Human Gene Module / Chromosome 7 / GPR37

GPR37G protein-coupled receptor 37

Score
3
Suggestive Evidence Criteria 3.1
Autism Reports / Total Reports
1 / 2
Rare Variants / Common Variants
5 / 4
Aliases
GPR37, EDNRBL,  PAELR,  hET(B)R-LP
Associated Syndromes
-
Genetic Category
Rare Single Gene Mutation
Chromosome Band
7q31.33
Associated Disorders
-
Relevance to Autism

Two rare mutations in the GPR37 gene were identified in ASD patients: 1585-1587 ttc del (Del312F) in one Japanese patient and G2324A (R558Q) in one Caucasian patient. In addition, a potential ASD-related GPR37 variant, T589M, was found in 7 affected Caucasian men from five different families (Fujita-Jimbo et al., 2012).

Molecular Function

This gene is a member of the G protein-coupled receptor family. The encoded protein contains seven transmembrane domains and is found in cell and endoplasmic reticulum membranes. G protein-coupled receptors are involved in translating outside signals into G protein mediated intracellular effects. This gene product interacts with Parkin and is involved in juvenile Parkinson disease.

Reports related to GPR37 (2 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary Mutation in Parkinson disease-associated, G-protein-coupled receptor 37 (GPR37/PaelR) is related to autism spectrum disorder. Fujita-Jimbo E , et al. (2012) Yes -
2 Recent Recommendation CASPR2 forms a complex with GPR37 via MUPP1 but not with GPR37(R558Q), an autism spectrum disorder-related mutation. Tanabe Y , et al. (2015) No -
Rare Variants   (5)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.*482C>T - missense_variant Familial Maternal Multiplex 23251443 Fujita-Jimbo E , et al. (2012)
c.2058C>G p.Ile469Met missense_variant Familial Maternal Unknown 23251443 Fujita-Jimbo E , et al. (2012)
c.240T>C p.Phe80%3D synonymous_variant Unknown Unknown Multiplex 23251443 Fujita-Jimbo E , et al. (2012)
c.1587_1589del p.Leu530del inframe_deletion Familial Paternal Simplex 23251443 Fujita-Jimbo E , et al. (2012)
c.*575C>T - missense_variant Familial Maternal (n=4); paternal (n=1) Multiplex 23251443 Fujita-Jimbo E , et al. (2012)
Common Variants   (4)
Status Allele Change Residue Change Variant Type Inheritance Pattern Paternal Transmission Family Type PubMed ID Author, Year
c.48T>C p.(=) synonymous_variant - - - 23251443 Fujita-Jimbo E , et al. (2012)
c.660C>T p.(=) synonymous_variant - - - 23251443 Fujita-Jimbo E , et al. (2012)
c.1047T>C p.(=) synonymous_variant - - - 23251443 Fujita-Jimbo E , et al. (2012)
c.1329G>C p.(=) synonymous_variant - - - 23251443 Fujita-Jimbo E , et al. (2012)
SFARI Gene score
3

Suggestive Evidence

Two rare mutations in the GPR37 gene were identified in ASD patients: 1585-1587 ttc del (Del312F) in one Japanese patient and G2324A (R558Q) in one Caucasian patient; neither of these variants were observed in ethnically-matched controls. In addition, a potential ASD-related GPR37 variant, T589M, was found in 7 affected Caucasian men from five different families (Fujita-Jimbo et al., 2012). GPR37 forms a complex with CNTNAP2 via MUPP1 (PMID 25977097).

Score Delta: Decreased from 4 to 3

3

Suggestive Evidence

See all Category 3 Genes

The literature is replete with relatively small studies of candidate genes, using either common or rare variant approaches, which do not reach the criteria set out for categories 1 and 2. Genes that had two such lines of supporting evidence were placed in category 3, and those with one line of evidence were placed in category 4. Some additional lines of "accessory evidence" (indicated as "acc" in the score cards) could also boost a gene from category 4 to 3.

10/1/2019
4
icon
3

Decreased from 4 to 3

New Scoring Scheme
Description

Two rare mutations in the GPR37 gene were identified in ASD patients: 1585-1587 ttc del (Del312F) in one Japanese patient and G2324A (R558Q) in one Caucasian patient; neither of these variants were observed in ethnically-matched controls. In addition, a potential ASD-related GPR37 variant, T589M, was found in 7 affected Caucasian men from five different families (Fujita-Jimbo et al., 2012). GPR37 forms a complex with CNTNAP2 via MUPP1 (PMID 25977097).

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

Increased from to 4

Description

Two rare mutations in the GPR37 gene were identified in ASD patients: 1585-1587 ttc del (Del312F) in one Japanese patient and G2324A (R558Q) in one Caucasian patient; neither of these variants were observed in ethnically-matched controls. In addition, a potential ASD-related GPR37 variant, T589M, was found in 7 affected Caucasian men from five different families (Fujita-Jimbo et al., 2012). GPR37 forms a complex with CNTNAP2 via MUPP1 (PMID 25977097).

Krishnan Probability Score

Score 0.4899749058289

Ranking 6313/25841 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.
ExAC Score

Score 0.79939071113317

Ranking 3949/18225 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
Sanders TADA Score

Score 0.93818025355177

Ranking 13775/18665 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).
Larsen Cumulative Evidence Score

Score 10

Ranking 186/461 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.
Zhang D Score

Score -0.14390371905052

Ranking 13952/20870 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.
Interaction Table
Interactor Symbol Interactor Name Interactor Organism Interactor Type Entrez ID Uniprot ID
ABCB8 ADNP Human Protein Binding 11194 Q9NUT2
C9ORF25 Protein FAM219A Human Protein Binding 203259 Q8IW50-3
GLP1R glucagon-like peptide 1 receptor Human Protein Binding 2740 P43220
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We are pleased to announce some changes to the ongoing curation of the data in SFARI Gene. In the context of a continued effort to develop the human gene module and its manually curated list of autism risk genes, we are modifying other aspects of the site to focus on the information that is of greatest interest to the research community. The version of SFARI Gene that has been developed until now will be frozen and will remain available as “SFARI Gene Archive”. Please see the announcement for more details.
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