Human Gene Module / Chromosome 1 / CSDE1

CSDE1cold shock domain containing E1

SFARI Gene Score
1S
High Confidence, Syndromic Criteria 1.1, Syndromic
Autism Reports / Total Reports
3 / 7
Rare Variants / Common Variants
31 / 0
EAGLE Score
15.55
Strong Learn More
Aliases
CSDE1, D1S155E,  UNR
Associated Syndromes
-
Chromosome Band
1p13.2
Associated Disorders
ADHD, EPS
Genetic Category
Rare Single Gene Mutation, Syndromic, Functional
Relevance to Autism

A de novo nonsense variant in the CSDE1 gene was identified in an ASD proband from the Simons Simplex Collection (SSC; Iossifov et al., 2014). Guo et al., 2019 initially targeted the coding region of the CSDE1 gene using a modified single-molecule molecular inversion probe approach among 4,045 ASD probands from the Autism Clinical and Genetic Resources in China (ACGC) cohort and identified de novo likely gene-disruptive variants in three simplex families. Analysis of the SSC proband, the three ACGC probands, and thirteen additional individuals with likely gene-disruptive variants in CSDE1 identified a new neurodevelopmental syndrome characterized by ASD (a formal diagnosis was made in 10/15 evaluated individuals), intellectual disability, language and motor delay, seizures, MRI brain abnormalities, seizures, macrocephaly, behavioral problems (including ADHD and anxiety), and eye abnormalities.

Molecular Function

RNA-binding protein. Required for internal initiation of translation of human rhinovirus RNA. May be involved in translationally coupled mRNA turnover. Implicated with other RNA-binding proteins in the cytoplasmic deadenylation/translational and decay interplay of the FOS mRNA mediated by the major coding-region determinant of instability (mCRD) domain.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to CSDE1 (7 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary The contribution of de novo coding mutations to autism spectrum disorder Iossifov I et al. (2014) Yes -
2 Recent Recommendation Disruptive variants of CSDE1 associate with autism and interfere with neuronal development and synaptic transmission Guo H , et al. (2019) Yes ADHD, epilepsy/seizures
3 Support - El Khouri E et al. (2021) No Stereotypy
4 Support - Gangfuß A et al. (2022) No -
5 Support - Zhou X et al. (2022) Yes -
6 Support - Shimelis H et al. (2023) No -
7 Recent Recommendation - Xiangling Meng et al. (2023) No -
Rare Variants   (31)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.1660C>T p.Arg554Ter stop_gained De novo - - 35982159 Zhou X et al. (2022)
c.1036G>A p.Gly346Arg missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.1567G>C p.Val523Leu missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.1570G>A p.Glu524Lys missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.2404C>T p.Arg802Cys missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.912C>A p.Ile304%3D synonymous_variant De novo - - 35982159 Zhou X et al. (2022)
c.367C>T p.Arg123Ter stop_gained De novo - Simplex 31579823 Guo H , et al. (2019)
c.1603-1G>A - splice_site_variant De novo - Simplex 31579823 Guo H , et al. (2019)
c.1108C>T p.Arg370Ter stop_gained De novo - Simplex 31579823 Guo H , et al. (2019)
c.1174G>T p.Glu392Ter stop_gained De novo - Simplex 31579823 Guo H , et al. (2019)
c.229C>T p.Arg77Ter stop_gained De novo - Simplex 25363768 Iossifov I et al. (2014)
c.362C>A p.Ser121Ter stop_gained De novo - Simplex 33867523 El Khouri E et al. (2021)
c.1111C>T p.Arg371Cys missense_variant De novo - Simplex 31579823 Guo H , et al. (2019)
c.2469G>T p.Arg823Ser missense_variant De novo - Simplex 31579823 Guo H , et al. (2019)
c.367C>T p.Arg123Ter stop_gained De novo - Simplex 34519148 Gangfuß A et al. (2022)
c.1567G>C p.Val523Leu missense_variant De novo - Multiplex 31579823 Guo H , et al. (2019)
c.367C>T p.Arg123Ter stop_gained Familial Maternal Unknown 31579823 Guo H , et al. (2019)
c.1753+2T>C - splice_site_variant Familial Paternal Simplex 31579823 Guo H , et al. (2019)
c.1330-1G>A - splice_site_variant Familial Paternal Unknown 31579823 Guo H , et al. (2019)
c.1639C>T p.Gln547Ter stop_gained Familial Paternal Unknown 31579823 Guo H , et al. (2019)
c.911_912insCG p.Lys305GlyfsTer5 frameshift_variant De novo - - 35982159 Zhou X et al. (2022)
c.149del p.Phe50SerfsTer14 frameshift_variant De novo - Simplex 31579823 Guo H , et al. (2019)
c.110dup p.Tyr37Ter frameshift_variant Familial Paternal Simplex 31579823 Guo H , et al. (2019)
c.1396dup p.Val466GlyfsTer23 frameshift_variant De novo - Simplex 31579823 Guo H , et al. (2019)
c.905_906del p.Lys302ArgfsTer12 frameshift_variant De novo - Unknown 31579823 Guo H , et al. (2019)
c.1173dup p.Glu392ArgfsTer7 frameshift_variant De novo - Simplex 36475376 Shimelis H et al. (2023)
c.105del p.Ser36LeufsTer28 frameshift_variant Familial Paternal Simplex 31579823 Guo H , et al. (2019)
c.1678dup p.Asp560GlyfsTer6 frameshift_variant Unknown Not maternal Unknown 31579823 Guo H , et al. (2019)
c.2368_2371del p.Lys790SerfsTer17 frameshift_variant Familial Maternal Simplex 31579823 Guo H , et al. (2019)
c.1225dup p.Arg409LysfsTer3 frameshift_variant Familial Maternal Multi-generational 31579823 Guo H , et al. (2019)
c.2333del p.Gly778AspfsTer30 frameshift_variant Unknown Not maternal Multi-generational 31579823 Guo H , et al. (2019)
Common Variants  

No common variants reported.

SFARI Gene score
1S

High Confidence, Syndromic

Score Delta: Score remained at 1S

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.

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."

4/1/2021
1
icon
1

Score remained at 1

Description

A de novo nonsense variant in the CSDE1 gene was identified in an ASD proband from the Simons Simplex Collection (SSC; Iossifov et al., 2014). Guo et al., 2019 initially targeted the coding region of the CSDE1 gene using a modified single-molecule molecular inversion probe approach among 4,045 ASD probands from the Autism Clinical and Genetic Resources in China (ACGC) cohort and identified de novo likely gene-disruptive variants in three simplex families. Analysis of the SSC proband, the three ACGC probands, and thirteen additional individuals with likely gene-disruptive variants in CSDE1 identified a new neurodevelopmental syndrome characterized by ASD (a formal diagnosis was made in 10/15 evaluated individuals), intellectual disability, language and motor delay, seizures, MRI brain abnormalities, seizures, macrocephaly, behavioral problems (including ADHD and anxiety), and eye abnormalities.

Reports Added
[Wnt/β-catenin pathway and cell adhesion deregulation in CSDE1-related intellectual disability and autism spectrum disorders2021]
10/1/2019
icon
1

Increased from to 1

New Scoring Scheme
Description

A de novo nonsense variant in the CSDE1 gene was identified in an ASD proband from the Simons Simplex Collection (SSC; Iossifov et al., 2014). Guo et al., 2019 initially targeted the coding region of the CSDE1 gene using a modified single-molecule molecular inversion probe approach among 4,045 ASD probands from the Autism Clinical and Genetic Resources in China (ACGC) cohort and identified de novo likely gene-disruptive variants in three simplex families. Analysis of the SSC proband, the three ACGC probands, and thirteen additional individuals with likely gene-disruptive variants in CSDE1 identified a new neurodevelopmental syndrome characterized by ASD (a formal diagnosis was made in 10/15 evaluated individuals), intellectual disability, language and motor delay, seizures, MRI brain abnormalities, seizures, macrocephaly, behavioral problems (including ADHD and anxiety), and eye abnormalities.

Reports Added
[New Scoring Scheme]
Krishnan Probability Score

Score 0.49092036609447

Ranking 5904/25841 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 0.99995156373162

Ranking 582/18225 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 0.27952200851702

Ranking 164/18665 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 0.076182035402907

Ranking 6624/20870 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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