Human Gene Module / Chromosome 7 / GRID2IP

GRID2IPGrid2 interacting protein

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
4 / 5
Rare Variants / Common Variants
7 / 0
Aliases
GRID2IP, tcag7.1041,  DELPHILIN
Associated Syndromes
-
Chromosome Band
7p22.1
Associated Disorders
-
Relevance to Autism

This gene was originally identified as an ASD candidate gene based on its enrichment in an autism-associated protein interaction module; sequencing of post-mortem brain tissue from 25 ASD cases resulted in the identification of significant non-synonymous variants in this gene with an expected false-positive rate at 0.1, confirming the involvement of this module with autism (Li et al., 2014).

Molecular Function

This gene encodes a postsynaptic scaffolding protein at the parallel fiber-Purkinje cell synapse, where it may serve to link GRID2 with actin cytoskeleton and various signaling molecules.

External Links
Gene CardOpen Targets PlatformgnomAD browserSynGO portalPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to GRID2IP (5 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Support Characterization of the delta2 glutamate receptor-binding protein delphilin: Splicing variants with differential palmitoylation and an additional PDZ domain Matsuda K , et al. (2006) No -
2 Primary Integrated systems analysis reveals a molecular network underlying autism spectrum disorders Li J , et al. (2015) Yes -
3 Support Integrative Analyses of De Novo Mutations Provide Deeper Biological Insights into Autism Spectrum Disorder Takata A , et al. (2018) Yes -
4 Support Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks Ruzzo EK , et al. (2019) Yes -
5 Support - Zhou X et al. (2022) Yes -
Rare Variants   (7)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
- - nonsynonymous_variant Unknown - Unknown 25549968 Li J , et al. (2015)
c.204G>C p.Leu68%3D synonymous_variant De novo - - 35982159 Zhou X et al. (2022)
c.1720G>A p.Val574Met missense_variant Unknown - Unknown 25549968 Li J , et al. (2015)
c.2993G>A p.Gly998Asp missense_variant Unknown - Unknown 25549968 Li J , et al. (2015)
c.922dup p.Ser308LysfsTer4 frameshift_variant De novo - - 35982159 Zhou X et al. (2022)
c.1474dup p.Gln492ProfsTer34 frameshift_variant De novo - Simplex 29346770 Takata A , et al. (2018)
c.550C>T p.Arg184Ter stop_gained Familial Paternal Multiplex (monozygotic twins) 31398340 Ruzzo EK , et al. (2019)
Common Variants  

No common variants reported.

SFARI Gene score
2

Strong Candidate

This gene was originally identified as an ASD candidate gene based on its enrichment in an autism-associated protein interaction module; sequencing of post-mortem brain tissue from 25 ASD cases resulted in the identification of significant non-synonymous variants in this gene with an expected false-positive rate at 0.1, confirming the involvement of this module with autism (Li et al., 2014). None of the three non-synonymous variants in GRID2IP identified in this study were reported in 1000 Genomes (as of Jan/ Feb. 2013), but two of those variants were reported in dbSNP. A rare de novo frameshift variant in the GRID2IP gene was identified in a Japanese ASD proband from a trio family in Takata et al., 2018. GRID2IP1 interacts with GRID2 and may control GRID2 signaling in Purkinje cells (Matsuda et al., 2006).

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

This gene was originally identified as an ASD candidate gene based on its enrichment in an autism-associated protein interaction module; sequencing of post-mortem brain tissue from 25 ASD cases resulted in the identification of significant non-synonymous variants in this gene with an expected false-positive rate at 0.1, confirming the involvement of this module with autism (Li et al., 2014). None of the three non-synonymous variants in GRID2IP identified in this study were reported in 1000 Genomes (as of Jan/ Feb. 2013), but two of those variants were reported in dbSNP. A rare de novo frameshift variant in the GRID2IP gene was identified in a Japanese ASD proband from a trio family in Takata et al., 2018. GRID2IP1 interacts with GRID2 and may control GRID2 signaling in Purkinje cells (Matsuda et al., 2006).

10/1/2019
4
icon
3

Decreased from 4 to 3

New Scoring Scheme
Description

This gene was originally identified as an ASD candidate gene based on its enrichment in an autism-associated protein interaction module; sequencing of post-mortem brain tissue from 25 ASD cases resulted in the identification of significant non-synonymous variants in this gene with an expected false-positive rate at 0.1, confirming the involvement of this module with autism (Li et al., 2014). None of the three non-synonymous variants in GRID2IP identified in this study were reported in 1000 Genomes (as of Jan/ Feb. 2013), but two of those variants were reported in dbSNP. A rare de novo frameshift variant in the GRID2IP gene was identified in a Japanese ASD proband from a trio family in Takata et al., 2018. GRID2IP1 interacts with GRID2 and may control GRID2 signaling in Purkinje cells (Matsuda et al., 2006).

Reports Added
[New Scoring Scheme]
7/1/2019
4
icon
4

Decreased from 4 to 4

Description

This gene was originally identified as an ASD candidate gene based on its enrichment in an autism-associated protein interaction module; sequencing of post-mortem brain tissue from 25 ASD cases resulted in the identification of significant non-synonymous variants in this gene with an expected false-positive rate at 0.1, confirming the involvement of this module with autism (Li et al., 2014). None of the three non-synonymous variants in GRID2IP identified in this study were reported in 1000 Genomes (as of Jan/ Feb. 2013), but two of those variants were reported in dbSNP. A rare de novo frameshift variant in the GRID2IP gene was identified in a Japanese ASD proband from a trio family in Takata et al., 2018. GRID2IP1 interacts with GRID2 and may control GRID2 signaling in Purkinje cells (Matsuda et al., 2006).

Reports Added
[Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks.2019]
10/1/2018
icon
4

Increased from to 4

Description

This gene was originally identified as an ASD candidate gene based on its enrichment in an autism-associated protein interaction module; sequencing of post-mortem brain tissue from 25 ASD cases resulted in the identification of significant non-synonymous variants in this gene with an expected false-positive rate at 0.1, confirming the involvement of this module with autism (Li et al., 2014). None of the three non-synonymous variants in GRID2IP identified in this study were reported in 1000 Genomes (as of Jan/ Feb. 2013), but two of those variants were reported in dbSNP. A rare de novo frameshift variant in the GRID2IP gene was identified in a Japanese ASD proband from a trio family in Takata et al., 2018. GRID2IP1 interacts with GRID2 and may control GRID2 signaling in Purkinje cells (Matsuda et al., 2006).

Krishnan Probability Score

Score 0.41191062628101

Ranking 22273/25841 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 0.31473442786336

Ranking 6426/18225 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 0.94324693396329

Ranking 15614/18665 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 -0.32704048646002

Ranking 17563/20870 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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