Human Gene Module / Chromosome 17 / PSMD11

PSMD11proteasome 26S subunit, non-ATPase 11

SFARI Gene Score
1
High Confidence Criteria 1.1
Autism Reports / Total Reports
2 / 3
Rare Variants / Common Variants
14 / 0
Aliases
-
Associated Syndromes
-
Chromosome Band
17q11.2
Associated Disorders
-
Relevance to Autism

Three rare and potentially damaging de novo missense variants in the PSMD11 gene have been identified in ASD probands from the SPARK cohort and the MSSNG cohort (Zhou et al., 2022), while two protein-truncating variants in this gene were observed in ASD probands, compared to none in controls, from a case-control cohort (Trost et al., 2022). Transmission and de novo association (TADA) analysis of whole-exome and whole-genome sequencing data from the Autism Sequencing Consortium, the Simons Simplex Collection, the MSSNG cohort, and the SPARK cohort in Trost et al., 2022 identified PSMD11 as an ASD-associated gene with a false discovery rate (FDR) < 0.1.

Molecular Function

The 26S proteasome is a multicatalytic proteinase complex with a highly ordered structure composed of 2 complexes, a 20S core and a 19S regulator. The 20S core is composed of 4 rings of 28 non-identical subunits; 2 rings are composed of 7 alpha subunits and 2 rings are composed of 7 beta subunits. The 19S regulator is composed of a base, which contains 6 ATPase subunits and 2 non-ATPase subunits, and a lid, which contains up to 10 non-ATPase subunits. Proteasomes are distributed throughout eukaryotic cells at a high concentration and cleave peptides in an ATP/ubiquitin-dependent process in a non-lysosomal pathway. This gene encodes a member of the proteasome subunit S9 family that functions as a non-ATPase subunit of the 19S regulator and is phosphorylated by AMP-activated protein kinase.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
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SFARI Genomic Platforms
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Reports related to PSMD11 (3 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary - Zhou X et al. (2022) Yes -
2 Recent Recommendation - Trost B et al. (2022) Yes -
3 Recent recommendation - Wallid Deb et al. (2024) No ASD, ADHD, epilepsy/seizures
Rare Variants   (14)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
- - copy_number_loss De novo - Simplex 38866022 Wallid Deb et al. (2024)
c.92-3C>T - splice_region_variant De novo - - 35982159 Zhou X et al. (2022)
c.522C>A p.Ser174Arg missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.760A>G p.Met254Val missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.559C>T p.Arg187Ter stop_gained De novo - Simplex 38866022 Wallid Deb et al. (2024)
c.612dup p.Lys205Ter stop_gained De novo - Simplex 38866022 Wallid Deb et al. (2024)
c.619C>T p.Gln207Ter stop_gained De novo - Simplex 38866022 Wallid Deb et al. (2024)
c.1009C>T p.Arg337Ter stop_gained De novo - Simplex 38866022 Wallid Deb et al. (2024)
c.1096T>C p.Ser366Pro missense_variant De novo - Simplex 35982159 Zhou X et al. (2022)
c.268C>T p.Arg90Ter stop_gained Familial Paternal Simplex 38866022 Wallid Deb et al. (2024)
c.788+2T>C - splice_site_variant Familial Maternal Simplex 38866022 Wallid Deb et al. (2024)
c.788C>T p.Thr263Ile missense_variant Familial Paternal Simplex 38866022 Wallid Deb et al. (2024)
c.914C>T p.Ala305Val missense_variant Familial Maternal Simplex 38866022 Wallid Deb et al. (2024)
c.851_854del p.Thr284LysfsTer3 frameshift_variant De novo - Simplex 38866022 Wallid Deb et al. (2024)
Common Variants  

No common variants reported.

SFARI Gene score
1

High Confidence

Score Delta: Score remained at 1

criteria met
See SFARI Gene'scoring criteria
1

High Confidence

See all Category 1 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.

1/1/2023
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1

Increased from to 1

Krishnan Probability Score

Score 0.5702713141783

Ranking 943/25841 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 0.99974580883303

Ranking 811/18225 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 0.82959299133177

Ranking 2840/18665 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
Zhang D Score

Score 0.36496107575856

Ranking 1842/20870 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
CNVs associated with PSMD11(1 CNVs)
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17q11.2 29 Deletion-Duplication 44  /  116
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