Human Gene Module / Chromosome 22 / CSNK1E

CSNK1Ecasein kinase 1 epsilon

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
5 / 8
Rare Variants / Common Variants
7 / 0
Aliases
CSNK1E, CKIepsilon,  HCKIE
Associated Syndromes
-
Chromosome Band
22q13.1
Associated Disorders
-
Relevance to Autism

Two de novo missense variants that were predicted in silico to be damaging were identified in the CSNK1E gene in ASD probands from the Autism Sequencing Consortium in De Rubeis et al., 2014. TADA-Denovo analysis using a combined dataset of previously published cohorts from the Simons Simplex Collection and the Autism Sequencing Consortium, as well as a novel cohort of 262 Japanese ASD trios, in Takata et al., 2018 identified CSNK1E as a gene significantly enriched in damaging de novo mutations in ASD cases (pBH < 0.05). Functional studies in Drosophila (Kloss et al., 1998), Syrian hamsters (Lowrey et al., 2000), and mice (Meng et al., 2008) have demonstrated a role for CSNK1E in circadian rhythms.

Molecular Function

The protein encoded by this gene is a serine/threonine protein kinase and a member of the casein kinase I protein family, whose members have been implicated in the control of cytoplasmic and nuclear processes, including DNA replication and repair. The encoded protein is found in the cytoplasm as a monomer and can phosphorylate a variety of proteins, including itself. This protein has been shown to phosphorylate period, a circadian rhythm protein.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
Mouse
Entrez GeneMouse Genome InformaticsAllen Brain Atlas
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to CSNK1E (8 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Support Positional syntenic cloning and functional characterization of the mammalian circadian mutation tau Lowrey PL , et al. (2000) No -
2 Support Setting clock speed in mammals: the CK1 epsilon tau mutation in mice accelerates circadian pacemakers by selectively destabilizing PERIOD proteins Meng QJ , et al. (2008) No -
3 Primary Synaptic, transcriptional and chromatin genes disrupted in autism De Rubeis S , et al. (2014) Yes -
4 Recent Recommendation Integrative Analyses of De Novo Mutations Provide Deeper Biological Insights into Autism Spectrum Disorder Takata A , et al. (2018) Yes -
5 Support - Krgovic D et al. (2022) Yes ADHD, DD
6 Support - Zhou X et al. (2022) Yes -
7 Support - Yuan B et al. (2023) Yes -
8 Support The Drosophila clock gene double-time encodes a protein closely related to human casein kinase Iepsilon Kloss B , et al. (1998) No -
Rare Variants   (7)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.188-1G>T - splice_site_variant Unknown - - 35813072 Krgovic D et al. (2022)
c.187G>A p.Val63Met missense_variant De novo - - 36881370 Yuan B et al. (2023)
c.529G>A p.Ala177Thr missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.706C>A p.Pro236Thr missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.406A>T p.Met136Leu missense_variant De novo - - 25363760 De Rubeis S , et al. (2014)
c.739G>A p.Glu247Lys missense_variant De novo - - 25363760 De Rubeis S , et al. (2014)
c.532C>T p.Arg178Cys missense_variant De novo - Simplex 35982159 Zhou X et al. (2022)
Common Variants  

No common variants reported.

SFARI Gene score
2

Strong Candidate

Two de novo missense variants that were predicted in silico to be damaging were identified in the CSNK1E gene in ASD probands from the Autism Sequencing Consortium in De Rubeis et al., 2014. TADA-Denovo analysis using a combined dataset of previously published cohorts from the Simons Simplex Collection and the Autism Sequencing Consortium, as well as a novel cohort of 262 Japanese ASD trios, in Takata et al., 2018 identified CSNK1E as a gene significantly enriched in damaging de novo mutations in ASD cases (pBH < 0.05). Functional studies in Drosophila (Kloss et al., 1998), Syrian hamsters (Lowrey et al., 2000), and mice (Meng et al., 2008) have demonstrated a role for CSNK1E in circadian rhythms.

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 de novo missense variants that were predicted in silico to be damaging were identified in the CSNK1E gene in ASD probands from the Autism Sequencing Consortium in De Rubeis et al., 2014. TADA-Denovo analysis using a combined dataset of previously published cohorts from the Simons Simplex Collection and the Autism Sequencing Consortium, as well as a novel cohort of 262 Japanese ASD trios, in Takata et al., 2018 identified CSNK1E as a gene significantly enriched in damaging de novo mutations in ASD cases (pBH < 0.05). Functional studies in Drosophila (Kloss et al., 1998), Syrian hamsters (Lowrey et al., 2000), and mice (Meng et al., 2008) have demonstrated a role for CSNK1E in circadian rhythms.

10/1/2019
4
icon
3

Decreased from 4 to 3

New Scoring Scheme
Description

Two de novo missense variants that were predicted in silico to be damaging were identified in the CSNK1E gene in ASD probands from the Autism Sequencing Consortium in De Rubeis et al., 2014. TADA-Denovo analysis using a combined dataset of previously published cohorts from the Simons Simplex Collection and the Autism Sequencing Consortium, as well as a novel cohort of 262 Japanese ASD trios, in Takata et al., 2018 identified CSNK1E as a gene significantly enriched in damaging de novo mutations in ASD cases (pBH < 0.05). Functional studies in Drosophila (Kloss et al., 1998), Syrian hamsters (Lowrey et al., 2000), and mice (Meng et al., 2008) have demonstrated a role for CSNK1E in circadian rhythms.

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

Increased from to 4

Description

Two de novo missense variants that were predicted in silico to be damaging were identified in the CSNK1E gene in ASD probands from the Autism Sequencing Consortium in De Rubeis et al., 2014. TADA-Denovo analysis using a combined dataset of previously published cohorts from the Simons Simplex Collection and the Autism Sequencing Consortium, as well as a novel cohort of 262 Japanese ASD trios, in Takata et al., 2018 identified CSNK1E as a gene significantly enriched in damaging de novo mutations in ASD cases (pBH < 0.05). Functional studies in Drosophila (Kloss et al., 1998), Syrian hamsters (Lowrey et al., 2000), and mice (Meng et al., 2008) have demonstrated a role for CSNK1E in circadian rhythms.

Krishnan Probability Score

Score 0.56604578215543

Ranking 1225/25841 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 0.96731923529575

Ranking 2420/18225 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 0.23112279490444

Ranking 130/18665 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 0.33100740876592

Ranking 2280/20870 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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