TEK

Summary

TEK (TEK receptor tyrosine kinase, HGNC:11724) is a protein-coding gene on chromosome 9p21.2, encoding Angiopoietin-1 receptor (Q02763). Tyrosine-protein kinase that acts as a cell-surface receptor for ANGPT1, ANGPT2 and ANGPT4 and regulates angiogenesis, endothelial cell survival, proliferation, migration, adhesion and cell spreading, reorganization of the actin cytoskeleton, but also maintenance of vascular qui….

This gene encodes a receptor that belongs to the protein tyrosine kinase Tie2 family. The encoded protein possesses a unique extracellular region that contains two immunoglobulin-like domains, three epidermal growth factor (EGF)-like domains and three fibronectin type III repeats. The ligand angiopoietin-1 binds to this receptor and mediates a signaling pathway that functions in embryonic vascular development. Mutations in this gene are associated with inherited venous malformations of the skin and mucous membranes. Alternative splicing results in multiple transcript variants. Additional alternatively spliced transcript variants of this gene have been described, but their full-length nature is not known.

Source: NCBI Gene 7010 — RefSeq curated summary.

At a glance

• Gene–disease (curated): TEK-related primary glaucoma (Definitive, ClinGen) — +4 more curated relationships
• GWAS associations: 11
• Clinical variants (ClinVar): 494 total — 24 pathogenic, 34 likely-pathogenic
• Phenotypes (HPO): 37
• Druggable target: yes — 46 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_000459

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11724
Approved symbol	TEK
Name	TEK receptor tyrosine kinase
Location	9p21.2
Locus type	gene with protein product
Status	Approved
Aliases	TIE2, TIE-2, VMCM1, CD202b
Ensembl gene	ENSG00000120156
Ensembl biotype	protein_coding
OMIM	600221
Entrez	7010

Gene structure

Transcript identifiers

Ensembl transcripts: 33 — 33 protein_coding

ENST00000380036, ENST00000406359, ENST00000519080, ENST00000519097, ENST00000615002, ENST00000856712, ENST00000856713, ENST00000856714, ENST00000856715, ENST00000856716, ENST00000856717, ENST00000856718, ENST00000856719, ENST00000856720, ENST00000856721, ENST00000856722, ENST00000856723, ENST00000856724, ENST00000856725, ENST00000856726, ENST00000856727, ENST00000856728, ENST00000923266, ENST00000923267, ENST00000944990, ENST00000944991, ENST00000944992, ENST00000944993, ENST00000944994, ENST00000944995, ENST00000944996, ENST00000944997, ENST00000944998

RefSeq mRNA: 5 — MANE Select: NM_000459 NM_000459, NM_001290077, NM_001290078, NM_001375475, NM_001375476

CCDS: CCDS6519, CCDS75825, CCDS78389

Canonical transcript exons

ENST00000380036 — 23 exons

Exon	Start	End
ENSE00000813529	27168495	27168605
ENSE00000813530	27169477	27169629
ENSE00000813531	27172616	27172747
ENSE00000813532	27173222	27173362
ENSE00000813533	27180240	27180368
ENSE00001374032	27157831	27158142
ENSE00001599995	27218777	27218817
ENSE00001614493	27190529	27190690
ENSE00001617075	27213484	27213597
ENSE00001621003	27209121	27209231
ENSE00001621905	27185485	27185629
ENSE00001635180	27217688	27217758
ENSE00001637869	27197315	27197599
ENSE00001695490	27206582	27206792
ENSE00001711672	27202820	27203119
ENSE00001712731	27228206	27228305
ENSE00001720679	27220049	27220145
ENSE00001748389	27204911	27205065
ENSE00001749181	27183459	27183610
ENSE00001750035	27192489	27192623
ENSE00001797382	27212707	27212897
ENSE00001838203	27229158	27230174
ENSE00003850681	27109225	27109642

Expression profiles

Bgee: expression breadth ubiquitous, 223 present calls, max score 93.38.

FANTOM5 (CAGE): breadth broad, TPM avg 6.4768 / max 202.0684, expressed in 736 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
96360	2.2614	538
96358	1.6160	537
96361	1.5483	397
96357	0.7385	416
96359	0.0880	37
96362	0.0853	42
96363	0.0838	41
205451	0.0556	25

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lung	UBERON:0002167	93.38	gold quality
diaphragm	UBERON:0001103	92.20	gold quality
visceral pleura	UBERON:0002401	90.93	gold quality
type B pancreatic cell	CL:0000169	89.82	gold quality
lung	UBERON:0002048	89.49	gold quality
pleura	UBERON:0000977	88.72	gold quality
upper lobe of left lung	UBERON:0008952	88.58	gold quality
upper lobe of lung	UBERON:0008948	88.47	gold quality
oocyte	CL:0000023	88.38	gold quality
olfactory bulb	UBERON:0002264	88.31	gold quality
metanephros cortex	UBERON:0010533	88.16	gold quality
parietal pleura	UBERON:0002400	87.85	gold quality
secondary oocyte	CL:0000655	87.51	gold quality
lower lobe of lung	UBERON:0008949	87.06	gold quality
metanephros	UBERON:0000081	86.81	gold quality
subcutaneous adipose tissue	UBERON:0002190	85.62	gold quality
metanephric glomerulus	UBERON:0004736	85.58	gold quality
placenta	UBERON:0001987	85.39	gold quality
heart left ventricle	UBERON:0002084	85.00	gold quality
apex of heart	UBERON:0002098	84.94	gold quality
cardiac ventricle	UBERON:0002082	84.89	gold quality
left ventricle myocardium	UBERON:0006566	84.77	silver quality
omental fat pad	UBERON:0010414	84.70	gold quality
peritoneum	UBERON:0002358	84.65	gold quality
renal glomerulus	UBERON:0000074	84.48	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	84.46	gold quality
adipose tissue of abdominal region	UBERON:0007808	84.46	gold quality
heart right ventricle	UBERON:0002080	84.40	gold quality
calcaneal tendon	UBERON:0003701	84.22	gold quality
smooth muscle tissue	UBERON:0001135	84.19	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-GEOD-131882	yes	1987.07
E-CURD-119	yes	37.77
E-MTAB-6678	yes	13.04
E-MTAB-10137	yes	3.60
E-MTAB-8205	no	199.47
E-ANND-3	no	0.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

4 targets.

Target	Regulation
MYH1	Activation
MYH2	Activation
MYOD1	Activation
MYOG	Activation

Upstream regulators (CollecTRI, top): ELF1, ELF2, EPAS1, ESR1, ETV2, FLI1, FOXC1, GATA3, GATA5, HOXA13, MECOM

miRNA regulators (miRDB)

84 targeting TEK, 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-5011-5P	100.00	83.46	5820
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-4760-3P	99.93	70.50	2385
HSA-MIR-3682-5P	99.93	67.97	1163
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-1323	99.83	69.89	2471
HSA-MIR-139-5P	99.80	69.50	1399
HSA-MIR-448	99.79	72.37	2103
HSA-MIR-202-5P	99.78	67.65	991
HSA-MIR-4713-5P	99.78	67.80	1794
HSA-MIR-548AG	99.77	69.25	1492
HSA-MIR-2681-5P	99.75	67.64	1655
HSA-MIR-148A-3P	99.74	73.77	1700
HSA-MIR-148B-3P	99.74	73.75	1700
HSA-MIR-152-3P	99.74	73.75	1703
HSA-MIR-556-3P	99.74	68.75	1203
HSA-MIR-548O-3P	99.74	69.30	2228
HSA-MIR-12129	99.72	67.45	1311

Literature-anchored findings (GeneRIF, showing 40)

• Tie2 mRNA and protein were up-regulated in the pathogenesis of hemangioma. (PMID:11733376)
• Role of Tie2 in the differentiation of endothelial cells during angiogenesis. (PMID:11824375)
• Vascular endothelial growth factor modulates the Tie-2:Tie-1 receptor complex (PMID:11866538)
• expression of NERF2 was increased under hypoxia and that this increase temporally correlated with the increase in Tie2 expression. Hypoxia-induced expression of NERF2 and Tie2 was blocked by angiopoietin-2, a competitive inhibitor of angiopoietin-1 (PMID:11967990)
• results indicate that there is a difference in the Ang/Tie2 gene expression between physiological and pathological angiogenesis in the ovary. (PMID:12138242)
• expression and function of TIE2 in hematopoietic stem cells in cord blood (PMID:12419314)
• Endothelial Tie2 interacts with ABIN-2. (PMID:12609966)
• tyrosine residue 1106 on Tie2 is critical for coupling downstream cell migration signal transduction pathways with Angiopoietin 1 stimulation in endothelial cells (PMID:12665569)
• Shear stress activates Tie2 receptor tyrosine kinase in vascular endothelial cells. (PMID:12711329)
• comparison of the hematopoietic and angiogenic abilities of human cord blood CD34+TEK+ and CD34+TEK- cells using a clonogenic assay and xenotransplantation into immunodeficient NOD/SCID mice showing TEK plays a crucial role (PMID:12731667)
• Angiopoietin-1 is implicated in the maturation and remodeling of the vascular network during embryo development and in adult life through its tyrosine kinase receptor Tie-2 stimulates endothelial cells to migrate and change shape. (PMID:12816861)
• Tie2 up-regulation is associated with infiltrating breast carcinoma (PMID:12878859)
• presence of Tie-2 in human peripheral and autonomic nervous tissue, suggesting a role for Tie-2 in neural tissue. (PMID:12887596)
• Tie2 signaling is an important angiogenic mediator that links the proinflammatory cytokine TNF alpha to pathologic angiogenesis. (PMID:13130465)
• there is a novel interaction between Tie2 with the adapter molecule ShcA that may play a role in the regulation of migration and three-dimensional organization of endothelial cells induced by angiopoietin-1 (PMID:14665640)
• In advanced arteriosclerotic lesions, the activation of the Tie2-mediated STAT5 signaling pathway may negatively regulate vessel growth. (PMID:14726409)
• The autocrine/paracrine signaling of the Ang/Tie2 system is important for the up-regulated angiogenesis in the RA synovium, as well as for synoviocyte behavior, by regulating chemotactic cell movement. (PMID:14991531)
• Tie-2/Tek expression proved more sensitive than CD31 expression in terms of prognostic significance (PMID:14991534)
• Tie-2 signaling synergistically amplifies and participates in TNF-alpha-mediated angiogenesis. (PMID:15210451)
• Blocking Akt function abolishes angiopoietin 1 (Ang1), a ligand for Tie2, mediated EC survival, and activating Akt rescues a Tie2 blockade-induced EC apoptosis. (PMID:15242771)
• Angiopoetin-Tie2 autocrine pathway works in primary acute meylocytic leukemia cells or not by using soluble Tie2-Fc, which inhibits Angiopoietins from binding to Tie2 receptor. (PMID:15297853)
• The Ang-Tie2 system appears to have an autoregulatory feedback system that may be regulating the overall activity of the Tie2 system in both physiological and pathological conditions. (PMID:15370298)
• a mutation of glycine to aspartic acid at the second glycine of the GXGXXG motif of Tie2 (G833DTie2) in human intramuscular haemangiomas (IMHs) of the capillary type (PMID:15377998)
• angiopoietin 1 stimulates directed migration and possibly inhibits vascular endothelial growth factor-induced eosinophil chemotaxis via its Tie-2 receptor. (PMID:15536413)
• Ang1 has a role in lymphatic vessel endothelial proliferation, Tie2 expression, and VEGFR-3 upregulation (PMID:15746084)
• proper oligomerization of Ang1 having at least four subunits by the intermolecular disulfide linkage involving cysteines 41 and 54 is critical for Tie2 binding and activation (PMID:15769741)
• the isolated receptor-binding domain of Ang1 is capable of mediating some effects of full-length Ang1 independently of Tie2 phosphorylation, possibly through integrin ligation (PMID:15781448)
• Tie2 mediates internal translation initiation (PMID:15802272)
• sTie2 did not reduce goiter mass or vascular volume when used alone but was essential for complete goiter inhibition. (PMID:15817662)
• 2.4 A crystal structure of the Angiopoietin-2 (Ang2) receptor binding region was determined. (PMID:15893672)
• In a series of immunohistochemical analysis on human ovarian tissues, there was a unique localization of Tie-2 to the primary cilia of ovarian surface epithelium. (PMID:15893943)
• an important role for a PECAM1-SHP2-Tie2 pathway in flow-mediated signal transduction. (PMID:15985432)
• Tie-2 receptor is expressed by human neutrophils whose active site ligation with either angiopoietin-1 or angiopoietin-2 exerts migratory effects on the one hand and arrests VEGF-mediated chemotaxis on the other (PMID:16020388)
• sTie-2 increased significantly in the AMI patients; viability of HUVECs and tube formation area measured after stimulated with recombinant Tie-2/Fc chimera were observed to decrease, suggesting angiogenesis might be inhibited (PMID:16037627)
• activation of tie-2 receptors by Ang-1 triggers the production of ROS through activation of NADPH oxidase (PMID:16049136)
• Stable interaction between integrin alpha5beta1 and Tie2 receptor regulates endothelial cell response to Ang-1. (PMID:16157706)
• the uORFs within the Tie2 5’ UTR serve to decrease the percent of ribosomes competent for reinitiation as these traverse the mRNA 5’ UTR, thus minimizing interference with the internal ribosome entry site (PMID:16457819)
• Participation of down-regulated TIE-2 in the placental tissues may indicate a role for this angiogenic factor in the development of placenta accreta. (PMID:16458662)
• expression of Ang-1 and Ang-2 is important for gastric tumor angiogenesis, and a possible autocrine/paracrine function of the angiopoietin/Tie2 system is involved in gastric cancer progression (PMID:16614513)
• Results showed that Tie-2 mRNA and protein expression from the eutopic endometrium did not differ significantly between endometriosis patients and normal controls. (PMID:16723371)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	tek	ENSDARG00000028663
mus_musculus	Tek	ENSMUSG00000006386
rattus_norvegicus	Tek	ENSRNOG00000008587

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), FLT3 (ENSG00000122025), KDR (ENSG00000128052), EPHB2 (ENSG00000133216), PDGFRA (ENSG00000134853), EPHA7 (ENSG00000135333), IGF1R (ENSG00000140443), NTRK3 (ENSG00000140538), ERBB2 (ENSG00000141736), EPHA2 (ENSG00000142627), EPHA5 (ENSG00000145242), EGFR (ENSG00000146648), EPHA1 (ENSG00000146904), NTRK2 (ENSG00000148053), MERTK (ENSG00000153208), EPHB1 (ENSG00000154928), KIT (ENSG00000157404), FGFR4 (ENSG00000160867), DDR2 (ENSG00000162733), RYK (ENSG00000163785), MST1R (ENSG00000164078), LMTK2 (ENSG00000164715)

Protein

Protein identifiers

Angiopoietin-1 receptor — Q02763 (reviewed: Q02763)

Alternative names: Endothelial tyrosine kinase, Tunica interna endothelial cell kinase, Tyrosine kinase with Ig and EGF homology domains-2, Tyrosine-protein kinase receptor TEK, Tyrosine-protein kinase receptor TIE-2, p140 TEK

All UniProt accessions (3): B5A954, E5RIV9, Q02763

UniProt curated annotations — full annotation on UniProt →

Function. Tyrosine-protein kinase that acts as a cell-surface receptor for ANGPT1, ANGPT2 and ANGPT4 and regulates angiogenesis, endothelial cell survival, proliferation, migration, adhesion and cell spreading, reorganization of the actin cytoskeleton, but also maintenance of vascular quiescence. Has anti-inflammatory effects by preventing the leakage of pro-inflammatory plasma proteins and leukocytes from blood vessels. Required for normal angiogenesis and heart development during embryogenesis. Required for post-natal hematopoiesis. After birth, activates or inhibits angiogenesis, depending on the context. Inhibits angiogenesis and promotes vascular stability in quiescent vessels, where endothelial cells have tight contacts. In quiescent vessels, ANGPT1 oligomers recruit TEK to cell-cell contacts, forming complexes with TEK molecules from adjoining cells, and this leads to preferential activation of phosphatidylinositol 3-kinase and the AKT1 signaling cascades. In migrating endothelial cells that lack cell-cell adhesions, ANGT1 recruits TEK to contacts with the extracellular matrix, leading to the formation of focal adhesion complexes, activation of PTK2/FAK and of the downstream kinases MAPK1/ERK2 and MAPK3/ERK1, and ultimately to the stimulation of sprouting angiogenesis. ANGPT1 signaling triggers receptor dimerization and autophosphorylation at specific tyrosine residues that then serve as binding sites for scaffold proteins and effectors. Signaling is modulated by ANGPT2 that has lower affinity for TEK, can promote TEK autophosphorylation in the absence of ANGPT1, but inhibits ANGPT1-mediated signaling by competing for the same binding site. Signaling is also modulated by formation of heterodimers with TIE1, and by proteolytic processing that gives rise to a soluble TEK extracellular domain. The soluble extracellular domain modulates signaling by functioning as decoy receptor for angiopoietins. TEK phosphorylates DOK2, GRB7, GRB14, PIK3R1; SHC1 and TIE1.

Subunit / interactions. Homodimer. Heterodimer with TIE1. Interacts with ANGPT1, ANGPT2 and ANGPT4. At cell-cell contacts in quiescent cells, forms a signaling complex composed of ANGPT1 plus TEK molecules from two adjoining cells. In the absence of endothelial cell-cell contacts, interaction with ANGPT1 mediates contacts with the extracellular matrix. Interacts with PTPRB; this promotes endothelial cell-cell adhesion. Interacts with DOK2, GRB2, GRB7, GRB14, PIK3R1 and PTPN11/SHP2. Colocalizes with DOK2 at contacts with the extracellular matrix in migrating cells. Interacts (tyrosine phosphorylated) with TNIP2. Interacts (tyrosine phosphorylated) with SHC1 (via SH2 domain).

Subcellular location. Cell membrane. Cell junction. Focal adhesion. Cytoplasm. Cytoskeleton. Secreted.

Tissue specificity. Detected in umbilical vein endothelial cells. Proteolytic processing gives rise to a soluble extracellular domain that is detected in blood plasma (at protein level). Predominantly expressed in endothelial cells and their progenitors, the angioblasts. Has been directly found in placenta and lung, with a lower level in umbilical vein endothelial cells, brain and kidney.

Post-translational modifications. Proteolytic processing leads to the shedding of the extracellular domain (soluble TIE-2 alias sTIE-2). Autophosphorylated on tyrosine residues in response to ligand binding. Autophosphorylation occurs in trans, i.e. one subunit of the dimeric receptor phosphorylates tyrosine residues on the other subunit. Autophosphorylation occurs in a sequential manner, where Tyr-992 in the kinase activation loop is phosphorylated first, followed by autophosphorylation at Tyr-1108 and at additional tyrosine residues. ANGPT1-induced phosphorylation is impaired during hypoxia, due to increased expression of ANGPT2. Phosphorylation is important for interaction with GRB14, PIK3R1 and PTPN11. Phosphorylation at Tyr-1102 is important for interaction with SHC1, GRB2 and GRB7. Phosphorylation at Tyr-1108 is important for interaction with DOK2 and for coupling to downstream signal transduction pathways in endothelial cells. Dephosphorylated by PTPRB. Ubiquitinated. The phosphorylated receptor is ubiquitinated and internalized, leading to its degradation.

Disease relevance. Dominantly inherited venous malformations (VMCM) [MIM:600195] An error of vascular morphogenesis characterized by dilated, serpiginous channels. The disease is caused by variants affecting the gene represented in this entry. Somatic mutations of TEK are associated with solitary and multiple sporadic venous malformations. May play a role in a range of diseases with a vascular component, including neovascularization of tumors, psoriasis and inflammation. Glaucoma 3, primary congenital, E (GLC3E) [MIM:617272] An autosomal dominant form of primary congenital glaucoma (PCG). PCG is characterized by marked increase of intraocular pressure at birth or early childhood, large ocular globes (buphthalmos) and corneal edema. It results from developmental defects of the trabecular meshwork and anterior chamber angle of the eye that prevent adequate drainage of aqueous humor. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Angiopoietin binding leads to receptor dimerization and activation by autophosphorylation at Tyr-992 on the kinase activation loop. Inhibited by staurosporine, K252a, PP2, damnacanthal, SB203580, CEP-11207, CEP-11981 and CE-245677. Inhibited by triazine, thienopyrimidine and thiazolopyrimidine derivatives.

Domain organisation. The soluble extracellular domain is functionally active in angiopoietin binding and can modulate the activity of the membrane-bound form by competing for angiopoietins.

Similarity. Belongs to the protein kinase superfamily. Tyr protein kinase family. Tie subfamily.

Isoforms (3)

UniProt ID	Names	Canonical?
Q02763-1	1	yes
Q02763-2	2
Q02763-3	3

RefSeq proteins (5): NP_000450, NP_001277006, NP_001277007, NP_001362404, NP_001362405 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000719	Prot_kinase_dom	Domain
IPR000742	EGF	Domain
IPR001245	Ser-Thr/Tyr_kinase_cat_dom	Domain
IPR002049	LE_dom	Domain
IPR003961	FN3_dom	Domain
IPR007110	Ig-like_dom	Domain
IPR008266	Tyr_kinase_AS	Active_site
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR013783	Ig-like_fold	Homologous_superfamily
IPR017441	Protein_kinase_ATP_BS	Binding_site
IPR018941	Tyr_kin_Tie2_Ig-like_dom-1_N	Domain
IPR020635	Tyr_kinase_cat_dom	Domain
IPR036116	FN3_sf	Homologous_superfamily
IPR036179	Ig-like_dom_sf	Homologous_superfamily
IPR050122	RTK	Family

Pfam: PF00041, PF07714, PF10430

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 (180 total): strand 66, sequence variant 30, helix 25, disulfide bond 14, domain 9, glycosylation site 9, turn 6, modified residue 4, splice variant 3, mutagenesis site 3, sequence conflict 3, binding site 2, topological domain 2, signal peptide 1, chain 1, active site 1, transmembrane region 1

Structure

Experimental structures (PDB)

17 structures.

PDB	Method	Resolution (Å)
3BEA	X-RAY DIFFRACTION	2.02
6MWE	X-RAY DIFFRACTION	2.05
7E72	X-RAY DIFFRACTION	2.09
1FVR	X-RAY DIFFRACTION	2.2
2OO8	X-RAY DIFFRACTION	2.2
3L8P	X-RAY DIFFRACTION	2.4
2P4I	X-RAY DIFFRACTION	2.5
4X3J	X-RAY DIFFRACTION	2.5
5UTK	X-RAY DIFFRACTION	2.5
5MYB	X-RAY DIFFRACTION	2.6
9LV4	ELECTRON MICROSCOPY	2.67
2OSC	X-RAY DIFFRACTION	2.8
2GY5	X-RAY DIFFRACTION	2.9
5MYA	X-RAY DIFFRACTION	2.9
2WQB	X-RAY DIFFRACTION	2.95
2GY7	X-RAY DIFFRACTION	3.7
4K0V	X-RAY DIFFRACTION	4.51

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q02763-F1	84.37	0.50

Antibody-complex structures (SAbDab): 1 — 7E72

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): 964 (proton acceptor)

Ligand- & substrate-binding residues (2): 830–838; 855

Post-translational modifications (4): 860, 992, 1102, 1108

Disulfide bonds (14): 44–102, 211–220, 224–233, 227–240, 242–251, 255–264, 268–274, 280–287, 289–298, 302–311, 315–323, 317–329, 331–340, 370–424

Glycosylation sites (9): 140, 158, 399, 438, 464, 560, 596, 649, 691

Mutagenesis-validated functional residues (3):

Position	Phenotype
224	reduces protein abundance.
855	loss of kinase activity.
1102	abolishes interaction with shc1.

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-210993	Tie2 Signaling
R-HSA-5673001	RAF/MAP kinase cascade
R-HSA-109582	Hemostasis
R-HSA-162582	Signal Transduction
R-HSA-202733	Cell surface interactions at the vascular wall
R-HSA-5683057	MAPK family signaling cascades
R-HSA-5684996	MAPK1/MAPK3 signaling

MSigDB gene sets: 395 (showing top): PID_SHP2_PATHWAY, GOBP_CARDIAC_CHAMBER_DEVELOPMENT, MODULE_92, GOBP_ESTABLISHMENT_OR_MAINTENANCE_OF_CELL_POLARITY, HARRIS_HYPOXIA, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_HEART_TRABECULA_MORPHOGENESIS, GOBP_INFLAMMATORY_RESPONSE, GOBP_CARDIAC_CHAMBER_MORPHOGENESIS, GOBP_CELLULAR_RESPONSE_TO_EXTERNAL_STIMULUS, MODULE_64, GOBP_FOCAL_ADHESION_ASSEMBLY, GOBP_POSITIVE_REGULATION_OF_VASCULATURE_DEVELOPMENT, GOBP_POSITIVE_REGULATION_OF_RHO_PROTEIN_SIGNAL_TRANSDUCTION, GOBP_REGULATION_OF_SMALL_GTPASE_MEDIATED_SIGNAL_TRANSDUCTION

GO Biological Process (42): angiogenesis (GO:0001525), endothelial cell proliferation (GO:0001935), positive regulation of endothelial cell proliferation (GO:0001938), sprouting angiogenesis (GO:0002040), cell surface receptor signaling pathway (GO:0007166), cell surface receptor protein tyrosine kinase signaling pathway (GO:0007169), cell-cell signaling (GO:0007267), heart development (GO:0007507), positive regulation of endothelial cell migration (GO:0010595), negative regulation of angiogenesis (GO:0016525), regulation of establishment or maintenance of cell polarity (GO:0032878), substrate adhesion-dependent cell spreading (GO:0034446), positive regulation of Rac protein signal transduction (GO:0035022), positive regulation of Rho protein signal transduction (GO:0035025), negative regulation of apoptotic process (GO:0043066), regulation of vascular permeability (GO:0043114), positive regulation of MAPK cascade (GO:0043410), positive regulation of angiogenesis (GO:0045766), Tie signaling pathway (GO:0048014), negative regulation of inflammatory response (GO:0050728), positive regulation of focal adhesion assembly (GO:0051894), positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0051897), definitive hemopoiesis (GO:0060216), heart trabecula formation (GO:0060347), positive regulation of ERK1 and ERK2 cascade (GO:0070374), cellular response to mechanical stimulus (GO:0071260), glomerulus vasculature development (GO:0072012), positive regulation of intracellular signal transduction (GO:1902533), regulation of endothelial cell apoptotic process (GO:2000351), negative regulation of endothelial cell apoptotic process (GO:2000352), regulation of endothelial cell proliferation (GO:0001936), protein phosphorylation (GO:0006468), positive regulation of signal transduction (GO:0009967), hemopoiesis (GO:0030097), cell differentiation (GO:0030154), regulation of cell migration (GO:0030334), cell-substrate adhesion (GO:0031589), regulation of angiogenesis (GO:0045765), positive regulation of cell adhesion (GO:0045785), positive regulation of multicellular organismal process (GO:0051240)

GO Molecular Function (11): protein kinase activity (GO:0004672), transmembrane receptor protein tyrosine kinase activity (GO:0004714), ATP binding (GO:0005524), transmembrane receptor protein kinase activity (GO:0019199), signaling receptor activity (GO:0038023), identical protein binding (GO:0042802), nucleotide binding (GO:0000166), protein tyrosine kinase activity (GO:0004713), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (19): extracellular region (GO:0005576), centrosome (GO:0005813), plasma membrane (GO:0005886), microvillus (GO:0005902), cell-cell junction (GO:0005911), focal adhesion (GO:0005925), basal plasma membrane (GO:0009925), cell surface (GO:0009986), basolateral plasma membrane (GO:0016323), apical plasma membrane (GO:0016324), ciliary basal body (GO:0036064), signaling receptor complex (GO:0043235), membrane raft (GO:0045121), stress fiber (GO:0001725), cytoplasm (GO:0005737), cytoskeleton (GO:0005856), actin filament (GO:0005884), membrane (GO:0016020), anchoring junction (GO:0070161)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Cell surface interactions at the vascular wall	1
MAPK1/MAPK3 signaling	1
Hemostasis	1
Signal Transduction	1
MAPK family signaling cascades	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
angiogenesis	3
plasma membrane region	3
regulation of angiogenesis	2
positive regulation of small GTPase mediated signal transduction	2
protein kinase activity	2
microtubule organizing center	2
blood vessel morphogenesis	1
anatomical structure formation involved in morphogenesis	1
epithelial cell proliferation	1
endothelial cell proliferation	1
regulation of endothelial cell proliferation	1
positive regulation of epithelial cell proliferation	1
signal transduction	1
enzyme-linked receptor protein signaling pathway	1
cell communication	1
signaling	1
animal organ development	1
circulatory system development	1
regulation of endothelial cell migration	1
positive regulation of cell migration	1
endothelial cell migration	1
negative regulation of blood vessel morphogenesis	1
establishment or maintenance of cell polarity	1
regulation of cellular process	1
cell-substrate adhesion	1
Rac protein signal transduction	1
regulation of Rac protein signal transduction	1
Rho protein signal transduction	1
regulation of Rho protein signal transduction	1
apoptotic process	1
regulation of apoptotic process	1
negative regulation of programmed cell death	1
vascular process in circulatory system	1
blood circulation	1
regulation of biological quality	1
MAPK cascade	1
regulation of MAPK cascade	1
positive regulation of intracellular signal transduction	1
positive regulation of vasculature development	1

Protein interactions and networks

STRING

2546 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TEK	ANGPT2	O15123	999
TEK	ANGPT1	Q15389	999
TEK	ANGPT4	Q9Y264	995
TEK	VEGFC	P49767	873
TEK	ANGPTL3	Q9Y5C1	871
TEK	CDH5	P33151	870
TEK	ANGPTL1	O95841	847
TEK	ANGPTL2	Q9UKU9	842
TEK	TNIP2	Q8NFZ5	821
TEK	FGF2	P09038	806
TEK	CXCL12	P48061	806
TEK	PECAM1	P16284	794
TEK	THPO	P40225	794
TEK	PTPRB	P23467	787
TEK	KITLG	P21583	772

IntAct

58 interactions, top by confidence:

A	B	Type	Score
MAPK3	MAPK1	psi-mi:“MI:0914”(association)	0.770
ANGPT2	TEK	psi-mi:“MI:0407”(direct interaction)	0.740
TEK	ANGPT2	psi-mi:“MI:0407”(direct interaction)	0.740
ANGPT1	TEK	psi-mi:“MI:0915”(physical association)	0.720
TEK	ANGPT1	psi-mi:“MI:0407”(direct interaction)	0.720
ANGPT1	TEK	psi-mi:“MI:0407”(direct interaction)	0.720
TEK	ANGPT2	psi-mi:“MI:0407”(direct interaction)	0.620
ANGPT2	TEK	psi-mi:“MI:0407”(direct interaction)	0.620
SHC1	TEK	psi-mi:“MI:0914”(association)	0.460
TEK	Angpt1	psi-mi:“MI:0407”(direct interaction)	0.440
TEK	Angpt2	psi-mi:“MI:0407”(direct interaction)	0.440
Angpt4	TEK	psi-mi:“MI:0407”(direct interaction)	0.440
ANGPT4	TEK	psi-mi:“MI:0407”(direct interaction)	0.440
PKM	TEK	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
CYP1B1	TEK	psi-mi:“MI:0915”(physical association)	0.400
	TEK	psi-mi:“MI:0915”(physical association)	0.400
ILKAP	TEK	psi-mi:“MI:0915”(physical association)	0.370
PTPRR	TEK	psi-mi:“MI:0915”(physical association)	0.370
DUSP18	TEK	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (158): TEK (Reconstituted Complex), PTPN11 (Two-hybrid), PTPRR (Two-hybrid), PTK2 (Co-localization), AKT1 (Co-localization), ILKAP (Two-hybrid), DUSP18 (Two-hybrid), STYX (Two-hybrid), TEK (Biochemical Activity), CAV1 (Co-localization), CAV1 (Affinity Capture-Western), TEK (Affinity Capture-Western), CAV1 (Biochemical Activity), TEK (Affinity Capture-MS), SHC1 (Affinity Capture-Western)

ESM2 similar proteins: A0A1S4GGP7, B1Q236, B8V7Q1, B8VIW9, F1QSQ0, F8W3X3, G5EDK5, H2A0L8, O02466, O15943, O44386, O44730, P28827, P34616, P35822, P55289, P70408, Q02763, Q02858, Q03600, Q03763, Q06807, Q09165, Q15262, Q19319, Q24247, Q24298, Q5RJH3, Q60ZN5, Q61495, Q68SP4, Q6W3B0, Q7TMD7, Q7TSF0, Q7TSF1, Q86SJ6, Q86WI1, Q8JHW2, Q8VHN7, Q8WXG9

Diamond homologs: D2IYS2, G3V9H8, O08775, O42127, O73791, O73798, O97799, P00529, P00545, P04048, P05532, P05622, P07333, P07949, P09581, P09619, P10721, P11362, P13369, P16092, P16234, P17948, P18460, P18461, P20786, P21802, P21803, P21804, P22182, P22455, P22607, P23049, P26618, P26619, P33497, P35546, P35590, P35916, P35917, P35918

SIGNOR signaling

26 interactions.

A	Effect	B	Mechanism
ANGPT4	up-regulates	TEK	binding
ANGPTL1	up-regulates	TEK	binding
N-[[3-fluoro-4-[[2-(1-methyl-4-imidazolyl)-7-thieno[3,2-b]pyridinyl]oxy]anilino]-sulfanylidenemethyl]-2-phenylacetamide	down-regulates	TEK	“chemical inhibition”
4-[4-(6-methoxy-2-naphthalenyl)-2-(4-methylsulfinylphenyl)-1H-imidazol-5-yl]pyridine	down-regulates	TEK	“chemical inhibition”
TEK	“up-regulates activity”	SHC1	binding
regorafenib	“down-regulates activity”	TEK	“chemical inhibition”
TEK	“up-regulates activity”	TEK	phosphorylation
PTPRB	“down-regulates activity”	TEK	dephosphorylation
TEK	“up-regulates activity”	STAT1	phosphorylation
TEK	“up-regulates activity”	GRB14	phosphorylation
TEK	“up-regulates activity”	TIE1	phosphorylation
ANGPT1	up-regulates	TEK	binding
ANGPT2	up-regulates	TEK	binding
TEK	“up-regulates quantity by expression”	MYOD1	“transcriptional regulation”
TEK	“up-regulates quantity by expression”	MYOG	“transcriptional regulation”
TEK	“up-regulates quantity by expression”	MYH2	“transcriptional regulation”
TEK	“up-regulates quantity by expression”	MYH1	“transcriptional regulation”
MECOM	“up-regulates quantity by expression”	TEK	“transcriptional regulation”
TEK	“up-regulates activity”	PIK3R1	binding
TEK	“down-regulates activity”	TEK	phosphorylation
TEK	“up-regulates activity”	PI3K	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 29 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Tie2 Signaling	5	167.0×	2e-08
Hemostasis	7	14.0×	5e-05
Neutrophil degranulation	5	6.4×	3e-03

GO biological processes:

GO term	Partners	Fold	FDR
protein dephosphorylation	6	55.4×	3e-07
angiogenesis	7	18.2×	6e-06

Disease & clinical

Cancer significance

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	24
Likely pathogenic	34
Uncertain significance	204
Likely benign	59
Benign	123

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1074388	NM_000459.5(TEK):c.3062del (p.Val1021fs)	Pathogenic
1074588	NM_000459.5(TEK):c.3142dup (p.Tyr1048fs)	Pathogenic
1453468	NM_000459.5(TEK):c.1762C>T (p.Gln588Ter)	Pathogenic
1691346	NM_000459.5(TEK):c.2689T>C (p.Tyr897His)	Pathogenic
1701565	NM_000459.5(TEK):c.3314_3316delinsACC (p.Thr1105_Thr1106delinsAsnPro)	Pathogenic
1956797	NM_000459.5(TEK):c.1840C>T (p.Arg614Ter)	Pathogenic
2664276	NM_000459.5(TEK):c.3323_3324del (p.Leu1107_Tyr1108insTer)	Pathogenic
30053	NM_000459.5(TEK):c.2690A>G (p.Tyr897Cys)	Pathogenic
3340431	NM_000459.5(TEK):c.3338dup (p.Tyr1113Ter)	Pathogenic
3340457	NM_000459.5(TEK):c.3324T>G (p.Tyr1108Ter)	Pathogenic
3664064	NM_000459.5(TEK):c.1753A>T (p.Lys585Ter)	Pathogenic
374838	NM_000459.5(TEK):c.921C>A (p.Tyr307Ter)	Pathogenic
374839	NM_000459.5(TEK):c.448G>T (p.Glu150Ter)	Pathogenic
3774515	NM_000459.5(TEK):c.3339del (p.Thr1112_Tyr1113insTer)	Pathogenic
3774520	NM_000459.5(TEK):c.3339_3342del (p.Thr1112_Tyr1113insTer)	Pathogenic
4075488	NM_000459.5(TEK):c.3103G>C (p.Gly1035Arg)	Pathogenic
4279984	NM_000459.5(TEK):c.2690A>T (p.Tyr897Phe)	Pathogenic
4832968	NM_000459.5(TEK):c.412_413dup (p.Asn138fs)	Pathogenic
832541	NC_000009.12:g.(?27157831)(27220145_?)del	Pathogenic
9293	NM_000459.5(TEK):c.2545C>T (p.Arg849Trp)	Pathogenic
981229	NM_000459.5(TEK):c.2740C>T (p.Leu914Phe)	Pathogenic
981230	NM_000459.5(TEK):c.3295C>T (p.Arg1099Ter)	Pathogenic
981231	NM_000459.5(TEK):c.3324T>A (p.Tyr1108Ter)	Pathogenic
981232	NM_000459.5(TEK):c.3343G>T (p.Gly1115Ter)	Pathogenic
1066433	NM_000459.5(TEK):c.1624+2T>A	Likely pathogenic
1177292	NM_000459.5(TEK):c.3314_3315delinsTGACCT (p.Thr1105fs)	Likely pathogenic
1285387	NM_000459.5(TEK):c.3110C>A (p.Thr1037Lys)	Likely pathogenic
1285388	NM_000459.5(TEK):c.3118T>C (p.Cys1040Arg)	Likely pathogenic
1333305	NM_000459.5(TEK):c.1490-1G>A	Likely pathogenic
1333408	NM_000459.5(TEK):c.470_471insTGGT (p.Lys157fs)	Likely pathogenic

SpliceAI

3760 predictions. Top by Δscore:

Variant	Effect	Δscore
9:27117628:G:GT	donor_gain	1.0000
9:27157829:A:AG	acceptor_gain	1.0000
9:27157830:G:GG	acceptor_gain	1.0000
9:27157830:GGAA:G	acceptor_gain	1.0000
9:27157995:G:GT	donor_gain	1.0000
9:27169627:GGA:G	donor_gain	1.0000
9:27169628:GA:G	donor_gain	1.0000
9:27169628:GAG:G	donor_gain	1.0000
9:27169630:G:GG	donor_gain	1.0000
9:27172611:A:AG	acceptor_gain	1.0000
9:27172611:AAAAG:A	acceptor_gain	1.0000
9:27172612:A:G	acceptor_gain	1.0000
9:27183458:GGC:G	acceptor_gain	1.0000
9:27183611:G:GG	donor_gain	1.0000
9:27185626:AAAGG:A	donor_loss	1.0000
9:27185630:G:GC	donor_loss	1.0000
9:27185631:T:G	donor_loss	1.0000
9:27203068:TC:T	donor_gain	1.0000
9:27209117:CCA:C	acceptor_loss	1.0000
9:27209118:CAG:C	acceptor_loss	1.0000
9:27209119:A:AG	acceptor_gain	1.0000
9:27209119:A:T	acceptor_loss	1.0000
9:27209120:G:GA	acceptor_gain	1.0000
9:27209120:GA:G	acceptor_gain	1.0000
9:27209120:GAA:G	acceptor_gain	1.0000
9:27209120:GAAT:G	acceptor_gain	1.0000
9:27209120:GAATA:G	acceptor_gain	1.0000
9:27209229:GAG:G	donor_gain	1.0000
9:27209231:GGT:G	donor_loss	1.0000
9:27209232:G:GG	donor_gain	1.0000

AlphaMissense

7402 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:27206694:T:C	F826S	1.000
9:27206708:G:A	G831R	1.000
9:27206708:G:C	G831R	1.000
9:27206708:G:T	G831W	1.000
9:27206709:G:A	G831E	1.000
9:27206714:G:C	G833R	1.000
9:27206714:G:T	G833C	1.000
9:27206715:G:A	G833D	1.000
9:27206715:G:T	G833V	1.000
9:27206720:T:A	F835I	1.000
9:27206720:T:C	F835L	1.000
9:27206720:T:G	F835V	1.000
9:27206721:T:C	F835S	1.000
9:27206721:T:G	F835C	1.000
9:27206722:T:A	F835L	1.000
9:27206722:T:G	F835L	1.000
9:27206723:G:C	G836R	1.000
9:27206724:G:A	G836D	1.000
9:27206724:G:T	G836V	1.000
9:27206730:T:A	V838D	1.000
9:27206733:T:C	L839P	1.000
9:27206738:G:C	A841P	1.000
9:27206739:C:A	A841E	1.000
9:27206771:G:C	A852P	1.000
9:27206772:C:A	A852D	1.000
9:27206774:G:C	A853P	1.000
9:27206775:C:A	A853D	1.000
9:27206778:T:A	I854N	1.000
9:27206780:A:C	K855Q	1.000
9:27206780:A:G	K855E	1.000

dbSNP variants (sampled 300 via entrez): RS1000004056 (9:27121752 A>G), RS1000018673 (9:27193802 G>A), RS1000035286 (9:27121551 T>C), RS1000040707 (9:27125265 A>T), RS1000056671 (9:27226875 T>C), RS1000090737 (9:27150661 C>T), RS1000100598 (9:27227064 G>A,T), RS1000137479 (9:27149683 T>C), RS1000166474 (9:27226210 A>G,T), RS1000174990 (9:27209866 G>A), RS1000190429 (9:27149441 T>A), RS1000190593 (9:27188556 C>A,T), RS1000206009 (9:27153850 A>G), RS1000282824 (9:27126377 C>T), RS1000283134 (9:27223512 T>C,G)

Disease associations

OMIM: gene MIM:600221 | disease phenotypes: MIM:600195, MIM:617272, MIM:614429, MIM:112200, MIM:600975, MIM:613107

GenCC curated gene-disease

Disease	Classification	Inheritance
multiple cutaneous and mucosal venous malformations	Definitive	Autosomal dominant
primary congenital glaucoma	Definitive	Autosomal dominant
glaucoma 3, primary congenital, E	Strong	Autosomal dominant
congenital glaucoma	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
TEK-related primary glaucoma	Definitive	AD

Mondo (10): multiple cutaneous and mucosal venous malformations (MONDO:0010842), glaucoma 3, primary congenital, E (MONDO:0014998), vascular malformation (MONDO:0024291), ventricular septal defect (MONDO:0002070), blue rubber bleb nevus (MONDO:0007203), glaucoma 3, primary infantile, B (MONDO:0010968), neutropenia, severe congenital, 2, autosomal dominant (MONDO:0013139), Bockenheimer syndrome (MONDO:0016311), congenital glaucoma (MONDO:0020366), primary congenital glaucoma (MONDO:0000365)

Orphanet (6): Mucocutaneous venous malformations (Orphanet:2451), Blue rubber bleb nevus (Orphanet:1059), Congenital glaucoma (Orphanet:98976), Autosomal dominant severe congenital neutropenia (Orphanet:486), Segmental venous malformation (Orphanet:217008), NON RARE IN EUROPE: Ventricular septal defect (Orphanet:1480)

HPO phenotypes

37 total (30 of 37 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000485	Megalocornea
HP:0000501	Glaucoma
HP:0000545	Myopia
HP:0000557	Buphthalmos
HP:0000572	Visual loss
HP:0000613	Photophobia
HP:0000643	Blepharospasm
HP:0000646	Amblyopia
HP:0000988	Skin rash
HP:0001048	Cavernous hemangioma
HP:0001089	Iris atrophy
HP:0001482	Subcutaneous nodule
HP:0001928	Abnormality of coagulation
HP:0001935	Microcytic anemia
HP:0002580	Volvulus
HP:0002584	Intestinal bleeding
HP:0002597	Abnormality of the vasculature
HP:0002653	Bone pain
HP:0003010	Prolonged bleeding time
HP:0005244	Gastrointestinal infarctions
HP:0007663	Reduced visual acuity
HP:0007765	Deep anterior chamber
HP:0007906	Ocular hypertension
HP:0007957	Corneal opacity
HP:0008007	Primary congenital glaucoma
HP:0009926	Epiphora
HP:0011490	Abnormal Descemet membrane morphology
HP:0012040	Corneal stromal edema

GWAS associations

11 associations (top):

Study	Trait	p-value
GCST002731_2	Endothelial growth factor levels	2.000000e-65
GCST003831_45	Asthma	7.000000e-10
GCST003831_47	Asthma	2.000000e-08
GCST003833_23	Adult asthma	3.000000e-07
GCST003833_24	Adult asthma	2.000000e-06
GCST003901_3	Cognitive decline (age-related)	4.000000e-07
GCST005196_169	Coronary artery disease	2.000000e-07
GCST006585_1507	Blood protein levels	3.000000e-11
GCST009440_7	Age-related cognitive decline (attention/processing speed) (slope of z-scores)	1.000000e-06
GCST009731_58	Blood protein levels in cardiovascular risk	1.000000e-30
GCST90006995_5	Gut microbiota relative abundance (unclassified genus belonging to family Lachnospiraceae)	3.000000e-06

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0006902	angiopoietin-2 receptor measurement
EFO:0007710	cognitive decline measurement
EFO:0010600	angiopoietin-1 receptor measurement
EFO:0007874	gut microbiome measurement

MeSH disease descriptors (7)

Descriptor	Name	Tree numbers
D006345	Heart Septal Defects, Ventricular	C14.240.400.560.540; C14.280.400.560.540; C16.131.240.400.560.540
D006871	Hydrophthalmos	C11.250.480; C11.525.381.407.480; C16.131.384.480; C16.614.438
D054079	Vascular Malformations	C14.240.850; C16.131.240.850
C536240	Blue rubber bleb nevus syndrome (supp.)
C536824	Glaucoma 3, primary infantile, B (supp.)
C567748	Neutropenia, Severe Congenital, Autosomal Dominant 2 (supp.)
C563977	Venous Malformations, Multiple Cutaneous and Mucosal (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL2111375 (SELECTIVITY GROUP), CHEMBL4128 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

46 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 663,611 (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
CHEMBL1000	CETIRIZINE	4	26,030
CHEMBL1287853	FEDRATINIB	4	3,554
CHEMBL1289494	TIVOZANIB	4	4,455
CHEMBL1289926	AXITINIB	4	15,732
CHEMBL1336	SORAFENIB	4	86,060
CHEMBL1448	NICLOSAMIDE	4	14,322
CHEMBL174	AMPICILLIN	4	334,414
CHEMBL180022	NERATINIB	4	9,404
CHEMBL1834657	INFIGRATINIB PHOSPHATE	4	285
CHEMBL1852688	INFIGRATINIB	4	2,209
CHEMBL1946170	REGORAFENIB	4	12,678
CHEMBL2105717	CABOZANTINIB	4	11,177
CHEMBL24828	VANDETANIB	4	42,230
CHEMBL255863	NILOTINIB	4	38,627
CHEMBL288441	BOSUTINIB	4	12,255
CHEMBL477772	PAZOPANIB	4	15,540
CHEMBL502835	NINTEDANIB	4	8,545
CHEMBL576982	QUIZARTINIB	4	4,432
CHEMBL601719	CRIZOTINIB	4	14,403
CHEMBL608533	MIDOSTAURIN	4	7,259
CHEMBL841	LOPERAMIDE	4
CHEMBL223360	LINIFANIB	3
CHEMBL377300	BRIVANIB	3
CHEMBL491473	CEDIRANIB	3
CHEMBL603469	LESTAURTINIB	3
CHEMBL103667	DORAMAPIMOD	2
CHEMBL1230609	FORETINIB	2
CHEMBL1738757	REBASTINIB	2
CHEMBL2010872	CEP-11981	2
CHEMBL215152	DEFOSBARASERTIB	2

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: catalytic receptor — Type XII RTKs: TIE family of angiopoietin receptors

Most potent curated ligand interactions (9 total), top 9:

Ligand	Action	Affinity	Parameter
pexmetinib	Inhibition	9.0	pIC50
compound 8h [PMID: 21561767]	Inhibition	8.66	pIC50
altiratinib	Inhibition	8.62	pIC50
merestinib	Inhibition	8.4	pIC50
CEP-11981	Inhibition	7.59	pIC50
linifanib	Inhibition	6.77	pIC50
compound 5 [PMID: 17618114]	Inhibition	6.6	pIC50
compound 8i [PMID: 22765894]	Inhibition	6.57	pIC50
DDR1/2 inhibitor 5n	Inhibition	6.43	pKd

Binding affinities (BindingDB)

373 measured of 422 human assays (422 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
3-cyano-N-[2,4-dimethyl-5-(6-pyridin-3-ylimidazo[2,1-e]pyrazol-1-yl)phenyl]-5-(pentafluoro-lambda6-sulfanyl)benzamide	IC50	0.2 nM	US-9394309: Substituted phenylimidazopyrazoles and their use
N-[4-methyl-3-(6-pyrazolidin-4-ylimidazo[2,1-e]pyrazol-1-yl)phenyl]-3-(pentafluoro-lambda6-sulfanyl)-5-piperazin-1-ylbenzamide	IC50	0.3 nM	US-9394309: Substituted phenylimidazopyrazoles and their use
N-[4-methyl-3-(3-methyl-6-pyrazolidin-4-ylimidazo[2,1-e]pyrazol-1-yl)phenyl]-3-(pentafluoro-lambda6-sulfanyl)-5-piperazin-1-ylbenzamide	IC50	0.3 nM	US-9394309: Substituted phenylimidazopyrazoles and their use
N-[4-methyl-3-(3-methyl-6-pyrazolidin-4-ylimidazo[2,1-e]pyrazol-1-yl)phenyl]-3-(4-methylpiperazin-1-yl)-5-(pentafluoro-lambda6-sulfanyl)benzamide	IC50	0.3 nM	US-9394309: Substituted phenylimidazopyrazoles and their use
N-[4-methyl-3-(6-pyridin-3-ylimidazo[2,1-e]pyrazol-1-yl)phenyl]-3-(pentafluoro-lambda6-sulfanyl)-5-piperazin-1-ylbenzamide	IC50	0.3 nM	US-9394309: Substituted phenylimidazopyrazoles and their use
3-(3-aminopropoxy)-N-[4-methyl-3-(6-pyridin-3-ylimidazo[2,1-e]pyrazol-1-yl)phenyl]-5-(pentafluoro-lambda6-sulfanyl)benzamide	IC50	0.3 nM	US-9394309: Substituted phenylimidazopyrazoles and their use
3-[(4-methylpiperazin-1-yl)methyl]-N-[4-methyl-3-(6-pyridin-3-ylimidazo[2,1-e]pyrazol-1-yl)phenyl]-5-(pentafluoro-lambda6-sulfanyl)benzamide	IC50	0.3 nM	US-9394309: Substituted phenylimidazopyrazoles and their use
3-tert-butyl-5-(2-methylimidazol-1-yl)-N-[4-methyl-3-(6-pyridin-3-ylimidazo[2,1-e]pyrazol-1-yl)phenyl]benzamide	IC50	0.3 nM	US-9394309: Substituted phenylimidazopyrazoles and their use
3-tert-butyl-5-(4-methylpiperazin-1-yl)-N-[4-methyl-3-(6-pyridin-3-ylimidazo[2,1-e]pyrazol-1-yl)phenyl]benzamide	IC50	0.3 nM	US-9394309: Substituted phenylimidazopyrazoles and their use
3-tert-butyl-5-(2-hydroxypropan-2-yl)-N-[4-methyl-3-(6-pyridin-3-ylimidazo[2,1-e]pyrazol-1-yl)phenyl]benzamide	IC50	0.3 nM	US-9394309: Substituted phenylimidazopyrazoles and their use
N-[2,4-dimethyl-5-(6-pyridin-3-ylimidazo[2,1-e]pyrazol-1-yl)phenyl]-3-(pentafluoro-lambda6-sulfanyl)benzamide	IC50	0.3 nM	US-9394309: Substituted phenylimidazopyrazoles and their use
3-tert-butyl-5-cyano-N-[2,4-dimethyl-5-(6-pyridin-3-ylimidazo[2,1-e]pyrazol-1-yl)phenyl]benzamide	IC50	0.3 nM	US-9394309: Substituted phenylimidazopyrazoles and their use
3-(2-amino-2-oxoethyl)-N-[2,4-dimethyl-5-(6-pyridin-3-ylimidazo[2,1-e]pyrazol-1-yl)phenyl]-5-(pentafluoro-lambda6-sulfanyl)benzamide	IC50	0.3 nM	US-9394309: Substituted phenylimidazopyrazoles and their use
3-cyano-N-[2,4-dimethyl-5-(6-pyrimidin-5-ylimidazo[2,1-e]pyrazol-1-yl)phenyl]-5-(pentafluoro-lambda6-sulfanyl)benzamide	IC50	0.3 nM	US-9394309: Substituted phenylimidazopyrazoles and their use
3-cyano-N-[2,4-dimethyl-5-(6-pyridazin-3-ylimidazo[2,1-e]pyrazol-1-yl)phenyl]-5-(pentafluoro-lambda6-sulfanyl)benzamide	IC50	0.3 nM	US-9394309: Substituted phenylimidazopyrazoles and their use
1-[2-(4-methylphenyl)-5-tert-butyl-pyrazol-3-yl]-3-[4-(2-morpholin-4-ylethoxy)naphthalen-1-yl]urea	KD	0.37 nM
3-(2-methylimidazol-1-yl)-N-[4-methyl-3-(3-methyl-6-pyrazolidin-4-ylimidazo[2,1-e]pyrazol-1-yl)phenyl]-5-(trifluoromethyl)benzamide	IC50	0.4 nM	US-9394309: Substituted phenylimidazopyrazoles and their use
3-(2-hydroxypropan-2-yl)-N-[4-methyl-3-(6-pyridin-3-ylimidazo[2,1-e]pyrazol-1-yl)phenyl]-5-(pentafluoro-lambda6-sulfanyl)benzamide	IC50	0.4 nM	US-9394309: Substituted phenylimidazopyrazoles and their use
3-(3-hydroxyazetidin-3-yl)-N-[4-methyl-3-(6-pyridin-3-ylimidazo[2,1-e]pyrazol-1-yl)phenyl]-5-(pentafluoro-lambda6-sulfanyl)benzamide	IC50	0.4 nM	US-9394309: Substituted phenylimidazopyrazoles and their use
3-tert-butyl-5-cyano-N-[2-fluoro-4-methyl-5-(6-pyridin-3-ylimidazo[2,1-e]pyrazol-1-yl)phenyl]benzamide	IC50	0.4 nM	US-9394309: Substituted phenylimidazopyrazoles and their use
N-[2,4-dimethyl-5-(6-pyridin-3-ylimidazo[2,1-e]pyrazol-1-yl)phenyl]-3-(2-hydroxypropan-2-yl)-5-(pentafluoro-lambda6-sulfanyl)benzamide	IC50	0.4 nM	US-9394309: Substituted phenylimidazopyrazoles and their use
methyl 2-[3-[[2,4-dimethyl-5-(6-pyridin-3-ylimidazo[2,1-e]pyrazol-1-yl)phenyl]carbamoyl]-5-(pentafluoro-lambda6-sulfanyl)phenyl]acetate	IC50	0.4 nM	US-9394309: Substituted phenylimidazopyrazoles and their use
N-[2,4-dimethyl-5-(6-pyridin-3-ylimidazo[2,1-e]pyrazol-1-yl)phenyl]-3-(2-hydroxy-2-methylpropyl)-5-(pentafluoro-lambda6-sulfanyl)benzamide	IC50	0.4 nM	US-9394309: Substituted phenylimidazopyrazoles and their use
N-[2,4-dimethyl-5-(6-pyrimidin-5-ylimidazo[2,1-e]pyrazol-1-yl)phenyl]-3-(pentafluoro-lambda6-sulfanyl)benzamide	IC50	0.4 nM	US-9394309: Substituted phenylimidazopyrazoles and their use
N-[4-methyl-3-(6-pyridin-3-ylimidazo[2,1-e]pyrazol-1-yl)phenyl]-3-(pentafluoro-lambda6-sulfanyl)-5-(piperazin-1-ylmethyl)benzamide	IC50	0.5 nM	US-9394309: Substituted phenylimidazopyrazoles and their use
3-(2-methylimidazol-1-yl)-N-[4-methyl-3-(6-pyridin-3-ylimidazo[2,1-e]pyrazol-1-yl)phenyl]-5-(trifluoromethyl)benzamide	IC50	0.5 nM	US-9394309: Substituted phenylimidazopyrazoles and their use
3-cyano-N-[2-fluoro-4-methyl-5-(6-pyridin-3-ylimidazo[2,1-e]pyrazol-1-yl)phenyl]-5-(pentafluoro-lambda6-sulfanyl)benzamide	IC50	0.5 nM	US-9394309: Substituted phenylimidazopyrazoles and their use
3-bromo-N-[2,4-dimethyl-5-(6-pyridin-3-ylimidazo[2,1-e]pyrazol-1-yl)phenyl]-5-(pentafluoro-lambda6-sulfanyl)benzamide	IC50	0.5 nM	US-9394309: Substituted phenylimidazopyrazoles and their use
2-tert-butyl-6-cyano-N-[2,4-dimethyl-5-(6-pyridin-3-ylimidazo[2,1-e]pyrazol-1-yl)phenyl]pyridine-4-carboxamide	IC50	0.5 nM	US-9394309: Substituted phenylimidazopyrazoles and their use
N-[2,4-dimethyl-5-(6-pyridin-3-ylimidazo[2,1-e]pyrazol-1-yl)phenyl]-3-(1,1,1-trifluoro-2-methylpropan-2-yl)benzamide	IC50	0.5 nM	US-9394309: Substituted phenylimidazopyrazoles and their use
N-[2,4-dimethyl-5-(6-pyridin-3-ylimidazo[2,1-e]pyrazol-1-yl)phenyl]-3-(3-methyloxetan-3-yl)benzamide	IC50	0.5 nM	US-9394309: Substituted phenylimidazopyrazoles and their use
N-[4-chloro-2-methyl-5-(6-pyridin-3-ylimidazo[2,1-e]pyrazol-1-yl)phenyl]-3-(pentafluoro-lambda6-sulfanyl)benzamide	IC50	0.5 nM	US-9394309: Substituted phenylimidazopyrazoles and their use
3-(2-hydroxypropan-2-yl)-N-[4-methyl-3-(6-pyrazolidin-4-ylimidazo[2,1-e]pyrazol-1-yl)phenyl]-5-(pentafluoro-lambda6-sulfanyl)benzamide	IC50	0.6 nM	US-9394309: Substituted phenylimidazopyrazoles and their use
3-(2-aminoethoxy)-N-[4-methyl-3-(6-pyridin-3-ylimidazo[2,1-e]pyrazol-1-yl)phenyl]-5-(pentafluoro-lambda6-sulfanyl)benzamide	IC50	0.6 nM	US-9394309: Substituted phenylimidazopyrazoles and their use
N-[2,4-dimethyl-5-(6-pyridin-3-ylimidazo[2,1-e]pyrazol-1-yl)phenyl]-3-fluoro-5-(pentafluoro-lambda6-sulfanyl)benzamide	IC50	0.6 nM	US-9394309: Substituted phenylimidazopyrazoles and their use
3-bromo-5-tert-butyl-N-[2,4-dimethyl-5-(6-pyridin-3-ylimidazo[2,1-e]pyrazol-1-yl)phenyl]benzamide	IC50	0.6 nM	US-9394309: Substituted phenylimidazopyrazoles and their use
3-(4-cyanopiperidin-1-yl)-N-[2,4-dimethyl-5-(6-pyridin-3-ylimidazo[2,1-e]pyrazol-1-yl)phenyl]-5-(pentafluoro-lambda6-sulfanyl)benzamide	IC50	0.6 nM	US-9394309: Substituted phenylimidazopyrazoles and their use
3-cyano-N-[4-methyl-3-(3-methyl-6-pyrazolidin-4-ylimidazo[2,1-e]pyrazol-1-yl)phenyl]-5-(pentafluoro-lambda6-sulfanyl)benzamide	IC50	0.7 nM	US-9394309: Substituted phenylimidazopyrazoles and their use
3-(2-methylimidazol-1-yl)-N-[4-methyl-3-(6-pyridin-3-ylimidazo[2,1-e]pyrazol-1-yl)phenyl]-5-(pentafluoro-lambda6-sulfanyl)benzamide	IC50	0.7 nM	US-9394309: Substituted phenylimidazopyrazoles and their use
3-(4-methylpiperazin-1-yl)-N-[4-methyl-3-(6-pyridin-3-ylimidazo[2,1-e]pyrazol-1-yl)phenyl]-5-(pentafluoro-lambda6-sulfanyl)benzamide	IC50	0.7 nM	US-9394309: Substituted phenylimidazopyrazoles and their use
3-tert-butyl-N-[4-methyl-3-(6-pyridin-3-ylimidazo[2,1-e]pyrazol-1-yl)phenyl]-5-(pyrrolidin-1-ylmethyl)benzamide	IC50	0.7 nM	US-9394309: Substituted phenylimidazopyrazoles and their use
3-chloro-N-[2,4-dimethyl-5-(6-pyridin-3-ylimidazo[2,1-e]pyrazol-1-yl)phenyl]-5-(pentafluoro-lambda6-sulfanyl)benzamide	IC50	0.7 nM	US-9394309: Substituted phenylimidazopyrazoles and their use
N-[2,4-dimethyl-5-(6-pyridin-3-ylimidazo[2,1-e]pyrazol-1-yl)phenyl]-3-methyl-5-(pentafluoro-lambda6-sulfanyl)benzamide	IC50	0.7 nM	US-9394309: Substituted phenylimidazopyrazoles and their use
N-[2,4-dimethyl-5-(6-pyridin-3-ylimidazo[2,1-e]pyrazol-1-yl)phenyl]-3-(methoxymethyl)-5-(pentafluoro-lambda6-sulfanyl)benzamide	IC50	0.7 nM	US-9394309: Substituted phenylimidazopyrazoles and their use
N-[2,4-dimethyl-5-(6-pyridin-3-ylimidazo[2,1-e]pyrazol-1-yl)phenyl]-3-(3-methoxyazetidin-1-yl)-5-(pentafluoro-lambda6-sulfanyl)benzamide	IC50	0.7 nM	US-9394309: Substituted phenylimidazopyrazoles and their use
N-[2,4-dimethyl-5-(6-pyridin-3-ylimidazo[2,1-e]pyrazol-1-yl)phenyl]-3-(2-methoxyethoxymethyl)-5-(pentafluoro-lambda6-sulfanyl)benzamide	IC50	0.7 nM	US-9394309: Substituted phenylimidazopyrazoles and their use
3-(azetidin-3-yloxy)-N-[4-methyl-3-(6-pyridin-3-ylimidazo[2,1-e]pyrazol-1-yl)phenyl]-5-(pentafluoro-lambda6-sulfanyl)benzamide	IC50	0.8 nM	US-9394309: Substituted phenylimidazopyrazoles and their use
N-[4-methyl-3-(6-pyridin-3-ylimidazo[2,1-e]pyrazol-1-yl)phenyl]-3-methylsulfonyl-5-(pentafluoro-lambda6-sulfanyl)benzamide	IC50	0.8 nM	US-9394309: Substituted phenylimidazopyrazoles and their use
2-tert-butyl-6-chloro-N-[2,4-dimethyl-5-(6-pyridin-3-ylimidazo[2,1-e]pyrazol-1-yl)phenyl]pyridine-4-carboxamide	IC50	0.8 nM	US-9394309: Substituted phenylimidazopyrazoles and their use
3-methylsulfonyl-N-[4-methyl-3-[6-(1,3-thiazol-5-yl)imidazo[2,1-e]pyrazol-1-yl]phenyl]-5-(pentafluoro-lambda6-sulfanyl)benzamide	IC50	0.8 nM	US-9394309: Substituted phenylimidazopyrazoles and their use

ChEMBL bioactivities

1161 potent at pChembl≥5 of 1227 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.89	IC50	0.13	nM	CHEMBL4087541
9.80	IC50	0.16	nM	CHEMBL4103584
9.70	IC50	0.2	nM	CHEMBL4115822
9.59	IC50	0.26	nM	CHEMBL4449700
9.55	IC50	0.28	nM	CHEMBL4447552
9.52	IC50	0.3	nM	CHEMBL4115787
9.52	IC50	0.3	nM	CHEMBL4115791
9.52	IC50	0.3	nM	CHEMBL4115792
9.52	IC50	0.3	nM	CHEMBL4115797
9.52	IC50	0.3	nM	CHEMBL4115803
9.52	IC50	0.3	nM	CHEMBL4115816
9.52	IC50	0.3	nM	CHEMBL3976004
9.52	IC50	0.3	nM	CHEMBL3950106
9.52	IC50	0.3	nM	CHEMBL3967492
9.52	IC50	0.3	nM	CHEMBL4115821
9.52	IC50	0.3	nM	CHEMBL3937186
9.52	IC50	0.3	nM	CHEMBL4115866
9.52	IC50	0.3	nM	CHEMBL4115878
9.52	IC50	0.3	nM	CHEMBL4115882
9.52	IC50	0.3	nM	CHEMBL4528844
9.44	IC50	0.36	nM	CHEMBL4452256
9.41	IC50	0.39	nM	SORAFENIB
9.40	IC50	0.4	nM	CHEMBL3978122
9.40	IC50	0.4	nM	CHEMBL4115812
9.40	IC50	0.4	nM	CHEMBL4115817
9.40	IC50	0.4	nM	CHEMBL3922694
9.40	IC50	0.4	nM	CHEMBL4115861
9.40	IC50	0.4	nM	CHEMBL4115865
9.40	IC50	0.4	nM	CHEMBL4115867
9.40	IC50	0.4	nM	CHEMBL4115876
9.35	IC50	0.45	nM	CHEMBL4570075
9.35	IC50	0.45	nM	BAY-826
9.30	IC50	0.5	nM	CHEMBL4115815
9.30	IC50	0.5	nM	CHEMBL3959425
9.30	IC50	0.5	nM	CHEMBL4115822
9.30	IC50	0.5	nM	CHEMBL4115823
9.30	IC50	0.5	nM	CHEMBL4115850
9.30	IC50	0.5	nM	CHEMBL3950414
9.30	IC50	0.5	nM	CHEMBL3896522
9.30	IC50	0.5	nM	CHEMBL3967691
9.30	IC50	0.5	nM	CHEMBL4115870
9.22	IC50	0.6	nM	CHEMBL4115790
9.22	IC50	0.6	nM	CHEMBL4115802
9.22	IC50	0.6	nM	CHEMBL4115848
9.22	IC50	0.6	nM	CHEMBL3944654
9.22	IC50	0.6	nM	CHEMBL4115858
9.22	IC50	0.6	nM	CHEMBL4115822
9.22	IC50	0.6	nM	CHEMBL4066813
9.15	IC50	0.7	nM	CHEMBL4115793
9.15	IC50	0.7	nM	CHEMBL4115796

PubChem BioAssay actives

1146 with measured affinity, of 2579 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-(2-aminoquinazolin-7-yl)phenyl]-3-(1,3-benzodioxol-5-yl)thiourea	1426701: Inhibition of TIE-2 (unknown origin) after 60 mins by ADP-Glo assay	ic50	0.0001	uM
1-[4-(2-aminoquinazolin-7-yl)phenyl]-3-[3,5-bis(trifluoromethyl)phenyl]thiourea	1426701: Inhibition of TIE-2 (unknown origin) after 60 mins by ADP-Glo assay	ic50	0.0002	uM
3-[4-[[4-(3-chlorophenyl)triazol-1-yl]methyl]phenyl]pyridine	1533550: Inhibition of TIE2 (unknown origin) after 4 hrs by ADP-Glo reagent based luminescent assay	ic50	0.0003	uM
2-methoxy-5-[4-[[4-(4-methylphenyl)triazol-1-yl]methyl]phenyl]pyridine	1533550: Inhibition of TIE2 (unknown origin) after 4 hrs by ADP-Glo reagent based luminescent assay	ic50	0.0003	uM
2-methoxy-5-[4-[[4-[4-(trifluoromethyl)phenyl]triazol-1-yl]methyl]phenyl]pyridine	1533550: Inhibition of TIE2 (unknown origin) after 4 hrs by ADP-Glo reagent based luminescent assay	ic50	0.0003	uM
5-[4-[[4-(3-chlorophenyl)triazol-1-yl]methyl]phenyl]-2-methoxypyridine	1533550: Inhibition of TIE2 (unknown origin) after 4 hrs by ADP-Glo reagent based luminescent assay	ic50	0.0004	uM
3-[4-[[4-(3-methylphenyl)triazol-1-yl]methyl]phenyl]pyridine	1533550: Inhibition of TIE2 (unknown origin) after 4 hrs by ADP-Glo reagent based luminescent assay	ic50	0.0004	uM
Sorafenib	1533550: Inhibition of TIE2 (unknown origin) after 4 hrs by ADP-Glo reagent based luminescent assay	ic50	0.0004	uM
1-[4-(2-aminoquinazolin-7-yl)phenyl]-3-[5-bromo-2-(trifluoromethoxy)phenyl]thiourea	1426701: Inhibition of TIE-2 (unknown origin) after 60 mins by ADP-Glo assay	ic50	0.0006	uM
3-[1-[[4-(6-methoxy-3-pyridinyl)phenyl]methyl]triazol-4-yl]aniline	1533550: Inhibition of TIE2 (unknown origin) after 4 hrs by ADP-Glo reagent based luminescent assay	ic50	0.0007	uM
4-[[2-[[4-[(4-ethylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]carbamoylamino]-1,3-benzothiazol-6-yl]oxy]-N-methylpyridine-2-carboxamide	1928227: Inhibition of Tie2 (unknown origin)	ic50	0.0008	uM
N-[3-[1-[[4-(1-methylpyrazol-4-yl)phenyl]methyl]triazol-4-yl]phenyl]cyclopropanecarboxamide	1623886: Inhibition of Tie-2 (unknown origin) after 1 hrs by ADP-Glo luminescence assay	ic50	0.0008	uM
7-(6,7-dimethoxyquinolin-4-yl)oxy-N-(3-methylphenyl)-2,3-dihydro-1,4-benzoxazine-4-carboxamide	325875: Inhibition of Tie2	ic50	0.0010	uM
N-[3-[3-(dimethylamino)propyl]-5-(trifluoromethyl)phenyl]-4-methyl-3-[(3-pyrimidin-4-yl-2-pyridinyl)amino]benzamide	1797330: Homogeneous Time-Resolved Fluorescence (HTRF) Enzyme Assay from Article 10.1021/jm061107l: “Evolution of a highly selective and potent 2-(pyridin-2-yl)-1,3,5-triazine Tie-2 kinase inhibitor.”	ic50	0.0010	uM
3-(2-aminoquinazolin-6-yl)-4-methyl-N-[3-(trifluoromethyl)phenyl]benzamide	1797326: Homogeneous Time-Resolved Fluorescence (HTRF) Enzyme Assay from Article 10.1021/jm061112p: “Alkynylpyrimidine amide derivatives as potent, selective, and orally active inhibitors of Tie-2 kinase.”	ic50	0.0010	uM
4-methyl-3-[[3-[2-(methylamino)pyrimidin-4-yl]-2-pyridinyl]oxy]-N-[3-(trifluoromethyl)phenyl]benzamide	1797326: Homogeneous Time-Resolved Fluorescence (HTRF) Enzyme Assay from Article 10.1021/jm061112p: “Alkynylpyrimidine amide derivatives as potent, selective, and orally active inhibitors of Tie-2 kinase.”	ic50	0.0010	uM
N-[4-[[3-[2-(methylamino)pyrimidin-4-yl]-2-pyridinyl]oxy]naphthalen-1-yl]-1H-benzimidazol-2-amine	392180: Inhibition of Tie2	ic50	0.0010	uM
1-(2-fluoro-5-methylphenyl)-3-(19-methyl-14-oxo-3-propyl-3,13,19,20-tetrazahexacyclo[14.7.0.02,10.04,9.011,15.017,21]tricosa-1(16),2(10),4(9),5,7,11(15),17,20-octaen-7-yl)urea	274179: Inhibition of Tie2	ic50	0.0010	uM
4-methyl-3-[[3-[4-(methylamino)-1,3,5-triazin-2-yl]-2-pyridinyl]oxy]-N-(3-propan-2-ylphenyl)benzamide	307021: Inhibition of Tie2 after 90 mins by HTRF assay	ic50	0.0010	uM
N-[4-methyl-3-[[3-[4-(methylamino)-1,3,5-triazin-2-yl]-2-pyridinyl]oxy]phenyl]-3-propan-2-ylbenzamide	307021: Inhibition of Tie2 after 90 mins by HTRF assay	ic50	0.0010	uM
N-[4-methyl-3-[[3-[2-(methylamino)-4-pyridinyl]-2-pyridinyl]oxy]phenyl]-3-propan-2-ylbenzamide	307021: Inhibition of Tie2 after 90 mins by HTRF assay	ic50	0.0010	uM
N-[4-[[3-[2-[(1-ethylpiperidin-4-yl)methylamino]pyrimidin-4-yl]-2-pyridinyl]oxy]naphthalen-1-yl]-1H-benzimidazol-2-amine	483437: Inhibition of Tie2	ic50	0.0010	uM
1-[4-(2-aminoquinazolin-7-yl)phenyl]-3-(3,4-dichlorophenyl)thiourea	1426701: Inhibition of TIE-2 (unknown origin) after 60 mins by ADP-Glo assay	ic50	0.0011	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	1318750: Inhibition of TIE-2 (unknown origin) using poly (Glu, Tyr) 4:1 as substrate after 2 hrs in presence of [33P]-gamma-ATP by microbeta scintillation counting	ic50	0.0011	uM
3-cyano-N-[2,4-dimethyl-5-(6-pyridin-3-ylimidazo[2,1-e]pyrazol-1-yl)phenyl]-5-(pentafluoro-lambda6-sulfanyl)benzamide	2155088: Inhibition of TIE2 autophosphorylation in human HUVEC cells by Western blot analysis	ec50	0.0013	uM
methyl N-[6-[4-[[2-fluoro-5-(trifluoromethyl)phenyl]carbamoylamino]phenoxy]imidazo[1,2-a]pyridin-2-yl]carbamate	297393: Inhibition of TIE-2/c-fms chimeric protein expressed in mouse 3T3 cells assessed as autophosphorylation level by ELISA	ic50	0.0015	uM
regorafenib anhydrous	1600258: Inhibition of GST-tagged TIE2 (unknown origin) using biotin-Ahx-EPKDDAYPLYSDFG peptide as substrate by HTRF method	ic50	0.0015	uM
1-[[4-(1-methylpyrazol-4-yl)phenyl]methyl]-4-[3-(trifluoromethyl)phenyl]triazole	1623886: Inhibition of Tie-2 (unknown origin) after 1 hrs by ADP-Glo luminescence assay	ic50	0.0018	uM
4-methyl-3-[2-(methylamino)quinazolin-6-yl]-N-[3-(trifluoromethyl)phenyl]benzamide	1799308: In Vitro BRAF Kinase Assay from Article 10.1021/jm901081g: “Selective inhibitors of the mutant B-Raf pathway: discovery of a potent and orally bioavailable aminoisoquinoline.”	ic50	0.0018	uM
1-N-[3-(3-amino-1H-indazol-4-yl)phenyl]-1-N’-[3-bromo-5-(trifluoromethyl)phenyl]cyclopropane-1,1-dicarboxamide	1426701: Inhibition of TIE-2 (unknown origin) after 60 mins by ADP-Glo assay	ic50	0.0019	uM
3-[2-(1H-imidazo[4,5-b]pyridin-6-yl)ethynyl]-4-methyl-N-[3-(trifluoromethyl)phenyl]benzamide	1797326: Homogeneous Time-Resolved Fluorescence (HTRF) Enzyme Assay from Article 10.1021/jm061112p: “Alkynylpyrimidine amide derivatives as potent, selective, and orally active inhibitors of Tie-2 kinase.”	ic50	0.0020	uM
N-[3-methyl-4-[[3-[2-(methylamino)pyrimidin-4-yl]-2-pyridinyl]oxy]naphthalen-1-yl]-1H-benzimidazol-2-amine	392180: Inhibition of Tie2	ic50	0.0020	uM
N-[4-[[3-[2-[2-(1-methylpyrrolidin-2-yl)ethylamino]pyrimidin-4-yl]-2-pyridinyl]oxy]naphthalen-1-yl]-1H-benzimidazol-2-amine	483437: Inhibition of Tie2	ic50	0.0020	uM
1-(4-methoxyphenyl)-3-(19-methyl-14-oxo-3-propyl-3,13,19,20-tetrazahexacyclo[14.7.0.02,10.04,9.011,15.017,21]tricosa-1(16),2(10),4(9),5,7,11(15),17,20-octaen-7-yl)urea	274179: Inhibition of Tie2	ic50	0.0020	uM
1-methyl-3-(19-methyl-14-oxo-3-propyl-3,13,19,20-tetrazahexacyclo[14.7.0.02,10.04,9.011,15.017,21]tricosa-1(16),2(10),4(9),5,7,11(15),17,20-octaen-7-yl)-1-phenylurea	274179: Inhibition of Tie2	ic50	0.0020	uM
1-(4-fluorophenyl)-3-(19-methyl-14-oxo-3-propyl-3,13,19,20-tetrazahexacyclo[14.7.0.02,10.04,9.011,15.017,21]tricosa-1(16),2(10),4(9),5,7,11(15),17,20-octaen-7-yl)urea	274179: Inhibition of Tie2	ic50	0.0020	uM
1-(3-fluorophenyl)-3-(19-methyl-14-oxo-3-propyl-3,13,19,20-tetrazahexacyclo[14.7.0.02,10.04,9.011,15.017,21]tricosa-1(16),2(10),4(9),5,7,11(15),17,20-octaen-7-yl)urea	274179: Inhibition of Tie2	ic50	0.0020	uM
1-(2-fluorophenyl)-3-(19-methyl-14-oxo-3-propyl-3,13,19,20-tetrazahexacyclo[14.7.0.02,10.04,9.011,15.017,21]tricosa-1(16),2(10),4(9),5,7,11(15),17,20-octaen-7-yl)urea	274179: Inhibition of Tie2	ic50	0.0020	uM
N-[4-methyl-3-[[3-[2-(methylamino)pyrimidin-4-yl]-2-pyridinyl]oxy]phenyl]-3-propan-2-ylbenzamide	307021: Inhibition of Tie2 after 90 mins by HTRF assay	ic50	0.0020	uM
1-[4-[4-amino-6-(4-methoxyphenyl)furo[2,3-d]pyrimidin-5-yl]phenyl]-3-[2-fluoro-6-(trifluoromethyl)phenyl]urea	314912: Inhibition of human recombinant TIE2 by HTRF assay	ic50	0.0020	uM
1-[4-[4-amino-6-(4-methoxyphenyl)furo[2,3-d]pyrimidin-5-yl]phenyl]-3-[2-fluoro-5-(trifluoromethyl)phenyl]urea	1795818: Homogeneous Time-resolved Fluorescence (HTRF) Assay from Article 10.1016/j.bmcl.2005.03.034: “Novel 4-amino-furo[2,3-d]pyrimidines as Tie-2 and VEGFR2 dual inhibitors.”	ic50	0.0020	uM
1-[4-(3-amino-1H-indazol-4-yl)phenyl]-3-[5-bromo-2-(trifluoromethoxy)phenyl]thiourea	1492668: Inhibition of TIE2 (unknown origin) after 4 hrs by ADP-Glo assay	ic50	0.0021	uM
5-[2-[5-[[4-[[4-(2-hydroxyethyl)piperazin-1-yl]methyl]-3-(trifluoromethyl)phenyl]carbamoyl]-2-methylphenyl]ethynyl]-N,1-dimethylimidazole-2-carboxamide	601225: Inhibition of human Tie2/TEK using poly[Glu:Tyr] by Hotspot assay	ic50	0.0022	uM
1-[4-(2-aminoquinazolin-7-yl)phenyl]-3-[3-bromo-5-(trifluoromethyl)phenyl]thiourea	1426701: Inhibition of TIE-2 (unknown origin) after 60 mins by ADP-Glo assay	ic50	0.0025	uM
N-[6-[4-[[2-fluoro-5-(trifluoromethyl)phenyl]carbamoylamino]phenoxy]-1H-benzimidazol-2-yl]acetamide	1797661: Homogeneous Time-Resolved Fluorescence (HTRF) Enzyme Assay from Article 10.1021/jm0611051: “Discovery of Novel Benzimidazoles as Potent Inhibitors of TIE-2 and VEGFR-2 Tyrosine Kinase Receptors.”	ic50	0.0026	uM
methyl N-[6-[4-[[3-(trifluoromethyl)phenyl]carbamoylamino]phenoxy]-1H-benzimidazol-2-yl]carbamate	297393: Inhibition of TIE-2/c-fms chimeric protein expressed in mouse 3T3 cells assessed as autophosphorylation level by ELISA	ic50	0.0026	uM
4-(2-fluorophenyl)-1-[[4-(1-methylpyrazol-4-yl)phenyl]methyl]triazole	1623886: Inhibition of Tie-2 (unknown origin) after 1 hrs by ADP-Glo luminescence assay	ic50	0.0027	uM
N-[6-[4-[[2-fluoro-5-(trifluoromethyl)phenyl]carbamoylamino]phenoxy]-1H-benzimidazol-2-yl]-2-(2-methoxyethoxy)acetamide	297393: Inhibition of TIE-2/c-fms chimeric protein expressed in mouse 3T3 cells assessed as autophosphorylation level by ELISA	ic50	0.0028	uM
N-[6-[[6-[[2-fluoro-5-(trifluoromethyl)phenyl]carbamoylamino]-3-pyridinyl]oxy]-1H-benzimidazol-2-yl]acetamide	1797661: Homogeneous Time-Resolved Fluorescence (HTRF) Enzyme Assay from Article 10.1021/jm0611051: “Discovery of Novel Benzimidazoles as Potent Inhibitors of TIE-2 and VEGFR-2 Tyrosine Kinase Receptors.”	ic50	0.0029	uM
3-[2-(2-aminopyrimidin-5-yl)ethynyl]-4-methyl-N-[3-(trifluoromethyl)phenyl]benzamide	1797326: Homogeneous Time-Resolved Fluorescence (HTRF) Enzyme Assay from Article 10.1021/jm061112p: “Alkynylpyrimidine amide derivatives as potent, selective, and orally active inhibitors of Tie-2 kinase.”	ic50	0.0030	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
(+)-JQ1 compound	decreases expression	3
methylmercuric chloride	increases expression	2
perfluorooctane sulfonic acid	decreases reaction, increases expression, decreases activity	2
ponatinib	decreases activity	2
Doxorubicin	decreases expression, increases expression	2
Valproic Acid	decreases expression	2
Aflatoxin B1	decreases methylation, increases methylation	2
lasiocarpine	decreases expression	1
bisphenol A	increases methylation	1
mancozeb	increases activity	1
sodium arsenite	increases expression	1
cobaltous chloride	decreases expression	1
perfluorooctanoic acid	affects activity	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, decreases expression	1
S 1 (combination)	decreases expression	1
CGP 52608	affects binding, increases reaction	1
2-palmitoylglycerol	increases expression	1
2,2’,4,4’,5-brominated diphenyl ether	decreases expression	1
ON 01910	decreases phosphorylation	1
bisphenol S	affects cotreatment, increases methylation	1
incobotulinumtoxinA	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Arsenic Trioxide	decreases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Lenalidomide	decreases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Benzo(a)pyrene	affects methylation	1
Capsaicin	increases expression	1
Cisplatin	decreases response to substance, increases expression	1

ChEMBL screening assays

707 unique, capped per target: 701 binding, 4 functional, 2 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL831302	Binding	Fold selectivity for KDR over TIE2 kinase	Isoindolinone ureas: a novel class of KDR kinase inhibitors. — Bioorg Med Chem Lett
CHEMBL4424914	ADMET	Inhibition of human N-terminal His6-tagged TIE2 (771 to end residues) expressed in baculovirus infected Sf21 insect cells using Poly (Glu4-Tyr) (4:1) as substrate	Optimization of an azetidine series as inhibitors of colony stimulating factor-1 receptor (CSF-1R) Type II to lead to the clinical candidate JTE-952. — Bioorg Med Chem Lett
CHEMBL834763	Functional	Concentration required to inhibit autophosphorylation of tyrosine protein kinase receptor TIE-2 transfected in 3T3 cells	Novel 4-amino-furo[2,3-d]pyrimidines as Tie-2 and VEGFR2 dual inhibitors. — Bioorg Med Chem Lett

Cellosaurus cell lines

6 cell lines: 6 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B8QK	Abcam HCT 116 TEK KO	Cancer cell line	Male
CVCL_B9T1	Abcam A-549 TEK KO	Cancer cell line	Male
CVCL_E0QM	Ubigene HeLa TEK KO	Cancer cell line	Female
CVCL_TR91	HAP1 TEK (-) 1	Cancer cell line	Male
CVCL_TR92	HAP1 TEK (-) 2	Cancer cell line	Male
CVCL_TR93	HAP1 TEK (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04999618	PHASE4	COMPLETED	A New Approach in Laser Surgery Using the Regenerative Solution in Children Diagnosed With Vascular Pathology
NCT02914652	PHASE4	COMPLETED	The Cardiopulmonary Effect of Inhaled Beta-2-agonists on Adult Patients Born With Ventricular Septum Defects.
NCT05688670	PHASE4	COMPLETED	Regional Anesthesia Following Pediatric Cardiac Surgery
NCT03767660	PHASE4	UNKNOWN	Efficacy of Rapamycin (Sirolimus) in the Treatment of BRBNS, Hereditary or Sporadic Venous Malformation
NCT02384122	PHASE3	COMPLETED	Efficacy of Octreotide on Blood and Iron Requirements in Patients With Anemia Due to Angiodysplasias
NCT02638389	PHASE3	RECRUITING	Efficacy and Safety of Sirolimus in Vascular Anomalies That Are Refractory to Standard Care
NCT03110783	PHASE3	COMPLETED	Bioseal Dural Sealing Study BIOS-14-001
NCT03987152	PHASE3	UNKNOWN	Treatment of Congenital Vascular Malformations Using Sirolimus: Improving Quality of Life
NCT00000470	PHASE3	COMPLETED	Infant Heart Surgery: Central Nervous System Sequelae of Circulatory Arrest
NCT00113698	PHASE3	TERMINATED	Angiotensin Converting Enzyme Inhibition in Children With Mitral Regurgitation
NCT05253209	PHASE3	TERMINATED	A Study Evaluating the Efficacy and Safety of IV L-Citrulline for the Prevention of Clinical Sequelae of Acute Lung Injury Induced by Cardiopulmonary Bypass in Pediatric Patients Undergoing Surgery for Congenital Heart Defects
NCT04947124	PHASE2	COMPLETED	A Study to Determine the Safety and Tolerability of 2 Concentrations of QLS-101
NCT02509468	PHASE2	COMPLETED	suPERficial Slow-flow Vascular malFORMations Treated With sirolimUS
NCT02754960	PHASE2	WITHDRAWN	Efficacy Study of Thalidomide in Gastrointestinal Vascular Malformation Related Bleeding
NCT02883023	PHASE2	UNKNOWN	Electrosclerotherapy for Capillary Malformations
NCT03972592	PHASE2	COMPLETED	Topical Sirolimus in Cutaneous Lymphatic Malformations
NCT05983159	PHASE2	RECRUITING	A Trial of Targeted Therapies for Patients With Slow-Flow or Fast-Flow Vascular Malformations
NCT06788314	PHASE2	RECRUITING	A Study of Enalapril in Treatment of Venous Malformations
NCT06789913	PHASE2	RECRUITING	A Phase 2 Study of Mutant-selective PI3Kα Inhibitor, RLY-2608, in Adults and Children With PIK3CA Related Overgrowth Spectrum and Malformations Driven by PIK3CA Mutation
NCT07037238	PHASE2	RECRUITING	An Open-Label, Single-Arm Exploratory Clinical Study of Everolimus for the Treatment of Vascular Malformations
NCT07477548	PHASE2	NOT_YET_RECRUITING	A Study to Evaluate the Efficacy and Safety of Everolimus in Patients With Teratment-refractory Vascular Anomalies
NCT07579962	PHASE2	NOT_YET_RECRUITING	Treatment of Low-flow Vascular Malformations With Bleomycin Electrosclerotherapy (BEST)
NCT00199771	PHASE2	COMPLETED	Hypertonic Saline Dextran in Pediatric Cardiac Surgery
NCT00556361	PHASE2	COMPLETED	Use of Ketamine Prior to Cardiopulmonary Bypass in Children
NCT00848393	PHASE2	COMPLETED	Measures to Lower the Stress Response in Pediatric Cardiac Surgery
NCT04017975	PHASE2	ACTIVE_NOT_RECRUITING	Optical Tissue Identification for Myocardial Architecture
NCT01460017	PHASE1	UNKNOWN	Comparison Between Deep Sclerectomy and Traditional Trabeculotomy & Trabeculectomy in Congenital Glaucoma
NCT02121171	PHASE1	UNKNOWN	Combined Trab+Trab Versus Combined Trab+Trab With Subconjunctival Implantation of Ologen for Primary Congenital Glaucoma
NCT01825369	PHASE1	WITHDRAWN	Aberrations in Carnitine Homeostasis in Congenital Heart Disease With Increased Pulmonary Blood Flow
NCT01915277	PHASE1	COMPLETED	A Phase I Study of Dexmedetomidine Bolus and Infusion in Corrective Infant Cardiac Surgery: Safety and Pharmacokinetics
NCT01020721	Not specified	UNKNOWN	The Genetic Characteristics in South Korean Patients With Primary Congenital Glaucoma
NCT01136460	Not specified	UNKNOWN	Genetic Testing in Primary Congenital Glaucoma Patients
NCT02945176	Not specified	COMPLETED	Safety and Performance Study of the ARGOS-IO System in Patients Undergoing Boston Keratoprosthesis Implantation
NCT03077789	Not specified	COMPLETED	Prospective Study of the Diagnostic and Therapeutic Management of Congenital Glaucoma in France
NCT03541551	Not specified	COMPLETED	Ologen® Collagen Matrix in Patients With Primary Congenital Glaucoma Undergoing Trabeculectomy
NCT04079725	Not specified	UNKNOWN	Iris Tissue in Primary Congenital Glaucoma
NCT04116450	Not specified	COMPLETED	MicrocatheterTrabeculotomy in Primary Congenital Glaucoma
NCT04381611	Not specified	ENROLLING_BY_INVITATION	INTEGRAL Study: A Longitudinal Study of Surgeries and Lasers in Glaucoma: Long-term Results and Success Predictors Analysed From a Large-scale Retrospective and Prospective Glaucoma Register
NCT04647929	Not specified	WITHDRAWN	Comparison of Surgical Treatment Options for Primary Congenital and Developmental Glaucomas
NCT04683289	Not specified	COMPLETED	Visco-Circumferential-Suture-Trabeculotomy Versus Trabeculotomy