Human Gene Module / Chromosome X / SLC7A3

SLC7A3Solute carrier family 7 (cationic amino acid transporter, y+ system), member 3

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
1 / 2
Rare Variants / Common Variants
4 / 0
Aliases
SLC7A3, ATRC3,  CAT-3,  CAT3
Associated Syndromes
-
Chromosome Band
Xq13.1
Associated Disorders
-
Relevance to Autism

A missense variant in the SLC7A3 gene was identified in two brothers with ASD and a maternal half-brother with language delay; sequencing of 148 male patients with ASD identified three additional missense variants in SLC7A3, two of which showed impaired CAT-3 function (Nava et al., 2015).

Molecular Function

This gene encodes a member of the solute carrier family 7 that functions as a sodium-independent cationic amino acid transporter and mediates the uptake of the cationic amino acids arginine, lysine and ornithine.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
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SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to SLC7A3 (2 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Support The cationic amino acid transporters CAT1 and CAT3 mediate NMDA receptor activation-dependent changes in elaboration of neuronal processes via the mammalian target of rapamycin mTOR pathway Huang Y , et al. (2007) No -
2 Primary Hypomorphic variants of cationic amino acid transporter 3 in males with autism spectrum disorders Nava C , et al. (2015) Yes -
Rare Variants   (4)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.1784G>C p.Ser595Thr missense_variant Unknown - Simplex 26215737 Nava C , et al. (2015)
c.1766G>C p.Ser589Thr missense_variant Unknown - Multiplex 26215737 Nava C , et al. (2015)
c.1289A>G p.Tyr430Cys missense_variant Familial Maternal Simplex 26215737 Nava C , et al. (2015)
c.991G>A p.Ala331Thr missense_variant Familial Maternal Multiplex 26215737 Nava C , et al. (2015)
Common Variants  

No common variants reported.

SFARI Gene score
2

Strong Candidate

A missense variant in the SLC7A3 gene was identified in two brothers with ASD and a maternal half-brother with language delay; this variant was absent in an unaffected maternal half-brother and in 630 controls (PMID 26215737). Sequencing of 148 male patients with ASD in PMID 26215737 also identified three additional missense variants in SLC7A3, two of which resulted in impaired function in CAT3, the protein encoded by the SLC7A3 gene. CAT3 has been shown to mediate NMDA receptor activation-dependent changes in elaboration of neuronal processes via the mammalian target of rapamycin mTOR pathway (PMID 17234578)

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.

10/1/2019
3
icon
2

Decreased from 3 to 2

New Scoring Scheme
Description

A missense variant in the SLC7A3 gene was identified in two brothers with ASD and a maternal half-brother with language delay; this variant was absent in an unaffected maternal half-brother and in 630 controls (PMID 26215737). Sequencing of 148 male patients with ASD in PMID 26215737 also identified three additional missense variants in SLC7A3, two of which resulted in impaired function in CAT3, the protein encoded by the SLC7A3 gene. CAT3 has been shown to mediate NMDA receptor activation-dependent changes in elaboration of neuronal processes via the mammalian target of rapamycin mTOR pathway (PMID 17234578)

Reports Added
[New Scoring Scheme]
7/1/2015
icon
3

Increased from to 3

Description

A missense variant in the SLC7A3 gene was identified in two brothers with ASD and a maternal half-brother with language delay; this variant was absent in an unaffected maternal half-brother and in 630 controls (PMID 26215737). Sequencing of 148 male patients with ASD in PMID 26215737 also identified three additional missense variants in SLC7A3, two of which resulted in impaired function in CAT3, the protein encoded by the SLC7A3 gene. CAT3 has been shown to mediate NMDA receptor activation-dependent changes in elaboration of neuronal processes via the mammalian target of rapamycin mTOR pathway (PMID 17234578)

Krishnan Probability Score

Score 0.49058652139267

Ranking 6051/25841 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 0.96779426617317

Ranking 2406/18225 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 0.93323591774256

Ranking 12210/18665 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 -0.17129714996423

Ranking 14739/20870 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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