SLC1A1solute carrier family 1 (neuronal/epithelial high affinity glutamate transporter, system Xag), member 1
Autism Reports / Total Reports
7 / 14Rare Variants / Common Variants
6 / 8Aliases
SLC1A1, EAAC1, EAAT3Associated Syndromes
-Chromosome Band
9p24.2Associated Disorders
BPDRelevance to Autism
Studies have found genetic association between polymorphisms of the SLC1A1 gene and autism.
Molecular Function
This gene encodes a member of the high-affinity glutamate transporters that play an essential role in transporting glutamate across plasma membranes. This transporter also transports aspartate.
External Links
SFARI Genomic Platforms
Reports related to SLC1A1 (14 Reports)
| # | Type | Title | Author, Year | Autism Report | Associated Disorders |
|---|---|---|---|---|---|
| 1 | Highly Cited | Modulation of the neuronal glutamate transporter EAAC1 by the interacting protein GTRAP3-18 | Lin CI , et al. (2001) | No | - |
| 2 | Highly Cited | Primary structure and functional characterization of a high-affinity glutamate transporter | Kanai Y and Hediger MA (1992) | No | - |
| 3 | Highly Cited | Glutamate transporter gene SLC1A1 associated with obsessive-compulsive disorder | Arnold PD , et al. (2006) | No | - |
| 4 | Primary | Family-Based Association Testing of OCD-associated SNPs of SLC1A1 in an autism sample | Brune CW , et al. (2009) | Yes | - |
| 5 | Positive Association | Glutamate transporter gene (SLC1A1) single nucleotide polymorphism (rs301430) and repetitive behaviors and anxiety in children with autism spectrum disorder | Gadow KD , et al. (2010) | Yes | - |
| 6 | Positive Association | Association of SNPs linked to increased expression of SLC1A1 with schizophrenia | Horiuchi Y , et al. (2011) | No | - |
| 7 | Support | A discovery resource of rare copy number variations in individuals with autism spectrum disorder | Prasad A , et al. (2013) | Yes | - |
| 8 | Support | Deletion at the SLC1A1 glutamate transporter gene co-segregates with schizophrenia and bipolar schizoaffective disorder in a 5-generation family | Myles-Worsley M , et al. (2013) | No | BPD |
| 9 | Support | Refinement and discovery of new hotspots of copy-number variation associated with autism spectrum disorder | Girirajan S , et al. (2013) | Yes | - |
| 10 | Support | Recessive gene disruptions in autism spectrum disorder | Doan RN , et al. (2019) | Yes | - |
| 11 | Support | - | Zhou X et al. (2022) | Yes | - |
| 12 | Negative Association | - | Liu J et al. (2023) | Yes | - |
| 13 | Highly Cited | Knockout of glutamate transporters reveals a major role for astroglial transport in excitotoxicity and clearance of glutamate | Rothstein JD , et al. (1996) | No | - |
| 14 | Highly Cited | EAAC1, a high-affinity glutamate tranporter, is localized to astrocytes and gabaergic neurons besides pyramidal cells in the rat cerebral cortex | Conti F , et al. (1998) | No | - |
Rare Variants (6)
| Status | Allele Change | Residue Change | Variant Type | Inheritance Pattern | Parental Transmission | Family Type | PubMed ID | Author, Year |
|---|---|---|---|---|---|---|---|---|
| - | - | copy_number_loss | Unknown | - | Unknown | 23275889 | Prasad A , et al. (2013) | |
| c.1371T>G | p.Phe457Leu | missense_variant | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
| - | - | copy_number_gain | Familial | Maternal | Simplex | 23375656 | Girirajan S , et al. (2013) | |
| - | - | copy_number_gain | Familial | Paternal | Simplex | 23375656 | Girirajan S , et al. (2013) | |
| c.142G>T | p.Glu48Ter | stop_gained | Familial | Both parents | Simplex | 31209396 | Doan RN , et al. (2019) | |
| - | - | copy_number_loss | Familial | Maternal & Paternal | Multi-generational | 23341099 | Myles-Worsley M , et al. (2013) |
Common Variants (8)
| Status | Allele Change | Residue Change | Variant Type | Inheritance Pattern | Paternal Transmission | Family Type | PubMed ID | Author, Year |
|---|---|---|---|---|---|---|---|---|
| c.91+14774A>C | - | intron_variant | - | - | - | 22095641 | Horiuchi Y , et al. (2011) | |
| c.91+23476A>G | - | intron_variant | - | - | - | 22095641 | Horiuchi Y , et al. (2011) | |
| c.1194-195T>C | T/C | intron_variant | - | - | - | 16818866 | Arnold PD , et al. (2006) | |
| c.1194-956C>T | T/C | intron_variant | - | - | - | 16818866 | Arnold PD , et al. (2006) | |
| c.232+200A>C | A/C | intron_variant | - | - | - | 22095641 | Horiuchi Y , et al. (2011) | |
| c.1193+88G>C | C to G | intron_variant | - | - | - | 19360657 | Brune CW , et al. (2009) | |
| c.1110T>C | p.(=) | synonymous_variant | - | - | - | 20155310 | Gadow KD , et al. (2010) | |
| c.92-16815C>G | C/G | intron_variant | - | - | - | 22095641 | Horiuchi Y , et al. (2011) |
SFARI Gene score
2
Strong Candidate
Association studies with positive association, which does not reach genome-wide significance (Brune et al., 2008; Gadow et al., 2010).
Score Delta: Score remained at 2
criteria met
See SFARI Gene'scoring criteriaWe 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
2
Decreased from 3 to 2
Description
Association studies with positive association, which does not reach genome-wide significance (Brune et al., 2008; Gadow et al., 2010).
10/1/2019
4
3
Decreased from 4 to 3
New Scoring Scheme
Description
Association studies with positive association, which does not reach genome-wide significance (Brune et al., 2008; Gadow et al., 2010).
Reports Added
[New Scoring Scheme]7/1/2019
4
4
Decreased from 4 to 4
Description
Association studies with positive association, which does not reach genome-wide significance (Brune et al., 2008; Gadow et al., 2010).
7/1/2014
No data
4
Increased from No data to 4
Description
Association studies with positive association, which does not reach genome-wide significance (Brune et al., 2008; Gadow et al., 2010).
4/1/2014
No data
4
Increased from No data to 4
Description
Association studies with positive association, which does not reach genome-wide significance (Brune et al., 2008; Gadow et al., 2010).
Krishnan Probability Score
Score 0.60669152418158
Ranking 314/25841 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 0.0012711667210719
Ranking 11610/18225 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 0.84354955973418
Ranking 3244/18665 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 434/461 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 0.15124247460906
Ranking 5150/20870 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.
External PIN Data
Interactome
- Protein Binding
- DNA Binding
- RNA Binding
- Protein Modification
- Direct Regulation
- ASD-Linked Genes
Interaction Table
| Interactor Symbol | Interactor Name | Interactor Organism | Interactor Type | Entrez ID | Uniprot ID |
|---|---|---|---|---|---|
| APOOL | MICOS complex subunit MIC27 | Human | Protein Binding | 139322 | Q6UXV4 |
| CST6 | Cystatin-M | Human | Protein Binding | 1474 | Q15828 |
| EAAT4 | solute carrier family 1 (high affinity aspartate/glutamate transporter), member 6 | Rat | Protein Binding | 84012 | O35921 |
| GOLGA7 | Golgin subfamily A member 7 | Human | Protein Binding | 51125 | Q7Z5G4 |
| PDZK1 | PDZ domain containing 1 | Mouse | Protein Binding | 59020 | Q9JIL4 |
| RTN2 | reticulon 2 | Rat | Protein Binding | 308410 | Q6WN19 |
| SBSN | Suprabasin | Human | Protein Binding | 374897 | E9PBV3 |