GRIA3glutamate ionotropic receptor AMPA type subunit 3
Autism Reports / Total Reports
2 / 16Rare Variants / Common Variants
22 / 1Aliases
-Associated Syndromes
-Chromosome Band
Xq25Associated Disorders
-Relevance to Autism
Mutations in the GRIA3 gene are responsible for Wu-type X-linked syndromic intellectual developmental disorder (MRXSW; OMIM 300699); autistic behavior has been observed in a subset of individuals with GRIA3 variants (Wu et al., 2007; Chiyonobu et al., 2007; Guilmatre et al., 2009; Philips et al., 2014). Roy et al., 2021 found that GRIA3 exhibited high expression in the anterodorsal thalamus (AD) of mice, and that knockdown of this gene in AD thalamus resulted in memory deficits similar to those observed in AD thalamus-specific PTCHD1 knock-down mice.
Molecular Function
Glutamate receptors are the predominant excitatory neurotransmitter receptors in the mammalian brain and are activated in a variety of normal neurophysiologic processes. These receptors are heteromeric protein complexes composed of multiple subunits, arranged to form ligand-gated ion channels. The classification of glutamate receptors is based on their activation by different pharmacologic agonists. The subunit encoded by this gene belongs to a family of AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate)-sensitive glutamate receptors, and is subject to RNA editing (AGA->GGA; R->G). Alternative splicing at this locus results in different isoforms, which may vary in their signal transduction properties.
External Links
SFARI Genomic Platforms
Reports related to GRIA3 (15 Reports)
| # | Type | Title | Author, Year | Autism Report | Associated Disorders |
|---|---|---|---|---|---|
| 1 | Support | - | Chiyonobu T et al. (2007) | No | Autistic features |
| 2 | Primary | - | Wu Y et al. (2007) | No | Epilepsy/seizures, autistic behavior |
| 3 | Support | - | Bonnet C et al. (2009) | No | - |
| 4 | Support | Recurrent rearrangements in synaptic and neurodevelopmental genes and shared biologic pathways in schizophrenia, autism, and mental retardation | Guilmatre A , et al. (2009) | Yes | - |
| 5 | Support | - | Philips AK et al. (2014) | No | Autistic features |
| 6 | Support | - | Roy DS et al. (2021) | No | - |
| 7 | Support | - | ÃÂlvarez-Mora MI et al. (2022) | No | - |
| 8 | Support | - | Brea-Fernández AJ et al. (2022) | No | Epilepsy/seizures |
| 9 | Recent Recommendation | - | Singh T et al. (2022) | No | - |
| 10 | Support | - | Carvalho LML et al. (2022) | No | - |
| 11 | Support | - | Peng SX et al. (2022) | No | DD, ID, epilepsy/seizures, autistic features, ster |
| 12 | Support | - | Hu C et al. (2022) | Yes | - |
| 13 | Support | - | Chen Y et al. (2021) | No | - |
| 14 | Support | - | Okano S et al. (2023) | No | - |
| 15 | Support | - | Sanchis-Juan A et al. (2023) | No | - |
Rare Variants (22)
| Status | Allele Change | Residue Change | Variant Type | Inheritance Pattern | Parental Transmission | Family Type | PubMed ID | Author, Year |
|---|---|---|---|---|---|---|---|---|
| - | - | copy_number_loss | Familial | Maternal | - | 17989220 | Wu Y et al. (2007) | |
| c.22G>A | p.Gly8Arg | missense_variant | Unknown | - | - | 35741772 | Hu C et al. (2022) | |
| - | - | copy_number_gain | Familial | Maternal | - | 17568425 | Chiyonobu T et al. (2007) | |
| c.1859G>C | p.Gly620Ala | missense_variant | Unknown | - | - | 35741772 | Hu C et al. (2022) | |
| - | - | copy_number_gain | Familial | Maternal | Multiplex | 19449417 | Bonnet C et al. (2009) | |
| - | - | copy_number_gain | Familial | Maternal | Simplex | 19736351 | Guilmatre A , et al. (2009) | |
| - | p.Arg450Gln | missense_variant | Familial | Maternal | Simplex | 17989220 | Wu Y et al. (2007) | |
| c.1888G>A | p.Gly630Arg | missense_variant | Unknown | - | Unknown | 35873028 | Chen Y et al. (2021) | |
| c.1982T>C | p.Met661Thr | missense_variant | De novo | - | Simplex | 36726007 | Okano S et al. (2023) | |
| c.527C>A | p.Ala176Glu | missense_variant | Unknown | - | Simplex | 37541188 | Sanchis-Juan A et al. (2023) | |
| c.1601T>A | p.Ile534Lys | missense_variant | De novo | - | - | 35322241 | Brea-Fernández AJ et al. (2022) | |
| - | p.Arg631Ser | missense_variant | Familial | Maternal | Extended multiplex | 17989220 | Wu Y et al. (2007) | |
| - | p.Gly833Arg | missense_variant | Familial | Maternal | Extended multiplex | 17989220 | Wu Y et al. (2007) | |
| - | p.Met706Thr | missense_variant | Familial | Maternal | Extended multiplex | 17989220 | Wu Y et al. (2007) | |
| c.1888G>C | p.Gly630Arg | missense_variant | Familial | Maternal | Simplex | 35697757 | Peng SX et al. (2022) | |
| c.2360A>G | p.Glu787Gly | missense_variant | Familial | Maternal | Simplex | 35697757 | Peng SX et al. (2022) | |
| c.1888G>C | p.Gly630Arg | missense_variant | Familial | Maternal | Multiplex | 35697757 | Peng SX et al. (2022) | |
| c.2440-2734C>T | - | missense_variant | Familial | Maternal | Multiplex | 37541188 | Sanchis-Juan A et al. (2023) | |
| c.2638T>A | p.Tyr880Asn | missense_variant | Familial | Maternal | - | 35322241 | Brea-Fernández AJ et al. (2022) | |
| c.2038_2040delinsTGT | p.Gly680Cys | missense_variant | De novo | - | Simplex | 35597848 | Carvalho LML et al. (2022) | |
| c.1892G>A | p.Arg631His | missense_variant | Familial | Maternal | Simplex | 35183220 | ÃÂlvarez-Mora MI et al. (2022) | |
| c.1888G>C | p.Gly630Arg | missense_variant | Familial | Maternal | Extended multiplex | 24721225 | Philips AK et al. (2014) |
Common Variants (1)
| Status | Allele Change | Residue Change | Variant Type | Inheritance Pattern | Paternal Transmission | Family Type | PubMed ID | Author, Year |
|---|---|---|---|---|---|---|---|---|
| - | - | intron_variant | - | - | - | 35697757 | Peng SX et al. (2022) |
SFARI Gene score
S
Syndromic
Score Delta: Score remained at S
criteria met
See SFARI Gene'scoring criteriaThe syndromic category includes mutations that are associated with a substantial degree of increased risk and consistently linked to additional characteristics not required for an ASD diagnosis. If there is independent evidence implicating a gene in idiopathic ASD, it will be listed as "#S" (e.g., 2S, 3S, etc.). If there is no such independent evidence, the gene will be listed simply as "S."
Krishnan Probability Score
Score 0.64050441237497
Ranking 52/25841 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 0.99865377764627
Ranking 1144/18225 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 0.94304823175193
Ranking 15538/18665 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).
Zhang D Score
Score 0.26629239651474
Ranking 3239/20870 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.