Human Gene Module / Chromosome 6 / SLC25A27

SLC25A27solute carrier family 25 member 27

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
1 / 1
Rare Variants / Common Variants
0 / 1
Aliases
SLC25A27, RP11-446F17.2,  UCP4
Associated Syndromes
-
Chromosome Band
6p12.3
Associated Disorders
-
Relevance to Autism

SLC25A27 showed consistently reduced expression in three brain regions (anterior cingulate gyrus, motor cortex, and thalamus) following gene expression analysis of postmortem brain tissue of autism patients. SLC25A27 also showed genetic association with autism in Japanese families (P=0.046; Z-score 1.990) (Anitha et al., 2012).

Molecular Function

Mitochondrial uncoupling proteins (UCP) are members of the larger family of mitochondrial anion carrier proteins (MACP). UCPs separate oxidative phosphorylation from ATP synthesis with energy dissipated as heat, also referred to as the mitochondrial proton leak. UCPs facilitate the transfer of anions from the inner to the outer mitochondrial membrane and the return transfer of protons from the outer to the inner mitochondrial membrane. They also reduce the mitochondrial membrane potential in mammalian cells. Tissue specificity occurs for the different UCPs and the exact methods of how UCPs transfer H+/OH- are not known. UCPs contain the three homologous protein domains of MACPs. Transcripts of this gene are only detected in brain tissue and are specifically modulated by various environmental conditions.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to SLC25A27 (1 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary Brain region-specific altered expression and association of mitochondria-related genes in autism Anitha A , et al. (2012) Yes -
Rare Variants  

No rare variants reported.

Common Variants   (1)
Status Allele Change Residue Change Variant Type Inheritance Pattern Paternal Transmission Family Type PubMed ID Author, Year
c.507-625A>G;c.363-625A>G;c.192-625A>G - intron_variant - - - 23116158 Anitha A , et al. (2012)
SFARI Gene score
2

Strong Candidate

SLC25A27 showed consistently reduced expression in three brain regions (anterior cingulate gyrus, motor cortex, and thalamus) following gene expression analysis of postmortem brain tissue of autism patients. SLC25A27 also showed nominal genetic association with autism in Japanese families (P=0.046; Z-score 1.990) (Anitha et al., 2012).

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

SLC25A27 showed consistently reduced expression in three brain regions (anterior cingulate gyrus, motor cortex, and thalamus) following gene expression analysis of postmortem brain tissue of autism patients. SLC25A27 also showed nominal genetic association with autism in Japanese families (P=0.046; Z-score 1.990) (Anitha et al., 2012).

10/1/2019
4
icon
3

Decreased from 4 to 3

New Scoring Scheme
Description

SLC25A27 showed consistently reduced expression in three brain regions (anterior cingulate gyrus, motor cortex, and thalamus) following gene expression analysis of postmortem brain tissue of autism patients. SLC25A27 also showed nominal genetic association with autism in Japanese families (P=0.046; Z-score 1.990) (Anitha et al., 2012).

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

Increased from to 4

Description

SLC25A27 showed consistently reduced expression in three brain regions (anterior cingulate gyrus, motor cortex, and thalamus) following gene expression analysis of postmortem brain tissue of autism patients. SLC25A27 also showed nominal genetic association with autism in Japanese families (P=0.046; Z-score 1.990) (Anitha et al., 2012).

Krishnan Probability Score

Score 0.50010169154032

Ranking 2104/25841 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 0.16072447828713

Ranking 7307/18225 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 0.72433596216676

Ranking 1328/18665 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 1

Ranking 435/461 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 -0.16850383554595

Ranking 14664/20870 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
Submit New Gene

Report an Error