Human Gene Module / Chromosome 7 / GPR85

GPR85G protein-coupled receptor 85

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
1 / 5
Rare Variants / Common Variants
3 / 2
Aliases
GPR85, SREB,  SREB2
Associated Syndromes
-
Chromosome Band
7q31.1
Associated Disorders
-
Relevance to Autism

Maternally-inherited missense variants in GPR85 that altered dendritic branching following expression in mouse hippocampal neurons were observed in two unrelated Japanese ASD cases and were not seen in Japanese controls (Fujita-Jimbo et al., 2015). Overexpression of this gene in mice resulted in several behavioral abnormalities, including decreased social interaction and impaired memory (Matsumoto et al., 2008).

Molecular Function

This gene encodes an orphan G-protein coupled receptor (GPCR) that is the most conserved GPCR throughout vertebrate evolution and is expressed abundantly in brain structures exhibiting high levels of plasticity, such as the hippocampus. Common variants in this gene have been identified that associate with schizophrenia (Matsumoto et al., 2008) and affect brain function in normal subjects (Radulescu et al., 2013).

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
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SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to GPR85 (5 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Positive Association The evolutionarily conserved G protein-coupled receptor SREB2/GPR85 influences brain size, behavior, and vulnerability to schizophrenia Matsumoto M , et al. (2008) No -
2 Support SREB2/GPR85, a schizophrenia risk factor, negatively regulates hippocampal adult neurogenesis and neurogenesis-dependent learning and memory Chen Q , et al. (2012) No -
3 Support Effect of schizophrenia risk-associated alleles in SREB2 (GPR85) on functional MRI phenotypes in healthy volunteers Radulescu E , et al. (2012) No -
4 Primary The association of GPR85 with PSD-95-neuroligin complex and autism spectrum disorder: a molecular analysis Fujita-Jimbo E , et al. (2015) Yes -
5 Support - N.Y.) (07/2) No -
Rare Variants   (3)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.1026A>C p.Ser342%3D synonymous_variant De novo - - 35901164 N.Y.) (07/2)
c.1033T>C p.Met152Thr missense_variant Familial Maternal Simplex 25780553 Fujita-Jimbo E , et al. (2015)
c.1239G>T p.Val221Leu missense_variant Familial Maternal Simplex 25780553 Fujita-Jimbo E , et al. (2015)
Common Variants   (2)
Status Allele Change Residue Change Variant Type Inheritance Pattern Paternal Transmission Family Type PubMed ID Author, Year
c.*2949A>G A/G 3_prime_UTR_variant - - - 18413613 Matsumoto M , et al. (2008)
c.-171+414G>C;c.-170-687G>C G/C intron_variant - - - 18413613 Matsumoto M , et al. (2008)
SFARI Gene score
2

Strong Candidate

Maternally-inherited missense variants in GPR85 that altered dendritic branching following expression in mouse hippocampal neurons were observed in two unrelated Japanese ASD cases and were not seen in Japanese controls (Fujita-Jimbo et al., 2015). Overexpression of this gene in mice resulted in several behavioral abnormalities, including decreased social interaction and impaired memory (Matsumoto et al., 2008).

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

Maternally-inherited missense variants in GPR85 that altered dendritic branching following expression in mouse hippocampal neurons were observed in two unrelated Japanese ASD cases and were not seen in Japanese controls (Fujita-Jimbo et al., 2015). Overexpression of this gene in mice resulted in several behavioral abnormalities, including decreased social interaction and impaired memory (Matsumoto et al., 2008).

10/1/2019
4
icon
3

Decreased from 4 to 3

New Scoring Scheme
Description

Maternally-inherited missense variants in GPR85 that altered dendritic branching following expression in mouse hippocampal neurons were observed in two unrelated Japanese ASD cases and were not seen in Japanese controls (Fujita-Jimbo et al., 2015). Overexpression of this gene in mice resulted in several behavioral abnormalities, including decreased social interaction and impaired memory (Matsumoto et al., 2008).

Reports Added
[New Scoring Scheme]
7/1/2015
icon
4

Increased from to 4

Description

Maternally-inherited missense variants in GPR85 that altered dendritic branching following expression in mouse hippocampal neurons were observed in two unrelated Japanese ASD cases and were not seen in Japanese controls (Fujita-Jimbo et al., 2015). Overexpression of this gene in mice resulted in several behavioral abnormalities, including decreased social interaction and impaired memory (Matsumoto et al., 2008).

Krishnan Probability Score

Score 0.52482647358847

Ranking 1628/25841 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 0.8104471003768

Ranking 3873/18225 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 0.9170756313341

Ranking 8588/18665 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 0.40368069126864

Ranking 1417/20870 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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