Human Gene Module / Chromosome 14 / CCNK

CCNKcyclin K

SFARI Gene Score
S
Syndromic Syndromic
Autism Reports / Total Reports
5 / 7
Rare Variants / Common Variants
8 / 0
Aliases
CCNK, CPR4
Associated Syndromes
-
Chromosome Band
14q32.2
Associated Disorders
ASD
Relevance to Autism

Four individuals with de novo variants affecting the CCNK gene presented with a syndromic neurodevelopmental disorder characterized by developmental delay and intellectual disability, language defects, and distinctive facial dysmorphisms; three individuals also displayed extremely severe deficits in social communication, with two further showing autistic features (Fan et al., 2018). Cyclin K, the protein encoded by the CCNK gene, binds to the protein encoded by the syndromic gene CDK13 (Greifenberg et al., 2016).

Molecular Function

The protein encoded by this gene is a member of the transcription cyclin family. These cyclins may regulate transcription through their association with and activation of cyclin-dependent kinases (CDK) that phosphorylate the C-terminal domain (CTD) of the large subunit of RNA polymerase II. This gene product may play a dual role in regulating CDK and RNA polymerase II activities.

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Reports related to CCNK (7 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Support Structural and Functional Analysis of the Cdk13/Cyclin K Complex Greifenberg AK , et al. (2016) No -
2 Primary De Novo Mutations of CCNK Cause a Syndromic Neurodevelopmental Disorder with Distinctive Facial Dysmorphism Fan Y , et al. (2018) No Social communication delay, autistic behavior
3 Support Exome sequencing of 457 autism families recruited online provides evidence for autism risk genes Feliciano P et al. (2019) Yes -
4 Recent Recommendation - Wilfert AB et al. (2021) Yes -
5 Support - Zhou X et al. (2022) Yes -
6 Support - M Cecilia Poli et al. () Yes -
7 Support - Soo-Whee Kim et al. (2024) Yes -
Rare Variants   (8)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
- - copy_number_loss De novo - - 30122539 Fan Y , et al. (2018)
c.331A>G p.Lys111Glu missense_variant De novo - - 30122539 Fan Y , et al. (2018)
c.1395C>T p.Tyr465%3D synonymous_variant De novo - - 35982159 Zhou X et al. (2022)
c.878C>T p.Pro293Leu missense_variant De novo - - 38177409 M Cecilia Poli et al. ()
c.448A>G p.Thr150Ala missense_variant De novo - - 31452935 Feliciano P et al. (2019)
c.921C>A p.Pro307= synonymous_variant De novo - - 39334436 Soo-Whee Kim et al. (2024)
c.702G>A p.Trp234Ter stop_gained Familial - Simplex 34312540 Wilfert AB et al. (2021)
c.883C>T p.Gln295Ter stop_gained Familial - Simplex 34312540 Wilfert AB et al. (2021)
Common Variants  

No common variants reported.

SFARI Gene score
S

Syndromic

Four individuals with de novo variants affecting the CCNK gene presented with a syndromic neurodevelopmental disorder characterized by developmental delay and intellectual disability, language defects, and distinctive facial dysmorphisms; three individuals also displayed extremely severe deficits in social communication, with two further showing autistic features (Fan et al., 2018).

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."

10/1/2019
S
icon
S

Score remained at S

New Scoring Scheme
Description

Four individuals with de novo variants affecting the CCNK gene presented with a syndromic neurodevelopmental disorder characterized by developmental delay and intellectual disability, language defects, and distinctive facial dysmorphisms; three individuals also displayed extremely severe deficits in social communication, with two further showing autistic features (Fan et al., 2018).

Reports Added
[Exome sequencing of 457 autism families recruited online provides evidence for autism risk genes2019] [New Scoring Scheme]
Krishnan Probability Score

Score 0.4875829640852

Ranking 6940/25841 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 0.99714433215512

Ranking 1350/18225 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 0.92564928124374

Ranking 10256/18665 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 -0.36388155817202

Ranking 17971/20870 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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