ANGPT1

Summary

ANGPT1 (angiopoietin 1, HGNC:484) is a protein-coding gene on chromosome 8q23.1, encoding Angiopoietin-1 (Q15389). Binds and activates TEK/TIE2 receptor by inducing its dimerization and tyrosine phosphorylation.

This gene encodes a secreted glycoprotein that belongs to the angiopoietin family. Members of this family play important roles in vascular development and angiogenesis. All angiopoietins bind with similar affinity to an endothelial cell-specific tyrosine-protein kinase receptor. The protein encoded by this gene is a secreted glycoprotein that activates the receptor by inducing its tyrosine phosphorylation. It plays a critical role in mediating reciprocal interactions between the endothelium and surrounding matrix and mesenchyme and inhibits endothelial permeability. The protein also contributes to blood vessel maturation and stability, and may be involved in early development of the heart. Mutations in this gene are associated with hereditary angioedema.

Source: NCBI Gene 284 — RefSeq curated summary.

At a glance

• Gene–disease (curated): glaucoma (Moderate, GenCC) — +2 more curated relationships
• GWAS associations: 51
• Clinical variants (ClinVar): 343 total — 1 pathogenic
• Phenotypes (HPO): 7
• Druggable target: yes
• MANE Select transcript: NM_001146

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:484
Approved symbol	ANGPT1
Name	angiopoietin 1
Location	8q23.1
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0003, Ang1, AGPT-1
Ensembl gene	ENSG00000154188
Ensembl biotype	protein_coding
OMIM	601667
Entrez	284

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 6 protein_coding, 2 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000297450, ENST00000517746, ENST00000518386, ENST00000520033, ENST00000520052, ENST00000520734, ENST00000521950, ENST00000522400, ENST00000949598

RefSeq mRNA: 3 — MANE Select: NM_001146 NM_001146, NM_001199859, NM_001314051

CCDS: CCDS56551, CCDS6306, CCDS83313

Canonical transcript exons

ENST00000517746 — 9 exons

Exon	Start	End
ENSE00002116118	107497262	107497918
ENSE00003545603	107321896	107322128
ENSE00003725768	107249482	107252015
ENSE00003992043	107284682	107284848
ENSE00003992044	107346942	107347097
ENSE00003992046	107336150	107336271
ENSE00003992050	107264221	107264351
ENSE00003992052	107303240	107303367
ENSE00003992053	107293936	107294037

Expression profiles

Bgee: expression breadth ubiquitous, 250 present calls, max score 93.17.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 11.2638 / max 861.4561, expressed in 982 samples.

FANTOM5 promoters (13 alternative TSS)

Promoter ID	TPM avg	Samples expressed
94382	3.8915	719
94380	1.6394	567
94383	1.4665	448
94375	1.2180	481
94379	0.8467	362
94374	0.6703	303
94376	0.5414	299
94381	0.3420	174
94371	0.2518	10
94377	0.1585	64

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lower lobe of lung	UBERON:0008949	93.17	gold quality
calcaneal tendon	UBERON:0003701	92.64	gold quality
cranial nerve II	UBERON:0000941	92.29	gold quality
right lung	UBERON:0002167	91.64	gold quality
blood vessel layer	UBERON:0004797	90.98	gold quality
popliteal artery	UBERON:0002250	89.51	gold quality
tibial artery	UBERON:0007610	89.48	gold quality
seminal vesicle	UBERON:0000998	88.81	gold quality
artery	UBERON:0001637	88.66	gold quality
urethra	UBERON:0000057	88.60	gold quality
stromal cell of endometrium	CL:0002255	88.56	gold quality
cauda epididymis	UBERON:0004360	88.51	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	87.94	gold quality
aorta	UBERON:0000947	86.81	gold quality
lung	UBERON:0002048	86.70	gold quality
visceral pleura	UBERON:0002401	86.24	gold quality
choroid plexus epithelium	UBERON:0003911	85.94	gold quality
gall bladder	UBERON:0002110	85.55	gold quality
biceps brachii	UBERON:0001507	85.52	gold quality
upper lobe of lung	UBERON:0008948	84.52	gold quality
right coronary artery	UBERON:0001625	84.50	gold quality
upper lobe of left lung	UBERON:0008952	84.18	gold quality
descending thoracic aorta	UBERON:0002345	83.95	gold quality
subcutaneous adipose tissue	UBERON:0002190	83.68	gold quality
adipose tissue	UBERON:0001013	83.64	gold quality
adrenal tissue	UBERON:0018303	83.63	gold quality
thoracic aorta	UBERON:0001515	83.40	gold quality
superficial temporal artery	UBERON:0001614	83.35	gold quality
ascending aorta	UBERON:0001496	83.29	gold quality
connective tissue	UBERON:0002384	83.21	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ENAD-20	yes	314.31
E-MTAB-9388	yes	287.14
E-CURD-119	yes	35.18
E-CURD-112	yes	35.14
E-HCAD-6	yes	18.77
E-ANND-3	yes	15.40

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

4 targets.

Target	Regulation
MYH1	Activation
MYH2	Activation
MYOD1	Activation
MYOG	Activation

Upstream regulators (CollecTRI, top): DBP, ELF2, ELF3, GRHL3, HIF1A, ING4, MECOM, NR2F2, PPARD, RUNX1, TXK, ZEB2, ZNF350

miRNA regulators (miRDB)

145 targeting ANGPT1, 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-3646	100.00	73.56	5283
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345

Literature-anchored findings (GeneRIF, showing 40)

• Angiopoietin-1 negatively regulates expression and activity of tissue factor in vascular endothelial cells (PMID:11729102)
• Angiopoietin-1 is normally expressed by periendothelial cells. (PMID:11776343)
• Genomic structures of the human angiopoietins show polymorphism in angiopoietin-2 (PMID:11856872)
• Angiopoietin 1 stabilizes tumor neovasculature and inhibits tumor growth (PMID:11870550)
• loss of normal Ang-1 expression may contribute to the excessive blood loss observed in menorrhagia (PMID:11891175)
• angiopoietin-1 regulates expression of NERF2 and its own receptor in hypoxic cells. (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)
• may play important role in placental biology and chorionic villus vascular development and remodeling in an autocrine/paracrine manner (PMID:12213874)
• Ang-1 is associated with neovascularization in the cancer stroma through vascular endothelial growth factor net-works in esophageal cancer (PMID:12239588)
• These results indicate that angiopoietin 1 promotes tumor angiogenesis and tumor vessel plasticity of human cervical cancer in mice. (PMID:12243755)
• angiopoietin-1 is an important regulator of angiogenesis and vascular permeability. (PMID:12402160)
• In focal nodular hyperplasia, Ang-1 was significantly up-regulated, Ang-2 was down-regulated, and the Ang-1/Ang-2 ratio was highly and specifically increased. (PMID:12612904)
• Angiopoietin-1 mRNA & protein is expressed by myeloma cell lines & tumor cells from approximately 47% of patients,suggesting that the angiopoietin system could be involved in MM-induced angiogenesis. (PMID:12649156)
• an increased expression of Ang-2/1 in the presence of VEGF may play a critical role in promoting tumor angiogenesis and progression in human hepatocellular carcinoma (PMID:12717391)
• Ang-1 is an important regulator of angiogenesis and vascular permeability and that this effect may be secondary to increasing periendothelial support and vessel stabilization. (PMID:12810673)
• angiopoietin-1 elicits chemokinesis of vascular endothelial cells by a phosphoinositide 3-OH kinase/son of sevenless-dependent modulation of Rac1 and RhoA. (PMID:12816861)
• MEK/ERK phosphorylation and migration induced by angiopoietin-1 in endothelial cells is affected by localization of Tie2 and phospholipase D in endothelial caveolae (PMID:12890486)
• Angiopoietin 1 recruits vascular smooth muscle cells via endothelial-derived heparin binding EGF-like growth factor. (PMID:12958167)
• angiopoietin-1 regulates migration and three-dimensional organization of endothelial cells along with Tie2 and ShcA (PMID:14665640)
• role of Ang1 in tumor angiogenesis (review) (PMID:14672554)
• results support a role for the ETS factor ESE-1 as a novel transcriptional regulator of angiopoietin-1 gene regulation in the setting of inflammation (PMID:14715662)
• 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)
• Recombinant human Ang1 prevented VEGF-Trap-induced tracheal blood vessel loss. Ang1 participates in blood vessel survival and plasticity in adult life. (PMID:15001532)
• Angiopoietin 1 is an important representative of the angiogenic factors and is involved in the angiogenic processes of these lesions. There were no significant differences in the expression and location within different lesion types for ANGPT1. (PMID:15019820)
• increased expression of Angiopoietin-1 and Angiopoietin-2 play a critical role in the process of vascular development in HCC (PMID:15094228)
• Reduced expression of Ang-1 protein and mRNA expression in human endometrial stromal cells. (PMID:15161644)
• the angiopoietin/Tie-2 system may participate in the angiogenic response to hypoxia in renal tissues and in tumor angiogenesis in renal carcinoma. (PMID:15198927)
• angiopoietins -1 and 2 have roles in endothelial development (PMID:15213103)
• 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)
• Under non-reducing conditions, angiopoietin 1 forms disulfide-linked multimers. (PMID:15284220)
• We show that Ang1cc can inhibit Tie2 activation and can inhibit Ang1 activity in vitro and in vivo. (PMID:15381091)
• Ang1 regulates Glioblastoma Multiforme (GBM) vascularity in a VEGF-A dependent manner, synergizing the initial pro-angiogenic response that is triggered by VEGF-A and promoting the vascular growth of GBM. (PMID:15453096)
• Ang1 demonstrates proinflmmatory potential by inducing endothelial P-selectin translocation and neutrophil adhesion onto vascular endothelial cells. (PMID:15498854)
• Plasma levels in type 2 diabetes are selectively not elevated in patients with diabetes and are associated with indexes of endothelial damage/dysfunction. (PMID:15562207)
• Recombinant human angiopoietin-1 activated human skeletal muscle cell & rat neonatal cardiac myocyte Akt(S473)& MAPK(p42/44) survival pathways. This new function contributes to developmental & cardioprotective actions of Angpt1. (PMID:15692086)
• TNF-alpha signals primarily through the p38, JNK, MAP kinase, and IKK pathways resulting in the activation of the transcription factors AP-1 and NF-kappa B. (PMID:15694363)
• 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)
• Ang-2 (but not Ang-1) was higher in patients with diabetes compared to controls (p<0.01), with no significant difference between patients with and without cardiovascular diseases (PMID:15823283)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	angpt1	ENSDARG00000030364
mus_musculus	Angpt1	ENSMUSG00000022309
rattus_norvegicus	Angpt1	ENSRNOG00000005854

Paralogs (25): TNC (ENSG00000041982), FCN1 (ENSG00000085265), ANGPT2 (ENSG00000091879), ANGPT4 (ENSG00000101280), FGL1 (ENSG00000104760), FN1 (ENSG00000115414), TNR (ENSG00000116147), ANGPTL1 (ENSG00000116194), TNN (ENSG00000120332), FGL2 (ENSG00000127951), FIBCD1 (ENSG00000130720), ANGPTL6 (ENSG00000130812), ANGPTL3 (ENSG00000132855), ANGPTL2 (ENSG00000136859), FCN3 (ENSG00000142748), FNDC7 (ENSG00000143107), FCN2 (ENSG00000160339), MFAP4 (ENSG00000166482), ANGPTL4 (ENSG00000167772), TNXB (ENSG00000168477), FGG (ENSG00000171557), FGA (ENSG00000171560), FGB (ENSG00000171564), ANGPTL7 (ENSG00000171819), ANGPTL5 (ENSG00000187151)

Protein

Protein identifiers

Angiopoietin-1 — Q15389 (reviewed: Q15389)

All UniProt accessions (4): Q15389, B4DTQ9, E5RFF4, E7ERK4

UniProt curated annotations — full annotation on UniProt →

Function. Binds and activates TEK/TIE2 receptor by inducing its dimerization and tyrosine phosphorylation. Plays an important role in the regulation of angiogenesis, endothelial cell survival, proliferation, migration, adhesion and cell spreading, reorganization of the actin cytoskeleton, but also maintenance of vascular quiescence. Required for normal angiogenesis and heart development during embryogenesis. 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. Mediates blood vessel maturation/stability. Implicated in endothelial developmental processes later and distinct from that of VEGF. Appears to play a crucial role in mediating reciprocal interactions between the endothelium and surrounding matrix and mesenchyme.

Subunit / interactions. Homooligomer. Interacts with TEK/TIE2. Interacts with SVEP1/polydom. Interacts with THBD; this interaction significantly inhibits the generation of activated PC and TAFIa/CPB2 by the thrombin/thrombomodulin complex.

Subcellular location. Secreted.

Post-translational modifications. Glycosylated.

Disease relevance. Angioedema, hereditary, 5 (HAE5) [MIM:619361] A form of angioedema, a disorder characterized by episodic local swelling involving subcutaneous or submucous tissue of the upper respiratory and gastrointestinal tracts, face, extremities, and genitalia. HAE5 is an autosomal dominant form characterized by onset of episodic swelling of the face, lips, hands, and abdomen in the second decade of life. The disease is caused by variants affecting the gene represented in this entry.

Miscellaneous. It may have a potential therapeutic utility since it can be used for specifically targeting tumor vasculature or for promoting angiogenic processes in certain organs such as an ischemic heart.

Isoforms (2)

UniProt ID	Names	Canonical?
Q15389-1	1	yes
Q15389-2	2, Gly-269 del

RefSeq proteins (3): NP_001137, NP_001186788, NP_001300980 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002181	Fibrinogen_a/b/g_C_dom	Domain
IPR014716	Fibrinogen_a/b/g_C_1	Homologous_superfamily
IPR020837	Fibrinogen_CS	Conserved_site
IPR036056	Fibrinogen-like_C	Homologous_superfamily
IPR037579	FIB_ANG-like	Family
IPR057439	ANG-1/2/4	Domain

Pfam: PF00147, PF25443

UniProt features (37 total): strand 12, helix 6, glycosylation site 5, sequence variant 4, disulfide bond 2, coiled-coil region 2, turn 2, signal peptide 1, chain 1, splice variant 1, domain 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
9IVT	X-RAY DIFFRACTION	1.75
4EPU	X-RAY DIFFRACTION	2.1
9IVU	X-RAY DIFFRACTION	2.28
4JYO	X-RAY DIFFRACTION	2.5
4K0V	X-RAY DIFFRACTION	4.51

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q15389-F1	83.46	0.67

Functional residue map

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

Disulfide bonds (2): 286–315, 439–452

Glycosylation sites (5): 92, 122, 154, 243, 295

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: 506 (showing top): PID_SHP2_PATHWAY, GSE45365_NK_CELL_VS_BCELL_DN, MODULE_52, AP1_01, GOBP_NEGATIVE_REGULATION_OF_NEURON_APOPTOTIC_PROCESS, GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_GROWTH_FACTOR_STIMULUS, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, MODULE_516, GOBP_VASCULAR_ENDOTHELIAL_GROWTH_FACTOR_SIGNALING_PATHWAY, GOBP_POSITIVE_REGULATION_OF_ENDOCYTOSIS, PAX4_01, TGCGCANK_UNKNOWN, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_REGULATION_OF_PHOSPHORYLATION, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT

GO Biological Process (41): angiogenesis (GO:0001525), in utero embryonic development (GO:0001701), sprouting angiogenesis (GO:0002040), positive regulation of receptor internalization (GO:0002092), negative regulation of cytokine production involved in immune response (GO:0002719), negative regulation of cell adhesion (GO:0007162), activation of transmembrane receptor protein tyrosine kinase activity (GO:0007171), blood coagulation (GO:0007596), positive regulation of endothelial cell migration (GO:0010595), positive regulation of gene expression (GO:0010628), regulation of skeletal muscle satellite cell proliferation (GO:0014842), hemopoiesis (GO:0030097), heparin proteoglycan biosynthetic process (GO:0030210), positive regulation of protein ubiquitination (GO:0031398), cell-substrate adhesion (GO:0031589), regulation of tumor necrosis factor production (GO:0032680), protein localization to cell surface (GO:0034394), negative regulation of protein import into nucleus (GO:0042308), negative regulation of apoptotic process (GO:0043066), negative regulation of vascular permeability (GO:0043116), regulation of canonical NF-kappaB signal transduction (GO:0043122), negative regulation of neuron apoptotic process (GO:0043524), positive regulation of blood vessel endothelial cell migration (GO:0043536), positive regulation of cell adhesion (GO:0045785), Tie signaling pathway (GO:0048014), positive regulation of peptidyl-tyrosine phosphorylation (GO:0050731), positive regulation of coagulation (GO:0050820), positive chemotaxis (GO:0050918), neuron apoptotic process (GO:0051402), positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0051897), positive regulation of ERK1 and ERK2 cascade (GO:0070374), glomerulus vasculature development (GO:0072012), negative regulation of vascular endothelial growth factor signaling pathway (GO:1900747), positive regulation of blood-brain barrier permeability (GO:1905605), negative regulation of endothelial cell apoptotic process (GO:2000352), regulation of macrophage migration inhibitory factor signaling pathway (GO:2000446), blood vessel development (GO:0001568), cell surface receptor protein tyrosine kinase signaling pathway (GO:0007169), cell differentiation (GO:0030154), negative regulation of blood coagulation (GO:0030195)

GO Molecular Function (5): receptor tyrosine kinase binding (GO:0030971), identical protein binding (GO:0042802), receptor ligand activity (GO:0048018), signaling receptor binding (GO:0005102), protein binding (GO:0005515)

GO Cellular Component (6): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), plasma membrane (GO:0005886), microvillus (GO:0005902), membrane raft (GO:0045121), extracellular exosome (GO:0070062)

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
cell adhesion	2
signaling receptor binding	2
protein binding	2
blood vessel morphogenesis	1
anatomical structure formation involved in morphogenesis	1
chordate embryonic development	1
angiogenesis	1
regulation of receptor internalization	1
receptor internalization	1
positive regulation of receptor-mediated endocytosis	1
negative regulation of cytokine production	1
cytokine production involved in immune response	1
negative regulation of production of molecular mediator of immune response	1
regulation of cytokine production involved in immune response	1
regulation of cell adhesion	1
negative regulation of cellular process	1
cell surface receptor protein tyrosine kinase signaling pathway	1
activation of protein kinase activity	1
protein-containing complex assembly	1
hemostasis	1
wound healing	1
coagulation	1
regulation of endothelial cell migration	1
positive regulation of cell migration	1
endothelial cell migration	1
gene expression	1
regulation of gene expression	1
positive regulation of macromolecule biosynthetic process	1
skeletal muscle satellite cell proliferation	1
regulation of skeletal muscle cell proliferation	1
cell development	1
heparin proteoglycan metabolic process	1
protein O-linked glycosylation via xylose	1
protein ubiquitination	1
regulation of protein ubiquitination	1
positive regulation of protein modification by small protein conjugation or removal	1
tumor necrosis factor production	1
regulation of tumor necrosis factor superfamily cytokine production	1
intracellular protein localization	1
protein import into nucleus	1

Protein interactions and networks

STRING

2156 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ANGPT1	TEK	Q02763	999
ANGPT1	TIE1	P35590	998
ANGPT1	NTRK1	P04629	991
ANGPT1	KDR	P35968	983
ANGPT1	FLT1	P16057	953
ANGPT1	FGF2	P09038	819
ANGPT1	CDH5	P33151	796
ANGPT1	PDGFB	P01127	767
ANGPT1	CXCR4	P30991	757
ANGPT1	FLT4	P35916	746
ANGPT1	PDGFRB	P09619	745
ANGPT1	VWF	P04275	744
ANGPT1	AKAP12	Q02952	732
ANGPT1	AKT1	P31749	730
ANGPT1	EGF	P01133	729
ANGPT1	FGF5	P12034	729

IntAct

18 interactions, top by confidence:

A	B	Type	Score
STK25	STRN	psi-mi:“MI:0914”(association)	0.900
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
ANGPT1	ANGPT1	psi-mi:“MI:0915”(physical association)	0.520
ANGPT1		psi-mi:“MI:0407”(direct interaction)	0.440
ANGPT1	TIE1	psi-mi:“MI:0407”(direct interaction)	0.440
RND3	ANGPT1	psi-mi:“MI:0915”(physical association)	0.400
ANGPT1		psi-mi:“MI:0915”(physical association)	0.370
ACTR2		psi-mi:“MI:0914”(association)	0.350
CAPZB	ENAH	psi-mi:“MI:0914”(association)	0.350
PLK1	RBM25	psi-mi:“MI:0914”(association)	0.350
TJP1	ANGPT1	psi-mi:“MI:0914”(association)	0.350
TUBG1	ZC3H11A	psi-mi:“MI:0914”(association)	0.350
ANGPT4	POTEF	psi-mi:“MI:0914”(association)	0.350

BioGRID (20): ANGPT1 (Two-hybrid), ANGPT1 (Affinity Capture-Luminescence), ANGPT1 (Affinity Capture-MS), TIE1 (Protein-peptide), ANGPT1 (Reconstituted Complex), ANGPT1 (Affinity Capture-Western), ANGPT1 (Reconstituted Complex), ANGPT1 (Affinity Capture-Western), FBLN7 (Reconstituted Complex), ANGPT1 (Reconstituted Complex), ANGPT1 (Affinity Capture-MS), ANGPT1 (Reconstituted Complex), ANGPT1 (Affinity Capture-MS), ANGPT1 (Affinity Capture-MS), ANGPT1 (Affinity Capture-MS)

ESM2 similar proteins: A0A8J8, O08538, O15123, O18920, O35460, O35462, O35608, O43827, O77802, O95841, P02675, P02676, P02678, P02679, P02680, P04115, P12799, P12804, P14480, P17634, P21758, P30204, P86239, Q02020, Q08830, Q0P4P2, Q14314, Q15389, Q1RMR1, Q29RY7, Q3SZZ7, Q5EA66, Q5M8C6, Q5XK91, Q60FC1, Q640P2, Q6AX44, Q71KU9, Q86XS5, Q8K0E8

Diamond homologs: A0A8J8, A2AV25, D8VNS7, D8VNS8, D8VNS9, D8VNT0, E2IYB3, E9PV24, O00602, O08538, O15123, O18920, O35460, O35462, O35608, O43827, O70165, O70497, O75636, O77802, O93526, O95841, P02671, P02675, P02676, P02678, P02679, P02680, P04115, P06399, P10039, P12799, P12804, P14448, P14480, P17634, P19477, P21520, P22105, P24821

SIGNOR signaling

7 interactions.

A	Effect	B	Mechanism
ANGPT1	up-regulates	TIE1	binding
ANGPT1	up-regulates	TEK	binding
ANGPT1	“up-regulates quantity by expression”	MYOD1	“transcriptional regulation”
ANGPT1	“up-regulates quantity by expression”	MYOG	“transcriptional regulation”
ANGPT1	“up-regulates quantity by expression”	MYH2	“transcriptional regulation”
ANGPT1	“up-regulates quantity by expression”	MYH1	“transcriptional regulation”
MECOM	“up-regulates quantity by expression”	ANGPT1	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	186
Likely benign	115
Benign	26

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
1703544	GRCh37/hg19 8p23.3-q24.3(chr8:158048-146295771)	Pathogenic

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

3333 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:107251926:A:G	W476R	1.000
8:107251926:A:T	W476R	1.000
8:107251996:A:C	C452W	1.000
8:107251997:C:A	C452F	1.000
8:107251997:C:G	C452S	1.000
8:107251997:C:T	C452Y	1.000
8:107251998:A:G	C452R	1.000
8:107251998:A:T	C452S	1.000
8:107252008:C:A	W448C	1.000
8:107252008:C:G	W448C	1.000
8:107252010:A:G	W448R	1.000
8:107252010:A:T	W448R	1.000
8:107252013:A:G	W447R	1.000
8:107252013:A:T	W447R	1.000
8:107264240:A:C	C439W	1.000
8:107264241:C:G	C439S	1.000
8:107264241:C:T	C439Y	1.000
8:107264242:A:G	C439R	1.000
8:107264242:A:T	C439S	1.000
8:107264259:T:A	D433V	1.000
8:107264259:T:G	D433A	1.000
8:107264279:G:C	S426R	1.000
8:107264279:G:T	S426R	1.000
8:107264281:T:G	S426R	1.000
8:107264283:A:C	F425C	1.000
8:107264283:A:G	F425S	1.000
8:107251871:C:G	R494P	0.999
8:107251924:C:A	W476C	0.999
8:107251924:C:G	W476C	0.999
8:107251934:C:T	G473E	0.999

dbSNP variants (sampled 300 via entrez): RS1000008147 (8:107438640 T>G), RS1000024132 (8:107384238 A>G), RS1000038760 (8:107431995 T>C), RS1000079926 (8:107333486 T>C), RS1000092211 (8:107312955 A>G), RS1000097140 (8:107264011 C>T), RS1000110321 (8:107378020 T>C), RS1000116716 (8:107478641 T>G), RS1000175725 (8:107414971 G>A,C,T), RS1000180214 (8:107353554 C>G,T), RS1000182483 (8:107281222 A>C), RS1000189343 (8:107348553 C>G), RS1000192301 (8:107414772 G>A), RS1000194928 (8:107496689 A>G,T), RS1000208915 (8:107260677 C>T)

Disease associations

OMIM: gene MIM:601667 | disease phenotypes: MIM:619361, MIM:603596, MIM:610618, MIM:615214

GenCC curated gene-disease

Disease	Classification	Inheritance
glaucoma	Moderate	Autosomal dominant
angioedema, hereditary, 5	Moderate	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
primary congenital glaucoma	Limited	AD

Mondo (5): angioedema, hereditary, 5 (MONDO:0030293), polydactyly (MONDO:0021003), hereditary angioedema type 3 (MONDO:0012526), agammaglobulinemia 7, autosomal recessive (MONDO:0014083), glaucoma (MONDO:0005041)

Orphanet (1): F12-related hereditary angioedema with normal C1Inh (Orphanet:100054)

HPO phenotypes

7 total (8 of 7 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000282	Facial edema
HP:0007514	Edema of the dorsum of hands
HP:0030254	Nail bed hemorrhage
HP:0031244	Swollen lip
HP:0033250	Nailfold capillary tortuosity
HP:0100665	Angioedema
HP:0010442	Polydactyly

GWAS associations

51 associations (top):

Study	Trait	p-value
GCST002304_4	Fractional exhaled nitric oxide (childhood)	3.000000e-06
GCST004612_45	High light scatter reticulocyte percentage of red cells	2.000000e-09
GCST004628_99	Immature fraction of reticulocytes	8.000000e-11
GCST005170_38	Intraocular pressure	2.000000e-10
GCST005580_115	Intraocular pressure	2.000000e-31
GCST005580_144	Intraocular pressure	9.000000e-31
GCST005803_13	Corneal astigmatism	7.000000e-06
GCST006065_25	Glaucoma (primary open-angle)	7.000000e-12
GCST006394_19	Intraocular pressure	1.000000e-28
GCST006394_20	Intraocular pressure	1.000000e-13
GCST006394_21	Intraocular pressure	2.000000e-17
GCST006395_11	Glaucoma	8.000000e-06
GCST006395_21	Glaucoma	5.000000e-12
GCST006395_39	Glaucoma	6.000000e-12
GCST006412_102	Intraocular pressure	1.000000e-28
GCST006412_103	Intraocular pressure	3.000000e-18
GCST006412_4	Intraocular pressure	4.000000e-14
GCST006585_2850	Blood protein levels	2.000000e-09
GCST006661_120	Male-pattern baldness	9.000000e-16
GCST007944_10	Medication use (antiglaucoma preparations and miotics)	2.000000e-09
GCST008158_6	Body mass index	7.000000e-06
GCST009309_5	Face memory	4.000000e-06
GCST009725_49	Intraocular pressure	9.000000e-11
GCST009725_8	Intraocular pressure	3.000000e-30
GCST009726_31	Glaucoma	2.000000e-10
GCST010002_310	Refractive error	3.000000e-08
GCST010703_268	Brain morphology (MOSTest)	4.000000e-13
GCST010726_38	Periventricular white matter hyperintensities	2.000000e-06
GCST010796_3609	Electrocardiogram morphology (amplitude at temporal datapoints)	7.000000e-17
GCST010796_3610	Electrocardiogram morphology (amplitude at temporal datapoints)	9.000000e-19

EFO canonical traits (14, from GWAS)

EFO ID	Trait name
EFO:0005536	nitric oxide exhalation measurement
EFO:0007986	reticulocyte count
EFO:0004695	intraocular pressure measurement
EFO:1002040	Corneal astigmatism
EFO:0009944	Antiglaucoma preparations and miotics use measurement
EFO:0004340	body mass index
EFO:0004874	memory performance
EFO:0004346	neuroimaging measurement
EFO:0005665	white matter hyperintensity measurement
EFO:0004327	electrocardiography
EFO:0004527	mean corpuscular hemoglobin
EFO:0010701	mean reticulocyte volume
EFO:0007984	platelet component distribution width
EFO:0004305	erythrocyte count

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D005901	Glaucoma	C11.525.381
D056828	Hereditary Angioedema Type III	C14.907.079.500.500; C17.800.862.945.066.500.500; C20.543.480.904.066.500.500
D017689	Polydactyly	C05.660.585.600; C16.131.621.585.600

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3217395 (SINGLE PROTEIN)

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs2445365	ANGPT1		0.00	0

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, affects cotreatment, increases expression, affects expression	7
sodium arsenite	decreases expression, decreases secretion, increases expression	4
trichostatin A	affects cotreatment, increases expression	3
Estradiol	affects cotreatment, increases expression, decreases expression	3
belinostat	increases expression, affects cotreatment	2
(+)-JQ1 compound	decreases expression	2
Vorinostat	affects cotreatment, increases expression	2
Panobinostat	affects cotreatment, increases expression	2
Air Pollutants	increases abundance, decreases expression	2
Arsenic	affects expression, decreases expression	2
Dexamethasone	affects cotreatment, increases expression	2
Doxorubicin	decreases reaction, increases expression, decreases response to substance, decreases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Tretinoin	increases expression, decreases expression	2
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression	2
Aflatoxin B1	affects expression, decreases expression	2
Cadmium Chloride	decreases expression, increases expression	2
Particulate Matter	decreases expression, increases abundance	2
bisphenol F	increases expression	1
geldanamycin	increases expression	1
testosterone enanthate	affects expression	1
methylmercuric chloride	decreases expression, increases expression	1
lasiocarpine	decreases expression	1
propionaldehyde	increases expression	1
bisphenol A	decreases expression	1
rutecarpine	decreases expression	1
cupric chloride	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment, decreases expression	1
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one	decreases reaction, increases expression, decreases response to substance	1
cylindrospermopsin	increases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3225612	Binding	Binding affinity to human Ang-1 (amino acid residues N21 to F496) at 0.125 to 2 uM by surface plasmon resonance assay	Binding region and interaction properties of sulfoquinovosylacylglycerol (SQAG) with human vascular endothelial growth factor 165 revealed by biosensor-based assays — Medchemcomm

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B8B8	Abcam HCT 116 ANGPT1 KO	Cancer cell line	Male
CVCL_B8SD	Abcam MCF-7 ANGPT1 KO	Cancer cell line	Female
CVCL_B9DB	Abcam A-549 ANGPT1 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00061503	PHASE4	COMPLETED	Mechanism of Action of TRAVATAN 0.004% in Subjects With Glaucoma or Ocular Hypertension
NCT00143208	PHASE4	COMPLETED	Evaluation Of Intraocular Pressure Lowering-Effect Of Xalacom In Patients With Poag Or Oh.
NCT00224289	PHASE4	COMPLETED	Effect of Age on Latanoprost 0.005% in Patients With Glaucoma
NCT00273221	PHASE4	UNKNOWN	Combined Phacotube vs Phacotrabeculectomy:A Randomized Controlled Trial
NCT00329095	PHASE4	COMPLETED	An Evaluation of Use of Topical Ocular Hypotensive Medication by Compliance
NCT00345046	PHASE4	COMPLETED	A Comparison of Three Different Formulations of Prednisolone Acetate 1%
NCT00346489	PHASE4	COMPLETED	Outcomes of Intraoperative 5-Fluorouracil Versus Mitomycin C
NCT00347035	PHASE4	TERMINATED	INFLUENCE OF TOPICAL INDOMETHACIN ON HYPOTHENSIVE EFFECT OF BRIMONIDINE
NCT00347802	PHASE4	COMPLETED	Diurnal Curves With Bimatoprost 0.03% Versus Travoprost 0.004%
NCT00347841	PHASE4	COMPLETED	Efficacy of Bimatoprost 0.03% in Patients Who Are Low-Responders to Latanoprost
NCT00348023	PHASE4	COMPLETED	Bimatoprost Monotherapy vs. Dual Therapy With Travoprost and Timolol in Patients With Glaucoma and Ocular Hypertension
NCT00348062	PHASE4	COMPLETED	A Multicenter Evaluation of Methods to Reduce Hyperemia Associated With Bimatoprost Therapy for Glaucoma or Ocular Hypertension
NCT00348400	PHASE4	COMPLETED	Brimonidine Purite 0.15% Versus Dorzolamide 2% Used as Adjunctive Therapy to Latanoprost
NCT00351429	PHASE4	COMPLETED	Study of PGA Suture in Ophthalmology
NCT00376974	PHASE4	UNKNOWN	The Effect of Education on Patient Compliance
NCT00379834	PHASE4	COMPLETED	12-Month Stability of Diurnal IOP Control on Cosopt
NCT00382226	PHASE4	COMPLETED	IOP-Lowering Efficacy of Brinzolamide 1.0% Added to Travoprost 0.004%/Timolol 0.5% Fixed Combination as Adjunctive Therapy
NCT00404729	PHASE4	COMPLETED	Neural Conduction Along the Visual Pathways After Oral Treatment With Citicoline in Patients With Optic Nerve Diseases
NCT00440011	PHASE4	COMPLETED	Bimatoprost 0.03% Versus Travoprost 0.004% in Patients Currently on Latanoprost 0.005%
NCT00440141	PHASE4	COMPLETED	Brimonidine 0.1% Versus Brinzolamide 1% as Adjunctive Therapy to Latanoprost 0.005%
NCT00442312	PHASE4	UNKNOWN	Combigan Ophthalmic Solution(Brimonidine 0.2% and Timolol 0.5%)With Latanoprost Compared With Latanoprost Monotherapy
NCT00444184	PHASE4	COMPLETED	24-hour Intraocular Pressure Control With Travoprost/Timolol Fixed Combination Versus Travoprost
NCT00444665	PHASE4	COMPLETED	Examining The Efficacy, Safety And Improved Tolerability Of Travoprost BAK Free Ophthalmic Solution (Travatan-Z) Compared To Prior Prostaglandin Therapy
NCT00449098	PHASE4	UNKNOWN	Ologen (OculusGen)-Glaucoma MMC Control Trial in India
NCT00466479	PHASE4	COMPLETED	Brimonidine vs ALTP in Progressing Human Glaucoma
NCT00468429	PHASE4	UNKNOWN	Subconjunctival Bevacizumab to Prevent Bleb Failure After Glaucoma Filtration Surgery
NCT00468988	PHASE4	COMPLETED	Short Term Comparative Study of Xalatan With Benzalkonium Chloride vs. Travatan Z Without Benzalkonium Chloride in Healthy Volunteers
NCT00471380	PHASE4	COMPLETED	A Phase IV Study of Travoprost + Brinzolamide to Treat Glaucoma or Ocular Hypertension
NCT00485238	PHASE4	UNKNOWN	ALPI vs Medical Therapy Effects on Optic Nerve Structure & Function
NCT00486486	PHASE4	COMPLETED	24-hour Intraocular Pressure (IOP) Control With the Bimatoprost/Timolol Fixed Combination
NCT00519753	PHASE4	COMPLETED	Success of Transitioning Uncontrolled Glaucoma Patients From Prior Mono or Adjunctive Therapy to DuoTrav
NCT00541242	PHASE4	COMPLETED	Safety and Efficacy of Bimatoprost Compared With Latanoprost in Patients With Glaucoma or Ocular Hypertension
NCT00557232	PHASE4	COMPLETED	Intraocular Bevacizumab (Avastin) for Rubeosis Iridis
NCT00597181	PHASE4	TERMINATED	A Clinical Study Comparing the Inflammatory Response of the Ex-Press Mini Shunt to Trabeculectomy
NCT00607685	PHASE4	COMPLETED	5FU vs 5FU With Viscoelastic Formulation for the Prevention of Scarring Post-trabeculectomy
NCT00626067	PHASE4	COMPLETED	Study of Patient Use and Perception of the Travatan Dosing Aid
NCT00666237	PHASE4	COMPLETED	Primary Tube Versus Trabeculectomy Study
NCT00698438	PHASE4	COMPLETED	Comparison Of Trabeculectomy Versus The Ex-PRESS Miniature Glaucoma Device In The Same Patient: A Prospective Randomized Study
NCT00705757	PHASE4	COMPLETED	The Effects of Xalatan, Travatan and Lumigan on Skin Pigmentation Near the Eye
NCT00708422	PHASE4	COMPLETED	Effects of Travatan Z and Xalatan on Ocular Surface Health