Human Gene Module / Chromosome 11 / SLC1A2

SLC1A2Solute carrier family 1 (glial high affinity glutamate transporter), member 2

SFARI Gene Score
3
Suggestive Evidence Criteria 3.1
Autism Reports / Total Reports
2 / 10
Rare Variants / Common Variants
6 / 0
Aliases
SLC1A2, EAAT2,  GLT-1
Associated Syndromes
WAGR syndrome
Chromosome Band
11p13
Associated Disorders
DD/NDD, ID, ASD
Relevance to Autism

Astrocyte-specific GLT1 inducible knockout mice exhibit pathological repetitive behaviors including excessive and injurious levels of self-grooming and tic-like head shakes; treatment with an N-methyl-D-aspartate (NMDA) receptor antagonist memantine ameliorated these pathological repetitive behaviors (Aida et al., 2015). A survey of 31 patients with WAGR (Wilms tumor, Aniridia, Genitourinary malformations and mental Retardation) syndrome caused by de novo 11p14-p12 deletions found that deletion of SLC1A2 occurred in patients with autism more frequently than in those without autism (Xu et al., 2008).

Molecular Function

This gene encodes a member of a family of solute transporter proteins. The membrane-bound protein is the principal transporter that clears the excitatory neurotransmitter glutamate from the extracellular space at synapses in the central nervous system.

External Links
Gene CardOpen Targets PlatformgnomAD browserSynGO portalPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
Mouse
Entrez GeneMouse Genome Informatics
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to SLC1A2 (10 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Support Mapping autism risk loci using genetic linkage and chromosomal rearrangements Autism Genome Project Consortium , et al. (2007) No -
2 Support Characterization of 11p14-p12 deletion in WAGR syndrome by array CGH for identifying genes contributing to mental retardation and autism Xu S , et al. (2008) No ASD, DD, ID
3 Negative Association Analysis of 9p24 and 11p12-13 regions in autism spectrum disorders: rs1340513 in the JMJD2C gene is associated with ASDs in Finnish sample Kantojrvi K , et al. (2010) No -
4 Positive Association Association of rare variation in the glutamate receptor gene SLC1A2 with susceptibility to bipolar disorder and schizophrenia Fiorentino A , et al. (2014) No -
5 Primary Astroglial glutamate transporter deficiency increases synaptic excitability and leads to pathological repetitive behaviors in mice Aida T , et al. (2015) No -
6 Support De Novo Mutations in SLC1A2 and CACNA1A Are Important Causes of Epileptic Encephalopathies Epi4K Consortium. Electronic address: epi4k@columbia.edu and Epi4K Consortium (2016) No -
7 Support - Mir A et al. (2021) No Autistic features
8 Support - Kovermann P et al. (2022) No -
9 Support - Zhou X et al. (2022) Yes -
10 Support - Sheth F et al. (2023) Yes DD, ID
Rare Variants   (6)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
- - copy_number_loss De novo - - 19096215 Xu S , et al. (2008)
c.952G>C p.Val318Leu missense_variant De novo - - 34797406 Mir A et al. (2021)
c.120G>A p.Lys40%3D synonymous_variant De novo - - 35982159 Zhou X et al. (2022)
c.1643A>G p.Asp548Gly missense_variant Familial Paternal Simplex 37543562 Sheth F et al. (2023)
c.244G>C p.Gly82Arg missense_variant De novo - - 27476654 Epi4K Consortium. Electronic address: epi4k@columbia.edu and Epi4K Consortium (2016)
c.254T>C p.Leu85Pro missense_variant De novo - - 27476654 Epi4K Consortium. Electronic address: epi4k@columbia.edu and Epi4K Consortium (2016)
Common Variants  

No common variants reported.

SFARI Gene score
3

Suggestive Evidence

Astrocyte-specific GLT1 inducible knockout mice exhibit pathological repetitive behaviors including excessive and injurious levels of self-grooming and tic-like head shakes; treatment with an N-methyl-D-aspartate (NMDA) receptor antagonist memantine ameliorated these pathological repetitive behaviors (Aida et al., 2015). A survey of 31 patients with WAGR (Wilms tumor, Aniridia, Genitourinary malformations and mental Retardation) syndrome caused by de novo 11p14-p12 deletions found that deletion of SLC1A2 occurred in patients with autism more frequently than in those without autism (Xu et al., 2008). SLC1A2 lies within a ASD-associated linkage region (PMID 17322880), but no association was detected at 11p12-p13 with ASD in PMID 20410850.

Score Delta: Score remained at 3

criteria met
See SFARI Gene'scoring criteria
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.

1/1/2023
S
icon
3

Increased from S to 3

Description

Astrocyte-specific GLT1 inducible knockout mice exhibit pathological repetitive behaviors including excessive and injurious levels of self-grooming and tic-like head shakes; treatment with an N-methyl-D-aspartate (NMDA) receptor antagonist memantine ameliorated these pathological repetitive behaviors (Aida et al., 2015). A survey of 31 patients with WAGR (Wilms tumor, Aniridia, Genitourinary malformations and mental Retardation) syndrome caused by de novo 11p14-p12 deletions found that deletion of SLC1A2 occurred in patients with autism more frequently than in those without autism (Xu et al., 2008). SLC1A2 lies within a ASD-associated linkage region (PMID 17322880), but no association was detected at 11p12-p13 with ASD in PMID 20410850.

10/1/2019
S
icon
S

Increased from S to S

New Scoring Scheme
Description

Astrocyte-specific GLT1 inducible knockout mice exhibit pathological repetitive behaviors including excessive and injurious levels of self-grooming and tic-like head shakes; treatment with an N-methyl-D-aspartate (NMDA) receptor antagonist memantine ameliorated these pathological repetitive behaviors (Aida et al., 2015). A survey of 31 patients with WAGR (Wilms tumor, Aniridia, Genitourinary malformations and mental Retardation) syndrome caused by de novo 11p14-p12 deletions found that deletion of SLC1A2 occurred in patients with autism more frequently than in those without autism (Xu et al., 2008). SLC1A2 lies within a ASD-associated linkage region (PMID 17322880), but no association was detected at 11p12-p13 with ASD in PMID 20410850.

Reports Added
[New Scoring Scheme]
7/1/2016
S
icon
S

Increased from S to S

Description

Astrocyte-specific GLT1 inducible knockout mice exhibit pathological repetitive behaviors including excessive and injurious levels of self-grooming and tic-like head shakes; treatment with an N-methyl-D-aspartate (NMDA) receptor antagonist memantine ameliorated these pathological repetitive behaviors (Aida et al., 2015). A survey of 31 patients with WAGR (Wilms tumor, Aniridia, Genitourinary malformations and mental Retardation) syndrome caused by de novo 11p14-p12 deletions found that deletion of SLC1A2 occurred in patients with autism more frequently than in those without autism (Xu et al., 2008). SLC1A2 lies within a ASD-associated linkage region (PMID 17322880), but no association was detected at 11p12-p13 with ASD in PMID 20410850.

Reports Added
[De Novo Mutations in SLC1A2 and CACNA1A Are Important Causes of Epileptic Encephalopathies.2016]
Krishnan Probability Score

Score 0.62768831754058

Ranking 71/25841 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 0.90779274749498

Ranking 3173/18225 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 0.93426178601071

Ranking 12515/18665 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 0.10358386481392

Ranking 6059/20870 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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