ANGPT1

angiopoietin 1, the group of Receptor ligands|Fibrinogen C domain containing

Basic information

Region (hg38): 8:107249481-107498055

Links

ENSG00000154188 ∙ NCBI:284 ∙ OMIM:601667 ∙ HGNC:484 ∙ Uniprot:Q15389 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• glaucoma (Moderate), mode of inheritance: AD
• angioedema, hereditary, 5 (Limited), mode of inheritance: Unknown
• primary congenital glaucoma (Limited), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Angioedema, hereditary, 5	AD	Allergy/Immunology/Infectious	Individuals have been described with episodes aof angioedema, and medical management (eg, with tranexamic acid) has been described as beneficial	Allergy/Immunology/Infectious	28601681; 29410040

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ANGPT1 gene.

• not provided (167 variants)
• Hereditary angioedema type 3 (2 variants)
• not specified (2 variants)
• ANGPT1-related condition (1 variants)
• Angioedema, hereditary, 5 (1 variants)
• Inborn genetic diseases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ANGPT1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				37	2	39
missense			78		1	79
nonsense			1			1
start loss						0
frameshift			3			3
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region			4	3	3	10
non coding				18	18	36
Total	0	0	82	55	21

Variants in ANGPT1

This is a list of pathogenic ClinVar variants found in the ANGPT1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
8-107251871-C-G			Uncertain significance (Aug 11, 2023)
8-107251871-C-T			Uncertain significance (Dec 16, 2023)
8-107251872-G-A			Uncertain significance (Nov 13, 2023)
8-107251875-T-C			Uncertain significance (May 04, 2022)
8-107251883-G-A			Uncertain significance (Jul 19, 2022)
8-107251892-C-T			Uncertain significance (Oct 18, 2023)
8-107251893-G-A			Uncertain significance (May 04, 2022)
8-107251896-A-G			Likely benign (Oct 28, 2022)
8-107251897-G-A			Likely benign (Jan 02, 2024)
8-107251921-G-A			Likely benign (Feb 07, 2023)
8-107251941-G-A			Likely benign (Oct 19, 2020)
8-107251941-G-T			Uncertain significance (Nov 16, 2020)
8-107251961-G-A			Uncertain significance (Apr 12, 2023)
8-107251964-G-T			Uncertain significance (Jan 22, 2024)
8-107251972-C-T			Uncertain significance (Aug 23, 2023)
8-107252033-A-C			Likely benign (May 09, 2021)
8-107252045-A-G			Benign (May 10, 2021)
8-107264207-C-T			Likely benign (Dec 10, 2023)
8-107264217-T-C			Uncertain significance (Feb 03, 2022)
8-107264288-A-G			Likely benign (Nov 27, 2023)
8-107264294-G-A			Likely benign (Aug 03, 2023)
8-107264302-T-A			Uncertain significance (Jun 15, 2023)
8-107264364-A-G			Likely benign (Apr 22, 2023)
8-107264365-GA-G			Benign (Jan 25, 2024)
8-107264365-G-GA			Benign (Oct 09, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ANGPT1	protein_coding	protein_coding	ENST00000517746	9	248563

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.952	0.0479	125741	0	5	125746	0.0000199

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.30	202	261	0.773	0.0000122	3316
Missense in Polyphen		47	95.86	0.4903		1226
Synonymous	0.507	84	90.1	0.932	0.00000434	856
Loss of Function	4.12	4	27.2	0.147	0.00000130	329

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000620	0.0000615
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.0000464	0.0000462
European (Non-Finnish)	0.0000276	0.0000264
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: 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. {ECO:0000269|PubMed:15284220, ECO:0000269|PubMed:18425119, ECO:0000269|PubMed:18425120, ECO:0000269|PubMed:9204896}.
• Pathway: PI3K-Akt signaling pathway - Homo sapiens (human);HIF-1 signaling pathway - Homo sapiens (human);Rap1 signaling pathway - Homo sapiens (human);Ras signaling pathway - Homo sapiens (human);MAPK signaling pathway - Homo sapiens (human);Rheumatoid arthritis - Homo sapiens (human);Angiogenesis overview;Rac1-Pak1-p38-MMP-2 pathway;Photodynamic therapy-induced HIF-1 survival signaling;Focal Adhesion-PI3K-Akt-mTOR-signaling pathway;PI3K-Akt Signaling Pathway;Signal Transduction;SHP2 signaling;Tie2 Signaling;Cell surface interactions at the vascular wall;Hemostasis;RAF/MAP kinase cascade;MAPK1/MAPK3 signaling;MAPK family signaling cascades;Angiopoietin receptor Tie2-mediated signaling (Consensus)

Recessive Scores

• pRec: 0.397

Intolerance Scores

• loftool: 0.0685
• rvis_EVS: -0.34
• rvis_percentile_EVS: 30.37

Haploinsufficiency Scores

• pHI: 0.271
• hipred: Y
• hipred_score: 0.825
• ghis: 0.581

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.801

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Angpt1
• Phenotype: homeostasis/metabolism phenotype; muscle phenotype; growth/size/body region phenotype; immune system phenotype; renal/urinary system phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); vision/eye phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); embryo phenotype

Zebrafish Information Network

• Gene name: angpt1
• Affected structure: subintestinal vein
• Phenotype tag: abnormal
• Phenotype quality: morphology

Gene ontology

• Biological process: MAPK cascade;in utero embryonic development;negative regulation of protein phosphorylation;regulation of endothelial cell proliferation;sprouting angiogenesis;positive regulation of receptor internalization;negative regulation of cytokine secretion involved in immune response;negative regulation of cell adhesion;activation of transmembrane receptor protein tyrosine kinase activity;positive regulation of endothelial cell migration;positive regulation of phosphatidylinositol 3-kinase signaling;regulation of skeletal muscle satellite cell proliferation;hemopoiesis;cell differentiation;heparin biosynthetic process;positive regulation of protein ubiquitination;cell-substrate adhesion;regulation of tumor necrosis factor production;positive regulation of peptidyl-serine phosphorylation;protein localization to cell surface;negative regulation of protein import into nucleus;negative regulation of apoptotic process;negative regulation of vascular permeability;regulation of I-kappaB kinase/NF-kappaB signaling;regulation of protein binding;negative regulation of neuron apoptotic process;positive regulation of blood vessel endothelial cell migration;positive regulation of cell adhesion;Tie signaling pathway;positive regulation of peptidyl-tyrosine phosphorylation;leukocyte migration;positive chemotaxis;positive regulation of protein kinase B signaling;positive regulation of ERK1 and ERK2 cascade;glomerulus vasculature development;negative regulation of endothelial cell apoptotic process;regulation of macrophage migration inhibitory factor signaling pathway
• Cellular component: extracellular region;extracellular space;plasma membrane;microvillus;membrane raft;extracellular exosome
• Molecular function: Ras guanyl-nucleotide exchange factor activity;receptor tyrosine kinase binding