AGTR1

Chr 3

angiotensin II receptor type 1

Also known as: AG2S, AGTR1B, AT1, AT1AR, AT1B, AT1BR, AT1R, AT2R1

NCBI Gene: 185 ENSG00000144891 UniProt: P30556

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]

Research

ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.35

Clinical Summary— AGTR1

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

13 unique Pathogenic / Likely Pathogenic· 111 VUS of 180 total submissions

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Clinical Trials

2 active or recruiting trials — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 521

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.35LOEUF

pLI 0.001

Z-score 0.86

OE 0.69 (0.37–1.35)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.43Z-score

OE missense 0.91 (0.81–1.03)

179 obs / 196.1 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.69 (0.37–1.35)

0≤0.351.4

Missense OE?0.91 (0.81–1.03)

0≤0.61.4

Synonymous OE?1.01

0≤1.21.6

LoF obs/exp: 6 / 8.8Missense obs/exp: 179 / 196.1Syn Z: -0.07

This gene — mechanism propensity

0.81top 10%

GOF

0.79top 10%

LOF

0.1895th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median

GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

180 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic4

Likely Pathogenic9

VUS111

Likely Benign31

Benign18

Conflicting6

Pathogenic

Likely Pathogenic

111

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	2	1	1	0	4
Likely Pathogenic	9	0	0	0	9
VUS	4	79	27	1	111
Likely Benign	0	4	5	22	31
Benign	0	0	15	3	18
Conflicting	—				6
Total	15	84	48	26	179

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

21 pathogenic / likely-pathogenic (of 23) ClinVar copy-number / structural variants overlap AGTR1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →