GAS6

Summary

GAS6 (growth arrest specific 6, HGNC:4168) is a protein-coding gene on chromosome 13q34, encoding Growth arrest-specific protein 6 (Q14393). Ligand for tyrosine-protein kinase receptors AXL, TYRO3 and MER whose signaling is implicated in cell growth and survival, cell adhesion and cell migration. In precision oncology, GAS6 EXPRESSION is associated with resistance to Docetaxel in Prostate Cancer (CIViC Level D).

This gene encodes a gamma-carboxyglutamic acid (Gla)-containing protein thought to be involved in the stimulation of cell proliferation. This gene is frequently overexpressed in many cancers and has been implicated as an adverse prognostic marker. Elevated protein levels are additionally associated with a variety of disease states, including venous thromboembolic disease, systemic lupus erythematosus, chronic renal failure, and preeclampsia.

Source: NCBI Gene 2621 — RefSeq curated summary.

At a glance

• GWAS associations: 24
• Clinical variants (ClinVar): 159 total
• Druggable target: yes
• Precision-oncology evidence (CIViC): 1 curated variant–drug association
• MANE Select transcript: NM_000820

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4168
Approved symbol	GAS6
Name	growth arrest specific 6
Location	13q34
Locus type	gene with protein product
Status	Approved
Aliases	AXSF, FLJ34709, DKFZp666G247
Ensembl gene	ENSG00000183087
Ensembl biotype	protein_coding
OMIM	600441
Entrez	2621

Gene structure

Transcript identifiers

Ensembl transcripts: 41 — 37 protein_coding, 3 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000327773, ENST00000476291, ENST00000480426, ENST00000608763, ENST00000610073, ENST00000881720, ENST00000881721, ENST00000881722, ENST00000881723, ENST00000881724, ENST00000881725, ENST00000881726, ENST00000881727, ENST00000881728, ENST00000881729, ENST00000881730, ENST00000881731, ENST00000881732, ENST00000881733, ENST00000881734, ENST00000881735, ENST00000881736, ENST00000881737, ENST00000881738, ENST00000881739, ENST00000881740, ENST00000952101, ENST00000952102, ENST00000952103, ENST00000952104, ENST00000952105, ENST00000952106, ENST00000952107, ENST00000952108, ENST00000952109, ENST00000952110, ENST00000952111, ENST00000952112, ENST00000952113, ENST00000952114, ENST00000952115

RefSeq mRNA: 1 — MANE Select: NM_000820 NM_000820

CCDS: CCDS45072

Canonical transcript exons

ENST00000327773 — 15 exons

Exon	Start	End
ENSE00001291358	113839728	113839850
ENSE00001297060	113835513	113835635
ENSE00001313199	113846527	113846589
ENSE00001314682	113838069	113838191
ENSE00001330699	113832634	113832752
ENSE00001887723	113863833	113864076
ENSE00001894162	113820549	113821018
ENSE00003466001	113826996	113827164
ENSE00003487356	113832299	113832488
ENSE00003530021	113863575	113863741
ENSE00003589604	113834551	113834672
ENSE00003596552	113828547	113828711
ENSE00003653272	113821958	113822186
ENSE00003670934	113848026	113848050
ENSE00003679798	113823375	113823550

Expression profiles

Bgee: expression breadth ubiquitous, 284 present calls, max score 99.58.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 88.0887 / max 1240.2774, expressed in 1621 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
138376	45.5459	1361
138377	39.9491	1591
138373	2.0098	532
138371	0.3864	188
138372	0.1976	93

Top tissues by expression

293 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
ascending aorta	UBERON:0001496	99.58	gold quality
thoracic aorta	UBERON:0001515	99.57	gold quality
descending thoracic aorta	UBERON:0002345	99.55	gold quality
right uterine tube	UBERON:0001302	99.47	gold quality
right coronary artery	UBERON:0001625	99.34	gold quality
aorta	UBERON:0000947	99.19	gold quality
endocervix	UBERON:0000458	99.13	gold quality
lower esophagus muscularis layer	UBERON:0035833	99.08	gold quality
lower esophagus	UBERON:0013473	99.07	gold quality
apex of heart	UBERON:0002098	99.01	gold quality
body of uterus	UBERON:0009853	98.96	gold quality
left uterine tube	UBERON:0001303	98.95	gold quality
popliteal artery	UBERON:0002250	98.95	gold quality
tibial artery	UBERON:0007610	98.95	gold quality
tibial nerve	UBERON:0001323	98.75	gold quality
left coronary artery	UBERON:0001626	98.72	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	98.71	gold quality
coronary artery	UBERON:0001621	98.65	gold quality
mucosa of stomach	UBERON:0001199	98.58	gold quality
ectocervix	UBERON:0012249	98.56	gold quality
skin of leg	UBERON:0001511	98.52	gold quality
skin of abdomen	UBERON:0001416	98.49	gold quality
right atrium auricular region	UBERON:0006631	98.41	gold quality
right lobe of thyroid gland	UBERON:0001119	98.33	gold quality
left ovary	UBERON:0002119	98.33	gold quality
left lobe of thyroid gland	UBERON:0001120	98.16	gold quality
right ovary	UBERON:0002118	98.08	gold quality
heart left ventricle	UBERON:0002084	98.01	gold quality
cardiac atrium	UBERON:0002081	97.95	gold quality
omental fat pad	UBERON:0010414	97.93	gold quality

Single-cell (SCXA)

Detected in 13 experiment(s), a significant marker in 13.

Experiment	Marker?	Max mean expression
E-MTAB-8495	yes	185.22
E-CURD-114	yes	61.75
E-CURD-122	yes	43.20
E-MTAB-7249	yes	39.29
E-HCAD-4	yes	24.52
E-GEOD-135922	yes	22.90
E-ANND-3	yes	19.52
E-HCAD-1	yes	14.61
E-MTAB-9067	yes	12.70
E-MTAB-6678	yes	11.28
E-MTAB-10137	yes	6.32
E-GEOD-137537	yes	5.38
E-GEOD-130148	yes	5.03

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

2 targets.

Target	Regulation
AXL	Activation
CDKN1B	Repression

Upstream regulators (CollecTRI, top): AR, ESR1, NFIA, NFIB, NFIX, NR3C2

miRNA regulators (miRDB)

14 targeting GAS6, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-944	99.82	70.85	3042
HSA-MIR-587	99.64	70.86	2611
HSA-MIR-3123	99.47	67.15	2693
HSA-MIR-5683	99.36	68.59	2083
HSA-MIR-3160-5P	99.28	69.07	1938
HSA-MIR-5587-5P	99.07	68.58	838
HSA-MIR-874-5P	96.93	63.92	1014
HSA-MIR-5702	96.68	68.21	958
HSA-MIR-3976	96.67	67.79	1187
HSA-MIR-7706	95.96	63.68	172
HSA-MIR-3917	88.03	62.50	44

Literature-anchored findings (GeneRIF, showing 40)

• Gas6-deficient mice are protected against thrombosis, indicating that a physiological function of Gas6 is that of a procoagulant. This effect is mediated, at least in part, through platelets, as Gas6-deficient platelets are less prone to aggregation. (PMID:11175853)
• Data suggest that Gas6 and Axl signal transduction is aberrantly stimulated in endometriotic endometria, and is plausibly related to its growth potential. (PMID:12029073)
• GAS6 has a V-shaped arrangement of laminin G-like LG domains strengthened by an interdomain calcium-binding site (PMID:12218057)
• Axl and Gas6 expression might be involved in childhood thyroid tumorigenesis around Chernobyl. (PMID:12490074)
• Gas6 sustains fetal oligodendrocyte viability by receptor activation and downstream signaling via the phosphatidylinositol 3-kinase-dependent/ proto-oncogene protein akt pathway. (PMID:12764109)
• Gas6, acting as a growth factor, is increased in the process of kidney allograft dysfunction and in chronic allograft nephropathy. (PMID:12768229)
• GAS6/Axl signaling is involved in human renal disease. (PMID:14750094)
• GAS6 intron-exon structure, identification of single nucleotide polymorphisms and possible association with stroke. (PMID:15108283)
• New information about the mechanism underlying Gas6 protection from apoptosis in primary endothelial cell cultures. (PMID:15130893)
• Gas6/Axl pathway could play a role in the complex events taking place during the early changes of ovarian cancer progression. (PMID:15452374)
• 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)
• 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)
• The crystal structure at 3.3 A resolution of a minimal human Gas6/Axl complex reveals an assembly of 2:2 stoichiometry. (PMID:16362042)
• Restoration of Gas6 mRNA by statins was mediated by mRNA stabilization, and not by an increase in transcriptional activity. (PMID:16556867)
• We conclude that gas6 signaling through the Axl receptor and the PI3 kinase/Akt1 survival pathway protects oligodendrocytes from growth factor withdrawal and TNFalpha-mediated cell death. (PMID:16723520)
• Gas6 has a role in aspirin resistance (PMID:16999853)
• the CACA haplotype, is less prevalent in patients with stroke (PMID:17721624)
• GAS6 signals via its receptor tyrosine kinases and plays a key role in the perpetuation of platelet aggregates and clot retraction. (PMID:17897008)
• Axl and Gas6 are frequently overexpressed in both glioma and vascular cells and predict poor prognosis in GBM patients (PMID:18172262)
• adiponectin antagonizes the stimulatory effect of TNFalpha on vascular calcification by restoration of the AMPK-dependent Gas6-mediated survival pathway. (PMID:18174285)
• Gas6-promoted phagocytosis was inhibited by L-type Ca(2+)-channel blockage, which in turn may be activated by integrin receptor stimulation. (PMID:18395422)
• These findings identify a role for Gas6 in plaque composition and stability. (PMID:18570189)
• gas6 protects endothelial cells from apoptosis by a mechanism that involves PI3K-Akt-dependent inactivation of FOXO1a. (PMID:18680538)
• The experiments described in this paper propose a novel functional role of gamma-carboxylation in gas6-mediated endothelial cell survival. (PMID:18760998)
• The Axl/Gas6 pathway contributes to normal human NK-cell development via an effect on the master regulatory transcription factor T-BET. (PMID:18840707)
• Found no association between plasma Gas6 levels and coronary artery disease. (PMID:19132213)
• GAS6 plasma concentrations at admission reflect the presence of common cardiovascular risk factors and can predict cardiovascular events. (PMID:19369636)
• Data show that Axl and Gas6 expression in RCC are associated with tumor advancement and patient survival. (PMID:19567592)
• Gas6/Axl-mediated signaling regulates human dendritic cell (DC) activities; this study identifies Gas6/Axl as a new DC chemotaxis pathway. (PMID:19657094)
• Data do not support the idea that Gas6 protein and Gas6 polymorphisms may be associated with thrombosis in sticky platelet syndrome. (PMID:19696043)
• Plasma concentration of growth arrest-specific protein 6 is increased in patients with acute pancreatitis. (PMID:19744001)
• 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)
• data suggest that growth arrest-specific-6 (GAS6)/MER receptor tyrosine kinase axis regulates homing and survival of the E2A/PBX1-positive B-cell precursor acute lymphoblastic leukemia in the bone marrow niche (PMID:19922767)
• These findings highlight a novel role for Gas6 in a positive amplification loop, whereby tumors promote their growth by educating infiltrating leukocytes to up-regulate the production of the mitogen Gas6. (PMID:19965679)
• These results indicate that androgen receptor signaling directly regulates Gas6 transcription, which leads to inhibition of vascular calcification, and provides a mechanistic insight into the cardioprotective action of androgens. (PMID:20048160)
• Gas6 in circulation is bound to sAxl suggesting circulating Gas6 to be inhibited and incapable of stimulating the TAM receptors. (PMID:20088931)
• GAS6 modulates macrophage cytokine secretion, triggering an “anti-inflammatory pathway” involving PI3K/Akt/GSK3 beta and NF-kappaB. (PMID:20103767)
• activation of GAS6 receptors on prostate cancer in the bone marrow environment may play a critical role as a molecular switch, establishing metastatic tumor cell dormancy. (PMID:20126470)
• Gas6 and soluble Axl have a role in critical limb ischemia, presumably connected to the inflammatory process (PMID:20417630)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	gas6	ENSDARG00000007804
mus_musculus	Gas6	ENSMUSG00000031451
rattus_norvegicus	Gas6	ENSRNOG00000018233

Paralogs (3): MEGF10 (ENSG00000145794), MEGF11 (ENSG00000157890), MEGF6 (ENSG00000162591)

Protein

Protein identifiers

Growth arrest-specific protein 6 — Q14393 (reviewed: Q14393)

Alternative names: AXL receptor tyrosine kinase ligand

All UniProt accessions (1): Q14393

UniProt curated annotations — full annotation on UniProt →

Function. Ligand for tyrosine-protein kinase receptors AXL, TYRO3 and MER whose signaling is implicated in cell growth and survival, cell adhesion and cell migration. 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. (Microbial infection) Can bridge virus envelope phosphatidylserine to the TAM receptor tyrosine kinase Axl to mediate viral entry by apoptotic mimicry. Plays a role in Dengue cell entry by apoptotic mimicry. Plays a role in Vaccinia virus cell entry by apoptotic mimicry. Plays a role in ebolavirus and marburgvirus cell entry by apoptotic mimicry.

Subunit / interactions. Heterodimer and heterotetramer with AXL.

Subcellular location. Secreted.

Tissue specificity. Plasma. Isoform 1 and isoform 2 are widely expressed, isoform 1 being expressed at higher levels than isoform 2 in most tissues. Isoform 2 is the predominant form in spleen.

Post-translational modifications. Proteolytically processed after secretion to yield a N-terminal 36 kDa protein and a C-terminal 50 kDa protein including the laminin G-like domains which activates AXL. Gamma-carboxyglutamate residues are formed by vitamin K dependent carboxylation. These residues are essential for the binding of calcium.

Isoforms (5)

UniProt ID	Names	Canonical?
Q14393-2	1	yes
Q14393-1	2, gas6SV
Q14393-3	3
Q14393-4	4
Q14393-5	5

RefSeq proteins (1): NP_000811* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000152	EGF-type_Asp/Asn_hydroxyl_site	PTM
IPR000294	GLA_domain	Domain
IPR000742	EGF	Domain
IPR001791	Laminin_G	Domain
IPR001881	EGF-like_Ca-bd_dom	Domain
IPR009030	Growth_fac_rcpt_cys_sf	Homologous_superfamily
IPR013032	EGF-like_CS	Conserved_site
IPR013320	ConA-like_dom_sf	Homologous_superfamily
IPR017857	Coagulation_fac-like_Gla_dom	Homologous_superfamily
IPR018097	EGF_Ca-bd_CS	Conserved_site
IPR026823	cEGF	Domain
IPR035972	GLA-like_dom_SF	Homologous_superfamily
IPR049883	NOTCH1_EGF-like	Domain
IPR051145	GAS-SHBG-PROS	Family

Pfam: PF00054, PF00594, PF02210, PF07645, PF12661, PF12662

UniProt features (96 total): strand 36, disulfide bond 16, helix 8, domain 7, sequence variant 7, mutagenesis site 5, binding site 4, modified residue 4, splice variant 4, signal peptide 1, chain 1, glycosylation site 1, sequence conflict 1, turn 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
1H30	X-RAY DIFFRACTION	2.2
5VXZ	X-RAY DIFFRACTION	2.3
4RA0	X-RAY DIFFRACTION	3.07
2C5D	X-RAY DIFFRACTION	3.3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q14393-F1	85.69	0.59

Functional residue map

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

Ligand- & substrate-binding residues (4): 331; 440; 656; 329

Post-translational modifications (4): 71, 621, 637, 640

Disulfide bonds (16): 65–70, 120–133, 125–142, 144–153, 160–171, 167–180, 182–195, 201–212, 207–221, 223–236, 242–251, 247–260, 262–277, 283–570, 444–470, 643–670

Glycosylation sites (1): 420

Mutagenesis-validated functional residues (5):

Position	Phenotype
310	strongly reduced affinity for axl. abolishes phosphorylation of axl.
312	strongly reduced affinity for axl. abolishes phosphorylation of axl.
487	decreases activation of axl.
620	reduces affinity for axl 15-fold and decreases activation of axl.
660	reduces affinity for axl 3-fold.

Function

Pathways and Gene Ontology

Reactome pathways

8 pathways

ID	Pathway
R-HSA-114608	Platelet degranulation
R-HSA-159740	Gamma-carboxylation of protein precursors
R-HSA-159763	Transport of gamma-carboxylated protein precursors from the endoplasmic reticulum to the Golgi apparatus
R-HSA-159782	Removal of aminoterminal propeptides from gamma-carboxylated proteins
R-HSA-202733	Cell surface interactions at the vascular wall
R-HSA-381426	Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)
R-HSA-8957275	Post-translational protein phosphorylation
R-HSA-9918485	Dengue Virus Attachment and Entry

MSigDB gene sets: 510 (showing top): GOBP_REGULATION_OF_CELL_ACTIVATION, LEE_NEURAL_CREST_STEM_CELL_DN, GOBP_DENDRITIC_CELL_DIFFERENTIATION, GOBP_NATURAL_KILLER_CELL_DIFFERENTIATION, GOBP_POSITIVE_REGULATION_OF_ENDOCYTOSIS, GOBP_DENDRITIC_CELL_MIGRATION, GOBP_POSITIVE_REGULATION_OF_HEMOPOIESIS, GOBP_REGULATION_OF_BLOOD_PRESSURE, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_CELL_CHEMOTAXIS, GOBP_NEGATIVE_REGULATION_OF_INTERLEUKIN_1_PRODUCTION, GOBP_REGULATION_OF_PHOSPHORYLATION, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, GOBP_RESPONSE_TO_PEPTIDE, GOBP_REGULATION_OF_LEUKOCYTE_APOPTOTIC_PROCESS

GO Biological Process (60): neuron migration (GO:0001764), positive regulation of protein phosphorylation (GO:0001934), positive regulation of cytokine-mediated signaling pathway (GO:0001961), positive regulation of glomerular filtration (GO:0003104), protein phosphorylation (GO:0006468), phagocytosis (GO:0006909), signal transduction (GO:0007165), cell surface receptor signaling pathway (GO:0007166), enzyme-linked receptor protein signaling pathway (GO:0007167), blood coagulation (GO:0007596), cellular response to starvation (GO:0009267), positive regulation of gene expression (GO:0010628), negative regulation of tumor necrosis factor-mediated signaling pathway (GO:0010804), fusion of virus membrane with host plasma membrane (GO:0019064), viral genome replication (GO:0019079), animal organ regeneration (GO:0031100), cell-substrate adhesion (GO:0031589), positive regulation of TOR signaling (GO:0032008), activation of protein kinase B activity (GO:0032148), negative regulation of type II interferon production (GO:0032689), negative regulation of interleukin-1 production (GO:0032692), negative regulation of interleukin-6 production (GO:0032715), negative regulation of tumor necrosis factor production (GO:0032720), positive regulation of natural killer cell differentiation (GO:0032825), myeloid cell apoptotic process (GO:0033028), negative regulation of myeloid cell apoptotic process (GO:0033033), cellular response to interferon-alpha (GO:0035457), B cell chemotaxis (GO:0035754), negative regulation of apoptotic process (GO:0043066), apoptotic cell clearance (GO:0043277), fibroblast apoptotic process (GO:0044346), positive regulation of protein kinase activity (GO:0045860), negative regulation of DNA-templated transcription (GO:0045892), symbiont entry into host cell (GO:0046718), receptor-mediated virion attachment to host cell (GO:0046813), positive regulation of protein export from nucleus (GO:0046827), positive regulation of fibroblast proliferation (GO:0048146), positive regulation of phagocytosis (GO:0050766), positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0051897), negative regulation of biomineral tissue development (GO:0070168)

GO Molecular Function (9): phosphatidylserine binding (GO:0001786), signaling receptor binding (GO:0005102), calcium ion binding (GO:0005509), protein-macromolecule adaptor activity (GO:0030674), receptor tyrosine kinase binding (GO:0030971), cysteine-type endopeptidase inhibitor activity involved in apoptotic process (GO:0043027), receptor ligand activity (GO:0048018), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (7): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), cytoplasm (GO:0005737), endoplasmic reticulum lumen (GO:0005788), Golgi lumen (GO:0005796), platelet alpha granule lumen (GO:0031093), extracellular exosome (GO:0070062)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
Gamma-carboxylation, transport, and amino-terminal cleavage of proteins	3
Response to elevated platelet cytosolic Ca2+	1
Hemostasis	1
Metabolism of proteins	1
Post-translational protein modification	1
Dengue Virus Infection	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
signal transduction	2
protein binding	2
signaling receptor binding	2
cellular anatomical structure	2
intracellular organelle lumen	2
cell migration	1
generation of neurons	1
regulation of protein phosphorylation	1
protein phosphorylation	1
positive regulation of protein modification process	1
positive regulation of phosphorylation	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
regulation of glomerular filtration	1
glomerular filtration	1
positive regulation of multicellular organismal process	1
phosphorylation	1
protein modification process	1
endocytosis	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
cell surface receptor signaling pathway	1
hemostasis	1
wound healing	1
coagulation	1
cellular response to nutrient levels	1
cellular response to stress	1
response to starvation	1
gene expression	1
regulation of gene expression	1
positive regulation of macromolecule biosynthetic process	1
negative regulation of cytokine-mediated signaling pathway	1
regulation of tumor necrosis factor-mediated signaling pathway	1
tumor necrosis factor-mediated signaling pathway	1
membrane fusion involved in viral entry into host cell	1

Protein interactions and networks

STRING

2152 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GAS6	TYRO3	Q06418	999
GAS6	MERTK	Q12866	999
GAS6	AXL	P30530	999
GAS6	MFGE8	Q08431	927
GAS6	NTRK1	P04629	892
GAS6	TULP1	O00294	828
GAS6	PROS1	P07225	819
GAS6	TIMD4	Q96H15	804
GAS6	SOCS1	O15524	792
GAS6	LGALS3	P17931	765
GAS6	ITGAV	P06756	707
GAS6	AKT1	P31749	698
GAS6	EGFR	P00533	651
GAS6	ADGRB1	O14514	647
GAS6	SCARB1	Q8WTV0	639

IntAct

88 interactions, top by confidence:

A	B	Type	Score
PCDHB16	UPK3BL1	psi-mi:“MI:0914”(association)	0.530
PCDHB5	RPL23	psi-mi:“MI:0914”(association)	0.530
FBXO2	TMEM131L	psi-mi:“MI:0914”(association)	0.530
C1orf54	EXTL3	psi-mi:“MI:0914”(association)	0.530
PCDHGB1	FAM171A2	psi-mi:“MI:0914”(association)	0.530
	VWA8	psi-mi:“MI:0914”(association)	0.350
	ESYT2	psi-mi:“MI:0914”(association)	0.350
E6	PLOD2	psi-mi:“MI:0914”(association)	0.350
E7	COPE	psi-mi:“MI:0914”(association)	0.350
	PGRMC1	psi-mi:“MI:0914”(association)	0.350
	HAX1	psi-mi:“MI:0914”(association)	0.350
BVLF1	VWA8	psi-mi:“MI:0914”(association)	0.350
BFRF1A	SHTN1	psi-mi:“MI:0914”(association)	0.350
AXL		psi-mi:“MI:0914”(association)	0.350
TMEM106A	QSOX1	psi-mi:“MI:0914”(association)	0.350
CLEC12B	GXYLT2	psi-mi:“MI:0914”(association)	0.350
MPPE1	FAM234B	psi-mi:“MI:0914”(association)	0.350
TCTN2	TMEM131L	psi-mi:“MI:0914”(association)	0.350
LLCFC1	POTEF	psi-mi:“MI:0914”(association)	0.350
BRICD5	POTEF	psi-mi:“MI:0914”(association)	0.350
KLRC1	METTL15	psi-mi:“MI:0914”(association)	0.350
ST14	LIPT2	psi-mi:“MI:0914”(association)	0.350
RLN1	RTL8C	psi-mi:“MI:0914”(association)	0.350
TMEM106A	RTL8C	psi-mi:“MI:0914”(association)	0.350
ADAM32	GPR89A	psi-mi:“MI:0914”(association)	0.350
HFE	PODXL	psi-mi:“MI:0914”(association)	0.350
CLEC12A	GOSR2	psi-mi:“MI:0914”(association)	0.350
PCDHA3	ABCD4	psi-mi:“MI:0914”(association)	0.350

BioGRID (99): GAS6 (Affinity Capture-MS), GAS6 (Affinity Capture-MS), GAS6 (Affinity Capture-MS), GAS6 (Affinity Capture-MS), GAS6 (Affinity Capture-MS), GAS6 (Affinity Capture-MS), GAS6 (Affinity Capture-MS), GAS6 (Affinity Capture-MS), GAS6 (Affinity Capture-MS), GAS6 (Affinity Capture-MS), GAS6 (Affinity Capture-MS), GAS6 (Affinity Capture-MS), GAS6 (Affinity Capture-MS), GAS6 (Affinity Capture-MS), GAS6 (Affinity Capture-MS)

ESM2 similar proteins: A0A8M9PFP2, A1X150, A2A863, A4IH88, B0S5G3, B2RXS4, F1LW30, F1R520, G5ED46, L7VG99, O08721, O08722, O08747, O60486, O73878, O94985, O95185, P10493, P14543, P16144, P35590, P54761, P55292, Q06806, Q0VCN6, Q14393, Q5FWR8, Q5R9Q9, Q61592, Q63772, Q64632, Q6DDG2, Q6Q0N0, Q6UXZ4, Q6ZN44, Q761X5, Q7T2Z5, Q8IZJ1, Q8K1S2, Q8K1S3

Diamond homologs: A0A1D5NSM8, A1A5Y0, A2AVA0, A2VCU8, A5A8Y8, B8JI71, O08999, O35806, O75095, P0C6B8, P10040, P25723, P41990, P98118, Q00918, Q08761, Q09165, Q14393, Q14766, Q14767, Q28019, Q2VWQ2, Q4LDE5, Q5RBP1, Q61592, Q62919, Q63772, Q6AZ60, Q6GUQ1, Q6MG84, Q6UXI9, Q75N90, Q7ZXL5, Q8AVH7, Q8CG19, Q8IUX8, Q8NDA2, Q91V88, Q92832, Q99944

SIGNOR signaling

10 interactions.

A	Effect	B	Mechanism
GAS6	up-regulates	AXL	binding
GGCX	“up-regulates activity”	GAS6	carboxylation
GAS6	“up-regulates activity”	AXL	binding
Neutrophil_activation	up-regulates	GAS6
GAS6	up-regulates	TYRO3	binding
GAS6	up-regulates	MERTK	binding
NFIA	“down-regulates quantity”	GAS6	“transcriptional regulation”
NFIB	“down-regulates quantity”	GAS6	“transcriptional regulation”
NFIX	“down-regulates quantity”	GAS6	“transcriptional regulation”

Disease & clinical

Cancer significance

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	108
Likely benign	13
Benign	8

Top pathogenic / likely-pathogenic (0)

SpliceAI

3033 predictions. Top by Δscore:

Variant	Effect	Δscore
13:113821014:CACAT:C	acceptor_gain	1.0000
13:113821016:CAT:C	acceptor_gain	1.0000
13:113821018:TC:T	acceptor_loss	1.0000
13:113821019:C:CC	acceptor_gain	1.0000
13:113821025:C:CT	acceptor_gain	1.0000
13:113821025:C:T	acceptor_gain	1.0000
13:113821953:CCTA:C	donor_loss	1.0000
13:113821954:CTA:C	donor_loss	1.0000
13:113821956:ACC:A	donor_loss	1.0000
13:113822182:ACCAG:A	acceptor_gain	1.0000
13:113822183:CCAG:C	acceptor_gain	1.0000
13:113822183:CCAGC:C	acceptor_gain	1.0000
13:113822184:CAG:C	acceptor_gain	1.0000
13:113822184:CAGC:C	acceptor_gain	1.0000
13:113822185:AG:A	acceptor_gain	1.0000
13:113822185:AGCT:A	acceptor_loss	1.0000
13:113822186:GC:G	acceptor_loss	1.0000
13:113822187:C:CC	acceptor_gain	1.0000
13:113822188:T:A	acceptor_loss	1.0000
13:113823546:CCGCA:C	acceptor_gain	1.0000
13:113823547:CGCA:C	acceptor_gain	1.0000
13:113823547:CGCAC:C	acceptor_gain	1.0000
13:113823548:GCA:G	acceptor_gain	1.0000
13:113823549:CA:C	acceptor_gain	1.0000
13:113823549:CAC:C	acceptor_gain	1.0000
13:113823550:ACTG:A	acceptor_loss	1.0000
13:113823551:C:CC	acceptor_gain	1.0000
13:113823551:C:CG	acceptor_loss	1.0000
13:113823552:T:A	acceptor_loss	1.0000
13:113826989:GACTT:G	donor_loss	1.0000

AlphaMissense

4428 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
13:113839835:C:G	C120S	0.998
13:113839836:A:T	C120S	0.998
13:113863621:C:G	C70S	0.998
13:113863622:A:T	C70S	0.998
13:113863636:C:G	C65S	0.998
13:113863637:A:T	C65S	0.998
13:113839736:C:G	C153S	0.997
13:113839737:A:T	C153S	0.997
13:113839750:C:A	W148C	0.997
13:113839750:C:G	W148C	0.997
13:113839796:C:G	C133S	0.997
13:113839797:A:T	C133S	0.997
13:113863594:A:C	F79C	0.997
13:113832305:C:A	W379C	0.996
13:113832305:C:G	W379C	0.996
13:113846586:C:G	C95S	0.996
13:113846587:A:T	C95S	0.996
13:113863593:G:C	F79L	0.996
13:113863593:G:T	F79L	0.996
13:113863595:A:G	F79L	0.996
13:113863620:G:C	C70W	0.996
13:113863621:C:T	C70Y	0.996
13:113863622:A:G	C70R	0.996
13:113863637:A:G	C65R	0.996
13:113832372:A:G	L357P	0.995
13:113838179:C:G	C160S	0.995
13:113838180:A:T	C160S	0.995
13:113839736:C:T	C153Y	0.995
13:113839769:C:G	C142S	0.995
13:113839770:A:T	C142S	0.995

dbSNP variants (sampled 300 via entrez): RS1000057786 (13:113823310 G>A,C), RS1000073529 (13:113826882 G>A,C), RS1000090831 (13:113855568 C>T), RS1000290084 (13:113848605 G>A), RS1000297159 (13:113853103 T>C), RS1000299460 (13:113850692 A>G), RS1000309360 (13:113820468 T>C), RS1000309563 (13:113840600 A>C,T), RS1000383005 (13:113840349 T>C), RS1000587416 (13:113834803 G>A,C), RS1000678950 (13:113825953 G>A), RS1000707942 (13:113820108 C>T), RS1000777321 (13:113831075 G>T), RS1000779799 (13:113822323 T>A,C), RS1000860751 (13:113845322 G>A)

Disease associations

OMIM: gene MIM:600441 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

24 associations (top):

Study	Trait	p-value
GCST003661_19	Triglycerides	5.000000e-07
GCST004601_172	Red blood cell count	2.000000e-10
GCST004621_63	Red cell distribution width	3.000000e-17
GCST006612_87	LDL cholesterol	3.000000e-08
GCST006613_7	Triglycerides	1.000000e-14
GCST007954_13	Glycated hemoglobin levels	1.000000e-08
GCST009145_6	Total cholesterol levels	9.000000e-12
GCST010173_15	Triglyceride levels	1.000000e-23
GCST010204_103	Low density lipoprotein cholesterol levels	2.000000e-28
GCST010206_1	Anorectal malformation	1.000000e-18
GCST010243_203	Apolipoprotein B levels	3.000000e-22
GCST010244_106	Triglyceride levels	6.000000e-09
GCST010244_227	Triglyceride levels	1.000000e-18
GCST010244_49	Triglyceride levels	6.000000e-38
GCST010245_140	LDL cholesterol levels	6.000000e-22
GCST90002383_251	Hematocrit	3.000000e-18
GCST90002384_330	Hemoglobin	9.000000e-21
GCST90002388_461	Lymphocyte count	3.000000e-12
GCST90002396_558	Mean reticulocyte volume	4.000000e-13
GCST90002397_69	Mean spheric corpuscular volume	2.000000e-13
GCST90002403_498	Red blood cell count	2.000000e-24
GCST90002404_384	Red cell distribution width	3.000000e-26
GCST90011899_83	Aspartate aminotransferase levels	7.000000e-16
GCST90011900_105	Serum alkaline phosphatase levels	2.000000e-10

EFO canonical traits (13, from GWAS)

EFO ID	Trait name
EFO:0004530	triglyceride measurement
EFO:0004305	erythrocyte count
EFO:0009188	Red cell distribution width
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004541	HbA1c measurement
EFO:0004574	total cholesterol measurement
EFO:0004615	apolipoprotein B measurement
EFO:0004348	hematocrit
EFO:0004509	hemoglobin measurement
EFO:0004587	lymphocyte count
EFO:0010701	mean reticulocyte volume
EFO:0004736	aspartate aminotransferase measurement
EFO:0004533	alkaline phosphatase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4804247 (SINGLE PROTEIN)

Clinical evidence (CIViC)

Drug × variant × indication: 1 predictive associations from 1 curated evidence items; also 1 prognostic.

Variant	Therapy	Indication	Effect	Level	CIViC
GAS6 EXPRESSION	Docetaxel	Prostate Cancer	Resistance	CIViC D	EID1656

PharmGKB: 1 entry (VIP=true, CPIC=false)

Binding affinities (BindingDB)

280 measured of 280 human assays (280 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
4-[[5-[5-[(1-adamantylmethylamino)methyl]-2-pyridinyl]-2-(butylamino)pyrimidin-4-yl]amino]cyclohexan-1-ol	IC50	0.43 nM	US-9649309: Therapeutic uses of selected pyrimidine compounds with anti-Mer tyrosine kinase activity
4-[[5-[5-(7-azabicyclo[2.2.1]heptan-7-ylmethyl)-2-pyridinyl]-2-(butylamino)pyrimidin-4-yl]amino]cyclohexan-1-ol	IC50	0.86 nM	US-9649309: Therapeutic uses of selected pyrimidine compounds with anti-Mer tyrosine kinase activity
4-[[5-[5-[(1-adamantylamino)methyl]-2-pyridinyl]-2-(butylamino)pyrimidin-4-yl]amino]cyclohexan-1-ol	IC50	1 nM	US-9649309: Therapeutic uses of selected pyrimidine compounds with anti-Mer tyrosine kinase activity
4-[[2-(butylamino)-5-[5-[[(8-methyl-8-azabicyclo[3.2.1]octan-3-yl)amino]methyl]-2-pyridinyl]pyrimidin-4-yl]amino]cyclohexan-1-ol	IC50	1.2 nM	US-9649309: Therapeutic uses of selected pyrimidine compounds with anti-Mer tyrosine kinase activity
4-[[2-(4-methylanilino)-5-[5-(pyrrolidin-1-ylmethyl)-2-pyridinyl]pyrimidin-4-yl]amino]cyclohexan-1-ol	IC50	1.2 nM	US-9649309: Therapeutic uses of selected pyrimidine compounds with anti-Mer tyrosine kinase activity
4-[[2-(3-fluoroanilino)-5-[5-(pyrrolidin-1-ylmethyl)-2-pyridinyl]pyrimidin-4-yl]amino]cyclohexan-1-ol	IC50	1.3 nM	US-9649309: Therapeutic uses of selected pyrimidine compounds with anti-Mer tyrosine kinase activity
4-[[2-(4-fluoroanilino)-5-[5-(pyrrolidin-1-ylmethyl)-2-pyridinyl]pyrimidin-4-yl]amino]cyclohexan-1-ol	IC50	1.5 nM	US-9649309: Therapeutic uses of selected pyrimidine compounds with anti-Mer tyrosine kinase activity
4-[[2-(4-methoxyanilino)-5-[5-(pyrrolidin-1-ylmethyl)-2-pyridinyl]pyrimidin-4-yl]amino]cyclohexan-1-ol	IC50	2.4 nM	US-9649309: Therapeutic uses of selected pyrimidine compounds with anti-Mer tyrosine kinase activity
4-[[2-(3-ethynylanilino)-5-pyridin-2-ylpyrimidin-4-yl]amino]cyclohexan-1-ol	IC50	2.6 nM	US-9649309: Therapeutic uses of selected pyrimidine compounds with anti-Mer tyrosine kinase activity
4-[[2-(2-fluoroanilino)-5-[5-(pyrrolidin-1-ylmethyl)-2-pyridinyl]pyrimidin-4-yl]amino]cyclohexan-1-ol	IC50	3.2 nM	US-9649309: Therapeutic uses of selected pyrimidine compounds with anti-Mer tyrosine kinase activity
4-[[2-(4-isocyanoanilino)-5-[5-(pyrrolidin-1-ylmethyl)-2-pyridinyl]pyrimidin-4-yl]amino]cyclohexan-1-ol	IC50	3.6 nM	US-9649309: Therapeutic uses of selected pyrimidine compounds with anti-Mer tyrosine kinase activity
4-[[2-(4-ethynylanilino)-5-pyridin-2-ylpyrimidin-4-yl]amino]cyclohexan-1-ol	IC50	3.7 nM	US-9649309: Therapeutic uses of selected pyrimidine compounds with anti-Mer tyrosine kinase activity
4-[[5-[5-(pyrrolidin-1-ylmethyl)-2-pyridinyl]-2-[4-(trifluoromethyl)anilino]pyrimidin-4-yl]amino]cyclohexan-1-ol	IC50	3.8 nM	US-9649309: Therapeutic uses of selected pyrimidine compounds with anti-Mer tyrosine kinase activity
4-[[5-[5-(8-azabicyclo[3.2.1]octan-8-ylmethyl)-2-pyridinyl]-2-(butylamino)pyrimidin-4-yl]amino]cyclohexan-1-ol	IC50	3.9 nM	US-9649309: Therapeutic uses of selected pyrimidine compounds with anti-Mer tyrosine kinase activity
4-[[2-(4-chloroanilino)-5-[5-(pyrrolidin-1-ylmethyl)-2-pyridinyl]pyrimidin-4-yl]amino]cyclohexan-1-ol	IC50	4.5 nM	US-9649309: Therapeutic uses of selected pyrimidine compounds with anti-Mer tyrosine kinase activity
4-[[2-(4-bromoanilino)-5-[5-(pyrrolidin-1-ylmethyl)-2-pyridinyl]pyrimidin-4-yl]amino]cyclohexan-1-ol	IC50	4.6 nM	US-9649309: Therapeutic uses of selected pyrimidine compounds with anti-Mer tyrosine kinase activity
4-[[5-pyridin-2-yl-2-(pyridin-4-ylamino)pyrimidin-4-yl]amino]cyclohexan-1-ol	IC50	5.1 nM	US-9649309: Therapeutic uses of selected pyrimidine compounds with anti-Mer tyrosine kinase activity
4-[[2-(butylamino)-5-[5-(diethylaminomethyl)-2-pyridinyl]pyrimidin-4-yl]amino]cyclohexan-1-ol	IC50	5.2 nM	US-9649309: Therapeutic uses of selected pyrimidine compounds with anti-Mer tyrosine kinase activity
6-[2-(butylamino)-4-[(4-hydroxycyclohexyl)amino]pyrimidin-5-yl]-N-methyl-N-(1-methylpiperidin-4-yl)pyridine-3-carboxamide	IC50	6.5 nM	US-9649309: Therapeutic uses of selected pyrimidine compounds with anti-Mer tyrosine kinase activity
4-[[2-(butylamino)-5-[5-(1-morpholin-4-ylcyclopentyl)-2-pyridinyl]pyrimidin-4-yl]amino]cyclohexan-1-ol	IC50	7.4 nM	US-9649309: Therapeutic uses of selected pyrimidine compounds with anti-Mer tyrosine kinase activity
4-[[2-(butylamino)-5-[5-[(2,2-dimethylpropylamino)methyl]-2-pyridinyl]pyrimidin-4-yl]amino]cyclohexan-1-ol	IC50	7.7 nM	US-9649309: Therapeutic uses of selected pyrimidine compounds with anti-Mer tyrosine kinase activity
4-[[2-(butylamino)-5-[5-[1-(4-methylpiperazin-1-yl)cyclobutyl]-2-pyridinyl]pyrimidin-4-yl]amino]cyclohexan-1-ol	IC50	7.7 nM	US-9649309: Therapeutic uses of selected pyrimidine compounds with anti-Mer tyrosine kinase activity
4-[[2-(butylamino)-5-[5-[[(8-methyl-8-azabicyclo[3.2.1]octan-3-yl)amino]methyl]-2-pyridinyl]pyrimidin-4-yl]amino]cyclohexan-1-ol	IC50	8 nM	US-9649309: Therapeutic uses of selected pyrimidine compounds with anti-Mer tyrosine kinase activity
4-[[2-(butylamino)-5-[5-[(1-propan-2-ylpiperidin-4-ylidene)methyl]-2-pyridinyl]pyrimidin-4-yl]amino]cyclohexan-1-ol	IC50	8.5 nM	US-9649309: Therapeutic uses of selected pyrimidine compounds with anti-Mer tyrosine kinase activity
4-[[2-(butylamino)-5-[5-[(tert-butylamino)methyl]-2-pyridinyl]pyrimidin-4-yl]amino]cyclohexan-1-ol	IC50	10 nM	US-9649309: Therapeutic uses of selected pyrimidine compounds with anti-Mer tyrosine kinase activity
4-[[2-(butylamino)-5-[5-[(cyclopropylmethylamino)methyl]-2-pyridinyl]pyrimidin-4-yl]amino]cyclohexan-1-ol	IC50	11 nM	US-9649309: Therapeutic uses of selected pyrimidine compounds with anti-Mer tyrosine kinase activity
4-[[2-(butylamino)-5-[5-[[(3R)-3-(dimethylamino)pyrrolidin-1-yl]methyl]-2-pyridinyl]pyrimidin-4-yl]amino]cyclohexan-1-ol	IC50	11 nM	US-9649309: Therapeutic uses of selected pyrimidine compounds with anti-Mer tyrosine kinase activity
4-[[2-(butylamino)-5-[5-(1-morpholin-4-ylcyclobutyl)-2-pyridinyl]pyrimidin-4-yl]amino]cyclohexan-1-ol	IC50	11 nM	US-9649309: Therapeutic uses of selected pyrimidine compounds with anti-Mer tyrosine kinase activity
4-[[2-(butylamino)-5-[5-[[(2,2,3,3-tetramethylcyclopropyl)amino]methyl]-2-pyridinyl]pyrimidin-4-yl]amino]cyclohexan-1-ol	IC50	12 nM	US-9649309: Therapeutic uses of selected pyrimidine compounds with anti-Mer tyrosine kinase activity
4-[[2-(butylamino)-5-[5-[(cyclobutylamino)methyl]-2-pyridinyl]pyrimidin-4-yl]amino]cyclohexan-1-ol	IC50	13 nM	US-9649309: Therapeutic uses of selected pyrimidine compounds with anti-Mer tyrosine kinase activity
4-[[2-(butylamino)-5-[5-(piperidin-4-ylidenemethyl)-2-pyridinyl]pyrimidin-4-yl]amino]cyclohexan-1-ol	IC50	13 nM	US-9649309: Therapeutic uses of selected pyrimidine compounds with anti-Mer tyrosine kinase activity
4-[[2-(butylamino)-5-[5-(pyrrolidin-1-ylmethyl)-1,3-thiazol-2-yl]pyrimidin-4-yl]amino]cyclohexan-1-ol	IC50	14 nM	US-9649309: Therapeutic uses of selected pyrimidine compounds with anti-Mer tyrosine kinase activity
4-[[5-pyridin-2-yl-2-(pyridin-3-ylamino)pyrimidin-4-yl]amino]cyclohexan-1-ol	IC50	14 nM	US-9649309: Therapeutic uses of selected pyrimidine compounds with anti-Mer tyrosine kinase activity
4-[[2-(butylamino)-5-[5-[(cyclopentylamino)methyl]-2-pyridinyl]pyrimidin-4-yl]amino]cyclohexan-1-ol	IC50	16 nM	US-9649309: Therapeutic uses of selected pyrimidine compounds with anti-Mer tyrosine kinase activity
4-[[2-(butylamino)-5-[4-chloro-5-(pyrrolidin-1-ylmethyl)-2-pyridinyl]pyrimidin-4-yl]amino]cyclohexan-1-ol	IC50	16 nM	US-9649309: Therapeutic uses of selected pyrimidine compounds with anti-Mer tyrosine kinase activity
4-[[2-(butylamino)-5-[5-(pyrrolidin-1-ylmethyl)-2-pyridinyl]pyrimidin-4-yl]amino]cyclohexan-1-ol	IC50	18 nM	US-9649309: Therapeutic uses of selected pyrimidine compounds with anti-Mer tyrosine kinase activity
4-[[2-(butylamino)-5-[5-(ethylaminomethyl)-2-pyridinyl]pyrimidin-4-yl]amino]cyclohexan-1-ol	IC50	18 nM	US-9649309: Therapeutic uses of selected pyrimidine compounds with anti-Mer tyrosine kinase activity
4-[[2-(butylamino)-5-[5-[(pyridin-4-ylmethylamino)methyl]-2-pyridinyl]pyrimidin-4-yl]amino]cyclohexan-1-ol	IC50	18 nM	US-9649309: Therapeutic uses of selected pyrimidine compounds with anti-Mer tyrosine kinase activity
4-[[2-(butylamino)-5-[5-(1-morpholin-4-ylcyclopropyl)-2-pyridinyl]pyrimidin-4-yl]amino]cyclohexan-1-ol	IC50	18 nM	US-9649309: Therapeutic uses of selected pyrimidine compounds with anti-Mer tyrosine kinase activity
4-[[2-(butylamino)-5-[5-[[(3R)-3-methylpiperazin-1-yl]methyl]-2-pyridinyl]pyrimidin-4-yl]amino]cyclohexan-1-ol	IC50	18 nM	US-9649309: Therapeutic uses of selected pyrimidine compounds with anti-Mer tyrosine kinase activity
4-[[2-(butylamino)-5-[5-[(2,2-dimethylpiperazin-1-yl)methyl]-2-pyridinyl]pyrimidin-4-yl]amino]cyclohexan-1-ol	IC50	19 nM	US-9649309: Therapeutic uses of selected pyrimidine compounds with anti-Mer tyrosine kinase activity
4-[[2-(butylamino)-5-[5-[[(1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl]methyl]-2-pyridinyl]pyrimidin-4-yl]amino]cyclohexan-1-ol	IC50	19 nM	US-9649309: Therapeutic uses of selected pyrimidine compounds with anti-Mer tyrosine kinase activity
4-[[2-(butylamino)-5-[5-[(2-hydroxyethylamino)methyl]-2-pyridinyl]pyrimidin-4-yl]amino]cyclohexan-1-ol	IC50	20 nM	US-9649309: Therapeutic uses of selected pyrimidine compounds with anti-Mer tyrosine kinase activity
4-[[2-(butylamino)-5-[5-[[(2S)-2-methylpiperazin-1-yl]methyl]-2-pyridinyl]pyrimidin-4-yl]amino]cyclohexan-1-ol	IC50	20 nM	US-9649309: Therapeutic uses of selected pyrimidine compounds with anti-Mer tyrosine kinase activity
4-[[2-(butylamino)-5-[5-[(1-methylpiperidin-4-ylidene)methyl]-2-pyridinyl]pyrimidin-4-yl]amino]cyclohexan-1-ol	IC50	20 nM	US-9649309: Therapeutic uses of selected pyrimidine compounds with anti-Mer tyrosine kinase activity
4-[[2-(butylamino)-5-[5-[(dimethylamino)methyl]-2-pyridinyl]pyrimidin-4-yl]amino]cyclohexan-1-ol	IC50	21 nM	US-9649309: Therapeutic uses of selected pyrimidine compounds with anti-Mer tyrosine kinase activity
4-[[2-(butylamino)-5-[5-[[(3S)-3-methylpiperazin-1-yl]methyl]-2-pyridinyl]pyrimidin-4-yl]amino]cyclohexan-1-ol	IC50	22 nM	US-9649309: Therapeutic uses of selected pyrimidine compounds with anti-Mer tyrosine kinase activity
4-[[2-(butylamino)-5-[5-[(1-propan-2-ylpiperidin-4-yl)methyl]-2-pyridinyl]pyrimidin-4-yl]amino]cyclohexan-1-ol	IC50	22 nM	US-9649309: Therapeutic uses of selected pyrimidine compounds with anti-Mer tyrosine kinase activity
4-[[5-(2-aminopyrimidin-4-yl)-2-(butylamino)pyrimidin-4-yl]amino]cyclohexan-1-ol	IC50	23 nM	US-9649309: Therapeutic uses of selected pyrimidine compounds with anti-Mer tyrosine kinase activity
4-[[2-(butylamino)-5-[5-[(cyclohexylamino)methyl]-2-pyridinyl]pyrimidin-4-yl]amino]cyclohexan-1-ol	IC50	24 nM	US-9649309: Therapeutic uses of selected pyrimidine compounds with anti-Mer tyrosine kinase activity

ChEMBL bioactivities

268 potent at pChembl≥5 of 281 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.92	IC50	1.2	nM	CHEMBL5954944
8.89	IC50	1.3	nM	CHEMBL6001325
8.89	IC50	1.3	nM	CHEMBL5890127
8.82	IC50	1.5	nM	CHEMBL6021490
8.62	IC50	2.4	nM	CHEMBL5804924
8.59	IC50	2.6	nM	CHEMBL6010923
8.49	IC50	3.2	nM	CHEMBL5752348
8.44	IC50	3.6	nM	CHEMBL5784143
8.43	IC50	3.7	nM	CHEMBL5827373
8.42	IC50	3.8	nM	CHEMBL5741729
8.41	IC50	3.9	nM	CHEMBL5951577
8.35	IC50	4.5	nM	CHEMBL6015124
8.34	IC50	4.6	nM	CHEMBL5918104
8.29	IC50	5.1	nM	CHEMBL6054980
8.28	IC50	5.2	nM	CHEMBL5978513
8.19	IC50	6.5	nM	CHEMBL5741936
8.19	IC50	6.4	nM	CHEMBL5793403
8.13	IC50	7.4	nM	CHEMBL5851446
8.11	IC50	7.7	nM	CHEMBL5965507
8.11	IC50	7.7	nM	CHEMBL6032630
8.10	IC50	8	nM	CHEMBL5757456
8.07	IC50	8.5	nM	CHEMBL5853010
8.06	IC50	8.7	nM	CHEMBL5757456
8.03	IC50	9.4	nM	CHEMBL5860166
8.00	IC50	10	nM	CHEMBL5798152
7.96	IC50	11	nM	CHEMBL5748457
7.96	IC50	11	nM	CHEMBL5896982
7.96	IC50	11	nM	CHEMBL5871924
7.92	IC50	12	nM	CHEMBL5787736
7.89	IC50	13	nM	CHEMBL5874094
7.89	IC50	13	nM	CHEMBL5991018
7.85	IC50	14	nM	CHEMBL6018124
7.85	IC50	14	nM	CHEMBL5987214
7.80	IC50	16	nM	CHEMBL5965646
7.80	IC50	16	nM	CHEMBL5764883
7.75	IC50	18	nM	CHEMBL6013410
7.75	IC50	18	nM	CHEMBL5790917
7.75	IC50	18	nM	CHEMBL5753009
7.75	IC50	18	nM	CHEMBL6017339
7.75	IC50	18	nM	CHEMBL5942238
7.72	IC50	19	nM	CHEMBL5893398
7.72	IC50	19	nM	CHEMBL5828059
7.70	IC50	20	nM	CHEMBL6046949
7.70	IC50	20	nM	CHEMBL5949787
7.70	IC50	20	nM	CHEMBL5852269
7.68	IC50	21	nM	CHEMBL5767197
7.66	IC50	22	nM	CHEMBL5981718
7.66	IC50	22	nM	CHEMBL5821668
7.64	IC50	23	nM	CHEMBL6001297
7.62	IC50	24	nM	CHEMBL5777271

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Estradiol	affects cotreatment, increases expression, decreases reaction	4
sodium arsenite	decreases expression, increases expression	3
Valproic Acid	affects expression, increases expression, increases methylation	3
methacrylaldehyde	affects cotreatment, increases expression, increases abundance	2
Acrolein	affects cotreatment, increases expression, increases abundance	2
Air Pollutants	increases expression, decreases expression, affects cotreatment, increases abundance	2
Benzo(a)pyrene	increases mutagenesis, affects methylation	2
Ozone	increases expression, increases abundance, affects cotreatment	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Tobacco Smoke Pollution	decreases expression	2
Particulate Matter	decreases expression, increases abundance, affects cotreatment, increases expression	2
bisphenol F	affects cotreatment, affects expression	1
sotorasib	affects cotreatment, increases expression	1
taxifolin	increases expression	1
alpha-pinene	affects cotreatment, increases expression, increases abundance	1
salinomycin	decreases expression	1
beta-lapachone	decreases expression	1
11-nor-delta(9)-tetrahydrocannabinol-9-carboxylic acid	affects methylation, increases abundance	1
cobaltous chloride	decreases expression	1
butyraldehyde	decreases expression	1
zinc chromate	decreases expression, increases abundance	1
potassium chromate(VI)	decreases expression	1
nickel sulfate	decreases expression	1
chromium hexavalent ion	decreases expression, increases abundance	1
4-phenylbutyric acid	decreases expression	1
CGP 52608	affects binding, increases reaction	1
monomethylarsonous acid	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
candoxin	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5731806	Binding	Activity Assay: Briefly, activity assays were performed in a 384 well, polypropylene microplate in a final volume of 50 μL of 50 mM Hepes, Ph 7.4 containing 10 mM MgCl2, 1.0 mM DTT, 0.01% Triton X-100, 0.1% Bovine Serum Albumin (BSA), conta	Therapeutic uses of selected pyrimidine compounds with anti-Mer tyrosine kinase activity

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B9VZ	Abcam HEK293 GAS6 KO	Transformed cell line	Female

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.