Human Gene Module / Chromosome 10 / GRID1

GRID1Glutamate receptor, ionotropic, delta 1

Score
3
Suggestive Evidence Criteria 3.1
Autism Reports / Total Reports
3 / 6
Rare Variants / Common Variants
5 / 1
Aliases
GRID1, RP11-93H12.1,  GluD1
Associated Syndromes
-
Genetic Category
Rare Single Gene Mutation, Genetic Association
Chromosome Band
10q23.1-q23.2
Associated Disorders
-
Relevance to Autism

Deletions involving the GRID1 gene were found to be over-represented in ASD patients (n=14) compared to controls (n=3) (odds ratio of 5.412, P-value of 0.0031) in a whole-genome CNV study (Glessner et al., 2009). A paternally-inherited deletion involving the GRID1 gene was identified in an ASD case as part of a study using genome-wide SNP array for CNV detection by two distinct algorithms in a European ancestry case-control data set (Griswold et al., 2012). GRID1 expression was shown to be down-regulated in induced pluripotent stem cells and upregulated in neuronal precursors and mature neurons derived from fibroblasts from patients with MECP2 and CDKL5 mutations (Livide et al., 2015).

Molecular Function

This gene encodes a subunit of glutamate receptor channels. These channels mediate most of the fast excitatory synaptic transmission in the central nervous system and play key roles in synaptic plasticity.[

Reports related to GRID1 (6 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary Autism genome-wide copy number variation reveals ubiquitin and neuronal genes. Glessner JT , et al. (2009) Yes -
2 Support Exome sequencing of ion channel genes reveals complex profiles confounding personal risk assessment in epilepsy. Klassen T , et al. (2011) No -
3 Support Evaluation of copy number variations reveals novel candidate genes in autism spectrum disorder-associated pathways. Griswold AJ , et al. (2012) Yes -
4 Recent Recommendation GluD1 is a common altered player in neuronal differentiation from both MECP2-mutated and CDKL5-mutated iPS cells. Livide G , et al. (2014) No -
5 Support Large-scale discovery of novel genetic causes of developmental disorders. Deciphering Developmental Disorders Study (2014) No -
6 Support Mutations in Human Accelerated Regions Disrupt Cognition and Social Behavior. Doan RN , et al. (2016) Yes -
Rare Variants   (5)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
insC - intron_variant - - Unknown 27667684 Doan RN , et al. (2016)
- - copy_number_loss Familial Paternal Simplex 22543975 Griswold AJ , et al. (2012)
c.1409T>A p.Val470Asp missense_variant Unknown - Unknown 21703448 Klassen T , et al. (2011)
c.2231C>T p.Ala744Val missense_variant Unknown - Unknown 21703448 Klassen T , et al. (2011)
c.1336G>C p.Glu446Gln missense_variant De novo - Unknown 25533962 Deciphering Developmental Disorders Study (2014)
Common Variants   (1)
Status Allele Change Residue Change Variant Type Inheritance Pattern Paternal Transmission Family Type PubMed ID Author, Year
- - copy_number_loss - - - 19404257 Glessner JT , et al. (2009)
SFARI Gene score
3

Suggestive Evidence

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.

4/1/2018
4.4 + acc

Initial score established: 4.4 + acc

Description

3

Krishnan Probability Score

Score 0.57199933403871

Ranking 730/25841 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 0.9507961259869

Ranking 2666/18225 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 0.94874070891821

Ranking 17807/18665 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 1

Ranking 422/461 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 0.009434857779347

Ranking 8376/20870 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.
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