Human Gene Module / Chromosome 19 / SAE1

SAE1SUMO1 activating enzyme subunit 1

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
4 / 4
Rare Variants / Common Variants
6 / 0
Aliases
SAE1, AOS1,  HSPC140,  SUA1,  UBLE1A
Associated Syndromes
-
Chromosome Band
19q13.32
Associated Disorders
-
Relevance to Autism

A novel recurrent 24.7 kb duplication involving the SAE1 gene was identified in 3/696 ASD cases vs. 1/5,139 controls (FET two-tailed p = 0.00616) in Prasad et al., 2012. Additional duplications affecting the SAE1 gene have been observed in ASD probands (Pinto et al., 2010; Turner et al., 2016).

Molecular Function

Posttranslational modification of proteins by the addition of the small protein SUMO (see SUMO1; MIM 601912), or sumoylation, regulates protein structure and intracellular localization. SAE1 and UBA2 (MIM 613295) form a heterodimer that functions as a SUMO-activating enzyme for the sumoylation of proteins.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to SAE1 (4 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Support Functional impact of global rare copy number variation in autism spectrum disorders Pinto D , et al. (2010) Yes -
2 Primary A discovery resource of rare copy number variations in individuals with autism spectrum disorder Prasad A , et al. (2013) Yes -
3 Recent Recommendation Genome Sequencing of Autism-Affected Families Reveals Disruption of Putative Noncoding Regulatory DNA Turner TN et al. (2016) Yes -
4 Support - Zhou X et al. (2022) Yes -
Rare Variants   (6)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
- - copy_number_gain Unknown - Unknown 23275889 Prasad A , et al. (2013)
- - copy_number_gain De novo - Simplex 26749308 Turner TN et al. (2016)
- - copy_number_gain Familial Paternal Multiplex 20531469 Pinto D , et al. (2010)
- - copy_number_gain Familial Paternal Multiplex 23275889 Prasad A , et al. (2013)
- - copy_number_gain Unknown Not maternal Simplex 23275889 Prasad A , et al. (2013)
c.991_993del p.Phe331del inframe_deletion De novo - - 35982159 Zhou X et al. (2022)
Common Variants  

No common variants reported.

SFARI Gene score
2

Strong Candidate

A novel recurrent 24.7 kb duplication involving the SAE1 gene was identified in 3/696 ASD cases vs. 1/5,139 controls (FET two-tailed p = 0.00616) in Prasad et al., 2012; further examination of the families of these ASD cases revealed that, in two families were paternal transmission of the SAE1 duplication was confirmed, the SAE1 duplication was also transmitted to all affected siblings. Additional duplications affecting the SAE1 gene have been observed in ASD probands (Pinto et al., 2010; Turner et al., 2016).

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 novel recurrent 24.7 kb duplication involving the SAE1 gene was identified in 3/696 ASD cases vs. 1/5,139 controls (FET two-tailed p = 0.00616) in Prasad et al., 2012; further examination of the families of these ASD cases revealed that, in two families were paternal transmission of the SAE1 duplication was confirmed, the SAE1 duplication was also transmitted to all affected siblings. Additional duplications affecting the SAE1 gene have been observed in ASD probands (Pinto et al., 2010; Turner et al., 2016).

Reports Added
[New Scoring Scheme]
10/1/2017
icon
3

Increased from to 3

Description

A novel recurrent 24.7 kb duplication involving the SAE1 gene was identified in 3/696 ASD cases vs. 1/5,139 controls (FET two-tailed p = 0.00616) in Prasad et al., 2012; further examination of the families of these ASD cases revealed that, in two families were paternal transmission of the SAE1 duplication was confirmed, the SAE1 duplication was also transmitted to all affected siblings. Additional duplications affecting the SAE1 gene have been observed in ASD probands (Pinto et al., 2010; Turner et al., 2016).

Krishnan Probability Score

Score 0.3296074584223

Ranking 24962/25841 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 0.98895242239694

Ranking 1843/18225 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 0.918135667904

Ranking 8769/18665 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 7

Ranking 246/461 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 0.11153480128168

Ranking 5887/20870 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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