ANGPT2

angiopoietin 2, the group of Fibrinogen C domain containing|Receptor ligands

Basic information

Region (hg38): 8:6499631-6563409

Links

ENSG00000091879 ∙ NCBI:285 ∙ OMIM:601922 ∙ HGNC:485 ∙ Uniprot:O15123 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• lymphatic malformation 10 (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Lymphatic malformation 10	AD	Allergy/Immunology/Infectious	The condition involves lymphatic malformations, and in some individuals, progression to cellulitis has been reported, such that awareness may allow prompt treatment of infectious sequelae	Allergy/Immunology/Infectious; Cardiovascular	32908006

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ANGPT2 gene.

• not provided (41 variants)
• Inborn genetic diseases (21 variants)
• Microcephaly 1, primary, autosomal recessive (8 variants)
• Autosomal recessive primary microcephaly (1 variants)
• not specified (1 variants)
• Intellectual disability (1 variants)
• Short stature;Intellectual disability (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ANGPT2 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				4	4	8
missense			17	1	4	22
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding		1	8	11	6	26
Total	0	1	25	16	14

Highest pathogenic variant AF is 0.0000394

Variants in ANGPT2

This is a list of pathogenic ClinVar variants found in the ANGPT2 region.

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

Position	Type	Phenotype	Significance	ClinVar
8-6499644-G-A			Likely benign (Feb 05, 2019)
8-6499670-T-C			Benign (Jul 03, 2018)
8-6499686-A-G			Likely benign (Jul 15, 2018)
8-6499714-A-T			Benign (Jun 26, 2018)
8-6499750-C-T			Likely benign (Jan 16, 2019)
8-6499786-T-C			Benign (Jun 26, 2018)
8-6499833-C-G			Likely benign (Jul 13, 2023)
8-6499833-C-T			Likely benign (Dec 26, 2023)
8-6499836-G-A			Likely benign (Nov 08, 2023)
8-6499839-G-C			Likely benign (Nov 17, 2023)
8-6499839-G-T			Likely benign (Nov 06, 2023)
8-6499841-G-A			Likely benign (Jan 03, 2024)
8-6499843-C-T			Likely benign (Dec 25, 2023)
8-6499845-C-T		Microcephaly 1, primary, autosomal recessive	Conflicting classifications of pathogenicity (Jan 19, 2024)
8-6499852-G-T			Uncertain significance (Dec 01, 2019)
8-6499857-A-G			Likely benign (Oct 04, 2023)
8-6499860-G-A		Microcephaly 1, primary, autosomal recessive • Intellectual disability • Autosomal recessive primary microcephaly • MCPH1-related disorder	Conflicting classifications of pathogenicity (Oct 25, 2023)
8-6499870-T-C			Likely benign (Aug 20, 2023)
8-6499875-T-A			Likely benign (Aug 04, 2023)
8-6499893-G-A			Likely benign (Jan 15, 2023)
8-6499895-C-T		Microcephaly 1, primary, autosomal recessive • Short stature;Intellectual disability • Inborn genetic diseases	Conflicting classifications of pathogenicity (Dec 01, 2023)
8-6499896-G-A			Likely benign (Jun 20, 2023)
8-6499899-C-T			Likely benign (Jan 29, 2024)
8-6499904-T-A		Inborn genetic diseases	Uncertain significance (Oct 26, 2022)
8-6499910-A-C		Inborn genetic diseases	Uncertain significance (Jun 06, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ANGPT2	protein_coding	protein_coding	ENST00000325203	9	63759

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.832	0.168	125737	0	11	125748	0.0000437

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.527	298	273	1.09	0.0000145	3308
Missense in Polyphen		74	107.57	0.68794		1285
Synonymous	-2.15	130	102	1.27	0.00000629	848
Loss of Function	4.02	5	27.9	0.179	0.00000127	329

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.0000704	0.0000703
Middle Eastern	0.0000544	0.0000544
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Binds to TEK/TIE2, competing for the ANGPT1 binding site, and modulating ANGPT1 signaling. Can induce tyrosine phosphorylation of TEK/TIE2 in the absence of ANGPT1. In the absence of angiogenic inducers, such as VEGF, ANGPT2-mediated loosening of cell-matrix contacts may induce endothelial cell apoptosis with consequent vascular regression. In concert with VEGF, it may facilitate endothelial cell migration and proliferation, thus serving as a permissive angiogenic signal. {ECO:0000269|PubMed:15284220, ECO:0000269|PubMed:19116766, ECO:0000269|PubMed:19223473, ECO:0000269|PubMed:9204896}.
• Pathway: PI3K-Akt signaling pathway - Homo sapiens (human);Kaposi,s sarcoma-associated herpesvirus infection - 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);Rac1-Pak1-p38-MMP-2 pathway;Photodynamic therapy-induced HIF-1 survival signaling;Hypothesized Pathways in Pathogenesis of Cardiovascular Disease;Focal Adhesion-PI3K-Akt-mTOR-signaling pathway;PI3K-Akt Signaling Pathway;Tie2 Signaling;Cell surface interactions at the vascular wall;Hemostasis;Angiopoietin receptor Tie2-mediated signaling (Consensus)

Recessive Scores

• pRec: 0.107

Intolerance Scores

• loftool: 0.230
• rvis_EVS: -0.42
• rvis_percentile_EVS: 25.73

Haploinsufficiency Scores

• pHI: 0.435
• hipred: Y
• hipred_score: 0.824
• ghis: 0.507

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.857

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Angpt2
• Phenotype: respiratory system phenotype; 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); 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); vision/eye phenotype; digestive/alimentary phenotype; homeostasis/metabolism phenotype; immune system phenotype; cellular phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan)

Zebrafish Information Network

• Gene name: angpt2b
• Affected structure: subintestinal vein
• Phenotype tag: abnormal
• Phenotype quality: decreased length

Gene ontology

• Biological process: angiogenesis;response to hypoxia;signal transduction;germ cell development;response to radiation;response to mechanical stimulus;response to glucose;negative regulation of cell-substrate adhesion;response to organic cyclic compound;response to activity;negative regulation of angiogenesis;animal organ regeneration;negative regulation of blood vessel endothelial cell migration;positive regulation of angiogenesis;Tie signaling pathway;leukocyte migration;negative regulation of positive chemotaxis;maternal process involved in female pregnancy;cellular response to growth factor stimulus;glomerulus vasculature development
• Cellular component: extracellular region;extracellular space;nucleus;plasma membrane;cell projection
• Molecular function: signaling receptor binding;protein binding;receptor tyrosine kinase binding;metal ion binding