AGTR1

protein-coding

angiotensin II receptor type 1, the group of Angiotensin receptors

Gene summary

Angiotensin II is a potent vasopressor hormone and a primary regulator of aldosterone secretion. It is an important effector controlling blood pressure and volume in the cardiovascular system. It acts through at least two types of receptors. This gene encodes the type 1 receptor which is thought to mediate the major cardiovascular effects of angiotensin II. This gene may play a role in the generation of reperfusion arrhythmias following restoration of blood flow to ischemic or infarcted myocardium. It was previously thought that a related gene, denoted as AGTR1B, existed; however, it is now believed that there is only one type 1 receptor gene in humans. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Aug 2020]

Previous symbols:

AGTR1B

MANE transcript

NM_000685.5

Inheritance

ClinVar variants

P:15U:83B:29

Top phenotype

Renal tubular dysgenesis

gnomAD constraint

pLI —, LoF o/e 0.69

Max pathogenic AF

—

Genomic locus

chr3:148,697,784-148,743,008

External References & Databases

Ensembl (ENSG00000144891)

Transcript & Mutation Effects

hg38 • Region Span ~45.2 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

essential hypertension, geneticNO_KNOWN

Inheritance Pattern: Unknown

Disease ID:MONDO:0007781

Submitter: Labcorp Genetics (formerly Invitae)

renal tubular dysgenesis of genetic originSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0009970

Submitter: PanelApp Australia

renal tubular dysgenesis of genetic originSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0009970

Submitter: Labcorp Genetics (formerly Invitae)

renal tubular dysgenesis of genetic originMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0009970

Submitter: Ambry Genetics

Clinical Genomic Database (CGD)

Renal tubular dysgenesisAR

Manifestation: Renal

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 8021009; 16116425; 17668390

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to AGTR1 variants in ClinVar

11 Conditions Cataloged

not providedTotal: 69

Renal tubular dysgenesis of genetic originTotal: 52

Essential hypertension, geneticTotal: 47

Inborn genetic diseasesTotal: 31

Renal tubular dysgenesisTotal: 23

AGTR1-related disorderTotal: 8

Retinitis pigmentosa 40Total: 1

AnhydramniosTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_000685.5. 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.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar	24 clinvar	1 clinvar	26
missense	1 clinvar	3 clinvar	78 clinvar	4 clinvar		86
nonsense	1 clinvar	2 clinvar				3
start loss						0
frameshift		8 clinvar	4 clinvar			12
splice donor/acceptor (+/-2bp)						0
Total	2	13	83	28	1	127

Highest pathogenic variant AF is 0.000048944352

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 61 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_000685.5	RefSeq	NP_000676.1	1	MANE Select
ENST00000349243.8	Ensembl	ENSP00000273430.3	1	MANE Select
NM_001382736.1	RefSeq	NP_001369665.1	1	Standard
NM_001382737.1	RefSeq	NP_001369666.1	1	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Agents Acting on the Renin-Angiotensin System Pathway, Pharmacodynamics
Cortisol synthesis and secretion - Homo sapiens (human)
Aldosterone synthesis and secretion - Homo sapiens (human)
AGE-RAGE signaling pathway in diabetic complications - Homo sapiens (human)
Cushing,s syndrome - Homo sapiens (human)

Biological Process

regulation of cell growth
kidney development
renin-angiotensin regulation of aldosterone production
regulation of blood vessel diameter by renin-angiotensin
regulation of systemic arterial blood pressure by renin-angiotensin

Molecular Function

angiotensin type I receptor activity
angiotensin type II receptor activity
protein binding
bradykinin receptor binding
protein heterodimerization activity

Cellular Component

plasma membrane
integral component of plasma membrane
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000542281
Coding exons: 1
Length: 45225
Individuals with no LoFs: 125705
Homozygous LoFs: 0
Heterozygous LoFs: 36
Defined: 125741
p: 0.000143

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.435	179	196	0.913	0.0000100	2360
Missense (PolyPhen)		62	72.314	0.85738		900
Synonymous	-0.0697	72	71.3	1.01	0.00000359	719
Loss of Function	0.863	6	8.76	0.685	4.98e-7	113

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00025	0.00025	rare
Latino/Admixed American	0.00032	0.00032	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000055	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000097	0.000097	rare
South Asian	0.00023	0.00023	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Receptor for angiotensin II. Mediates its action by association with G proteins that activate a phosphatidylinositol- calcium second messenger system.;
Disease: 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: 0.823

Intolerance Scores

LoFtool: 0.821
RVIS EVS: 0.11
RVIS percentile EVS: 61.73

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.636

Gene Damage Prediction

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