GeneBe

AGT

protein-coding

angiotensinogen, the group of Neuropeptides|Serpin peptidase inhibitors

Gene summary

The protein encoded by this gene, pre-angiotensinogen or angiotensinogen precursor, is expressed in the liver and is cleaved by the enzyme renin in response to lowered blood pressure. The resulting product, angiotensin I, is then cleaved by angiotensin converting enzyme (ACE) to generate the physiologically active enzyme angiotensin II. The protein is involved in maintaining blood pressure, body fluid and electrolyte homeostasis, and in the pathogenesis of essential hypertension and preeclampsia. Mutations in this gene are associated with susceptibility to essential hypertension, and can cause renal tubular dysgenesis, a severe disorder of renal tubular development. Defects in this gene have also been associated with non-familial structural atrial fibrillation, and inflammatory bowel disease. [provided by RefSeq, Nov 2019]

Previous symbols:
  • SERPINA8

MANE transcript

NM_001384479.1

Inheritance

AR

ClinVar variants

P:21U:118B:78

Top phenotype

Renal tubular dysgenesis

gnomAD constraint

pLI —, LoF o/e 0.89

Max pathogenic AF

—

Genomic locus

chr1:230,690,776-230,745,576

External References & Databases

Ensembl (ENSG00000135744)NCBI Gene (183)OMIM (106150)HGNC:333GenCCUniProt (P01019)AlphaFoldClinVar (AGT)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~54.8 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

renal tubular dysgenesis of genetic originSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0009970

Submitter: Orphanet

renal tubular dysgenesis of genetic originSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0009970

Submitter: Labcorp Genetics (formerly Invitae)

renal tubular dysgenesis of genetic originSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0009970

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Renal tubular dysgenesisAR

Manifestation: Renal

Intervention: Renal

Rationale: Treatment with fresh frozen plasma in the neonatal period has been reported as effective in terms of maintaing blood pressure and allowing survival

Refs: 1394429; 8348146; 8513325; 8132767; 7649545; 9120024; 9120002; 9259580; 9421481; 10585456; 11829142; 11731937; 15023884; 16116425; 17047091; 17036344; 20978123; 22685354Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to AGT variants in ClinVar

11 Conditions Cataloged
not providedTotal: 125
Renal tubular dysgenesis of genetic originTotal: 103
Renal tubular dysgenesisTotal: 41
Inborn genetic diseasesTotal: 27
Essential hypertension, geneticTotal: 22
AGT-related disorderTotal: 16
AnhydramniosTotal: 3
not specifiedTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001384479.1. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
7
clinvar
53
clinvar
2
clinvar
 62
missense
5
clinvar
106
clinvar
22
clinvar
 133
nonsense
3
clinvar
5
clinvar
1
clinvar
 9
start loss
1
clinvar
 1
frameshift
3
clinvar
4
clinvar
3
clinvar
 10
splice donor/acceptor (+/-2bp)
1
clinvar
1
clinvar
 2
Total615118762217

Highest pathogenic variant AF is 0.000026030337

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 23 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_001384479.1RefSeqNP_001371408.14MANE Select
ENST00000366667.6EnsemblENSP00000355627.54MANE Select
NM_001382817.3RefSeqNP_001369746.24Standard
ENST00000679684.1EnsemblENSP00000505981.14Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • 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

Biological Process

  • regulation of cell growth
  • positive regulation of cytokine production
  • kidney development
  • blood vessel remodeling
  • regulation of blood volume by renin-angiotensin

Molecular Function

  • serine-type endopeptidase inhibitor activity
  • hormone activity
  • protein binding
  • growth factor activity
  • type 1 angiotensin receptor binding

Cellular Component

  • extracellular region
  • extracellular space
  • cytosol
  • extracellular exosome
  • blood microparticle

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000366667
Coding exons
4
Length
11775
Individuals with no LoFs
125706
Homozygous LoFs
0
Heterozygous LoFs
42
Defined
125748
p
0.000167
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense-0.1992752661.030.00001563144
Missense (PolyPhen)5967.5880.87293859
Synonymous-1.041361211.120.000007541052
Loss of Function0.3601213.40.8946.78e-7138

Population LoF Frequency

PopulationCAFp-valueStatus
African0.000190.00018rare
Latino/Admixed American0.0000580.000058rare
Ashkenazi Jewish0.000400.00040rare
East Asian0.00130.0013notable
Finnish00.0absent
European (Non-Finnish)0.0000530.000053rare
South Asian0.0000980.000098rare
Other0.000160.00016rare

dbNSFP Gene Annotations

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.;

Recessive Scores

pRec
0.623

Intolerance Scores

LoFtool
0.0694
RVIS EVS
0.49
RVIS percentile EVS
79.61

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
E
Indispensability score
0.927

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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