMINATED	Follicle Stimulating Hormone (FSH) to Improve Testicular Development in Men With Hypogonadism
NCT00130117	Phase 2	COMPLETED	Study of Leptin for the Treatment of Hypothalamic Amenorrhea
NCT00152282	Phase 2	COMPLETED	A Study to Evaluate the Safety and Effectiveness of Asoprisnil and Estrogen Administration to Postmenopausal Women
NCT00196391	Phase 2	COMPLETED	A Trial to Evaluate DR-2021 in Women With Secondary Amenorrhea
NCT00383656	Phase 2	UNKNOWN	Pulsatile GnRH in Anovulatory Infertility
NCT00429494	Phase 2	COMPLETED	GnRH Analogue for Ovarian Function Preservation in Hematopoietic Stem Cell Transplantation Patients
NCT00392756	Phase 1	COMPLETED	Examination of Idiopathic Hypogonadotropic Hypogonadism (IHH)and Kallmann Syndrome (KS)
NCT00493961	Phase 1	COMPLETED	Studying the Effects of 7 Days of Gonadotropin Releasing Hormone (GnRH) Treatment in Men With Hypogonadism
NCT00914823	Phase 1	COMPLETED	Kisspeptin Administration in the Adult
NCT01438034	Phase 1	COMPLETED	Kisspeptin in the Evaluation of Delayed Puberty
NCT03118479	Phase 1	TERMINATED	Effect of Varying Testosterone Levels on Insulin Sensitivity in Men With Idiopathic Hypogonadotropic Hypogonadism (IHH)
NCT00881608	Phase 1	TERMINATED	Study to Evaluate Menses Induction in Women Administered Proellex
NCT07152730	Phase 1	WITHDRAWN	A Study to Measure Pharmacokinetic (PK) Concentrations of Gonadotropin-Releasing Hormone Delivered by the OmniPod Pump
NCT00392457	Not specified	COMPLETED	Investigating the Regulation of Reproductive Hormones in Adult Men
NCT00494169	Not specified	COMPLETED	Investigation of the Genetic Causes of Kallmann Syndrome and Reproductive Disorders
NCT00623116	Not specified	UNKNOWN	A Study to Characterize Epidemiology, Clinical and Genetic Features of Kallmann Syndrome in Finland
NCT01601171	Not specified	RECRUITING	Genetics of Reproductive Disorders (Including Kallmann Syndrome) and Cleft Lip and/or Palate
NCT01914172	Not specified	COMPLETED	Health Needs of Patients With Kallmann Syndrome
NCT04463316	Not specified	RECRUITING	GROWing Up With Rare GENEtic Syndromes
NCT04733274	Not specified	ACTIVE_NOT_RECRUITING	Patient and Healthcare Professional Views on Genetic/Genomic Information and Testing
NCT05971836	Not specified	COMPLETED	The Molecular Basis of Inherited Reproductive Disorders
NCT03916978	Phase 2/3	RECRUITING	Autologous PRP Intra Ovarian Infusion to Restore Ovarian Function in Menopausal Women
NCT00556400	Phase 1/2	TERMINATED	Treatment of Menorrhagia in Women With Thrombocytopenia Using Platelets or Platelets and Hormones
NCT01187043	Phase 1/2	COMPLETED	Determination of the Lowest, Safe and Effective Dose of Proellex
NCT00001275	Not specified	COMPLETED	Ovarian Follicle Function in Patients With Primary Ovarian Failure
NCT00011388	Not specified	COMPLETED	Reproductive Effects of Pesticide, PCB and Mercury Exposure in Laotian Immigrants
NCT00243607	Not specified	COMPLETED	Hydrotherapy Against Menopausal Symptoms in Breast Cancer Survivors
NCT00260286	Not specified	COMPLETED	Effects of Gynecological Age on LH Sensitivity to Energy Availability
NCT00456274	Not specified	UNKNOWN	Baselines in Reproductive Disorders
NCT00589654	Not specified	ACTIVE_NOT_RECRUITING	Menstrual Cycle Maintenance and Quality of Life: A Prospective Study
NCT01423487	Not specified	WITHDRAWN	Efficacy and Safety of Metformin in Preventing Patients With Risperidone From Weight Gain and Amenorrhea
NCT01500447	Not specified	RECRUITING	Inherited Reproductive Disorders
NCT01511588	Not specified	COMPLETED	Hormonal Regulation of Puberty and Fertility
NCT01785719	Not specified	COMPLETED	Evaluation of Ovarian Morphology and Function in Overweight Women During Weight Loss
NCT01927432	Not specified	COMPLETED	Ultrasound Characterization of Ovarian Follicle Dynamics in Women With Amenorrhea
NCT02224976	Not specified	COMPLETED	Effect of Intense Training on Ovarian Function and Bone Turnover
NCT04135729	Not specified	COMPLETED	Mental Health in Fitness Instructors
NCT04424576	Not specified	UNKNOWN	Ovarian Morphology in Girls
NCT04938622	Not specified	COMPLETED	Bioenergetics of Exercise-Induced Menstrual Disturbances
NCT06280807	Not specified	RECRUITING	Observation of Environment and Reproductive-Endocrine Effects
NCT06800170	Not specified	COMPLETED	Treatment of Menstrual Cycle Alterations in Adolescents
NCT07015476	Not specified	RECRUITING	Retrospective Observational Evaluation of the Bone Mineral Density Outcome in Young Women With Amenorrhea
NCT07164248	Not specified	COMPLETED	Evaluation of Bone Mineral Density Indications and Outcomes in Female Adolescents: Implications for Early Detection of Osteopenia/Osteoporosis and Gynecologic Practice
NCT07612735	Not specified	NOT_YET_RECRUITING	Effects of Resistance Training on Women With Functional Hypothalamic Amenorrhea

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for AXL across ~30M SureChEMBL compounds — explore on Sugi Predict.