Human Gene Module / Chromosome 7 / SLC29A4

SLC29A4solute carrier family 29 member 4

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
2 / 2
Rare Variants / Common Variants
5 / 0
Aliases
SLC29A4, PSEC0113,  ENT4,  PMAT
Associated Syndromes
-
Chromosome Band
7p22.1
Associated Disorders
-
Relevance to Autism

Two novel missense variants in the SLC29A4 gene that reduced transport uptake activity in cellular assays (c.412G>A/p.Ala138Thr and c.978T>G/p.Asp326Glu) were identified in a total of six individuals out of a cohort of 248 Caucasian ASD cases (Adamsen et al., 2014).

Molecular Function

This gene encodes a member of the SLC29A/ENT transporter protein family. The encoded membrane protein catalyzes the reuptake of monoamines into presynaptic neurons, thus determining the intensity and duration of monoamine neural signaling. It has been shown to transport several compounds, including serotonin, dopamine, and the neurotoxin 1-methyl-4-phenylpyridinium.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
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SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to SLC29A4 (2 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary Autism spectrum disorder associated with low serotonin in CSF and mutations in the SLC29A4 plasma membrane monoamine transporter (PMAT) gene Adamsen D , et al. (2014) Yes -
2 Support - Zhou X et al. (2022) Yes -
Rare Variants   (5)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.416-6C>T - splice_region_variant De novo - - 35982159 Zhou X et al. (2022)
c.782A>G p.Tyr261Cys missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.86A>G p.Asp29Gly missense_variant Familial - Unknown 25802735 Adamsen D , et al. (2014)
c.978T>G p.Asp326Glu missense_variant Familial - Simplex 25802735 Adamsen D , et al. (2014)
c.412G>A p.Ala138Thr missense_variant Familial - Simplex (n=1), multiplex (n=2), unknown (n=2) 25802735 Adamsen D , et al. (2014)
Common Variants  

No common variants reported.

SFARI Gene score
2

Strong Candidate

Two novel missense variants in the SLC29A4 gene that reduced transport uptake activity in cellular assays (c.412G>A/p.Ala138Thr and c.978T>G/p.Asp326Glu) were identified in a total of six individuals out of a cohort of 248 Caucasian ASD cases (Adamsen et al., 2014).

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

Two novel missense variants in the SLC29A4 gene that reduced transport uptake activity in cellular assays (c.412G>A/p.Ala138Thr and c.978T>G/p.Asp326Glu) were identified in a total of six individuals out of a cohort of 248 Caucasian ASD cases (Adamsen et al., 2014).

10/1/2019
4
icon
3

Decreased from 4 to 3

New Scoring Scheme
Description

Two novel missense variants in the SLC29A4 gene that reduced transport uptake activity in cellular assays (c.412G>A/p.Ala138Thr and c.978T>G/p.Asp326Glu) were identified in a total of six individuals out of a cohort of 248 Caucasian ASD cases (Adamsen et al., 2014).

Reports Added
[New Scoring Scheme]
7/1/2018
icon
4

Increased from to 4

Description

Two novel missense variants in the SLC29A4 gene that reduced transport uptake activity in cellular assays (c.412G>A/p.Ala138Thr and c.978T>G/p.Asp326Glu) were identified in a total of six individuals out of a cohort of 248 Caucasian ASD cases (Adamsen et al., 2014).

Krishnan Probability Score

Score 0.4471512012743

Ranking 13956/25841 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 0.0011474880521654

Ranking 11687/18225 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 0.94802277888465

Ranking 17514/18665 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
Larsen Cumulative Evidence Score

Score 13

Ranking 151/461 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.
Original Source
Zhang D Score

Score -0.4628006355384

Ranking 18931/20870 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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