Human Gene Module / Chromosome 3 / GRM7

GRM7Glutamate receptor, metabotropic 7

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
7 / 18
Rare Variants / Common Variants
12 / 13
Aliases
GRM7, GLUR7,  GPRC1G,  MGLU7,  MGLUR7,  PPP1R87
Associated Syndromes
-
Chromosome Band
3p26.1
Associated Disorders
-
Relevance to Autism

SNPs in GRM7 associated with ASD in a pilot study of Chinese ASD cases (Yang et al., 2013). A de novo exonic deletion in GRM7 was identified in a proband with ASD and hyperactivity; three of the exons within the breakpoint boundaries of this deletion were predicted to be under purifying selection and highly expressed in prenatal brain regions (Liu et al., 2015). A de novo missense variant in GRM7 was also identified in an ASD proband from the Simons Simplex Collection (Sanders et al., 2012).

Molecular Function

This gene encodes for a G-protein coupled receptor for glutamate. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Variants in this gene have been shown to associate with schizophrenia, ADHD, and bipolar disorder.

External Links
Gene CardOpen Targets PlatformgnomAD browserSynGO portalPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to GRM7 (18 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Positive Association A polymorphism of the metabotropic glutamate receptor mGluR7 (GRM7) gene is associated with schizophrenia Ohtsuki T , et al. (2008) No -
2 Positive Association Association study of polymorphisms in the group III metabotropic glutamate receptor genes, GRM4 and GRM7, with schizophrenia Shibata H , et al. (2009) No -
3 Positive Association A family-based association study of DNA sequence variants in GRM7 with schizophrenia in an Indonesian population Ganda C , et al. (2009) No -
4 Positive Association Genome-wide copy number variation study associates metabotropic glutamate receptor gene networks with attention deficit hyperactivity disorder Elia J , et al. (2011) No -
5 Support De novo mutations revealed by whole-exome sequencing are strongly associated with autism Sanders SJ , et al. (2012) No -
6 Primary Role of metabotropic glutamate receptor 7 in autism spectrum disorders: a pilot study Yang Y and Pan C (2012) Yes -
7 Positive Association Association between the GRM7 rs3792452 polymorphism and attention deficit hyperacitiveity disorder in a Korean sample Park S , et al. (2013) No -
8 Positive Association Allelic association, DNA resequencing and copy number variation at the metabotropic glutamate receptor GRM7 gene locus in bipolar disorder Kandaswamy R , et al. (2014) No -
9 Negative Association Lack of association between the GRM7 gene and attention deficit hyperactivity disorder Akutagava-Martins GC , et al. (2014) No -
10 Support Rare de novo deletion of metabotropic glutamate receptor 7 (GRM7) gene in a patient with autism spectrum disorder Liu Y , et al. (2015) Yes -
11 Positive Association Glutamate receptor, metabotropic 7 (GRM7) gene variations and susceptibility to autism: A case-control study Noroozi R , et al. (2016) Yes -
12 Support Exome sequencing in mostly consanguineous Arab families with neurologic disease provides a high potential molecular diagnosis rate Charng WL , et al. (2016) No -
13 Support Diagnostic Yield and Novel Candidate Genes by Exome Sequencing in 152 Consanguineous Families With Neurodevelopmental Disorders Reuter MS , et al. (2017) No -
14 Support - Wang X et al. (2021) Yes -
15 Support - Mitani T et al. (2021) No -
16 Support - Woodbury-Smith M et al. (2022) Yes -
17 Support - Zhou X et al. (2022) Yes -
18 Negative Association - Liu J et al. (2023) Yes -
Rare Variants   (12)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
- - copy_number_loss De novo - Simplex 25921429 Liu Y , et al. (2015)
c.352C>G p.Gln118Glu missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.1709A>G p.Asn570Ser missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.804T>C p.Asp268%3D synonymous_variant De novo - - 35982159 Zhou X et al. (2022)
c.804T>C p.Asp268%3D synonymous_variant De novo - Simplex 35982159 Zhou X et al. (2022)
c.1558G>A p.Ala520Thr missense_variant Unknown - - 35205252 Woodbury-Smith M et al. (2022)
c.1865G>A p.Arg622Gln missense_variant De novo - Simplex 22495306 Sanders SJ , et al. (2012)
c.1972C>T p.Arg658Trp missense_variant Familial - Multiplex 27435318 Charng WL , et al. (2016)
c.2024C>A p.Thr675Lys missense_variant Familial - Multiplex 27435318 Charng WL , et al. (2016)
c.1757G>A p.Trp586Ter stop_gained Familial Both parents Multiplex 28097321 Reuter MS , et al. (2017)
c.2671G>A p.Glu891Lys missense_variant Familial Both parents Simplex 34582790 Mitani T et al. (2021)
c.461T>C p.Ile154Thr missense_variant Familial Both parents Multiplex 27435318 Charng WL , et al. (2016)
Common Variants   (13)
Status Allele Change Residue Change Variant Type Inheritance Pattern Paternal Transmission Family Type PubMed ID Author, Year
- - copy_number_loss - - - 22138692 Elia J , et al. (2011)
c.2451+45740C>T - intron_variant - - - 23295062 Park S , et al. (2013)
c.519+18164C>T - intron_variant - - - 19638256 Ganda C , et al. (2009)
c.1175-9823T>C - intron_variant - - - 23201551 Yang Y and Pan C (2012)
c.1376-3623C>T - intron_variant - - - 23201551 Yang Y and Pan C (2012)
c.1175-9823T>C - intron_variant - - - 27312574 Noroozi R , et al. (2016)
c.1033+45994C>G - intron_variant - - - 19351574 Shibata H , et al. (2009)
c.1515+34967T>G - intron_variant - - - 19351574 Shibata H , et al. (2009)
c.222C>T p.(=) synonymous_variant - - - 18329248 Ohtsuki T , et al. (2008)
c.736+53390G>A - intron_variant - - - 24804643 Kandaswamy R , et al. (2014)
c.736+57886C>T - intron_variant - - - 24804643 Kandaswamy R , et al. (2014)
c.736+63078A>G - intron_variant - - - 24804643 Kandaswamy R , et al. (2014)
c.*401A>T;c.*472A>T - 3_prime_UTR_variant - - - 24804643 Kandaswamy R , et al. (2014)
SFARI Gene score
2

Strong Candidate

SNPs in GRM7 associated with ASD in a pilot study of Chinese ASD cases (Yang et al., 2013). A de novo exonic deletion in GRM7 was identified in a proband with ASD and hyperactivity; three of the exons within the breakpoint boundaries of this deletion were predicted to be under purifying selection and highly expressed in prenatal brain regions (Liu et al., 2015). A de novo missense variant in GRM7 was also identified in an ASD proband from the Simons Simplex Collection (Sanders et al., 2012).

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

SNPs in GRM7 associated with ASD in a pilot study of Chinese ASD cases (Yang et al., 2013). A de novo exonic deletion in GRM7 was identified in a proband with ASD and hyperactivity; three of the exons within the breakpoint boundaries of this deletion were predicted to be under purifying selection and highly expressed in prenatal brain regions (Liu et al., 2015). A de novo missense variant in GRM7 was also identified in an ASD proband from the Simons Simplex Collection (Sanders et al., 2012).

10/1/2019
4
icon
3

Decreased from 4 to 3

New Scoring Scheme
Description

SNPs in GRM7 associated with ASD in a pilot study of Chinese ASD cases (Yang et al., 2013). A de novo exonic deletion in GRM7 was identified in a proband with ASD and hyperactivity; three of the exons within the breakpoint boundaries of this deletion were predicted to be under purifying selection and highly expressed in prenatal brain regions (Liu et al., 2015). A de novo missense variant in GRM7 was also identified in an ASD proband from the Simons Simplex Collection (Sanders et al., 2012).

Reports Added
[New Scoring Scheme]
1/1/2017
4
icon
4

Decreased from 4 to 4

Description

SNPs in GRM7 associated with ASD in a pilot study of Chinese ASD cases (Yang et al., 2013). A de novo exonic deletion in GRM7 was identified in a proband with ASD and hyperactivity; three of the exons within the breakpoint boundaries of this deletion were predicted to be under purifying selection and highly expressed in prenatal brain regions (Liu et al., 2015). A de novo missense variant in GRM7 was also identified in an ASD proband from the Simons Simplex Collection (Sanders et al., 2012).

Reports Added
[Diagnostic Yield and Novel Candidate Genes by Exome Sequencing in 152 Consanguineous Families With Neurodevelopmental Disorders.2017]
7/1/2016
4
icon
4

Decreased from 4 to 4

Description

SNPs in GRM7 associated with ASD in a pilot study of Chinese ASD cases (Yang et al., 2013). A de novo exonic deletion in GRM7 was identified in a proband with ASD and hyperactivity; three of the exons within the breakpoint boundaries of this deletion were predicted to be under purifying selection and highly expressed in prenatal brain regions (Liu et al., 2015). A de novo missense variant in GRM7 was also identified in an ASD proband from the Simons Simplex Collection (Sanders et al., 2012).

Reports Added
[Glutamate receptor, metabotropic 7 (GRM7) gene variations and susceptibility to autism: A case-control study.2016] [Exome sequencing in mostly consanguineous Arab families with neurologic disease provides a high potential molecular diagnosis rate.2016]
7/1/2015
icon
4

Increased from to 4

Description

SNPs in GRM7 associated with ASD in a pilot study of Chinese ASD cases (Yang et al., 2013). A de novo exonic deletion in GRM7 was identified in a proband with ASD and hyperactivity; three of the exons within the breakpoint boundaries of this deletion were predicted to be under purifying selection and highly expressed in prenatal brain regions (Liu et al., 2015). A de novo missense variant in GRM7 was also identified in an ASD proband from the Simons Simplex Collection (Sanders et al., 2012).

Krishnan Probability Score

Score 0.61317196558866

Ranking 147/25841 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 0.99916906867981

Ranking 1029/18225 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 0.9314098783263

Ranking 11692/18665 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
Zhang D Score

Score 0.19047655636065

Ranking 4417/20870 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
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