Human Gene Module / Chromosome 12 / DDX23

DDX23DEAD-box helicase 23

SFARI Gene Score
S
Syndromic Syndromic
Autism Reports / Total Reports
1 / 4
Rare Variants / Common Variants
11 / 0
Aliases
DDX23, PRPF28,  SNRNP100,  U5-100K,  U5-100KD,  prp28
Associated Syndromes
-
Chromosome Band
12q13.12
Associated Disorders
ASD, EPS
Relevance to Autism

Burns et al., 2021 described a cohort of nine unrelated individuals with de novo missense variants in the DDX23 gene presenting with a syndromic neurodevelopmental disorder characterized by developmental delay, abnormal muscle tone, autism spectrum disorder or autistic features, seizures, short stature, decreased body weight, and dysmorphic facial features. A de novo missense variant in the DDX23 gene had previously been identified in an ASD proband from the Simons Simplex Collection in Iossifov et al., 2014.

Molecular Function

This gene encodes a member of the DEAD box protein family. DEAD box proteins, characterized by the conserved motif Asp-Glu-Ala-Asp (DEAD), are putative RNA helicases. They are implicated in a number of cellular processes involving alteration of RNA secondary structure, such as translation initiation, nuclear and mitochondrial splicing, and ribosome and spliceosome assembly. The protein encoded by this gene is a component of the U5 snRNP complex; it may facilitate conformational changes in the spliceosome during nuclear pre-mRNA splicing.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to DDX23 (4 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Support The contribution of de novo coding mutations to autism spectrum disorder Iossifov I et al. (2014) Yes -
2 Primary - Burns W et al. (2021) No ASD or autistic features, epilepsy/seizures
3 Support - Axel Schmidt et al. (2024) No -
4 Support - Liene Thys et al. (2024) No DD, epilepsy/seizures, autistic features
Rare Variants   (11)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.1582C>T p.Arg528Cys missense_variant De novo - - 34050707 Burns W et al. (2021)
c.1583G>A p.Arg528His missense_variant De novo - - 34050707 Burns W et al. (2021)
c.1625G>A p.Arg542His missense_variant De novo - - 34050707 Burns W et al. (2021)
c.1646A>T p.Asp549Val missense_variant De novo - - 34050707 Burns W et al. (2021)
c.1812G>T p.Met604Ile missense_variant De novo - - 34050707 Burns W et al. (2021)
c.1886T>G p.Ile629Ser missense_variant De novo - - 34050707 Burns W et al. (2021)
c.2180G>A p.Gly727Asp missense_variant De novo - - 34050707 Burns W et al. (2021)
c.2264C>T p.Thr755Met missense_variant De novo - - 34050707 Burns W et al. (2021)
c.2177G>A p.Arg726His missense_variant De novo - - 39213953 Liene Thys et al. (2024)
c.1886T>G p.Ile629Ser missense_variant De novo - - 39039281 Axel Schmidt et al. (2024)
c.2117C>T p.Ala706Val missense_variant De novo - Simplex 25363768 Iossifov I et al. (2014)
Common Variants  

No common variants reported.

SFARI Gene score
S

Syndromic

Score Delta: Score remained at S

criteria met
See SFARI Gene'scoring criteria
S

Syndromic

See all Category S Genes

The syndromic category includes mutations that are associated with a substantial degree of increased risk and consistently linked to additional characteristics not required for an ASD diagnosis. If there is independent evidence implicating a gene in idiopathic ASD, it will be listed as "#S" (e.g., 2S, 3S, etc.). If there is no such independent evidence, the gene will be listed simply as "S."

Krishnan Probability Score

Score 0.48011831485941

Ranking 8085/25841 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 0.9995583033161

Ranking 909/18225 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 0.8300529267432

Ranking 2852/18665 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 -0.061858960218612

Ranking 10853/20870 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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