Human Gene Module / Chromosome 21 / SOD1

SOD1superoxide dismutase 1

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
2 / 3
Rare Variants / Common Variants
1 / 2
Aliases
SOD1, ALS,  ALS1,  HEL-S-44,  IPOA,  SOD,  hSod1,  homodimer
Associated Syndromes
-
Chromosome Band
21q22.11
Associated Disorders
-
Relevance to Autism

Two rare SNPs located in noncoding, potentially regulatory regions of the SOD1 gene were identifed that associated with ASD in a Slovenian case-cohort analysis (Kovac et al., 2013).

Molecular Function

The protein encoded by this gene binds copper and zinc ions and is one of two isozymes responsible for destroying free superoxide radicals in the body. The encoded isozyme is a soluble cytoplasmic protein, acting as a homodimer to convert naturally-occuring but harmful superoxide radicals to molecular oxygen and hydrogen peroxide. Defects in this gene are associated with amyotrophic lateral sclerosis 1 (ALS1) [MIM:105400].

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
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SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to SOD1 (3 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Support A novel function for fragile X mental retardation protein in translational activation Bechara EG , et al. (2009) No -
2 Primary Rare single nucleotide polymorphisms in the regulatory regions of the superoxide dismutase genes in autism spectrum disorder Kova J , et al. (2013) Yes -
3 Support - Rodin RE et al. (2021) Yes -
Rare Variants   (1)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
ENSG00000142168:ENST00000389995:exon4:c.G224C:p.G75A,ENSG00000142168:ENST00000270142:exon4:c.G281C:p - missense_variant De novo - - 33432195 Rodin RE et al. (2021)
Common Variants   (2)
Status Allele Change Residue Change Variant Type Inheritance Pattern Paternal Transmission Family Type PubMed ID Author, Year
c.239+34A>C - intron_variant - - - 24155217 Kova J , et al. (2013)
c.-1808C>G - 2KB_upstream_variant - - - 24155217 Kova J , et al. (2013)
SFARI Gene score
2

Strong Candidate

Two rare SNPs located in noncoding, potentially regulatory regions of the SOD1 gene were identifed that associated with ASD in a Slovenian case-cohort analysis (Kovac et al., 2013). Bechara et al., 2009 demonstrated that FMRP, the protein encoded by the Fragile X gene FMR1, specifically bound to Sod1 mRNA with high affinity, and that the absence of FMRP in FMR1 null mice resulted in decreased expression of Sod1.

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 rare SNPs located in noncoding, potentially regulatory regions of the SOD1 gene were identifed that associated with ASD in a Slovenian case-cohort analysis (Kovac et al., 2013). Bechara et al., 2009 demonstrated that FMRP, the protein encoded by the Fragile X gene FMR1, specifically bound to Sod1 mRNA with high affinity, and that the absence of FMRP in FMR1 null mice resulted in decreased expression of Sod1.

1/1/2021
3
icon
3

Decreased from 3 to 3

Description

Two rare SNPs located in noncoding, potentially regulatory regions of the SOD1 gene were identifed that associated with ASD in a Slovenian case-cohort analysis (Kovac et al., 2013). Bechara et al., 2009 demonstrated that FMRP, the protein encoded by the Fragile X gene FMR1, specifically bound to Sod1 mRNA with high affinity, and that the absence of FMRP in FMR1 null mice resulted in decreased expression of Sod1.

Reports Added
[The landscape of somatic mutation in cerebral cortex of autistic and neurotypical individuals revealed by ultra-deep whole-genome sequencing2021]
10/1/2019
4
icon
3

Decreased from 4 to 3

New Scoring Scheme
Description

Two rare SNPs located in noncoding, potentially regulatory regions of the SOD1 gene were identifed that associated with ASD in a Slovenian case-cohort analysis (Kovac et al., 2013). Bechara et al., 2009 demonstrated that FMRP, the protein encoded by the Fragile X gene FMR1, specifically bound to Sod1 mRNA with high affinity, and that the absence of FMRP in FMR1 null mice resulted in decreased expression of Sod1.

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

Increased from to 4

Description

Two rare SNPs located in noncoding, potentially regulatory regions of the SOD1 gene were identifed that associated with ASD in a Slovenian case-cohort analysis (Kovac et al., 2013). Bechara et al., 2009 demonstrated that FMRP, the protein encoded by the Fragile X gene FMR1, specifically bound to Sod1 mRNA with high affinity, and that the absence of FMRP in FMR1 null mice resulted in decreased expression of Sod1.

Krishnan Probability Score

Score 0.49493716618058

Ranking 3330/25841 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 0.44218872369882

Ranking 5761/18225 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 0.92802509650275

Ranking 10813/18665 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 4

Ranking 323/461 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 0.55632590196379

Ranking 219/20870 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
Interactome
Interaction Table
Interactor Symbol Interactor Name Interactor Organism Interactor Type Entrez ID Uniprot ID
APOL2 Apolipoprotein L2 Human Protein Binding 23780 Q9BQE5
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