MERTK

Summary

MERTK (MER proto-oncogene, tyrosine kinase, HGNC:7027) is a protein-coding gene on chromosome 2q13, encoding Tyrosine-protein kinase Mer (Q12866). Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding to several ligands including LGALS3, TUB, TULP1 or GAS6. In precision oncology, MERTK OVEREXPRESSION confers sensitivity to UNC1062 in Melanoma (CIViC Level D).

This gene is a member of the MER/AXL/TYRO3 receptor kinase family and encodes a transmembrane protein with two fibronectin type-III domains, two Ig-like C2-type (immunoglobulin-like) domains, and one tyrosine kinase domain. Mutations in this gene have been associated with disruption of the retinal pigment epithelium (RPE) phagocytosis pathway and onset of autosomal recessive retinitis pigmentosa (RP).

Source: NCBI Gene 10461 — RefSeq curated summary.

At a glance

• Gene–disease (curated): MERTK-related retinopathy (Definitive, ClinGen) — +2 more curated relationships
• GWAS associations: 17
• Clinical variants (ClinVar): 898 total — 97 pathogenic, 40 likely-pathogenic
• Phenotypes (HPO): 38
• Druggable target: yes — 48 molecules with ChEMBL bioactivity
• Precision-oncology evidence (CIViC): 1 curated variant–drug association
• MANE Select transcript: NM_006343

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7027
Approved symbol	MERTK
Name	MER proto-oncogene, tyrosine kinase
Location	2q13
Locus type	gene with protein product
Status	Approved
Aliases	mer, RP38, c-Eyk, Tyro12
Ensembl gene	ENSG00000153208
Ensembl biotype	protein_coding
OMIM	604705
Entrez	10461

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 4 protein_coding, 1 nonsense_mediated_decay, 1 retained_intron

ENST00000295408, ENST00000409780, ENST00000439966, ENST00000449344, ENST00000473065, ENST00000953051

RefSeq mRNA: 1 — MANE Select: NM_006343 NM_006343

CCDS: CCDS2094

Canonical transcript exons

ENST00000295408 — 19 exons

Exon	Start	End
ENSE00001254759	111898607	111898796
ENSE00001427300	112028351	112029561
ENSE00002530474	111929120	111929540
ENSE00003459308	112008383	112008475
ENSE00003467795	112022258	112022394
ENSE00003476444	111975289	111975472
ENSE00003494349	112009948	112010066
ENSE00003506211	111982842	111982993
ENSE00003523089	111997323	111997476
ENSE00003526276	111968137	111968252
ENSE00003552200	111947394	111947567
ENSE00003594489	112021422	112021581
ENSE00003595852	111994251	111994404
ENSE00003609183	112003092	112003187
ENSE00003629973	112001201	112001286
ENSE00003638379	112019413	112019522
ENSE00003668040	111944960	111945060
ENSE00003670750	112003904	112003984
ENSE00003685191	111965191	111965277

Expression profiles

Bgee: expression breadth ubiquitous, 246 present calls, max score 96.96.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 19.5975 / max 399.4197, expressed in 1172 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
21963	17.5596	1135
202345	0.8080	362
202343	0.5351	291
202344	0.4296	241
21964	0.1052	46
21962	0.0801	22
21961	0.0798	24

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right adrenal gland cortex	UBERON:0035827	96.96	gold quality
mucosa of stomach	UBERON:0001199	95.98	gold quality
right adrenal gland	UBERON:0001233	95.93	gold quality
left adrenal gland	UBERON:0001234	95.18	gold quality
left adrenal gland cortex	UBERON:0035825	94.80	gold quality
adrenal cortex	UBERON:0001235	94.52	gold quality
adrenal gland	UBERON:0002369	94.08	gold quality
popliteal artery	UBERON:0002250	93.43	gold quality
tibial artery	UBERON:0007610	93.43	gold quality
aorta	UBERON:0000947	92.37	gold quality
descending thoracic aorta	UBERON:0002345	92.29	gold quality
adrenal tissue	UBERON:0018303	91.68	gold quality
thoracic aorta	UBERON:0001515	91.40	gold quality
ascending aorta	UBERON:0001496	91.28	gold quality
left coronary artery	UBERON:0001626	90.77	gold quality
spleen	UBERON:0002106	90.65	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	90.00	gold quality
right coronary artery	UBERON:0001625	89.98	gold quality
left uterine tube	UBERON:0001303	89.92	gold quality
adenohypophysis	UBERON:0002196	89.15	gold quality
secondary oocyte	CL:0000655	88.94	gold quality
right lung	UBERON:0002167	88.14	gold quality
left testis	UBERON:0004533	88.02	gold quality
coronary artery	UBERON:0001621	87.99	gold quality
caudate nucleus	UBERON:0001873	87.98	gold quality
right testis	UBERON:0004534	87.95	gold quality
small intestine Peyer’s patch	UBERON:0003454	87.35	gold quality
body of stomach	UBERON:0001161	87.03	gold quality
lower esophagus muscularis layer	UBERON:0035833	87.02	gold quality
lower esophagus	UBERON:0013473	86.98	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-6075	yes	372.80
E-HCAD-35	yes	27.85
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

50 targeting MERTK, 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-3924	100.00	72.09	2394
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-5011-5P	100.00	83.46	5820
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-3646	100.00	73.56	5283
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-664B-3P	99.84	71.65	3590
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-33A-3P	99.70	70.27	3362
HSA-MIR-7154-5P	99.69	70.52	1900
HSA-MIR-466	99.67	70.85	2863
HSA-MIR-7-5P	99.67	70.53	1809
HSA-MIR-298	99.63	67.56	1916
HSA-MIR-2053	99.57	69.15	1635
HSA-MIR-12123	99.52	71.79	2990
HSA-MIR-671-5P	99.52	67.11	1277
HSA-MIR-4643	99.49	67.63	1791

Literature-anchored findings (GeneRIF, showing 40)

• retinal dystrophy due to paternal isodisomy for chromosome 1 or chromosome 2, with homoallelism for mutations in RPE65 or MERTK, respectively (PMID:11727200)
• 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)
• The present study reports the identification of R844C, the first putative pathogenic MERTK missense mutation that results in severe retinal degeneration with childhood onset (PMID:15111602)
• mer, presumably through activation by its ligand Gas6, participates in regulation of platelet function in vitro and platelet-dependent thrombosis in vivo. (PMID:15130911)
• Axl, Sky and Mer are Gas6 receptors that enhance platelet activation and regulate thrombotic responses (PMID:15733062)
• Transforming Mer signals may contribute to T-cell leukemogenesis, and abnormal Mer expression may be a novel therapeutic target in pediatric acute lymhpocytic leukemia therapy. (PMID:16675557)
• Mutations in the MERTK gene are relatively rare in Japanese patients with autosomal recessive retinitis pigmentosa. (PMID:16710167)
• 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)
• cleavage results in production of a soluble Mer protein that prevented Gas6-mediated stimulation of membrane-bound Mer. Mer inhibition led to defective macrophage-mediated engulfment of apoptotic cells and decreased platelet aggregation (PMID:17047157)
• Mer is highly expressed on Jurkat cells, and could inhibit cell apoptosis via Bcl-2 signaling pathway. (PMID:17626743)
• Tyr-867 in Mer receptor tyrosine kinase allows for dissociation of multiple signaling pathways for phagocytosis of apoptotic cells and down-modulation of lipopolysaccharide-inducible NF-kappaB transcriptional activation (PMID:18039660)
• Overexpressed Mer tyrosine kinase receptor can inhibit the migration and angiogenesis of HMEC-1 cells through VEGF-C/VEGFR-2 signal pathway. (PMID:18246816)
• MerTK macrophage receptor is an essential component required for serum-stimulated phagocytosis of apoptotic cells. (PMID:18250462)
• MERTK, a cell surface receptor that recognizes apoptotic cells, is expressed on human alveolar macrophages (AMs), and its expression is up-regulated in AMs of cigarette smokers. (PMID:18587056)
• Possible strategies for targeted inhibition of the TAM family in the treatment of human cancer. (PMID:18620092)
• IVS16+1G>T disrupts the splice donor site causing exon 16 skipping. Absence of exon 16 causes a frameshift and the introduction of a premature termination codon into exon 17 creating an altered mRNA with a seriously affected tyrosine kinase domain. (PMID:18815424)
• human protein S can inhibit the expression and activity of SR-A through Mer RTK in macrophages, suggesting that human protein S is a modulator for macrophage functions in uptaking of modified lipoproteins (PMID:18922854)
• The splice site mutation c.2189+1G>T in MERTK causes rod-cone dystrophy with a distinct macular phenotype. (PMID:19403518)
• 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 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)
• Homozygosity mapping and mutation analysis in the distant family member affected by RP revealed a homozygous mutation in MERTK, but no CEP290 mutations. (PMID:20130272)
• The phenotype associated with these identified MERTK mutations is of a childhood onset rod-cone dystrophy with early macular atrophy. (PMID:20300561)
• results strongly suggest that the nonsense mutation in MERTK, leading to premature termination of the protein, is responsible for retinitis pigmentosa phenotype in the affected individuals of the Pakistani family. (PMID:20538656)
• Gas6 and Tyro3, Axl and Mer (TAM) receptors have roles in human and murine platelet activation and thrombus stabilization (PMID:20546121)
• correlation of decreased protein S levels with lupus disease activity is consistent with a role for the TAM receptors in scavenging apoptotic cells and controlling inflammation (PMID:20637106)
• The lower activity of PKC and the higher expression of MERTK are very important for sustaining the phagocytic process of ROS by human retinal pigment epithelial cells. (PMID:20654219)
• Findings indicate genetic association between MERTK and TYRO3 allelic variants and carotid atherosclerosis. (PMID:20664904)
• PMN-Ect interacted with the macrophages by activation of the MerTK pathway responsible for down-modulation of the proinflammatory signals generated by ZymA. (PMID:20959443)
• Tubby and Tulp1 are bridging molecules with their N-terminal region as MERTK-binding domain and C-terminal region as phagocytosis prey-binding domain. (PMID:20978472)
• MERTK gene is a novel risk gene for multiple sclerosis susceptibility (PMID:21347448)
• overexpressed in atherosclerotic carotid plaques (PMID:21384080)
• plasma concentrations of sMer and sTyro3 were significantly increased in patients with active systemic lupus erythematosis and Rheumatoid arthritis (PMID:21496228)
• Gene expression profile is changed by the dysfunction of Mer during retinal pigment epithelium phagocytosis.( (PMID:21542987)
• A novel MERTK deletion is a common founder mutation in the Faroe Islands and is responsible for a high proportion of retinitis pigmentosa cases. (PMID:21677792)
• This study identified galectin-3 as a new MerTK ligand by an advanced dual functional cloning strategy. (PMID:21792939)
• MERTK mutations lead to severe retinitis pigmentosa with discrete dot-like autofluorescent deposits at early stages, which are a hallmark of this MERTK-specific dystrophy. (PMID:22180149)
• The present study explores Mer behavior following prolonged exposure to Gas6. (PMID:22363695)
• Mer receptor tyrosine kinase promotes invasion and survival in glioblastoma multiforme. (PMID:22469987)
• The single nucleotide polymorphisms rs4374383 and rs9380516 were linked to the functionally related genes MERTK and TULP1, which encode factors involved in phagocytosis of apoptotic cells by macrophages. (PMID:22841784)
• These results indicate that Mer and Axl have complementary and overlapping roles in Non-small cell lung cancer (PMID:22890323)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	mertka	ENSDARG00000074695
mus_musculus	Mertk	ENSMUSG00000014361
rattus_norvegicus	Mertk	ENSRNOG00000017319

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), EPHB1 (ENSG00000154928), KIT (ENSG00000157404), FGFR4 (ENSG00000160867), DDR2 (ENSG00000162733), RYK (ENSG00000163785), MST1R (ENSG00000164078), LMTK2 (ENSG00000164715)

Protein

Protein identifiers

Tyrosine-protein kinase Mer — Q12866 (reviewed: Q12866)

Alternative names: Proto-oncogene c-Mer, Receptor tyrosine kinase MerTK

All UniProt accessions (4): Q12866, E9PD22, E9PHX8, H7C3L9

UniProt curated annotations — full annotation on UniProt →

Function. Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding to several ligands including LGALS3, TUB, TULP1 or GAS6. Regulates many physiological processes including cell survival, migration, differentiation, and phagocytosis of apoptotic cells (efferocytosis). Ligand binding at the cell surface induces autophosphorylation of MERTK on its intracellular domain that provides docking sites for downstream signaling molecules. Following activation by ligand, interacts with GRB2 or PLCG2 and induces phosphorylation of MAPK1, MAPK2, FAK/PTK2 or RAC1. MERTK signaling plays a role in various processes such as macrophage clearance of apoptotic cells, platelet aggregation, cytoskeleton reorganization and engulfment. Functions in the retinal pigment epithelium (RPE) as a regulator of rod outer segments fragments phagocytosis. Also plays an important role in inhibition of Toll-like receptors (TLRs)-mediated innate immune response by activating STAT1, which selectively induces production of suppressors of cytokine signaling SOCS1 and SOCS3.

Subunit / interactions. Interacts (upon activation) with TNK2; stimulates TNK2 autophosphorylation. Interacts (via N-terminus) with extracellular ligands LGALS3, TUB, TULP1 and GAS6. Interacts with VAV1 in a phosphotyrosine-independent manner. Interacts with TIMD4; this interaction enhances TIMD4-mediated efferocytosis.

Subcellular location. Cell membrane.

Tissue specificity. Not expressed in normal B- and T-lymphocytes but is expressed in numerous neoplastic B- and T-cell lines. Highly expressed in testis, ovary, prostate, lung, and kidney, with lower expression in spleen, small intestine, colon, and liver.

Post-translational modifications. Autophosphorylated on Tyr-749, Tyr-753 and Tyr-754 in the activation loop allowing full activity. Autophosphorylated on Tyr-872 leading to recruitment of downstream partners of the signaling cascade such as PLCG2.

Disease relevance. Retinitis pigmentosa 38 (RP38) [MIM:613862] A retinal dystrophy belonging to the group of pigmentary retinopathies. Retinitis pigmentosa is characterized by retinal pigment deposits visible on fundus examination and primary loss of rod photoreceptor cells followed by secondary loss of cone photoreceptors. Patients typically have night vision blindness and loss of midperipheral visual field. As their condition progresses, they lose their far peripheral visual field and eventually central vision as well. The disease is caused by variants affecting the gene represented in this entry.

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

RefSeq proteins (1): NP_006334* (*=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
IPR013151	Immunoglobulin_dom	Domain
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, PF00047, 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), 1 shown:

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

UniProt features (102 total): sequence variant 23, strand 20, helix 15, glycosylation site 14, sequence conflict 8, modified residue 6, domain 5, binding site 2, topological domain 2, disulfide bond 2, signal peptide 1, chain 1, active site 1, transmembrane region 1, turn 1

Structure

Experimental structures (PDB)

42 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
7AB0	X-RAY DIFFRACTION	1.74
7AAX	X-RAY DIFFRACTION	1.76
7AB2	X-RAY DIFFRACTION	1.78
7AAZ	X-RAY DIFFRACTION	1.85
7AAY	X-RAY DIFFRACTION	1.87
7OLS	X-RAY DIFFRACTION	1.89
7AW0	X-RAY DIFFRACTION	1.89
3BRB	X-RAY DIFFRACTION	1.9
7AB1	X-RAY DIFFRACTION	1.93
7AW1	X-RAY DIFFRACTION	1.98
7AW4	X-RAY DIFFRACTION	1.98
7OLX	X-RAY DIFFRACTION	1.98
7AW3	X-RAY DIFFRACTION	1.99
7AVZ	X-RAY DIFFRACTION	2.04
9BHI	X-RAY DIFFRACTION	2.07
5U6C	X-RAY DIFFRACTION	2.1
7AW2	X-RAY DIFFRACTION	2.1
9BHK	X-RAY DIFFRACTION	2.11
7OLV	X-RAY DIFFRACTION	2.13
7XHY	X-RAY DIFFRACTION	2.16
5K0X	X-RAY DIFFRACTION	2.23
5TC0	X-RAY DIFFRACTION	2.24
9KRY	X-RAY DIFFRACTION	2.25
9BHJ	X-RAY DIFFRACTION	2.29
7AVY	X-RAY DIFFRACTION	2.31
2P0C	X-RAY DIFFRACTION	2.4
7AVX	X-RAY DIFFRACTION	2.44
4MH7	X-RAY DIFFRACTION	2.51
5K0K	X-RAY DIFFRACTION	2.54
4MHA	X-RAY DIFFRACTION	2.59

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q12866-F1	72.78	0.38

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): 723 (proton acceptor)

Ligand- & substrate-binding residues (2): 593–601; 615

Post-translational modifications (6): 543, 749, 753, 754, 872, 935

Disulfide bonds (2): 115–175, 218–262

Glycosylation sites (14): 114, 170, 207, 215, 234, 294, 316, 329, 336, 354, 389, 395, 442, 454

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-202733	Cell surface interactions at the vascular wall
R-HSA-9918485	Dengue Virus Attachment and Entry
R-HSA-109582	Hemostasis

MSigDB gene sets: 352 (showing top): GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_UP, GOBP_REGULATION_OF_CELL_ACTIVATION, MODULE_92, DAVIES_MULTIPLE_MYELOMA_VS_MGUS_DN, WANG_CLIM2_TARGETS_UP, GOBP_NATURAL_KILLER_CELL_DIFFERENTIATION, GOBP_POSITIVE_REGULATION_OF_ENDOCYTOSIS, GOBP_MYELOID_CELL_HOMEOSTASIS, GOBP_REGULATION_OF_LEUKOCYTE_APOPTOTIC_PROCESS, GOBP_PLATELET_ACTIVATION, GOBP_APOPTOTIC_CELL_CLEARANCE, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_MALE_GAMETE_GENERATION, GOBP_CELL_CELL_SIGNALING, GOBP_REGULATION_OF_VESICLE_MEDIATED_TRANSPORT

GO Biological Process (23): natural killer cell differentiation (GO:0001779), negative regulation of cytokine production (GO:0001818), protein phosphorylation (GO:0006468), phagocytosis (GO:0006909), cell surface receptor signaling pathway (GO:0007166), cell surface receptor protein tyrosine kinase signaling pathway (GO:0007169), cell-cell signaling (GO:0007267), spermatogenesis (GO:0007283), nervous system development (GO:0007399), cell migration (GO:0016477), platelet activation (GO:0030168), secretion by cell (GO:0032940), substrate adhesion-dependent cell spreading (GO:0034446), positive regulation of phagocytosis (GO:0050766), negative regulation of lymphocyte activation (GO:0051250), establishment of localization in cell (GO:0051649), positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0051897), retina development in camera-type eye (GO:0060041), vagina development (GO:0060068), neutrophil clearance (GO:0097350), negative regulation of leukocyte apoptotic process (GO:2000107), apoptotic cell clearance (GO:0043277), lymphocyte activation (GO:0046649)

GO Molecular Function (9): transmembrane receptor protein tyrosine kinase activity (GO:0004714), ATP binding (GO:0005524), nucleotide binding (GO:0000166), protein kinase activity (GO:0004672), protein tyrosine kinase activity (GO:0004713), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740), metal ion binding (GO:0046872)

GO Cellular Component (6): photoreceptor outer segment (GO:0001750), obsolete extracellular space (GO:0005615), cytoplasm (GO:0005737), plasma membrane (GO:0005886), signaling receptor complex (GO:0043235), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Hemostasis	1
Dengue Virus Infection	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
phagocytosis	2
lymphocyte differentiation	1
natural killer cell activation	1
cytokine production	1
regulation of cytokine production	1
negative regulation of gene expression	1
negative regulation of multicellular organismal process	1
phosphorylation	1
protein modification process	1
endocytosis	1
signal transduction	1
enzyme-linked receptor protein signaling pathway	1
cell communication	1
signaling	1
developmental process involved in reproduction	1
male gamete generation	1
system development	1
cell motility	1
cell activation	1
blood coagulation	1
secretion	1
export from cell	1
cell-substrate adhesion	1
positive regulation of endocytosis	1
regulation of phagocytosis	1
negative regulation of leukocyte activation	1
lymphocyte activation	1
regulation of lymphocyte activation	1
establishment of localization	1
cellular localization	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
camera-type eye development	1
anatomical structure development	1
female genitalia development	1
neutrophil homeostasis	1
apoptotic cell clearance	1
protein tyrosine kinase activity	1

Protein interactions and networks

STRING

2560 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MERTK	GAS6	Q14393	999
MERTK	PROS1	P07225	997
MERTK	TULP1	O00294	949
MERTK	LGALS3	P17931	914
MERTK	RPE65	Q16518	896
MERTK	MFGE8	Q08431	815
MERTK	GUCA1B	Q9UMX6	812
MERTK	LRAT	O95237	797
MERTK	MEGF10	Q96KG7	794
MERTK	RDH12	Q96NR8	736
MERTK	AIPL1	Q9NZN9	728
MERTK	BEST1	O76090	720
MERTK	CRX	O43186	711
MERTK	GUCY2D	Q02846	706
MERTK	CERKL	Q49MI3	704

IntAct

40 interactions, top by confidence:

A	B	Type	Score
FBXO2	TMEM131L	psi-mi:“MI:0914”(association)	0.530
LGALS1	PODXL	psi-mi:“MI:0914”(association)	0.530
MERTK	PKM	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
	MERTK	psi-mi:“MI:0915”(physical association)	0.400
MERTK	HSP90AB1	psi-mi:“MI:0915”(physical association)	0.400
MERTK		psi-mi:“MI:0915”(physical association)	0.370
MERTK	Pgm1	psi-mi:“MI:0914”(association)	0.350
AXL	PIK3R2	psi-mi:“MI:0914”(association)	0.350
MERTK	LANCL1	psi-mi:“MI:0914”(association)	0.350
KCNE3	PIK3R2	psi-mi:“MI:0914”(association)	0.350
MFSD14A	FAM171A2	psi-mi:“MI:0914”(association)	0.350
NIPA1	UNC119B	psi-mi:“MI:0914”(association)	0.350
SLC44A1	UPK3BL1	psi-mi:“MI:0914”(association)	0.350
	TBKBP1	psi-mi:“MI:0914”(association)	0.350
MERTK	NDUFA4	psi-mi:“MI:2364”(proximity)	0.270
AKT1	MERTK	psi-mi:“MI:2364”(proximity)	0.270
FBXW7	MERTK	psi-mi:“MI:2364”(proximity)	0.270
SMAD4	MERTK	psi-mi:“MI:2364”(proximity)	0.270
MERTK	SMARCA4	psi-mi:“MI:2364”(proximity)	0.270
SMARCA4	MERTK	psi-mi:“MI:2364”(proximity)	0.270
SPOP	MERTK	psi-mi:“MI:2364”(proximity)	0.270
MERTK	SPOP	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (135): MERTK (Affinity Capture-Western), MERTK (Affinity Capture-RNA), MERTK (PCA), MERTK (Affinity Capture-Western), MERTK (Co-localization), MERTK (Affinity Capture-RNA), MERTK (Reconstituted Complex), MERTK (Affinity Capture-MS), MERTK (Affinity Capture-MS), MERTK (Affinity Capture-MS), HSPA1B (Proximity Label-MS), PRKDC (Proximity Label-MS), PARP1 (Proximity Label-MS), HYOU1 (Proximity Label-MS), H2AFY (Proximity Label-MS)

ESM2 similar proteins: A0A6I8TCE0, B0X4T2, F1NY98, O00533, O35158, O55005, O60469, O89026, O97394, P12960, P14781, P16092, P17790, P18460, P18461, P21802, P21803, P28685, P29074, P35331, P35832, P57097, P70232, P97686, Q12860, Q12866, Q28106, Q32MD9, Q3UH53, Q4KMG0, Q60805, Q61851, Q63198, Q7Z5N4, Q7ZXX1, Q810U4, Q8AV58, Q8AXZ4, Q8JG38, Q8VHZ8

Diamond homologs: A0JM20, A0M8R7, A0M8S8, A1X150, F1QVU0, G3V9H8, O02466, O35346, P00519, P00520, P00521, P00522, P00529, P06213, P07949, P08069, P08581, P08941, P09760, P0DV84, P10447, P13368, P14617, P16056, P20806, P22182, P23049, P30530, P33497, P34152, P34925, P35546, P35590, P42684, P55144, P55146, P57097, P70451, P97523, P97793

SIGNOR signaling

6 interactions.

A	Effect	B	Mechanism
MK-2461	down-regulates	MERTK	“chemical inhibition”
MERTK	“up-regulates quantity by stabilization”	MLKL	phosphorylation
MERTK	up-regulates	MERTK	phosphorylation
GAS6	up-regulates	MERTK	binding

Disease & clinical

Cancer significance

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	97
Likely pathogenic	40
Uncertain significance	418
Likely benign	235
Benign	24

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1065760	NM_006343.3(MERTK):c.2190-1G>T	Pathogenic
1067939	NM_006343.3(MERTK):c.1868-1G>A	Pathogenic
1068621	NM_006343.3(MERTK):c.267del (p.Lys89fs)	Pathogenic
1070953	NM_006343.3(MERTK):c.2390del (p.Gly797fs)	Pathogenic
1072545	NC_000002.11:g.(?112656313)(112786441_?)del	Pathogenic
1072546	NC_000002.11:g.(?112751828)(112753086_?)del	Pathogenic
1072547	NC_000002.11:g.(?112656313)(112733049_?)del	Pathogenic
1072548	NC_000002.11:g.(?112702517)(112786441_?)del	Pathogenic
1074891	NM_006343.3(MERTK):c.1192dup (p.Ser398fs)	Pathogenic
1075430	NM_006343.3(MERTK):c.1724del (p.Asn575fs)	Pathogenic
1075717	NM_006343.3(MERTK):c.154del (p.Ser52fs)	Pathogenic
1330299	NM_006343.3(MERTK):c.2190-2A>G	Pathogenic
1378327	NM_006343.3(MERTK):c.2352G>A (p.Trp784Ter)	Pathogenic
143139	NM_006343.3(MERTK):c.225del (p.Gly76fs)	Pathogenic
1431964	NM_006343.3(MERTK):c.2187C>A (p.Cys729Ter)	Pathogenic
1457061	NM_006343.3(MERTK):c.1867+2_1867+3del	Pathogenic
1459244	NC_000002.11:g.(?112740399)(112740590_?)del	Pathogenic
1691718	NM_006343.3(MERTK):c.1647T>G (p.Tyr549Ter)	Pathogenic
1723184	NM_006343.3(MERTK):c.2194C>T (p.Arg732Ter)	Pathogenic
191123	NM_006343.3(MERTK):c.325A>T (p.Lys109Ter)	Pathogenic
191124	NM_006343.3(MERTK):c.1604+2T>G	Pathogenic
1929275	NM_006343.3(MERTK):c.349_352del (p.Ile117fs)	Pathogenic
1992796	NM_006343.3(MERTK):c.584-1_584dup	Pathogenic
2110010	NM_006343.3(MERTK):c.912G>A (p.Trp304Ter)	Pathogenic
2114906	NM_006343.3(MERTK):c.263C>G (p.Ser88Ter)	Pathogenic
2115879	NM_006343.3(MERTK):c.280_281del (p.Leu94fs)	Pathogenic
2119008	NM_006343.3(MERTK):c.14del (p.Pro5fs)	Pathogenic
2122177	NM_006343.3(MERTK):c.2576_2579del (p.Glu859fs)	Pathogenic
2126653	NM_006343.3(MERTK):c.938del (p.Pro313fs)	Pathogenic
2203132	NM_006343.3(MERTK):c.296_297del (p.Thr99fs)	Pathogenic

SpliceAI

3410 predictions. Top by Δscore:

Variant	Effect	Δscore
2:111944957:CA:C	acceptor_loss	1.0000
2:111944958:A:AG	acceptor_gain	1.0000
2:111944958:AG:A	acceptor_loss	1.0000
2:111944959:G:GT	acceptor_gain	1.0000
2:111944959:GC:G	acceptor_gain	1.0000
2:111944959:GCA:G	acceptor_gain	1.0000
2:111944959:GCAT:G	acceptor_gain	1.0000
2:111944959:GCATA:G	acceptor_gain	1.0000
2:111945056:ACAAG:A	donor_gain	1.0000
2:111945058:AAG:A	donor_gain	1.0000
2:111945059:AG:A	donor_gain	1.0000
2:111945060:GG:G	donor_gain	1.0000
2:111945061:G:GA	donor_loss	1.0000
2:111945061:G:GG	donor_gain	1.0000
2:111947564:CCAGG:C	donor_loss	1.0000
2:111947566:AGGTA:A	donor_loss	1.0000
2:111947568:G:GG	donor_gain	1.0000
2:111947568:GTAA:G	donor_loss	1.0000
2:111947569:T:A	donor_loss	1.0000
2:111962993:GCCTC:G	donor_gain	1.0000
2:111965185:TTCCA:T	acceptor_loss	1.0000
2:111965186:TCCAG:T	acceptor_loss	1.0000
2:111965187:CCAGG:C	acceptor_loss	1.0000
2:111965188:CAGG:C	acceptor_loss	1.0000
2:111965189:A:AG	acceptor_gain	1.0000
2:111965190:G:GG	acceptor_gain	1.0000
2:111965190:GGCCT:G	acceptor_gain	1.0000
2:111965276:AGG:A	donor_loss	1.0000
2:111965277:GGTAA:G	donor_loss	1.0000
2:111965278:G:GA	donor_loss	1.0000

AlphaMissense

6565 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:112003909:T:C	F598L	1.000
2:112003911:T:A	F598L	1.000
2:112003911:T:G	F598L	1.000
2:112003974:G:C	K619N	1.000
2:112003974:G:T	K619N	1.000
2:112019507:C:A	A725D	1.000
2:112021448:T:A	V739D	1.000
2:112021528:T:A	W766R	1.000
2:112021528:T:C	W766R	1.000
2:112021530:G:C	W766C	1.000
2:112021530:G:T	W766C	1.000
2:112021573:A:C	S781R	1.000
2:112021575:T:A	S781R	1.000
2:112021575:T:G	S781R	1.000
2:112022258:T:A	W784R	1.000
2:112022258:T:C	W784R	1.000
2:112008461:T:A	V649D	0.999
2:112010023:T:C	L679P	0.999
2:112019498:G:C	R722P	0.999
2:112019501:A:C	D723A	0.999
2:112019501:A:G	D723G	0.999
2:112019501:A:T	D723V	0.999
2:112019504:T:C	L724S	0.999
2:112019510:C:A	A726D	0.999
2:112019513:G:C	R727P	0.999
2:112019513:G:T	R727L	0.999
2:112019515:A:G	N728D	0.999
2:112019516:A:C	N728T	0.999
2:112019517:C:A	N728K	0.999
2:112019517:C:G	N728K	0.999

dbSNP variants (sampled 300 via entrez): RS1000002770 (2:111908471 C>G), RS1000013319 (2:111964300 C>A,T), RS1000047873 (2:111993205 C>T), RS1000071014 (2:111943128 C>G), RS1000089139 (2:111950201 G>T), RS1000126182 (2:112017068 C>T), RS1000162865 (2:111973672 T>C), RS1000164764 (2:111948782 C>G,T), RS1000198412 (2:111958142 C>G), RS1000221229 (2:111966961 A>G), RS1000233591 (2:112014884 C>A,G), RS1000267955 (2:111986910 G>A), RS1000310265 (2:112002249 C>A), RS1000315950 (2:111897124 C>G,T), RS1000325189 (2:111927631 T>C)

Disease associations

OMIM: gene MIM:604705 | disease phenotypes: MIM:613862, MIM:268000, MIM:120970

GenCC curated gene-disease

Disease	Classification	Inheritance
retinitis pigmentosa 38	Definitive	Autosomal recessive
retinitis pigmentosa	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
MERTK-related retinopathy	Definitive	AR

Mondo (6): inherited retinal dystrophy (MONDO:0019118), retinitis pigmentosa 38 (MONDO:0013469), retinitis pigmentosa (MONDO:0019200), cone-rod dystrophy (MONDO:0015993), optic atrophy (MONDO:0003608), retinal disorder (MONDO:0005283)

Orphanet (3): OBSOLETE: Inherited retinal disorder (Orphanet:71862), Retinitis pigmentosa (Orphanet:791), Cone rod dystrophy (Orphanet:1872)

HPO phenotypes

38 total (30 of 38 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000405	Conductive hearing impairment
HP:0000407	Sensorineural hearing impairment
HP:0000501	Glaucoma
HP:0000505	Visual impairment
HP:0000510	Rod-cone dystrophy
HP:0000512	Abnormal electroretinogram
HP:0000529	Progressive visual loss
HP:0000543	Optic disc pallor
HP:0000546	Retinal degeneration
HP:0000551	Color vision defect
HP:0000563	Keratoconus
HP:0000602	Ophthalmoplegia
HP:0000613	Photophobia
HP:0000618	Blindness
HP:0000639	Nystagmus
HP:0000648	Optic atrophy
HP:0000662	Nyctalopia
HP:0000842	Hyperinsulinemia
HP:0001105	Retinal atrophy
HP:0001133	Constriction of peripheral visual field
HP:0007401	Macular atrophy
HP:0007663	Reduced visual acuity
HP:0007675	Progressive night blindness
HP:0007703	Abnormal retinal pigmentation
HP:0007737	Spicular pigmentation of the retina
HP:0007787	Posterior subcapsular cataract
HP:0007843	Attenuation of retinal blood vessels
HP:0007994	Peripheral visual field loss
HP:0008046	Abnormal retinal vascular morphology

GWAS associations

17 associations (top):

Study	Trait	p-value
GCST001198_32	Multiple sclerosis	1.000000e-08
GCST001623_2	Hepatitis C induced liver fibrosis	1.000000e-09
GCST005194_189	Coronary artery disease	3.000000e-06
GCST006624_66	Systolic blood pressure	3.000000e-12
GCST006979_21	Heel bone mineral density	7.000000e-10
GCST009597_47	Multiple sclerosis	1.000000e-11
GCST010481_7	Acute anterior uveitis in ankylosing spondylitis	3.000000e-06
GCST010866_37	Coronary artery disease	3.000000e-09
GCST011365_15	Myocardial infarction	8.000000e-07
GCST012478_2	Cluster headache	7.000000e-17
GCST90000025_813	Appendicular lean mass	4.000000e-13
GCST90002399_155	Neutrophil percentage of white cells	4.000000e-11
GCST90011898_65	Alanine aminotransferase levels	3.000000e-08
GCST90011899_112	Aspartate aminotransferase levels	9.000000e-10
GCST90013663_89	Alanine aminotransferase levels	2.000000e-11
GCST90013664_63	Aspartate aminotransferase levels	3.000000e-11
GCST90014033_13	Haemorrhoidal disease	1.000000e-11

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0006335	systolic blood pressure
EFO:0009270	heel bone mineral density
EFO:0004980	appendicular lean mass
EFO:0007990	neutrophil percentage of leukocytes
EFO:0004736	aspartate aminotransferase measurement

MeSH disease descriptors (5)

Descriptor	Name	Tree numbers
D000071700	Cone-Rod Dystrophies	C11.270.152; C11.768.585.658.250; C16.320.290.152
D009896	Optic Atrophy	C10.292.700.225; C11.640.451
D012164	Retinal Diseases	C11.768
D058499	Retinal Dystrophies	C11.768.585.658
D012174	Retinitis Pigmentosa	C11.270.684; C11.768.585.658.500; C16.320.290.684

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL3137284 (CHIMERIC PROTEIN), CHEMBL5331 (SINGLE PROTEIN), CHEMBL6066566 (PROTEIN FAMILY)

Molecules with ChEMBL bioactivity

48 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 787,992 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1287853	FEDRATINIB	4	3,554
CHEMBL1289926	AXITINIB	4	15,732
CHEMBL1336	SORAFENIB	4	86,060
CHEMBL180022	NERATINIB	4	9,404
CHEMBL2105717	CABOZANTINIB	4	11,177
CHEMBL24828	VANDETANIB	4	42,230
CHEMBL288441	BOSUTINIB	4	12,255
CHEMBL3301607	FILGOTINIB	4	2,905
CHEMBL428647	PACLITAXEL	4	332,542
CHEMBL477772	PAZOPANIB	4	15,540
CHEMBL502835	NINTEDANIB	4	8,545
CHEMBL535	SUNITINIB	4	79,020
CHEMBL553	ERLOTINIB	4	108,300
CHEMBL576982	QUIZARTINIB	4	4,432
CHEMBL601719	CRIZOTINIB	4	14,403
CHEMBL608533	MIDOSTAURIN	4	7,259
CHEMBL223360	LINIFANIB	3	3,925
CHEMBL3622820	ITACITINIB	3	2,274
CHEMBL428690	ALVOCIDIB	3	27,781
CHEMBL4297190	SURUFATINIB	3	654
CHEMBL491473	CEDIRANIB	3
CHEMBL5095079	POVORCITINIB	3
CHEMBL522892	DOVITINIB	3
CHEMBL603469	LESTAURTINIB	3
CHEMBL103667	DORAMAPIMOD	2
CHEMBL1230609	FORETINIB	2
CHEMBL124660	TANDUTINIB	2
CHEMBL1721885	SU-014813	2
CHEMBL1738757	REBASTINIB	2
CHEMBL1822792	MK-2461	2

Clinical evidence (CIViC)

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

Variant	Therapy	Indication	Effect	Level	CIViC
MERTK OVEREXPRESSION	UNC1062	Melanoma	Sensitivity/Response	CIViC D	EID2991

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

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 (17 total), top 17:

Ligand	Action	Affinity	Parameter
UNC4203	Inhibition	9.37	pKi
merestinib	Inhibition	9.1	pKd
denfivontinib	Inhibition	9.0	pIC50
UNC8969	Inhibition	8.96	pIC50
sitravatinib	Inhibition	8.7	pIC50
gilteritinib	Inhibition	8.52	pIC50
A-910	Inhibition	8.38	pIC50
LDC1267	Inhibition	8.3	pIC50
zanzalintinib	Inhibition	8.0	pIC50
BMS-777607	Inhibition	7.85	pIC50
belizatinib	Inhibition	7.74	pKd
MerTK inhibitor 11	Inhibition	7.67	pIC50
MK-2461	Inhibition	7.62	pIC50
RIPK1 inhibitor 22b	Inhibition	7.54	pIC50
adrixetinib	Inhibition	7.0	pKd
metatinib	Inhibition	6.89	pIC50
SLC-391	Inhibition	6.3	pIC50

Binding affinities (BindingDB)

1322 measured of 2711 human assays (2711 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
1-[2-(4-methylphenyl)-5-tert-butyl-pyrazol-3-yl]-3-[4-(2-morpholin-4-ylethoxy)naphthalen-1-yl]urea	KD	0.37 nM
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-(butylamino)-5-[4-(4-methylpiperazin-1-yl)phenyl]pyrrolo[2,3-d]pyrimidin-7-yl]cyclohexan-1-ol	IC50	1.5 nM	US-10004755: Therapeutic uses of selected pyrrolopyrimidine compounds with anti-mer tyrosine kinase activity
Staurosporine	KD	1.7 nM
4-[5-[4-(azepan-4-ylamino)phenyl]-2-(butylamino)pyrrolo[2,3-d]pyrimidin-7-yl]cyclohexan-1-ol	IC50	2 nM	US-10004755: Therapeutic uses of selected pyrrolopyrimidine compounds with anti-mer tyrosine kinase activity
4-[2-(4-hydroxybutylamino)-5-[4-[(4-methylpiperazin-1-yl)methyl]phenyl]pyrrolo[2,3-d]pyrimidin-7-yl]cyclohexan-1-ol	IC50	2.1 nM	US-10004755: Therapeutic uses of selected pyrrolopyrimidine 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-(butylamino)-5-[4-[(4-methyl-1,4-diazepan-1-yl)methyl]phenyl]pyrrolo[2,3-d]pyrimidin-7-yl]cyclohexan-1-ol	IC50	3 nM	US-10004755: Therapeutic uses of selected pyrrolopyrimidine 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-hydroxybutylamino)-5-[4-(morpholin-4-ylmethyl)phenyl]pyrrolo[2,3-d]pyrimidin-7-yl]cyclohexan-1-ol	IC50	3.3 nM	US-10004755: Therapeutic uses of selected pyrrolopyrimidine 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-[2-(butylamino)-5-[4-(piperidin-4-ylamino)phenyl]pyrrolo[2,3-d]pyrimidin-7-yl]cyclohexan-1-ol	IC50	5 nM	US-10004755: Therapeutic uses of selected pyrrolopyrimidine 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
4-[2-(butylamino)-5-[4-[(1-methylpiperidin-4-yl)amino]phenyl]pyrrolo[2,3-d]pyrimidin-7-yl]cyclohexan-1-ol	IC50	5.3 nM	US-10004755: Therapeutic uses of selected pyrrolopyrimidine 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
N-[4-(4-amino-7-methylpyrrolo[2,1-f][1,2,4]triazin-5-yl)-3-fluorophenyl]-1-(4-fluorophenyl)-2-oxopyridine-3-carboxamide	IC50	7.5 nM	US-9981975: Pyrrolotriazine compounds as tam inhibitors
N-[4-[4-amino-7-(oxan-4-yl)pyrrolo[2,1-f][1,2,4]triazin-5-yl]phenyl]-2-oxo-1-phenylpyridine-3-carboxamide	IC50	7.5 nM	US-9981975: Pyrrolotriazine compounds as tam inhibitors
N-[4-[4-amino-7-(1-methylpiperidin-4-yl)pyrrolo[2,1-f][1,2,4]triazin-5-yl]phenyl]-2-oxo-1-phenylpyridine-3-carboxamide	IC50	7.5 nM	US-9981975: Pyrrolotriazine compounds as tam inhibitors
methyl 4-[4-amino-5-[4-[(2-oxo-1-phenylpyridine-3-carbonyl)amino]phenyl]pyrrolo[2,1-f][1,2,4]triazin-7-yl]piperidine-1-carboxylate	IC50	7.5 nM	US-9981975: Pyrrolotriazine compounds as tam inhibitors
N-[4-[4-amino-7-(1-methylsulfonylpiperidin-4-yl)pyrrolo[2,1-f][1,2,4]triazin-5-yl]phenyl]-2-oxo-1-phenylpyridine-3-carboxamide	IC50	7.5 nM	US-9981975: Pyrrolotriazine compounds as tam inhibitors
N-[4-[4-amino-7-[1-(2-methoxyethyl)piperidin-4-yl]pyrrolo[2,1-f][1,2,4]triazin-5-yl]phenyl]-2-oxo-1-phenylpyridine-3-carboxamide	IC50	7.5 nM	US-9981975: Pyrrolotriazine compounds as tam inhibitors
N-[4-[4-amino-7-[1-[ethyl(methyl)carbamoyl]piperidin-4-yl]pyrrolo[2,1-f][1,2,4]triazin-5-yl]phenyl]-1-(4-fluorophenyl)-2-oxopyridine-3-carboxamide	IC50	7.5 nM	US-9981975: Pyrrolotriazine compounds as tam inhibitors
N-[4-[4-amino-7-[1-[ethyl(methyl)carbamoyl]piperidin-4-yl]pyrrolo[2,1-f][1,2,4]triazin-5-yl]phenyl]-1-(4-fluorophenyl)-2,5-dioxo-7,8-dihydro-6H-quinoline-3-carboxamide	IC50	7.5 nM	US-9981975: Pyrrolotriazine compounds as tam inhibitors
N-[4-[4-amino-7-[1-[ethyl(methyl)carbamoyl]piperidin-4-yl]pyrrolo[2,1-f][1,2,4]triazin-5-yl]-3-fluorophenyl]-1-(4-fluorophenyl)-2,5-dioxo-7,8-dihydro-6H-quinoline-3-carboxamide	IC50	7.5 nM	US-9981975: Pyrrolotriazine compounds as tam inhibitors
N-[4-[4-amino-7-[1-(2-hydroxyethyl)piperidin-4-yl]pyrrolo[2,1-f][1,2,4]triazin-5-yl]-3-fluorophenyl]-1-(4-fluorophenyl)-2,5-dioxo-7,8-dihydro-6H-quinoline-3-carboxamide	IC50	7.5 nM	US-9981975: Pyrrolotriazine compounds as tam inhibitors
N-[4-[4-amino-7-[1-[ethyl(methyl)carbamoyl]piperidin-4-yl]pyrrolo[2,1-f][1,2,4]triazin-5-yl]phenyl]-3-(4-fluorophenyl)-2,4-dioxo-1-propan-2-yl-1,3-diazinane-5-carboxamide	IC50	7.5 nM	US-9981975: Pyrrolotriazine compounds as tam inhibitors
N-[4-[4-amino-7-[1-[ethyl(methyl)carbamoyl]piperidin-4-yl]pyrrolo[2,1-f][1,2,4]triazin-5-yl]phenyl]-3-(2-fluorophenyl)-2,4-dioxo-1-propan-2-yl-1,3-diazinane-5-carboxamide	IC50	7.5 nM	US-9981975: Pyrrolotriazine compounds as tam inhibitors
N-[4-[4-amino-7-[1-(2-methylpropanoyl)piperidin-4-yl]pyrrolo[2,1-f][1,2,4]triazin-5-yl]phenyl]-3-(3-fluorophenyl)-2,4-dioxo-1-propan-2-yl-1,3-diazinane-5-carboxamide	IC50	7.5 nM	US-9981975: Pyrrolotriazine compounds as tam inhibitors
N-[4-[4-amino-7-[1-(dimethylcarbamoyl)piperidin-4-yl]pyrrolo[2,1-f][1,2,4]triazin-5-yl]phenyl]-1-ethyl-3-(3-fluorophenyl)-2,4-dioxo-1,3-diazinane-5-carboxamide	IC50	7.5 nM	US-9981975: Pyrrolotriazine compounds as tam inhibitors
N-[4-[4-amino-7-[1-(2-methylpropanoyl)piperidin-4-yl]pyrrolo[2,1-f][1,2,4]triazin-5-yl]phenyl]-1-ethyl-3-(3-fluorophenyl)-2,4-dioxo-1,3-diazinane-5-carboxamide	IC50	7.5 nM	US-9981975: Pyrrolotriazine compounds as tam inhibitors
N-[4-[4-amino-7-[1-(2-methylpropanoyl)piperidin-4-yl]pyrrolo[2,1-f][1,2,4]triazin-5-yl]phenyl]-3-(2,5-difluorophenyl)-2,4-dioxo-1-propan-2-yl-1,3-diazinane-5-carboxamide	IC50	7.5 nM	US-9981975: Pyrrolotriazine compounds as tam inhibitors
N-[4-[4-amino-7-[1-(cyclopropanecarbonyl)piperidin-4-yl]pyrrolo[2,1-f][1,2,4]triazin-5-yl]phenyl]-1-(2-hydroxypropyl)-2,4-dioxo-3-phenyl-1,3-diazinane-5-carboxamide	IC50	7.5 nM	US-9981975: Pyrrolotriazine compounds as tam inhibitors
N-[4-[4-amino-7-[1-(cyclopropanecarbonyl)azetidin-3-yl]pyrrolo[2,1-f][1,2,4]triazin-5-yl]phenyl]-2,4-dioxo-3-phenyl-1-propan-2-yl-1,3-diazinane-5-carboxamide	IC50	7.5 nM	US-9981975: Pyrrolotriazine compounds as tam inhibitors
N-[4-[4-amino-7-[1-(2-methylpropanoyl)piperidin-4-yl]pyrrolo[2,1-f][1,2,4]triazin-5-yl]phenyl]-6-methyl-5-(2-methylpyrazol-3-yl)-4-oxo-1-propan-2-ylpyridine-3-carboxamide	IC50	7.5 nM	US-9981975: Pyrrolotriazine compounds as tam inhibitors
N-[4-[4-amino-7-[1-(2-methylpropanoyl)piperidin-4-yl]pyrrolo[2,1-f][1,2,4]triazin-5-yl]phenyl]-6-(6-methyl-3-pyridinyl)-2-oxo-1-phenylpyridine-3-carboxamide	IC50	7.5 nM	US-9981975: Pyrrolotriazine compounds as tam inhibitors
N-[4-[4-amino-7-[1-(2-methylpropanoyl)piperidin-4-yl]pyrrolo[2,1-f][1,2,4]triazin-5-yl]phenyl]-6-methyl-5-(1-methylpyrazol-4-yl)-2-oxo-1-phenylpyridine-3-carboxamide	IC50	7.5 nM	US-9981975: Pyrrolotriazine compounds as tam inhibitors

ChEMBL bioactivities

2975 potent at pChembl≥5 of 3094 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.00	IC50	0.1	nM	CHEMBL6151959
9.92	IC50	0.12	nM	CHEMBL5774701
9.82	IC50	0.15	nM	CHEMBL2036807
9.72	Ki	0.19	nM	CHEMBL4877347
9.70	IC50	0.2	nM	CHEMBL6163959
9.70	IC50	0.2	nM	CHEMBL6170266
9.70	IC50	0.2	nM	CHEMBL6146201
9.60	IC50	0.25	nM	CHEMBL2036806
9.57	Kd	0.27	nM	FORETINIB
9.54	IC50	0.29	nM	CHEMBL6048647
9.52	IC50	0.3	nM	CHEMBL6048647
9.52	IC50	0.3	nM	CHEMBL5916811
9.52	IC50	0.3	nM	CHEMBL6172586
9.52	IC50	0.3	nM	CHEMBL6173640
9.52	IC50	0.3	nM	CHEMBL6161683
9.48	Ki	0.33	nM	CHEMBL3326002
9.44	IC50	0.36	nM	CHEMBL5825584
9.40	IC50	0.4	nM	CHEMBL5542282
9.40	IC50	0.4	nM	CHEMBL6171026
9.40	IC50	0.4	nM	CHEMBL6176439
9.38	IC50	0.42	nM	CHEMBL5756274
9.37	Ki	0.43	nM	CHEMBL4283353
9.37	IC50	0.43	nM	CHEMBL6001325
9.34	IC50	0.46	nM	CHEMBL3326006
9.33	IC50	0.47	nM	CHEMBL5753009
9.31	IC50	0.49	nM	CHEMBL5874094
9.30	IC50	0.5	nM	CHEMBL6166016
9.30	IC50	0.5	nM	CHEMBL6166548
9.30	IC50	0.5	nM	CABOZANTINIB
9.30	IC50	0.5	nM	GLESATINIB
9.30	IC50	0.5	nM	MERESTINIB
9.28	IC50	0.52	nM	CHEMBL6176437
9.27	IC50	0.54	nM	CHEMBL5783827
9.25	Ki	0.56	nM	CHEMBL2036807
9.25	IC50	0.56	nM	CHEMBL5748457
9.24	IC50	0.57	nM	CHEMBL3326004
9.22	IC50	0.6	nM	CHEMBL4283353
9.22	IC50	0.6	nM	CHEMBL6165211
9.22	IC50	0.6	nM	CHEMBL5879666
9.21	IC50	0.61	nM	CHEMBL5851446
9.20	IC50	0.63	nM	CHEMBL5965646
9.17	IC50	0.67	nM	CHEMBL5798152
9.16	IC50	0.69	nM	CHEMBL3092795
9.16	IC50	0.69	nM	CHEMBL3092793
9.16	IC50	0.69	nM	CHEMBL5777271
9.16	IC50	0.69	nM	CHEMBL5767338
9.15	IC50	0.7	nM	CHEMBL3092792
9.15	IC50	0.7	nM	CHEMBL5558074
9.15	IC50	0.7	nM	CHEMBL6172030
9.14	Ki	0.73	nM	CHEMBL2036806

PubChem BioAssay actives

647 with measured affinity, of 1625 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
1-[(4-aminocyclohexyl)methyl]-N-(3-phenylpropyl)-3-(4-piperazin-1-ylphenyl)pyrazolo[3,4-d]pyrimidin-6-amine	663570: Inhibition of Mer expressed in Escherichia coli BL21 (DE3) cells using EFPIYDFLPAKKK-CONH2 as substrate after 180 mins by microfluid capillary electrophoresis assay	ic50	0.0001	uM
(2,6-dimethyl-4-pyridinyl)-[4-[7-(4-hydroxycyclohexyl)-2-[[(2S)-pentan-2-yl]amino]pyrrolo[2,3-d]pyrimidin-5-yl]piperidin-1-yl]methanone	1779143: ATP competitive inhibition of MERTK (unknown origin)	ki	0.0002	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	624767: Binding constant for MERTK kinase domain	kd	0.0003	uM
1-[(4-aminocyclohexyl)methyl]-N-butyl-3-(4-piperazin-1-ylphenyl)pyrazolo[3,4-d]pyrimidin-6-amine	663570: Inhibition of Mer expressed in Escherichia coli BL21 (DE3) cells using EFPIYDFLPAKKK-CONH2 as substrate after 180 mins by microfluid capillary electrophoresis assay	ic50	0.0003	uM
4-[6-(butylamino)-3-(4-morpholin-4-ylsulfonylphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]cyclohexan-1-ol	1185881: Inhibition of Mer (unknown origin) by Off-chip Mobility Shift Assay	ki	0.0003	uM
4-[5-[4-[(4-methyl-1,4-diazepan-1-yl)methyl]phenyl]-2-[[(2S)-pentan-2-yl]amino]pyrrolo[2,3-d]pyrimidin-7-yl]cyclohexan-1-ol	1409231: Inhibition of MERTK (unknown origin) using 5’-FAM-EFPIYDFLPAKKK-CONH2 as substrate after 180 mins by MCE assay	ki	0.0004	uM
N-[4-[5-(4-acetamidophenyl)-6-(1-methylpyrazol-4-yl)furo[2,3-d]pyrimidin-4-yl]oxyphenyl]-1-(4-fluorophenyl)-2-oxopyridine-3-carboxamide	2065914: Inhibition of MER (unknown origin) expressed in mouse BaF3 cells co-expressing TMEM assessed as inhibition of MER-driven cell proliferation incubated for 72 hrs by MTS assay	ic50	0.0004	uM
4-[2-(butylamino)-5-[4-[(4-methylpiperazin-1-yl)methyl]phenyl]pyrrolo[2,3-d]pyrimidin-7-yl]cyclohexan-1-ol	1409253: Inhibition of N-terminal GST-tagged human MERTK cytoplasmic domain (528 to 999 end residues) expressed in baculovirus expression system using fluorecence-labeled substrate by MCE assay	ic50	0.0005	uM
4-[2-(butylamino)-5-[3-fluoro-4-(4-methylpiperazin-1-yl)sulfonylphenyl]pyrrolo[2,3-d]pyrimidin-7-yl]cyclohexan-1-ol	1185881: Inhibition of Mer (unknown origin) by Off-chip Mobility Shift Assay	ic50	0.0006	uM
1-(4-fluorophenyl)-N-[4-[5-[4-(4-methylpiperazin-1-yl)phenyl]-6-(1-methylpyrazol-4-yl)furo[2,3-d]pyrimidin-4-yl]oxyphenyl]-2-oxopyridine-3-carboxamide	2065914: Inhibition of MER (unknown origin) expressed in mouse BaF3 cells co-expressing TMEM assessed as inhibition of MER-driven cell proliferation incubated for 72 hrs by MTS assay	ic50	0.0007	uM
4-[[2-(butylamino)-5-(5-morpholin-4-ylsulfonyl-2-pyridinyl)pyrimidin-4-yl]amino]cyclohexan-1-ol	1058166: Inhibition of Mer kinase (unknown origin) using 5-FAM-EFPIYDFLPAKKK-CONH2 as substrate after 180 mins by microfluidic capillary electrophoresis assay	ic50	0.0007	uM
6-[2-(butylamino)-4-[(4-hydroxycyclohexyl)amino]pyrimidin-5-yl]-N-(1-methylpiperidin-4-yl)pyridine-3-carboxamide	1058166: Inhibition of Mer kinase (unknown origin) using 5-FAM-EFPIYDFLPAKKK-CONH2 as substrate after 180 mins by microfluidic capillary electrophoresis assay	ic50	0.0007	uM
4-[[2-(butylamino)-5-[5-[(cyclohexylamino)methyl]-2-pyridinyl]pyrimidin-4-yl]amino]cyclohexan-1-ol	1058166: Inhibition of Mer kinase (unknown origin) using 5-FAM-EFPIYDFLPAKKK-CONH2 as substrate after 180 mins by microfluidic capillary electrophoresis assay	ic50	0.0007	uM
(6S)-6-amino-22-[4-[(4-methylpiperazin-1-yl)methyl]phenyl]-1,8,17,19,25-pentazatricyclo[16.5.2.021,24]pentacosa-18,20,22,24-tetraen-7-one	1325797: Inhibition of MerTK (unknown origin) by microfluidic capillary electrophoresis assay	ic50	0.0008	uM
N-[2-(3-cyclopentylpropoxy)pyrimidin-5-yl]-6-methoxy-7-(3-piperidin-1-ylpropoxy)quinazolin-4-amine	1733270: Inhibition of 6His/thrombin cleavage site-fused Avi-tagged dephosphorylated MER (unknown origin) (R528 to M999 residues) using Axltide (CKKSRGDYMTMQJG-acid) peptide as substrate preincubated for 30 mins followed by substrate and ATP addition at Km concentration measured after 120 mins by RapidFire LC-MS analysis	ic50	0.0008	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	2065915: Inhibition of MER (unknown origin) by KINOMEScan assay	ic50	0.0008	uM
1-[(4-aminocyclohexyl)methyl]-N-(3-phenylpropyl)-3-(6-piperazin-1-yl-3-pyridinyl)pyrazolo[3,4-d]pyrimidin-6-amine	663570: Inhibition of Mer expressed in Escherichia coli BL21 (DE3) cells using EFPIYDFLPAKKK-CONH2 as substrate after 180 mins by microfluid capillary electrophoresis assay	ic50	0.0008	uM
4-[[2-(butylamino)-5-[5-[(2-hydroxyethylamino)methyl]-2-pyridinyl]pyrimidin-4-yl]amino]cyclohexan-1-ol	1058166: Inhibition of Mer kinase (unknown origin) using 5-FAM-EFPIYDFLPAKKK-CONH2 as substrate after 180 mins by microfluidic capillary electrophoresis assay	ic50	0.0008	uM
(2,6-dimethyl-4-pyridinyl)-[4-[2-[[(1S,2S)-2-ethylcyclopropyl]amino]-7-(4-hydroxycyclohexyl)pyrrolo[2,3-d]pyrimidin-5-yl]piperidin-1-yl]methanone	1779115: Inhibition of MERTK (unknown origin)	ic50	0.0009	uM
1-cyclopropyl-3-[5-[6-(morpholin-4-ylmethyl)-1H-benzimidazol-2-yl]-1H-pyrazol-4-yl]urea	412602: Inhibition of Mer	ic50	0.0010	uM
N-[4-[5-(3-acetamidophenyl)-6-(1-methylpyrazol-4-yl)furo[2,3-d]pyrimidin-4-yl]oxyphenyl]-1-(4-fluorophenyl)-2-oxopyridine-3-carboxamide	2065914: Inhibition of MER (unknown origin) expressed in mouse BaF3 cells co-expressing TMEM assessed as inhibition of MER-driven cell proliferation incubated for 72 hrs by MTS assay	ic50	0.0010	uM
(10Z)-N-[4-[2-(diethylamino)ethylcarbamoyl]cyclohexyl]-15-methyl-13-oxa-2,6,8,19-tetrazatricyclo[12.3.1.13,7]nonadeca-1(18),3(19),4,6,10,14,16-heptaene-4-carboxamide	2082949: Inhibition of MERTK (unknown origin) expressed in HEK293 cells by MCE assay	ic50	0.0011	uM
4-[[2-(butylamino)-5-[5-[(4,4-difluoropiperidin-1-yl)methyl]-2-pyridinyl]pyrimidin-4-yl]amino]cyclohexan-1-ol	1058166: Inhibition of Mer kinase (unknown origin) using 5-FAM-EFPIYDFLPAKKK-CONH2 as substrate after 180 mins by microfluidic capillary electrophoresis assay	ic50	0.0011	uM
4-[2-[[(2S)-pentan-2-yl]amino]-5-(2-piperazin-1-yl-4-pyridinyl)pyrrolo[2,3-d]pyrimidin-7-yl]cyclohexan-1-ol	1409231: Inhibition of MERTK (unknown origin) using 5’-FAM-EFPIYDFLPAKKK-CONH2 as substrate after 180 mins by MCE assay	ic50	0.0012	uM
[4-[2-(butylamino)-7-(4-hydroxycyclohexyl)pyrrolo[2,3-d]pyrimidin-5-yl]piperidin-1-yl]-(2,6-dimethyl-4-pyridinyl)methanone	1779115: Inhibition of MERTK (unknown origin)	ic50	0.0012	uM
[4-[7-(4-hydroxycyclohexyl)-2-[[(2S)-pentan-2-yl]amino]pyrrolo[2,3-d]pyrimidin-5-yl]piperidin-1-yl]-(2-methyl-4-pyridinyl)methanone	1779115: Inhibition of MERTK (unknown origin)	ic50	0.0012	uM
1-(4-fluorophenyl)-N-[4-[5-[3-(methylamino)phenyl]-6-(1-methylpyrazol-4-yl)furo[2,3-d]pyrimidin-4-yl]oxyphenyl]-2-oxopyridine-3-carboxamide	2065914: Inhibition of MER (unknown origin) expressed in mouse BaF3 cells co-expressing TMEM assessed as inhibition of MER-driven cell proliferation incubated for 72 hrs by MTS assay	ic50	0.0012	uM
N-[4-[5-(4-aminophenyl)-6-(1-methylpyrazol-4-yl)furo[2,3-d]pyrimidin-4-yl]oxyphenyl]-1-(4-fluorophenyl)-2-oxopyridine-3-carboxamide	2065914: Inhibition of MER (unknown origin) expressed in mouse BaF3 cells co-expressing TMEM assessed as inhibition of MER-driven cell proliferation incubated for 72 hrs by MTS assay	ic50	0.0012	uM
4-[2-(butylamino)-5-[4-[1-(4-methylpiperazin-1-yl)cyclopropyl]phenyl]pyrrolo[2,3-d]pyrimidin-7-yl]cyclohexan-1-ol	1409231: Inhibition of MERTK (unknown origin) using 5’-FAM-EFPIYDFLPAKKK-CONH2 as substrate after 180 mins by MCE assay	ic50	0.0013	uM
[4-[7-(4-hydroxycyclohexyl)-2-[[(2S)-pentan-2-yl]amino]pyrrolo[2,3-d]pyrimidin-5-yl]piperidin-1-yl]-pyridin-4-ylmethanone	1779115: Inhibition of MERTK (unknown origin)	ic50	0.0013	uM
4-[[2-(butylamino)-5-[5-[(cyclopropylamino)methyl]-2-pyridinyl]pyrimidin-4-yl]amino]cyclohexan-1-ol	1058166: Inhibition of Mer kinase (unknown origin) using 5-FAM-EFPIYDFLPAKKK-CONH2 as substrate after 180 mins by microfluidic capillary electrophoresis assay	ic50	0.0013	uM
4-[2-(2-cyclopropylethylamino)-5-[4-[(4-methylpiperazin-1-yl)methyl]phenyl]pyrrolo[2,3-d]pyrimidin-7-yl]cyclohexan-1-ol	1185881: Inhibition of Mer (unknown origin) by Off-chip Mobility Shift Assay	ic50	0.0013	uM
N-[4-(6,7-dimethoxyquinazolin-4-yl)oxy-3-fluorophenyl]-6-ethyl-1,2-dimethyl-4-oxoquinoline-3-carboxamide	1626967: Binding affinity to human MER	kd	0.0014	uM
(2,6-dimethyl-4-pyridinyl)-[4-[2-[[(1R,2R)-2-ethylcyclopropyl]amino]-7-(4-hydroxycyclohexyl)pyrrolo[2,3-d]pyrimidin-5-yl]piperidin-1-yl]methanone	1779115: Inhibition of MERTK (unknown origin)	ic50	0.0015	uM
[4-[7-(4-hydroxycyclohexyl)-2-[[(2S)-pentan-2-yl]amino]pyrrolo[2,3-d]pyrimidin-5-yl]piperidin-1-yl]-[(3S)-1-methylpiperidin-3-yl]methanone	1779115: Inhibition of MERTK (unknown origin)	ic50	0.0016	uM
4-[4-[5-[imidazo[1,2-a]pyridin-6-ylmethyl(methyl)amino]-1,3,4-oxadiazol-2-yl]-3-methylphenyl]-1,3-dimethylpyrazole-5-carbonitrile	1768943: Inhibition of MER (unknown origin) by LC-MS analysis	ic50	0.0016	uM
1-(4-fluorophenyl)-N-[4-[6-(1-methylpyrazol-4-yl)-5-(4-piperazin-1-ylphenyl)furo[2,3-d]pyrimidin-4-yl]oxyphenyl]-2-oxopyridine-3-carboxamide	2065914: Inhibition of MER (unknown origin) expressed in mouse BaF3 cells co-expressing TMEM assessed as inhibition of MER-driven cell proliferation incubated for 72 hrs by MTS assay	ic50	0.0016	uM
N-[4-[5-[4-[(dimethylamino)methyl]phenyl]-6-(1-methylpyrazol-4-yl)furo[2,3-d]pyrimidin-4-yl]oxyphenyl]-1-(4-fluorophenyl)-2-oxopyridine-3-carboxamide	2065914: Inhibition of MER (unknown origin) expressed in mouse BaF3 cells co-expressing TMEM assessed as inhibition of MER-driven cell proliferation incubated for 72 hrs by MTS assay	ic50	0.0016	uM
1-(4-fluorophenyl)-N-[3-fluoro-4-[(3-phenyl-1H-pyrrolo[2,3-b]pyridin-4-yl)oxy]phenyl]-2,3-dimethyl-5-oxopyrazole-4-carboxamide	1733270: Inhibition of 6His/thrombin cleavage site-fused Avi-tagged dephosphorylated MER (unknown origin) (R528 to M999 residues) using Axltide (CKKSRGDYMTMQJG-acid) peptide as substrate preincubated for 30 mins followed by substrate and ATP addition at Km concentration measured after 120 mins by RapidFire LC-MS analysis	ic50	0.0016	uM
4-[2-(2-cyclopropylethylamino)-5-[2-fluoro-4-(4-methylpiperazin-1-yl)sulfonylphenyl]pyrrolo[2,3-d]pyrimidin-7-yl]cyclohexan-1-ol	1185881: Inhibition of Mer (unknown origin) by Off-chip Mobility Shift Assay	ic50	0.0016	uM
4-[[2-(butylamino)-5-[5-[(dimethylamino)methyl]-2-pyridinyl]pyrimidin-4-yl]amino]cyclohexan-1-ol	1058166: Inhibition of Mer kinase (unknown origin) using 5-FAM-EFPIYDFLPAKKK-CONH2 as substrate after 180 mins by microfluidic capillary electrophoresis assay	ic50	0.0017	uM
4-[[2-(butylamino)-5-[5-(morpholin-4-ylmethyl)-2-pyridinyl]pyrimidin-4-yl]amino]cyclohexan-1-ol	1058166: Inhibition of Mer kinase (unknown origin) using 5-FAM-EFPIYDFLPAKKK-CONH2 as substrate after 180 mins by microfluidic capillary electrophoresis assay	ic50	0.0017	uM
18-[4-[(4-methylpiperazin-1-yl)methyl]phenyl]-1,13,15,21-tetrazatricyclo[12.5.2.017,20]henicosa-14,16,18,20-tetraen-5-ol	1325797: Inhibition of MerTK (unknown origin) by microfluidic capillary electrophoresis assay	ic50	0.0018	uM
1-[(4-aminocyclohexyl)methyl]-N-butyl-3-(6-piperazin-1-yl-3-pyridinyl)pyrazolo[3,4-d]pyrimidin-6-amine	663570: Inhibition of Mer expressed in Escherichia coli BL21 (DE3) cells using EFPIYDFLPAKKK-CONH2 as substrate after 180 mins by microfluid capillary electrophoresis assay	ic50	0.0018	uM
4-N-(4-aminocyclohexyl)-2-N-butyl-5-pyridin-2-ylpyrimidine-2,4-diamine	1058166: Inhibition of Mer kinase (unknown origin) using 5-FAM-EFPIYDFLPAKKK-CONH2 as substrate after 180 mins by microfluidic capillary electrophoresis assay	ic50	0.0018	uM
[4-[7-(4-hydroxycyclohexyl)-2-[[(2S)-pentan-2-yl]amino]pyrrolo[2,3-d]pyrimidin-5-yl]piperidin-1-yl]-pyridazin-4-ylmethanone	1779115: Inhibition of MERTK (unknown origin)	ic50	0.0019	uM
4-[5-[4-(7-azabicyclo[2.2.1]heptan-7-ylmethyl)phenyl]-2-[[(2S)-pentan-2-yl]amino]pyrrolo[2,3-d]pyrimidin-7-yl]cyclohexan-1-ol	1409231: Inhibition of MERTK (unknown origin) using 5’-FAM-EFPIYDFLPAKKK-CONH2 as substrate after 180 mins by MCE assay	ic50	0.0020	uM
5-[4-(1,5-dimethylpyrazol-4-yl)-2-methylphenyl]-N-(imidazo[1,2-a]pyridin-6-ylmethyl)-N-methyl-1,3,4-oxadiazol-2-amine	1768943: Inhibition of MER (unknown origin) by LC-MS analysis	ic50	0.0020	uM
1-[(4-aminocyclohexyl)methyl]-3-(4-fluorophenyl)-N-(3-phenylpropyl)pyrazolo[3,4-d]pyrimidin-6-amine	663575: Inhibition of Mer using EFPIYDFLPAKKK-CONH2 as substrate by Michaelis-Menten equation	ki	0.0020	uM
N-[4-[5-(2-aminophenyl)-6-(1-methylpyrazol-4-yl)furo[2,3-d]pyrimidin-4-yl]oxyphenyl]-1-(4-fluorophenyl)-2-oxopyridine-3-carboxamide	2065914: Inhibition of MER (unknown origin) expressed in mouse BaF3 cells co-expressing TMEM assessed as inhibition of MER-driven cell proliferation incubated for 72 hrs by MTS assay	ic50	0.0021	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression	7
Benzo(a)pyrene	affects methylation, decreases expression, increases mutagenesis	4
Aflatoxin B1	increases methylation, decreases expression	3
trichostatin A	affects expression, decreases expression	2
sodium arsenite	decreases expression, increases expression	2
(+)-JQ1 compound	increases expression	2
Arsenic Trioxide	decreases expression, increases expression	2
Air Pollutants	increases abundance, increases expression	2
Cisplatin	affects expression, affects cotreatment, increases expression	2
Estradiol	affects cotreatment, increases expression, decreases expression, decreases reaction	2
Lipopolysaccharides	increases cleavage, affects response to substance, increases expression, affects cotreatment, decreases expression	2
Nickel	decreases expression	2
napabucasin	decreases expression	1
pirinixic acid	increases activity, increases expression, affects binding	1
2-methyl-4-isothiazolin-3-one	increases expression	1
arsenite	decreases reaction, affects binding	1
sodium bichromate	decreases expression	1
nickel chloride	decreases expression	1
perfluorooctanoic acid	increases expression	1
potassium chromate(VI)	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment, decreases expression	1
arsenic disulfide	decreases expression	1
perfluorooctane sulfonic acid	increases expression	1
CGP 52608	increases reaction, affects binding	1
2-palmitoylglycerol	increases expression	1
monomethylarsonous acid	increases expression	1
calix(6)arene	decreases expression	1
abrine	decreases expression	1
jinfukang	affects cotreatment, increases expression	1
NSC 689534	affects binding, increases expression	1

ChEMBL screening assays

443 unique, capped per target: 442 binding, 1 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3094763	Binding	Inhibition of EGF-induced human intracellular domain of Mer/extracellular domain of EGFR phosphorylation expressed in mouse 32D-EMC cells after 1 hr by Western blot analysis	Discovery of Mer specific tyrosine kinase inhibitors for the treatment and prevention of thrombosis. — J Med Chem
CHEMBL5209918	Functional	Affinity Phenotypic Cellular interaction (CellTiter-Glo assay (Promega, proliferation in H1703 cell line)) EUB0000147b MERTK	Affinity Phenotypic Cellular Literature for EUbOPEN Chemogenomics Library wave 3

Cellosaurus cell lines

13 cell lines: 8 cancer cell line, 3 induced pluripotent stem cell, 1 embryonic stem cell, 1 finite cell line

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

Cellosaurus	Name	Category	Sex
CVCL_A7IL	WAe009-A-39	Embryonic stem cell	Female
CVCL_B1WZ	Abcam HeLa MERTK KO	Cancer cell line	Female
CVCL_C7LK	GM27987	Finite cell line	Male
CVCL_D1XL	Abcam A-549 MERTK KO	Cancer cell line	Male
CVCL_D2BW	Abcam HCT 116 MERTK KO	Cancer cell line	Male
CVCL_D7UZ	Ubigene A-549 MERTK KO	Cancer cell line	Male
CVCL_SX83	HAP1 MERTK (-) 1	Cancer cell line	Male
CVCL_SX84	HAP1 MERTK (-) 2	Cancer cell line	Male
CVCL_SX85	HAP1 MERTK (-) 3	Cancer cell line	Male
CVCL_UL77	RCPFi003-A	Induced pluripotent stem cell	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00717080	PHASE4	COMPLETED	The Role of Capsular Tension Ring (CTR) in Anterior Capsular Contraction
NCT00000114	PHASE3	COMPLETED	Randomized Trial of Vitamin A and Vitamin E Supplementation for Retinitis Pigmentosa
NCT00000116	PHASE3	COMPLETED	Randomized Trial of DHA for Retinitis Pigmentosa Patients Receiving Vitamin A
NCT00346333	PHASE3	COMPLETED	Clinical Trial of Lutein for Patients With Retinitis Pigmentosa Receiving Vitamin A
NCT01786395	PHASE3	TERMINATED	Phase III Efficacy and Safety Clinical Study of UF-021 for Treatment of Retinitis Pigmentosa
NCT04224207	PHASE3	COMPLETED	Management of Retinitis Pigmentosa by Mesenchymal Stem Cells by Wharton’s Jelly Derived Mesenchymal Stem Cells
NCT04636853	PHASE3	COMPLETED	CB-PRP in Retinitis Pigmentosa and Dry Age-related Macular Degeneration
NCT05537220	PHASE3	ACTIVE_NOT_RECRUITING	Oral N-acetylcysteine for Retinitis Pigmentosa
NCT05800301	PHASE3	COMPLETED	Management of Retinitis Pigmentosa Via Combination of Wharton’s Jelly-derived Mesenchymal Stem Cells and Magnovision
NCT05926583	PHASE3	ACTIVE_NOT_RECRUITING	A Study of AAV5-hRKp.RPGR for the Treatment of Japanese Participants With X-linked Retinitis Pigmentosa
NCT06388200	PHASE3	ACTIVE_NOT_RECRUITING	A Phase 3 Study Of OCU400 Gene Therapy for the Treatment Of Retinitis Pigmentosa
NCT07082855	PHASE3	NOT_YET_RECRUITING	A Multicenter, Randomized, Double-Blind, Controlled Clinical Study of Minocycline for the Treatment of Retinitis Pigmentosa
NCT07290530	PHASE3	NOT_YET_RECRUITING	24-Month Trial of NPI-001 for the Preservation of Photoreceptors in Retinitis Pigmentosa Associated With Usher Syndrome
NCT00100230	PHASE2	COMPLETED	DHA and X-Linked Retinitis Pigmentosa
NCT00447980	PHASE2	COMPLETED	A Study of Encapsulated Cell Technology (ECT) Implant for Participants With Early Stage Retinitis Pigmentosa
NCT00447993	PHASE2	COMPLETED	A Study of Encapsulated Cell Technology (ECT) Implant for Patients With Late Stage Retinitis Pigmentosa
NCT01233609	PHASE2	COMPLETED	Trial of Oral Valproic Acid for Retinitis Pigmentosa
NCT01399515	PHASE2	COMPLETED	Efficacy and Safety of Oral Valproic Acid for Retinitis Pigmentosa
NCT01530659	PHASE2	COMPLETED	Retinal Imaging in CNTF -Releasing Encapsulated Cell Implant Treated Patients for Early-stage Retinitis Pigmentosa
NCT01560715	PHASE2	COMPLETED	Autologous Bone Marrow-Derived Stem Cells Transplantation For Retinitis Pigmentosa
NCT02609165	PHASE2	COMPLETED	Nerve Growth Factor Eye Drops Treatment in Patients With Retinitis Pigmentosa and Cystoid Macular Edema
NCT02661711	PHASE2	COMPLETED	Aflibercept for Macular Oedema With Underlying Retinitis Pigmentosa (AMOUR) Study
NCT02804360	PHASE2	UNKNOWN	Intravitreal Dexamethasone Implant in Retinitis Pigmentosa-related Macular Edema- a Retrospective Study
NCT02837640	PHASE2	UNKNOWN	Studying a Potential Protective Effect of L-Dopa on Retinitis Pigmentosa
NCT03073733	PHASE2	COMPLETED	Safety and Efficacy of Intravitreal Injection of Human Retinal Progenitor Cells in Adults With Retinitis Pigmentosa
NCT04068207	PHASE2	COMPLETED	Minocycline Treatment in Retinitis Pigmentosa
NCT04356716	PHASE2	COMPLETED	Sildenafil for Treatment of Choroidal Ischemia
NCT04604899	PHASE2	COMPLETED	Safety of Repeat Intravitreal Injection of Human Retinal Progenitor Cells (jCell) in Adult Subjects With Retinitis Pigmentosa
NCT04763369	PHASE2	UNKNOWN	Investigation of Therapeutic Efficacy and Safety of UMSCs for the Management of Retinitis Pigmentosa (RP)
NCT04864496	PHASE2	UNKNOWN	Effects of Treatment With N- Acetylcysteine on Visual Outcomes in Patients With Retinitis Pigmentosa
NCT04945772	PHASE2	COMPLETED	Efficacy and Safety of MCO-010 Optogenetic Therapy in Adults With Retinitis Pigmentosa [RESTORE]
NCT05085964	PHASE2	TERMINATED	An Open-Label Extension Study to Evaluate Safety & Tolerability of QR-421a in Subjects With Retinitis Pigmentosa
NCT05392179	PHASE2	COMPLETED	A Study in Subjects With Retinitis Pigmentosa
NCT06627179	PHASE2	RECRUITING	Study to Evaluate Ultevursen in Subjects With Retinitis Pigmentosa (RP) Due to Mutations in Exon 13 of the USH2A Gene
NCT06628947	PHASE2	RECRUITING	A Phase II Study of Intravitreal KIO-301 in Patients With Late-stage Retinitis Pigmentosa
NCT06912633	PHASE2	RECRUITING	Safety of a Single, Intravitreal Injection of 6.0M jCell (Famzeretcel) in Retinitis Pigmentosa (RP)
NCT03763227	PHASE2	COMPLETED	Intravitreal Ranibizumab (Lucentis®) in the Treatment of Non-leaking Macular Cysts in Retinal Dystrophy
NCT00063765	PHASE1	COMPLETED	Evaluation of Safety of Ciliary Neurotrophic Factor Implants in the Eye
NCT00065455	PHASE1	COMPLETED	Investigating the Effect of Vitamin A Supplementation on Retinitis Pigmentosa
NCT00458575	PHASE1	TERMINATED	A Study to Evaluate the Safety of CNTO 2476 in Patients With Advanced Retinitis Pigmentosa