Human Gene Module / Chromosome 14 / SLC7A7

SLC7A7solute carrier family 7 member 7

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
4 / 6
Rare Variants / Common Variants
7 / 0
Aliases
SLC7A7, LAT3,  LPI,  MOP-2,  Y+LAT1,  y+LAT-1
Associated Syndromes
-
Chromosome Band
14q11.2
Associated Disorders
-
Relevance to Autism

A de novo nonsense variant in the SLC7A7 gene was detected in an ASD proband from the Simons Simplex Collection in O'Roak et al., 2012. Targeted sequencing of 536 Chinese ASD probands and 1457 Chinese controls in Guo et al., 2017 detected one rare inherited loss-of-function variant and one rare inherited damaging missense variant in Chinese ASD probands. Transmission and De Novo Association (TADA) analysis of a combined cohort consisting of Chinese ASD cases and controls, as well as ASD probands and controls from the Simons Simplex Collection and the Autism Sequencing Consortium, in Guo et al., 2017 identified SLC7A7 as an ASD candidate gene with a PTADA of 0.005861.

Molecular Function

The protein encoded by this gene is the light subunit of a cationic amino acid transporter. This sodium-independent transporter is formed when the light subunit encoded by this gene dimerizes with the heavy subunit transporter protein SLC3A2. This transporter is found in epithelial cell membranes where it transfers cationic and large neutral amino acids from the cell to the extracellular space. Defects in this gene are a cause of lysinuric protein intolerance (LPI).

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to SLC7A7 (6 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations O'Roak BJ , et al. (2012) Yes -
2 Recent Recommendation Targeted sequencing and functional analysis reveal brain-size-related genes and their networks in autism spectrum disorders Li J , et al. (2017) Yes -
3 Support Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks Ruzzo EK , et al. (2019) Yes -
4 Support - Cirnigliaro M et al. (2023) Yes -
5 Support - Balasar et al. (2023) No -
6 Support - Thomas V Fernandez et al. (2023) No -
Rare Variants   (7)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.725G>A p.Trp242Ter stop_gained Familial - - 28831199 Li J , et al. (2017)
c.677G>A p.Gly226Asp missense_variant Familial - - 28831199 Li J , et al. (2017)
c.1228C>T p.Arg410Ter stop_gained De novo - Simplex 22495309 O'Roak BJ , et al. (2012)
c.347C>T p.Ala116Val missense_variant De novo - Simplex 37788244 Thomas V Fernandez et al. (2023)
c.158C>T p.Ser53Leu missense_variant Familial Both parents Simplex 37524782 Balasar et al. (2023)
c.1461del p.Cys487Ter frameshift_variant Familial Maternal Multiplex 31398340 Ruzzo EK , et al. (2019)
c.1460del p.Cys487LeufsTer32 frameshift_variant Familial Maternal Multiplex 37506195 Cirnigliaro M et al. (2023)
Common Variants  

No common variants reported.

SFARI Gene score
2

Strong Candidate

A de novo nonsense variant in the SLC7A7 gene was detected in an ASD proband from the Simons Simplex Collection in O'Roak et al., 2012. Targeted sequencing of 536 Chinese ASD probands and 1457 Chinese controls in Guo et al., 2017 detected one rare inherited loss-of-function variant and one rare inherited damaging missense variant in Chinese ASD probands. Transmission and De Novo Association (TADA) analysis of a combined cohort consisting of Chinese ASD cases and controls, as well as ASD probands and controls from the Simons Simplex Collection and the Autism Sequencing Consortium, in Guo et al., 2017 identified SLC7A7 as an ASD candidate gene with a PTADA of 0.005861.

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.

4/1/2022
3
icon
2

Decreased from 3 to 2

Description

A de novo nonsense variant in the SLC7A7 gene was detected in an ASD proband from the Simons Simplex Collection in O'Roak et al., 2012. Targeted sequencing of 536 Chinese ASD probands and 1457 Chinese controls in Guo et al., 2017 detected one rare inherited loss-of-function variant and one rare inherited damaging missense variant in Chinese ASD probands. Transmission and De Novo Association (TADA) analysis of a combined cohort consisting of Chinese ASD cases and controls, as well as ASD probands and controls from the Simons Simplex Collection and the Autism Sequencing Consortium, in Guo et al., 2017 identified SLC7A7 as an ASD candidate gene with a PTADA of 0.005861.

10/1/2019
4
icon
3

Decreased from 4 to 3

New Scoring Scheme
Description

A de novo nonsense variant in the SLC7A7 gene was detected in an ASD proband from the Simons Simplex Collection in O'Roak et al., 2012. Targeted sequencing of 536 Chinese ASD probands and 1457 Chinese controls in Guo et al., 2017 detected one rare inherited loss-of-function variant and one rare inherited damaging missense variant in Chinese ASD probands. Transmission and De Novo Association (TADA) analysis of a combined cohort consisting of Chinese ASD cases and controls, as well as ASD probands and controls from the Simons Simplex Collection and the Autism Sequencing Consortium, in Guo et al., 2017 identified SLC7A7 as an ASD candidate gene with a PTADA of 0.005861.

Reports Added
[New Scoring Scheme]
7/1/2019
4
icon
4

Decreased from 4 to 4

Description

A de novo nonsense variant in the SLC7A7 gene was detected in an ASD proband from the Simons Simplex Collection in O'Roak et al., 2012. Targeted sequencing of 536 Chinese ASD probands and 1457 Chinese controls in Guo et al., 2017 detected one rare inherited loss-of-function variant and one rare inherited damaging missense variant in Chinese ASD probands. Transmission and De Novo Association (TADA) analysis of a combined cohort consisting of Chinese ASD cases and controls, as well as ASD probands and controls from the Simons Simplex Collection and the Autism Sequencing Consortium, in Guo et al., 2017 identified SLC7A7 as an ASD candidate gene with a PTADA of 0.005861.

Reports Added
[Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks.2019]
7/1/2017
icon
4

Increased from to 4

Description

A de novo nonsense variant in the SLC7A7 gene was detected in an ASD proband from the Simons Simplex Collection in O'Roak et al., 2012. Targeted sequencing of 536 Chinese ASD probands and 1457 Chinese controls in Guo et al., 2017 detected one rare inherited loss-of-function variant and one rare inherited damaging missense variant in Chinese ASD probands. Transmission and De Novo Association (TADA) analysis of a combined cohort consisting of Chinese ASD cases and controls, as well as ASD probands and controls from the Simons Simplex Collection and the Autism Sequencing Consortium, in Guo et al., 2017 identified SLC7A7 as an ASD candidate gene with a PTADA of 0.005861.

Krishnan Probability Score

Score 0.40600711940092

Ranking 23137/25841 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 0.0020911949689639

Ranking 11236/18225 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 0.61697533970636

Ranking 767/18665 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 -0.12638852056315

Ranking 13356/20870 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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