Human Gene Module / Chromosome X / AGTR2

AGTR2angiotensin II receptor, type 2

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
1 / 5
Rare Variants / Common Variants
8 / 0
Aliases
AGTR2, AT2,  ATGR2,  MRX88
Associated Syndromes
-
Chromosome Band
Xq23
Associated Disorders
-
Relevance to Autism

This gene has been associated with syndromic autism, where a subpopulation of individuals with a given syndrome develop autism. Rare mutations in the AGTR2 gene have also been identified with mental retardation. These mutations included translocation, frameshift and missense variations.

Molecular Function

The protein encoded by this gene is an integral membrane protein that belongs to the G-protein coupled receptor 1 family, and functions as a receptor for angiotensin II.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to AGTR2 (5 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary AGTR2 mutations in X-linked mental retardation Vervoort VS , et al. (2002) No -
2 Recent Recommendation Angiotensin II type-2 receptor stimulation prevents neural damage by transcriptional activation of methyl methanesulfonate sensitive 2 Mogi M , et al. (2006) No -
3 Support Novel AGTR2 missense mutation in a Japanese boy with severe mental retardation, pervasive developmental disorder, and epilepsy Takeshita E , et al. (2012) No -
4 Support De Novo Damaging DNA Coding Mutations Are Associated With Obsessive-Compulsive Disorder and Overlap With Tourette's Disorder and Autism Cappi C , et al. (2019) No -
5 Support Genetic landscape of autism spectrum disorder in Vietnamese children Tran KT et al. (2020) Yes -
Rare Variants   (8)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
- - translocation De novo - - 12089445 Vervoort VS , et al. (2002)
c.62G>T p.Gly21Val missense_variant - - - 12089445 Vervoort VS , et al. (2002)
c.971G>A p.Arg324Gln missense_variant - - - 12089445 Vervoort VS , et al. (2002)
c.1009A>G p.Ile337Val missense_variant - - - 12089445 Vervoort VS , et al. (2002)
c.244T>C p.Tyr82His missense_variant De novo - Simplex 31771860 Cappi C , et al. (2019)
c.757C>T p.Gln253Ter stop_gained Familial Maternal Simplex 32193494 Tran KT et al. (2020)
c.402del p.Phe134LeufsTer5 frameshift_variant - - Multiplex 12089445 Vervoort VS , et al. (2002)
c.572G>A p.Gly191Glu missense_variant Familial Maternal Simplex 22269148 Takeshita E , et al. (2012)
Common Variants  

No common variants reported.

SFARI Gene score
2

Strong Candidate

A screen of indivduals with FMR1-negative X-linked mental retardation resulted in the identification of rare variants in AGTR2 in 9/590 individuals, Of the 9 carrying a mutation, 2 had autism, one of which was a frameshift mutation. No controls were evaluated (Vervoort V.S. et al.).

Score Delta: Score remained at 2

criteria met
See SFARI Gene'scoring criteria
2

Strong Candidate

See all Category 2 Genes

We considered a rigorous statistical comparison between cases and controls, yielding genome-wide statistical significance, with independent replication, to be the strongest possible evidence for a gene. These criteria were relaxed slightly for category 2.

4/1/2022
3
icon
2

Decreased from 3 to 2

Description

A screen of indivduals with FMR1-negative X-linked mental retardation resulted in the identification of rare variants in AGTR2 in 9/590 individuals, Of the 9 carrying a mutation, 2 had autism, one of which was a frameshift mutation. No controls were evaluated (Vervoort V.S. et al.).

4/1/2020
3
icon
3

Decreased from 3 to 3

Description

A screen of indivduals with FMR1-negative X-linked mental retardation resulted in the identification of rare variants in AGTR2 in 9/590 individuals, Of the 9 carrying a mutation, 2 had autism, one of which was a frameshift mutation. No controls were evaluated (Vervoort V.S. et al.).

Reports Added
[Genetic landscape of autism spectrum disorder in Vietnamese children2020]
1/1/2020
3
icon
3

Decreased from 3 to 3

Description

A screen of indivduals with FMR1-negative X-linked mental retardation resulted in the identification of rare variants in AGTR2 in 9/590 individuals, Of the 9 carrying a mutation, 2 had autism, one of which was a frameshift mutation. No controls were evaluated (Vervoort V.S. et al.).

Reports Added
[De Novo Damaging DNA Coding Mutations Are Associated With Obsessive-Compulsive Disorder and Overlap With Tourette's Disorder and Autism.2019]
10/1/2019
4
icon
3

Decreased from 4 to 3

New Scoring Scheme
Description

A screen of indivduals with FMR1-negative X-linked mental retardation resulted in the identification of rare variants in AGTR2 in 9/590 individuals, Of the 9 carrying a mutation, 2 had autism, one of which was a frameshift mutation. No controls were evaluated (Vervoort V.S. et al.).

Reports Added
[New Scoring Scheme]
7/1/2014
No data
icon
4

Increased from No data to 4

Description

A screen of indivduals with FMR1-negative X-linked mental retardation resulted in the identification of rare variants in AGTR2 in 9/590 individuals, Of the 9 carrying a mutation, 2 had autism, one of which was a frameshift mutation. No controls were evaluated (Vervoort V.S. et al.).

4/1/2014
No data
icon
4

Increased from No data to 4

Description

A screen of indivduals with FMR1-negative X-linked mental retardation resulted in the identification of rare variants in AGTR2 in 9/590 individuals, Of the 9 carrying a mutation, 2 had autism, one of which was a frameshift mutation. No controls were evaluated (Vervoort V.S. et al.).

Krishnan Probability Score

Score 0.54393820453169

Ranking 1418/25841 scored genes


[Show Scoring Methodology]
Krishnan and colleagues generated probability scores genome-wide by using a machine learning approach on a human brain-specific gene network. The method was first presented in Nat Neurosci 19, 1454-1462 (2016), and scores for more than 25,000 RefSeq genes can be accessed in column G of supplementary table 3 (see: http://www.nature.com/neuro/journal/v19/n11/extref/nn.4353-S5.xlsx). A searchable browser, with the ability to view networks of associated ASD risk genes, can be found at asd.princeton.edu.
Original Source
ExAC Score

Score 0.012548957992114

Ranking 9835/18225 scored genes


[Show Scoring Methodology]
The Exome Aggregation Consortium (ExAC) is a summary database of 60,706 exomes that has been widely used to estimate 'constraint' on mutation for individual genes. It was introduced by Lek et al. Nature 536, 285-291 (2016), and the ExAC browser can be found at exac.broadinstitute.org. The pLI score was developed as measure of intolerance to loss-of- function mutation. A pLI > 0.9 is generally viewed as highly constrained, and thus any loss-of- function mutations in autism in such a gene would be more likely to confer risk. For a full list of pLI scores see: ftp://ftp.broadinstitute.org/pub/ExAC_release/release0.3.1/functional_gene_constraint/fordist_cle aned_exac_nonTCGA_z_pli_rec_null_data.txt
Original Source
Sanders TADA Score

Score 0.94028519706741

Ranking 14512/18665 scored genes


[Show Scoring Methodology]
The TADA score ('Transmission and De novo Association') was introduced by He et al. PLoS Genet 9(8):e1003671 (2013), and is a statistic that integrates evidence from both de novo and transmitted mutations. It forms the basis for the claim of 65 individual genes being strongly associated with autism risk at a false discovery rate of 0.1 (Sanders et al. Neuron 87, 1215-1233 (2015)). The calculated TADA score for 18,665 RefSeq genes can be found in column P of Supplementary Table 6 in the Sanders et al. paper (the column headed 'tadaFdrAscSscExomeSscAgpSmallDel'), which represents a combined analysis of exome data and small de novo deletions (see www.cell.com/cms/attachment/2038545319/2052606711/mmc7.xlsx).
Original Source
Larsen Cumulative Evidence Score

Score 2

Ranking 374/461 scored genes


[Show Scoring Methodology]
Larsen and colleagues generated gene scores based on the sum of evidence for all available ASD-associated variants in a gene, with assessments based on mode of inheritance, effect size, and variant frequency in the general population. The approach was first presented in Mol Autism 7:44 (2016), and scores for 461 genes can be found in column I in supplementary table 4 from that paper.
Original Source
Zhang D Score

Score -0.67585617733251

Ranking 20249/20870 scored genes


[Show Scoring Methodology]
The DAMAGES score (disease-associated mutation analysis using gene expression signatures), or D score, was developed to combine evidence from de novo loss-of- function mutation with evidence from cell-type- specific gene expression in the mouse brain (specifically translational profiles of 24 specific mouse CNS cell types isolated from 6 different brain regions). Genes with positive D scores are more likely to be associated with autism risk, with higher-confidence genes having higher D scores. This statistic was first presented by Zhang & Shen (Hum Mutat 38, 204- 215 (2017), and D scores for more than 20,000 RefSeq genes can be found in column M in supplementary table 2 from that paper.
Original Source
External PIN Data
BioGRIDHuman Protein Reference Database
Interactome
Interaction Table
Interactor Symbol Interactor Name Interactor Organism Interactor Type Entrez ID Uniprot ID
Agtrap angiotensin II, type I receptor-associated protein Mouse Protein Binding 11610 Q9WVK0
MTUS1 microtubule associated tumor suppressor 1 Human Protein Binding 57509 Q9ULD2
Submit New Gene

Report an Error