AGT

angiotensinogen, the group of Neuropeptides|Serpin peptidase inhibitors

Basic information

Region (hg38): 1:230690775-230745576

Previous symbols: [ "SERPINA8" ]

Links

ENSG00000135744 ∙ NCBI:183 ∙ OMIM:106150 ∙ HGNC:333 ∙ Uniprot:P01019 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• renal tubular dysgenesis of genetic origin (Supportive), mode of inheritance: AR
• renal tubular dysgenesis of genetic origin (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Renal tubular dysgenesis	AR	Renal	Treatment with fresh frozen plasma in the neonatal period has been reported as effective in terms of maintaing blood pressure and allowing survival	Renal	1394429; 8348146; 8513325; 8132767; 7649545; 9120024; 9120002; 9259580; 9421481; 10585456; 11829142; 11731937; 15023884; 16116425; 17047091; 17036344; 20978123; 22685354

ClinVar

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

• not provided (120 variants)
• Renal tubular dysgenesis (72 variants)
• Essential hypertension, genetic;Renal tubular dysgenesis of genetic origin (20 variants)
• Inborn genetic diseases (18 variants)
• Congenital disorder of glycosylation, type IIq (15 variants)
• Renal tubular dysgenesis of genetic origin;Essential hypertension, genetic (5 variants)
• not specified (3 variants)
• Hypertension, essential, susceptibility to (2 variants)
• Large fontanelles;Anhydramnios (2 variants)
• Susceptibility to progression to renal failure in IgA nephropathy (1 variants)
• Crohn disease, association with (1 variants)
• Preeclampsia, susceptibility to (1 variants)
• Anhydramnios (1 variants)
• AGT-related condition (1 variants)
• Hypertensive disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the AGT 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			5	29	4	38
missense	1		46	11	3	61
nonsense	1	1				2
start loss				1		1
frameshift		2	1			3
inframe indel				1		1
splice donor/acceptor (+/-2bp)		1				1
splice region				1		1
non coding			34	22	22	78
Total	2	4	86	64	29

Highest pathogenic variant AF is 0.0000460

Variants in AGT

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

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

Position	Type	Phenotype	Significance	ClinVar
1-230691381-A-G		Congenital disorder of glycosylation, type IIq	Uncertain significance (Nov 06, 2022)
1-230691397-G-A		not specified	Uncertain significance (Oct 25, 2022)
1-230691398-T-C		not specified	Uncertain significance (Sep 16, 2021)
1-230691406-G-A		Congenital disorder of glycosylation, type IIq	Likely benign (Sep 13, 2023)
1-230691414-C-T		Congenital disorder of glycosylation, type IIq	Likely benign (Apr 27, 2021)
1-230691426-G-A		Congenital disorder of glycosylation, type IIq	Likely benign (Jul 09, 2023)
1-230691475-G-A		Congenital disorder of glycosylation, type IIq • not specified	Conflicting classifications of pathogenicity (Apr 25, 2022)
1-230691481-C-T		not specified	Uncertain significance (Feb 15, 2023)
1-230691483-C-T		Congenital disorder of glycosylation, type IIq	Likely benign (Jun 17, 2020)
1-230691486-C-T			Benign (Nov 16, 2018)
1-230691502-A-G		not specified	Uncertain significance (Sep 13, 2023)
1-230691510-C-T		Congenital disorder of glycosylation, type IIq	Likely benign (Aug 04, 2023)
1-230691514-G-T		Congenital disorder of glycosylation, type IIq	Uncertain significance (Sep 10, 2018)
1-230691559-G-A		Congenital disorder of glycosylation, type IIq	Likely benign (Jan 24, 2024)
1-230691571-C-T		Congenital disorder of glycosylation, type IIq	Likely benign (Sep 07, 2022)
1-230691578-C-T		Congenital disorder of glycosylation, type IIq	Likely benign (Jan 25, 2024)
1-230691582-G-A		Congenital disorder of glycosylation, type IIq	Likely benign (Sep 23, 2022)
1-230691841-A-G			Likely benign (Sep 06, 2019)
1-230693014-A-G			Benign (Sep 05, 2018)
1-230693019-G-T			Benign (Jul 27, 2018)
1-230693127-A-G			Benign (Sep 05, 2018)
1-230693233-T-C			Likely benign (Mar 06, 2020)
1-230693241-C-A			Benign (Jul 27, 2018)
1-230693282-G-A			Likely benign (Jun 16, 2018)
1-230693314-CAAGT-C		Congenital disorder of glycosylation, type IIq	Uncertain significance (Oct 17, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
AGT	protein_coding	protein_coding	ENST00000366667	4	11775

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
4.97e-8	0.230	125706	0	42	125748	0.000167

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.199	275	266	1.03	0.0000156	3144
Missense in Polyphen		59	67.588	0.87293		859
Synonymous	-1.04	136	121	1.12	0.00000754	1052
Loss of Function	0.360	12	13.4	0.894	6.78e-7	138

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000244	0.000242
Ashkenazi Jewish	0.000397	0.000397
East Asian	0.00125	0.00125
Finnish	0.00	0.00
European (Non-Finnish)	0.0000533	0.0000527
Middle Eastern	0.00125	0.00125
South Asian	0.0000980	0.0000980
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Essential component of the renin-angiotensin system (RAS), a potent regulator of blood pressure, body fluid and electrolyte homeostasis.; FUNCTION: Angiotensin-3: stimulates aldosterone release.
• Disease: DISEASE: Essential hypertension (EHT) [MIM:145500]: A condition in which blood pressure is consistently higher than normal with no identifiable cause. {ECO:0000269|PubMed:1394429, ECO:0000269|PubMed:8513325}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.; DISEASE: Renal tubular dysgenesis (RTD) [MIM:267430]: Autosomal recessive severe disorder of renal tubular development characterized by persistent fetal anuria and perinatal death, probably due to pulmonary hypoplasia from early-onset oligohydramnios (the Potter phenotype). {ECO:0000269|PubMed:16116425}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Agents Acting on the Renin-Angiotensin System Pathway, Pharmacodynamics;Renin-angiotensin system - Homo sapiens (human);Renin secretion - Homo sapiens (human);ACE Inhibitor Pathway, Pharmacodynamics;Temocapril Action Pathway;Olmesartan Action Pathway;Losartan Action Pathway;Irbesartan Action Pathway;Forasartan Action Pathway;Valsartan Action Pathway;Telmisartan Action Pathway;Angiotensin Metabolism;Spirapril Action Pathway;Trandolapril Action Pathway;Ramipril Action Pathway;Rescinnamine Action Pathway;Perindopril Action Pathway;Quinapril Action Pathway;Lisinopril Action Pathway;Moexipril Action Pathway;Candesartan Action Pathway;Eprosartan Action Pathway;Fosinopril Action Pathway;Enalapril Action Pathway;Benazepril Action Pathway;Cilazapril Action Pathway;Captopril Action Pathway;Physiological and Pathological Hypertrophy of the Heart;MicroRNAs in cardiomyocyte hypertrophy;Adipogenesis;Regulation of lipid metabolism by Peroxisome proliferator-activated receptor alpha (PPARalpha);IL-6 signaling pathway;ACE Inhibitor Pathway;Monoamine Transport;Signaling by GPCR;Signal Transduction;bioactive peptide induced signaling pathway;g-protein signaling through tubby proteins;Peptide hormone metabolism;role of egf receptor transactivation by gpcrs in cardiac hypertrophy;angiotensin ii mediated activation of jnk pathway via pyk2 dependent signaling;corticosteroids and cardioprotection;cystic fibrosis transmembrane conductance regulator (cftr) and beta 2 adrenergic receptor (b2ar) pathway;ion channels and their functional role in vascular endothelium;activation of csk by camp-dependent protein kinase inhibits signaling through the t cell receptor;chrebp regulation by carbohydrates and camp;role of -arrestins in the activation and targeting of map kinases;activation of camp-dependent protein kinase pka;Metabolism of proteins;Metabolism of Angiotensinogen to Angiotensins;GPCR signaling-G alpha q;GPCR signaling-cholera toxin;GPCR signaling-pertussis toxin;Peptide ligand-binding receptors;Class A/1 (Rhodopsin-like receptors);roles of arrestin dependent recruitment of src kinases in gpcr signaling;GPCR ligand binding;GPCR signaling-G alpha s Epac and ERK;activation of pkc through g-protein coupled receptors;GPCR signaling-G alpha s PKA and ERK;-arrestins in gpcr desensitization;G alpha (i) signalling events;GPCR signaling-G alpha i;G alpha (q) signalling events;GPCR downstream signalling;AP-1 transcription factor network;Signaling events mediated by PRL (Consensus)

Recessive Scores

• pRec: 0.623

Intolerance Scores

• loftool: 0.0694
• rvis_EVS: 0.49
• rvis_percentile_EVS: 79.61

Haploinsufficiency Scores

• pHI: 0.502
• hipred: N
• hipred_score: 0.173
• ghis: 0.556

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.927

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Agt
• Phenotype: behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); liver/biliary system 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); reproductive 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); 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); immune system phenotype; renal/urinary system phenotype; growth/size/body region phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); muscle phenotype; homeostasis/metabolism phenotype

Gene ontology

• Biological process: regulation of cell growth;positive regulation of cytokine production;kidney development;blood vessel remodeling;regulation of blood volume by renin-angiotensin;renin-angiotensin regulation of aldosterone production;regulation of renal output by angiotensin;regulation of heart rate;regulation of blood vessel diameter by renin-angiotensin;renal system process;angiotensin-mediated drinking behavior;positive regulation of extracellular matrix constituent secretion;protein import into nucleus;cellular sodium ion homeostasis;cell surface receptor signaling pathway;G protein-coupled receptor signaling pathway;G protein-coupled receptor signaling pathway coupled to cGMP nucleotide second messenger;phospholipase C-activating G protein-coupled receptor signaling pathway;activation of phospholipase C activity;positive regulation of cytosolic calcium ion concentration;nitric oxide mediated signal transduction;cell-cell signaling;female pregnancy;aging;regulation of blood pressure;associative learning;regulation of signaling receptor activity;positive regulation of activation of Janus kinase activity;positive regulation of endothelial cell migration;positive regulation of cardiac muscle hypertrophy;positive regulation of cardiac muscle cell apoptotic process;positive regulation of macrophage derived foam cell differentiation;positive regulation of cholesterol esterification;negative regulation of endopeptidase activity;positive regulation of neuron projection development;regulation of norepinephrine secretion;positive regulation of phosphatidylinositol 3-kinase signaling;artery smooth muscle contraction;response to muscle activity involved in regulation of muscle adaptation;negative regulation of angiogenesis;regulation of lipid metabolic process;regulation of vasoconstriction;negative regulation of cell growth;positive regulation of cellular protein metabolic process;response to estradiol;positive regulation of superoxide anion generation;positive regulation of NAD(P)H oxidase activity;negative regulation of tissue remodeling;low-density lipoprotein particle remodeling;operant conditioning;regulation of renal sodium excretion;positive regulation of renal sodium excretion;regulation of cell population proliferation;vasodilation;positive regulation of nitric oxide biosynthetic process;positive regulation of epidermal growth factor receptor signaling pathway;positive regulation of blood pressure;positive regulation of transcription, DNA-templated;positive regulation of insulin receptor signaling pathway;fibroblast proliferation;positive regulation of fibroblast proliferation;regulation of long-term neuronal synaptic plasticity;smooth muscle cell proliferation;cytokine secretion;positive regulation of inflammatory response;positive regulation of peptidyl-tyrosine phosphorylation;positive regulation of NF-kappaB transcription factor activity;negative regulation of neurotrophin TRK receptor signaling pathway;stress-activated MAPK cascade;regulation of calcium ion transport;regulation of transmission of nerve impulse;cell growth involved in cardiac muscle cell development;positive regulation of protein tyrosine kinase activity;ERK1 and ERK2 cascade;uterine smooth muscle contraction;cellular response to mechanical stimulus;positive regulation of branching involved in ureteric bud morphogenesis;regulation of extracellular matrix assembly;positive regulation of gap junction assembly;regulation of cardiac conduction;cellular response to angiotensin;positive regulation of vascular smooth muscle cell proliferation;positive regulation of vascular associated smooth muscle cell migration;positive regulation of L-lysine import across plasma membrane;positive regulation of L-arginine import across plasma membrane;positive regulation of reactive oxygen species metabolic process;positive regulation of extrinsic apoptotic signaling pathway
• Cellular component: extracellular region;extracellular space;cytosol;extracellular exosome;blood microparticle
• Molecular function: serine-type endopeptidase inhibitor activity;hormone activity;protein binding;growth factor activity;type 1 angiotensin receptor binding;type 2 angiotensin receptor binding