Human Gene Module / Chromosome 5 / CPEB4

CPEB4cytoplasmic polyadenylation element binding protein 4

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
2 / 3
Rare Variants / Common Variants
2 / 0
Aliases
CPEB4, CPE-BP4,  hCPEB-4
Associated Syndromes
-
Chromosome Band
5q35.2
Associated Disorders
-
Relevance to Autism

Parras et al., 2018 reported that: (1) CPEB4 bound to the transcripts of a number of high-confidence ASD risk genes, including AUTS2, DYRK1A, CUL3, and PTCHD1; (2) the brains of idiopathic ASD cases showed imbalances in CPEB4 transcript isoforms that resulted from decreased inclusion of a neuron-specific microexon and reduced poly (A)-tail length in 9% of the transcriptome, with this percentage being much higher for high-confidence ASD risk genes, correlating with reduced expression of the protein products of these risk genes; and (3) tgCPEB44 mice showed ASD-like polyadenylation and protein expression changes, as well as ASD-related neuroanatomical, electrophysiological and behavioral phenotypes.

Molecular Function

This gene encodes a sequence-specific RNA-binding protein that binds to the cytoplasmic polyadenylation element (CPE), an uridine-rich sequence element (consensus sequence 5'-UUUUUAU-3') within the mRNA 3'-UTR.

External Links
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Human
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SFARI Genomic Platforms
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Reports related to CPEB4 (3 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary Autism-like phenotype and risk gene mRNA deadenylation by CPEB4 mis-splicing Parras A , et al. (2018) Yes -
2 Support - Oll I et al. (2023) No -
3 Support - Sheth F et al. (2023) Yes DD, ID, epilepsy/seizures
Rare Variants   (2)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.361G>A p.Asp121Asn missense_variant Unknown - Simplex 37543562 Sheth F et al. (2023)
c.2165G>A p.Arg722Gln missense_variant Familial Maternal Simplex 37543562 Sheth F et al. (2023)
Common Variants  

No common variants reported.

SFARI Gene score
2

Strong Candidate

Parras et al., 2018 reported that: (1) CPEB4 bound to the transcripts of a number of high-confidence ASD risk genes, including AUTS2, DYRK1A, CUL3, and PTCHD1; (2) the brains of idiopathic ASD cases showed imbalances in CPEB4 transcript isoforms that resulted from decreased inclusion of a neuron-specific microexon and reduced poly (A)-tail length in 9% of the transcriptome, with this percentage being much higher for high-confidence ASD risk genes, correlating with reduced expression of the protein products of these risk genes; and (3) tgCPEB44 mice showed ASD-like polyadenylation and protein expression changes, as well as ASD-related neuroanatomical, electrophysiological and behavioral phenotypes.

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

Parras et al., 2018 reported that: (1) CPEB4 bound to the transcripts of a number of high-confidence ASD risk genes, including AUTS2, DYRK1A, CUL3, and PTCHD1; (2) the brains of idiopathic ASD cases showed imbalances in CPEB4 transcript isoforms that resulted from decreased inclusion of a neuron-specific microexon and reduced poly (A)-tail length in 9% of the transcriptome, with this percentage being much higher for high-confidence ASD risk genes, correlating with reduced expression of the protein products of these risk genes; and (3) tgCPEB44 mice showed ASD-like polyadenylation and protein expression changes, as well as ASD-related neuroanatomical, electrophysiological and behavioral phenotypes.

Reports Added
[New Scoring Scheme]
7/1/2018
icon
3

Increased from to 3

Description

Parras et al., 2018 reported that: (1) CPEB4 bound to the transcripts of a number of high-confidence ASD risk genes, including AUTS2, DYRK1A, CUL3, and PTCHD1; (2) the brains of idiopathic ASD cases showed imbalances in CPEB4 transcript isoforms that resulted from decreased inclusion of a neuron-specific microexon and reduced poly (A)-tail length in 9% of the transcriptome, with this percentage being much higher for high-confidence ASD risk genes, correlating with reduced expression of the protein products of these risk genes; and (3) tgCPEB44 mice showed ASD-like polyadenylation and protein expression changes, as well as ASD-related neuroanatomical, electrophysiological and behavioral phenotypes.

Krishnan Probability Score

Score 0.56975478301433

Ranking 1002/25841 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 0.99685472782005

Ranking 1382/18225 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 0.93711323993114

Ranking 13417/18665 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 0.39103731896519

Ranking 1554/20870 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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