Human Gene Module / Chromosome 6 / CSNK2B

CSNK2Bcasein kinase 2 beta

SFARI Gene Score
S
Syndromic Syndromic
Autism Reports / Total Reports
1 / 12
Rare Variants / Common Variants
59 / 0
Aliases
CSNK2B, CK2B,  CK2N,  CSK2B,  Ckb1,  Ckb2,  G5A,  POBINDS
Associated Syndromes
Poirier-Bienvenu neurodevelopmental syndrome, DD,
Chromosome Band
6p21.33
Associated Disorders
DD/NDD, ID, ASD, EPS
Relevance to Autism

Heterozygous variants in the CSNK2B gene are responsible for Poirier-Bienvenu neurodevelopmental syndrome, a neurologic disorder characterized in most cases by early-onset seizures and variably impaired intellectual development (ID); autism spectrum disorder or autistic features have been observed in a subset of affected individuals (Poirier et al., 2017; Sakaguchi et al., 2017; Nakashima et al., 2019; Li et al., 2019; Ernst et al., 2021). Two de novo splice-site variants in the CSNK2B gene were reported in ASD probands in Zhou et al., 2022; a two-stage analysis of rare de novo and inherited coding variants in 42,607 ASD cases, including 35,130 new cases from the SPARK cohort, in this report identified CSNK2B as a gene reaching study-wide significance based on 5,754 constraint genes (P < 8.69E-06).

Molecular Function

This gene encodes the beta subunit of casein kinase II, a ubiquitous protein kinase which regulates metabolic pathways, signal transduction, transcription, translation, and replication. The enzyme is composed of three subunits, alpha, alpha prime and beta, which form a tetrameric holoenzyme. The alpha and alpha prime subunits are catalytic, while the beta subunit serves regulatory functions. The enzyme localizes to the endoplasmic reticulum and the Golgi apparatus.

External Links
Gene CardOpen Targets PlatformgnomAD browserSynGO portalPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to CSNK2B (12 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary - Poirier K et al. (2017) No Autistic features, epilepsy/seizures
2 Support - Sakaguchi Y et al. (2017) No -
3 Support Identification of de novo CSNK2A1 and CSNK2B variants in cases of global developmental delay with seizures Nakashima M et al. (2019) No -
4 Support - Li J et al. (2019) No DD, ID
5 Recent Recommendation - Ernst ME et al. (2021) No ASD or autistic features
6 Support - Valentino F et al. (2021) No DD, epilepsy/seizures
7 Support - Wilke MVMB et al. (2022) No -
8 Support - Yang Q et al. (2022) No ID, learning disability
9 Support - Asif M et al. (2022) No Epilepsy/seizures
10 Support - Zhang W et al. (2022) No DD, autistic features
11 Recent Recommendation - Zhou X et al. (2022) Yes -
12 Support - Kirsten Furley et al. () No ASD, ID, epilepsy/seizures
Rare Variants   (59)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.367+5del - splice_site_variant Unknown - - 35571680 Asif M et al. (2022)
c.58G>T p.Glu20Ter stop_gained De novo - - 35774559 Zhang W et al. (2022)
c.374C>G p.Ser125Ter stop_gained De novo - - 35571680 Asif M et al. (2022)
c.142C>T p.Gln48Ter stop_gained De novo - - 35774559 Zhang W et al. (2022)
c.292-1G>A - splice_site_variant De novo - - 35774559 Zhang W et al. (2022)
c.367+5G>A - splice_site_variant De novo - - 35774559 Zhang W et al. (2022)
c.58G>T p.Glu20Ter stop_gained Unknown - - 34041744 Ernst ME et al. (2021)
c.73-2A>G - splice_site_variant De novo - - 34041744 Ernst ME et al. (2021)
c.124C>T p.Gln42Ter stop_gained De novo - - 34041744 Ernst ME et al. (2021)
c.139C>T p.Arg47Ter stop_gained De novo - - 34041744 Ernst ME et al. (2021)
c.181G>T p.Glu61Ter stop_gained De novo - - 34041744 Ernst ME et al. (2021)
c.548+1G>A - splice_site_variant Unknown - - 34041744 Ernst ME et al. (2021)
c.558-2A>G - splice_site_variant Unknown - - 34041744 Ernst ME et al. (2021)
c.13G>T p.Glu5Ter stop_gained De novo - Simplex 31784560 Li J et al. (2019)
c.367+6T>C - splice_region_variant De novo - - 35774559 Zhang W et al. (2022)
c.94G>A p.Asp32Asn missense_variant De novo - - 35571680 Asif M et al. (2022)
c.94G>A p.Asp32Asn missense_variant Unknown - - 35571680 Asif M et al. (2022)
c.94G>C p.Asp32His missense_variant De novo - - 35571680 Asif M et al. (2022)
c.368-2A>G - splice_site_variant De novo - Simplex 31784560 Li J et al. (2019)
c.94G>A p.Asp32Asn missense_variant De novo - - 34041744 Ernst ME et al. (2021)
c.176-2A>G - splice_site_variant De novo - Simplex 35982159 Zhou X et al. (2022)
c.325T>C p.Cys109Arg missense_variant De novo - - 35774559 Zhang W et al. (2022)
c.497T>G p.Met166Arg missense_variant De novo - - 35774559 Zhang W et al. (2022)
c.101T>C p.Phe34Ser missense_variant De novo - - 34041744 Ernst ME et al. (2021)
c.105T>A p.Asn35Lys missense_variant De novo - - 34041744 Ernst ME et al. (2021)
c.229G>A p.Glu77Lys missense_variant De novo - - 34041744 Ernst ME et al. (2021)
c.256C>T p.Arg86Cys missense_variant De novo - - 34041744 Ernst ME et al. (2021)
c.291G>A p.Met97Ile missense_variant De novo - - 34041744 Ernst ME et al. (2021)
c.27del p.Trp9Ter frameshift_variant De novo - - 34041744 Ernst ME et al. (2021)
c.316T>G p.Phe106Val missense_variant De novo - - 34041744 Ernst ME et al. (2021)
c.409T>C p.Cys137Arg missense_variant De novo - - 34041744 Ernst ME et al. (2021)
c.94G>T p.Asp32Tyr missense_variant De novo - - 34983633 Wilke MVMB et al. (2022)
c.292-2A>G - splice_site_variant De novo - Multiplex 35982159 Zhou X et al. (2022)
c.1A>G p.Met1? initiator_codon_variant De novo - - 34041744 Ernst ME et al. (2021)
c.2T>A p.Met1? initiator_codon_variant De novo - - 34041744 Ernst ME et al. (2021)
c.149T>C p.Leu50Pro missense_variant Unknown - - 38536866 Kirsten Furley et al. ()
c.256C>T p.Arg86Cys missense_variant De novo - Simplex 31784560 Li J et al. (2019)
c.175+2T>G - splice_site_variant De novo - Simplex 28585349 Poirier K et al. (2017)
c.367+2T>C - splice_site_variant De novo - Simplex 28585349 Poirier K et al. (2017)
c.332G>C p.Arg111Pro missense_variant De novo - Simplex 31784560 Li J et al. (2019)
c.409T>G p.Cys137Gly missense_variant De novo - Simplex 31784560 Li J et al. (2019)
c.410G>T p.Cys137Phe missense_variant De novo - Simplex 31784560 Li J et al. (2019)
c.560T>G p.Leu187Arg missense_variant De novo - Simplex 31784560 Li J et al. (2019)
c.332G>C p.Arg111Pro missense_variant De novo - Simplex 35370893 Yang Q et al. (2022)
c.1A>G p.Met1? initiator_codon_variant De novo - Simplex 35370893 Yang Q et al. (2022)
c.78_83dup p.Glu27_Asp28dup inframe_insertion De novo - - 34041744 Ernst ME et al. (2021)
c.542del p.Asn181ThrfsTer46 frameshift_variant De novo - - 34041744 Ernst ME et al. (2021)
c.494A>G p.His165Arg missense_variant De novo - Simplex 34983633 Wilke MVMB et al. (2022)
c.494A>G p.His165Arg missense_variant De novo - Simplex 30655572 Nakashima M et al. (2019)
c.265del p.Thr90ProfsTer41 frameshift_variant De novo - Simplex 31784560 Li J et al. (2019)
c.170del p.Glu57GlyfsTer15 frameshift_variant De novo - - 34356170 Valentino F et al. (2021)
c.612dup p.Lys205GlnfsTer38 frameshift_variant De novo - Simplex 31784560 Li J et al. (2019)
c.455_458del p.Asp152AlafsTer71 frameshift_variant De novo - - 35774559 Zhang W et al. (2022)
c.102del p.Phe34LeufsTer17 frameshift_variant De novo - Simplex 35370893 Yang Q et al. (2022)
c.394_404del p.Met132LeufsTer110 frameshift_variant Unknown - - 34041744 Ernst ME et al. (2021)
c.158_159insA p.Asp55GlyfsTer5 frameshift_variant De novo - Simplex 35370893 Yang Q et al. (2022)
c.108dup p.Thr37TyrfsTer5 frameshift_variant De novo - Simplex 28762608 Sakaguchi Y et al. (2017)
c.303C>A p.Tyr101Ter stop_gained De novo - Multiplex (monozygotic twins) 34041744 Ernst ME et al. (2021)
c.533_534insGT p.Pro179TyrfsTer49 frameshift_variant De novo - Simplex 30655572 Nakashima M et al. (2019)
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 0.57062628199658

Ranking 894/25841 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 0.94385669908463

Ranking 2784/18225 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 0.90669949444225

Ranking 7111/18665 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 -0.10286599618063

Ranking 12460/20870 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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