Human Gene Module / Chromosome 7 / SLC29A4

SLC29A4solute carrier family 29 member 4

Score
3
Suggestive Evidence Criteria 3.1
Autism Reports / Total Reports
1 / 1
Rare Variants / Common Variants
3 / 0
Aliases
SLC29A4, PSEC0113,  ENT4,  PMAT
Associated Syndromes
-
Genetic Category
Rare Single Gene Mutation
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.

Reports related to SLC29A4 (1 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 -
Rare Variants   (3)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
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
3

Suggestive Evidence

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 4

3

Suggestive Evidence

See all Category 3 Genes

The literature is replete with relatively small studies of candidate genes, using either common or rare variant approaches, which do not reach the criteria set out for categories 1 and 2. Genes that had two such lines of supporting evidence were placed in category 3, and those with one line of evidence were placed in category 4. Some additional lines of "accessory evidence" (indicated as "acc" in the score cards) could also boost a gene from category 4 to 3.

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]
4/1/2018
icon
4.4

Increased from to 4.4

Description

4

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.
ExAC Score

Score 0.0011474880521655

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
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).
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.
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.
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SFARI Gene Update

We are pleased to announce some changes to the ongoing curation of the data in SFARI Gene. In the context of a continued effort to develop the human gene module and its manually curated list of autism risk genes, we are modifying other aspects of the site to focus on the information that is of greatest interest to the research community. The version of SFARI Gene that has been developed until now will be frozen and will remain available as “SFARI Gene Archive”. Please see the announcement for more details.
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