AGTR2

angiotensin II receptor type 2, the group of Angiotensin receptors

Basic information

Region (hg38): X:116170743-116174974

Links

ENSG00000180772 ∙ NCBI:186 ∙ OMIM:300034 ∙ HGNC:338 ∙ Uniprot:P50052 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• non-syndromic X-linked intellectual disability (Supportive), mode of inheritance: XL
• X-linked complex neurodevelopmental disorder (Disputed Evidence), mode of inheritance: XL

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Mental retardation, X-linked 88	XL	General	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	Neurologic	12089445; 12746399; 14598163; 14722754; 16463274; 22269148; 23871722
The evidence of variants as related to disease causation has been questioned due to subsequent population-based studies

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the AGTR2 gene.

• not provided (24 variants)
• Inborn genetic diseases (18 variants)
• not specified (3 variants)
• Intellectual disability, X-linked 88 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the AGTR2 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					3	3
missense			23	3	2	28
nonsense			1			1
start loss						0
frameshift			2	1		3
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	26	4	5

Variants in AGTR2

This is a list of pathogenic ClinVar variants found in the AGTR2 region.

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

Position	Type	Phenotype	Significance	ClinVar
X-116172341-G-A			Uncertain significance (Jan 27, 2017)
X-116172342-G-T		not specified • Intellectual disability, X-linked 88	Benign/Likely benign (Dec 11, 2015)
X-116172356-T-C		not specified	Uncertain significance (Aug 26, 2022)
X-116172366-A-G		not specified	Uncertain significance (Jan 23, 2024)
X-116172370-G-C		not specified	Uncertain significance (Feb 12, 2024)
X-116172389-C-G		not specified	Uncertain significance (Jan 26, 2022)
X-116172401-G-A			Uncertain significance (Apr 04, 2013)
X-116172425-A-G		not specified	Likely benign (Jun 06, 2023)
X-116172437-A-T			Uncertain significance (Aug 08, 2013)
X-116172450-T-C		not specified	Uncertain significance (Jan 03, 2024)
X-116172491-T-A		not specified	Conflicting classifications of pathogenicity (Nov 17, 2022)
X-116172511-G-T			Uncertain significance (Apr 22, 2014)
X-116172516-C-G			Uncertain significance (Jul 28, 2022)
X-116172578-T-C			Uncertain significance (Oct 14, 2016)
X-116172594-C-G		not specified	Uncertain significance (Aug 12, 2021)
X-116172658-G-A		AGTR2-related disorder	Benign/Likely benign (Jun 04, 2019)
X-116172674-AT-A		not specified • AGTR2-related disorder	Likely benign (Mar 28, 2019)
X-116172674-A-AT			Uncertain significance (May 06, 2020)
X-116172682-T-TA			Uncertain significance (Aug 30, 2021)
X-116172691-C-A			Uncertain significance (Feb 13, 2022)
X-116172720-T-A		not specified	Uncertain significance (Aug 18, 2014)
X-116172723-A-G			Uncertain significance (Aug 14, 2017)
X-116172778-T-C		not specified	Benign (Jul 31, 2018)
X-116172786-G-T		AGTR2-related disorder	Uncertain significance (Dec 18, 2023)
X-116172812-A-G		not specified	Uncertain significance (Jan 30, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
AGTR2	protein_coding	protein_coding	ENST00000371906	1	4251

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00823	0.806	125444	72	138	125654	0.000836

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.0723	139	137	1.02	0.0000101	2386
Missense in Polyphen		50	42.99	1.163		826
Synonymous	-0.287	52	49.4	1.05	0.00000371	722
Loss of Function	1.03	4	6.93	0.577	4.96e-7	129

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000861	0.000759
Ashkenazi Jewish	0.000134	0.0000992
East Asian	0.00325	0.00245
Finnish	0.000125	0.0000924
European (Non-Finnish)	0.00166	0.00119
Middle Eastern	0.00325	0.00245
South Asian	0.000472	0.000294
Other	0.000443	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Receptor for angiotensin II. Cooperates with MTUS1 to inhibit ERK2 activation and cell proliferation. {ECO:0000269|PubMed:15123706}.
• Pathway: Agents Acting on the Renin-Angiotensin System Pathway, Pharmacodynamics;Renin-angiotensin system - Homo sapiens (human);Adrenergic signaling in cardiomyocytes - Homo sapiens (human);Neuroactive ligand-receptor interaction - Homo sapiens (human);ACE Inhibitor Pathway, Pharmacodynamics;Peptide GPCRs;GPCRs, Class A Rhodopsin-like;ACE Inhibitor Pathway;Signaling by GPCR;Signal Transduction;bioactive peptide induced signaling pathway;role of egf receptor transactivation by gpcrs in cardiac hypertrophy;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;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;GPCR signaling-G alpha s PKA and ERK;-arrestins in gpcr desensitization;G alpha (i) signalling events;GPCR signaling-G alpha i;GPCR downstream signalling (Consensus)

Recessive Scores

• pRec: 0.425

Intolerance Scores

• loftool: 0.659
• rvis_EVS: 0.31
• rvis_percentile_EVS: 72.23

Haploinsufficiency Scores

• pHI: 0.648
• hipred: N
• hipred_score: 0.432
• ghis: 0.401

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.659

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Agtr2
• Phenotype: adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); endocrine/exocrine gland 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); growth/size/body region phenotype; cellular phenotype; homeostasis/metabolism phenotype; 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); muscle phenotype; digestive/alimentary phenotype; neoplasm; 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); 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); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); skeleton phenotype; renal/urinary system phenotype

Gene ontology

• Biological process: blood vessel remodeling;regulation of systemic arterial blood pressure by circulatory renin-angiotensin;renin-angiotensin regulation of aldosterone production;angiotensin-mediated vasodilation involved in regulation of systemic arterial blood pressure;brain renin-angiotensin system;cellular sodium ion homeostasis;inflammatory response;cell surface receptor signaling pathway;G protein-coupled receptor signaling pathway;G protein-coupled receptor signaling pathway coupled to cGMP nucleotide second messenger;nitric oxide mediated signal transduction;brain development;regulation of blood pressure;positive regulation of cell population proliferation;negative regulation of heart rate;negative regulation of norepinephrine secretion;cerebellar cortex development;negative regulation of cell growth;negative regulation of icosanoid secretion;positive regulation of phosphoprotein phosphatase activity;intracellular signal transduction;regulation of metanephros size;exploration behavior;positive regulation of renal sodium excretion;aldosterone secretion;angiotensin-activated signaling pathway;regulation of protein import into nucleus;vasodilation;dopamine biosynthetic process;negative regulation of blood vessel endothelial cell migration;positive regulation of nitric oxide biosynthetic process;positive regulation of transcription, DNA-templated;negative regulation of fibroblast proliferation;positive regulation of cytokine secretion;positive regulation of nitric-oxide synthase activity;negative regulation of neurotrophin TRK receptor signaling pathway;cell growth involved in cardiac muscle cell development;cellular response to dexamethasone stimulus;positive regulation of metanephric glomerulus development;positive regulation of branching involved in ureteric bud morphogenesis;extracellular negative regulation of signal transduction;positive regulation of extrinsic apoptotic signaling pathway
• Cellular component: extracellular region;plasma membrane;integral component of plasma membrane;perinuclear region of cytoplasm
• Molecular function: angiotensin type II receptor activity;protein binding;transcription factor binding;peptide hormone binding;receptor antagonist activity