Human Gene Module / Chromosome 7 / CDK13

CDK13cyclin dependent kinase 13

SFARI Gene Score
S
Syndromic Syndromic
Autism Reports / Total Reports
7 / 22
Rare Variants / Common Variants
68 / 0
Aliases
CDK13, CDC2L,  CDC2L5,  CHDFIDD,  CHED,  hCDK13
Associated Syndromes
-
Chromosome Band
7p14.1
Associated Disorders
ADHD, ASD
Relevance to Autism

Heterozygous mutations in the CDK13 gene are associated with congenital heart defects, dysmorphic facial features, and intellectual developmental disorder (CHDFIDD; OMIM 617360) (Sifrim et al., 2016; Bostwick et al., 2017). Phenotypic characterization of 16 individuals with heterozygous CDK13 variants in Hamilton et al., 2017 demonstrated that, in addition to previously identified phenotypes such as developmental delay, structural cardiac anomalies, and dysmorphic features, six patients had a diagnosis of autism spectrum disorder, while an additional two patients displayed autistic traits or stereotypies. A de novo missense variant that was predicted to be damaging was identified in an ASD proband from the Simons Simplex Collection in Iossifov et al., 2014.

Molecular Function

The protein encoded by this gene is a member of the cyclin-dependent serine/threonine protein kinase family. Cyclin-dependent kinase which displays CTD kinase activity and is required for RNA splicing. Has CTD kinase activity by hyperphosphorylating the C-terminal heptapeptide repeat domain (CTD) of the largest RNA polymerase II subunit RPB1, thereby acting as a key regulator of transcription elongation. Required for RNA splicing, probably by phosphorylating SRSF1/SF2.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to CDK13 (22 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Support The contribution of de novo coding mutations to autism spectrum disorder Iossifov I et al. (2014) Yes -
2 Support Structural and Functional Analysis of the Cdk13/Cyclin K Complex Greifenberg AK , et al. (2016) No -
3 Support Distinct genetic architectures for syndromic and nonsyndromic congenital heart defects identified by exome sequencing Sifrim A , et al. (2016) No -
4 Support Phenotypic and molecular characterisation of CDK13-related congenital heart defects, dysmorphic facial features and intellectual developmental disorders Bostwick BL , et al. (2017) No -
5 Primary Heterozygous mutations affecting the protein kinase domain of CDK13 cause a syndromic form of developmental delay and intellectual disability Hamilton MJ , et al. (2017) No ASD
6 Support Redefining the phenotypic spectrum of de novo heterozygous CDK13 variants: Three patients without cardiac defects Uehara T , et al. (2017) No -
7 Support De novo variants in CDK13 associated with syndromic ID/DD: Molecular and clinical delineation of 15 individuals and a further review van den Akker WMR , et al. (2018) No ASD, ADHD
8 Support Variant recurrence in neurodevelopmental disorders: the use of publicly available genomic data identifies clinically relevant pathogenic missense variants Lecoquierre F , et al. (2019) No -
9 Support Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks Ruzzo EK , et al. (2019) Yes -
10 Support Excess of de novo variants in genes involved in chromatin remodelling in patients with marfanoid habitus and intellectual disability Chevarin M et al. (2020) No Marfanoid habitus
11 Support - Hildebrand MS et al. (2020) No DD
12 Support Large-scale targeted sequencing identifies risk genes for neurodevelopmental disorders Wang T et al. (2020) Yes -
13 Support - Alonso-Gonzalez A et al. (2021) Yes -
14 Support - Pode-Shakked B et al. (2021) Yes -
15 Support - Cui X et al. (2022) No Autistic features
16 Support - Marwaha A et al. (2022) No -
17 Recent Recommendation - Morison LD et al. (2023) No ASD, ADHD, ID
18 Support - Yuan B et al. (2023) Yes -
19 Support - Spataro N et al. (2023) No -
20 Recent Recommendation - Timberlake AT et al. (2023) No ASD
21 Support - Marketa Wayhelova et al. (2024) No -
22 Support - Soo-Whee Kim et al. (2024) Yes -
Rare Variants   (68)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.2995C>T p.Arg999Ter stop_gained De novo - - 33004838 Wang T et al. (2020)
c.3688+1G>A - splice_site_variant De novo - - 36599938 Morison LD et al. (2023)
c.1630C>T p.Gln544Ter stop_gained De novo - - 36599938 Morison LD et al. (2023)
c.1928G>A p.Arg643Gln missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.2080G>T p.Asp694Tyr missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.2149G>A p.Gly717Arg missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.2620G>T p.Val874Leu missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.2638C>A p.Arg880Ser missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.2669G>A p.Arg890Gln missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.2602C>T p.Arg868Trp missense_variant De novo - - 36881370 Yuan B et al. (2023)
c.2898-1G>A - splice_site_variant De novo - - 29021403 Hamilton MJ , et al. (2017)
c.2149G>A p.Gly717Arg missense_variant De novo - - 29222009 Uehara T , et al. (2017)
c.2525A>G p.Asn842Ser missense_variant De novo - - 29222009 Uehara T , et al. (2017)
c.2638C>T p.Arg880Cys missense_variant De novo - - 36980980 Spataro N et al. (2023)
c.478G>C p.Gly160Arg missense_variant Unknown - - 36599938 Morison LD et al. (2023)
c.2578C>T p.Arg860Ter stop_gained Familial Paternal - 33004838 Wang T et al. (2020)
c.2140G>T p.Gly714Cys missense_variant De novo - - 36599938 Morison LD et al. (2023)
c.2149G>A p.Gly717Arg missense_variant De novo - - 36599938 Morison LD et al. (2023)
c.2201A>G p.Lys734Arg missense_variant De novo - - 36599938 Morison LD et al. (2023)
c.2263A>T p.Ile755Phe missense_variant De novo - - 36599938 Morison LD et al. (2023)
c.2511T>G p.Asp837Glu missense_variant De novo - - 36599938 Morison LD et al. (2023)
c.2519G>A p.Cys840Tyr missense_variant De novo - - 36599938 Morison LD et al. (2023)
c.2525A>G p.Asn842Ser missense_variant De novo - - 36599938 Morison LD et al. (2023)
c.2525A>G p.Asn842Ser missense_variant Unknown - - 36599938 Morison LD et al. (2023)
c.2563G>C p.Asp855His missense_variant De novo - - 36599938 Morison LD et al. (2023)
c.2579G>A p.Arg860Gln missense_variant De novo - - 36599938 Morison LD et al. (2023)
c.2638C>T p.Arg880Cys missense_variant De novo - - 36599938 Morison LD et al. (2023)
c.2956C>T p.Arg986Cys missense_variant De novo - - 36599938 Morison LD et al. (2023)
c.2200A>G p.Lys734Glu missense_variant De novo - - 28807008 Bostwick BL , et al. (2017)
c.2524A>G p.Asn842Asp missense_variant De novo - - 28807008 Bostwick BL , et al. (2017)
c.2525A>G p.Asn842Ser missense_variant De novo - - 28807008 Bostwick BL , et al. (2017)
c.2525A>G p.Asn842Ser missense_variant Unknown - - 28807008 Bostwick BL , et al. (2017)
c.2140G>C p.Gly714Arg missense_variant De novo - - 29021403 Hamilton MJ , et al. (2017)
c.2149G>A p.Gly717Arg missense_variant De novo - - 29021403 Hamilton MJ , et al. (2017)
c.2156T>G p.Val719Gly missense_variant De novo - - 29021403 Hamilton MJ , et al. (2017)
c.2201A>G p.Lys734Arg missense_variant De novo - - 29021403 Hamilton MJ , et al. (2017)
c.2252G>A p.Arg751Gln missense_variant De novo - - 29021403 Hamilton MJ , et al. (2017)
c.2524A>G p.Asn842Asp missense_variant De novo - - 29021403 Hamilton MJ , et al. (2017)
c.2525A>G p.Asn842Ser missense_variant De novo - - 29021403 Hamilton MJ , et al. (2017)
c.2620G>T p.Val874Leu missense_variant De novo - - 29021403 Hamilton MJ , et al. (2017)
c.2686G>A p.Asp896Asn missense_variant De novo - - 29021403 Hamilton MJ , et al. (2017)
c.2995C>T p.Arg999Ter stop_gained De novo - - 29393965 van den Akker WMR , et al. (2018)
c.2751del p.Gln918ArgfsTer6 frameshift_variant Unknown - - 33004838 Wang T et al. (2020)
c.2525A>G p.Asn842Ser missense_variant De novo - - 31036916 Lecoquierre F , et al. (2019)
c.3073C>T p.Arg1025Ter stop_gained De novo - - 29393965 van den Akker WMR , et al. (2018)
c.2149G>A p.Gly717Arg missense_variant De novo - Simplex 35043535 Marwaha A et al. (2022)
c.2375A>T p.Glu792Val missense_variant De novo - Simplex 25363768 Iossifov I et al. (2014)
c.2525A>G p.Asn842Ser missense_variant De novo - Simplex 32277047 Chevarin M et al. (2020)
c.336del p.Gln113ArgfsTer28 frameshift_variant De novo - - 36599938 Morison LD et al. (2023)
c.2141G>A p.Gly714Asp missense_variant De novo - - 29393965 van den Akker WMR , et al. (2018)
c.2209C>T p.Arg737Cys missense_variant De novo - - 29393965 van den Akker WMR , et al. (2018)
c.2525A>G p.Asn842Ser missense_variant De novo - - 29393965 van den Akker WMR , et al. (2018)
c.2638C>T p.Arg880Cys missense_variant De novo - - 29393965 van den Akker WMR , et al. (2018)
c.484dup p.Ala162GlyfsTer108 frameshift_variant De novo - - 36599938 Morison LD et al. (2023)
c.1876C>T p.Arg626Ter stop_gained De novo - Simplex 33431980 Alonso-Gonzalez A et al. (2021)
c.2322_2325del p.Glu775MetfsTer23 frameshift_variant Unknown - - 33004838 Wang T et al. (2020)
c.2609A>G p.Tyr870Cys missense_variant De novo - Simplex 32345733 Hildebrand MS et al. (2020)
c.2149G>A p.Gly717Arg missense_variant Familial Maternal Simplex 35034425 Cui X et al. (2022)
c.484dup p.Ala162GlyfsTer108 frameshift_variant De novo - - 39334436 Soo-Whee Kim et al. (2024)
c.2579G>A p.Arg860Gln missense_variant De novo - Multiplex 29021403 Hamilton MJ , et al. (2017)
c.2201A>C p.Lys734Thr missense_variant De novo - Simplex 34580403 Pode-Shakked B et al. (2021)
c.4156_4157insTA p.His1386LeufsTer20 frameshift_variant Unknown - - 33004838 Wang T et al. (2020)
c.3400G>T p.Gly1134Ter stop_gained Familial Paternal Multiplex 31398340 Ruzzo EK , et al. (2019)
c.2671T>C p.Tyr891His missense_variant De novo - Simplex 33431980 Alonso-Gonzalez A et al. (2021)
c.2572C>G p.Leu858Val missense_variant De novo - Simplex 38321498 Marketa Wayhelova et al. (2024)
c.484dup p.Ala162GlyfsTer108 frameshift_variant De novo - - 29393965 van den Akker WMR , et al. (2018)
c.484dup p.Ala162GlyfsTer108 frameshift_variant Unknown - - 29393965 van den Akker WMR , et al. (2018)
c.2600+4940A>G - splice_site_variant De novo - Multiplex (monozygotic twins) 29393965 van den Akker WMR , et al. (2018)
Common Variants  

No common variants reported.

SFARI Gene score
S

Syndromic

Heterozygous mutations in the CDK13 gene are associated with congenital heart defects, dysmorphic facial features, and intellectual developmental disorder (CHDFIDD; OMIM 617360) (Sifrim et al., 2016; Bostwick et al., 2017). Phenotypic characterization of 16 individuals with heterozygous CDK13 variants in Hamilton et al., 2017 demonstrated that, in addition to previously identified phenotypes such as developmental delay, structural cardiac anomalies, and dysmorphic features, six patients had a diagnosis of autism spectrum disorder, while an additional two patients displayed autistic traits or stereotypies. A de novo missense variant that was predicted to be damaging was identified in an ASD proband from the Simons Simplex Collection in Iossifov et al., 2014. A clinical evaluation of fifteen previously unreported individuals with CDK13 variants in van den Akker et al., 2018 demonstrated that autism spectrum disorders were observed in five of these individuals.

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."

1/1/2021
S
icon
S

Score remained at S

Description

Heterozygous mutations in the CDK13 gene are associated with congenital heart defects, dysmorphic facial features, and intellectual developmental disorder (CHDFIDD; OMIM 617360) (Sifrim et al., 2016; Bostwick et al., 2017). Phenotypic characterization of 16 individuals with heterozygous CDK13 variants in Hamilton et al., 2017 demonstrated that, in addition to previously identified phenotypes such as developmental delay, structural cardiac anomalies, and dysmorphic features, six patients had a diagnosis of autism spectrum disorder, while an additional two patients displayed autistic traits or stereotypies. A de novo missense variant that was predicted to be damaging was identified in an ASD proband from the Simons Simplex Collection in Iossifov et al., 2014. A clinical evaluation of fifteen previously unreported individuals with CDK13 variants in van den Akker et al., 2018 demonstrated that autism spectrum disorders were observed in five of these individuals.

Reports Added
[Exploring the biological role of postzygotic and germinal de novo mutations in ASD2021]
10/1/2020
S
icon
S

Score remained at S

Description

Heterozygous mutations in the CDK13 gene are associated with congenital heart defects, dysmorphic facial features, and intellectual developmental disorder (CHDFIDD; OMIM 617360) (Sifrim et al., 2016; Bostwick et al., 2017). Phenotypic characterization of 16 individuals with heterozygous CDK13 variants in Hamilton et al., 2017 demonstrated that, in addition to previously identified phenotypes such as developmental delay, structural cardiac anomalies, and dysmorphic features, six patients had a diagnosis of autism spectrum disorder, while an additional two patients displayed autistic traits or stereotypies. A de novo missense variant that was predicted to be damaging was identified in an ASD proband from the Simons Simplex Collection in Iossifov et al., 2014. A clinical evaluation of fifteen previously unreported individuals with CDK13 variants in van den Akker et al., 2018 demonstrated that autism spectrum disorders were observed in five of these individuals.

Reports Added
[Large-scale targeted sequencing identifies risk genes for neurodevelopmental disorders2020]
4/1/2020
S
icon
S

Score remained at S

Description

Heterozygous mutations in the CDK13 gene are associated with congenital heart defects, dysmorphic facial features, and intellectual developmental disorder (CHDFIDD; OMIM 617360) (Sifrim et al., 2016; Bostwick et al., 2017). Phenotypic characterization of 16 individuals with heterozygous CDK13 variants in Hamilton et al., 2017 demonstrated that, in addition to previously identified phenotypes such as developmental delay, structural cardiac anomalies, and dysmorphic features, six patients had a diagnosis of autism spectrum disorder, while an additional two patients displayed autistic traits or stereotypies. A de novo missense variant that was predicted to be damaging was identified in an ASD proband from the Simons Simplex Collection in Iossifov et al., 2014. A clinical evaluation of fifteen previously unreported individuals with CDK13 variants in van den Akker et al., 2018 demonstrated that autism spectrum disorders were observed in five of these individuals.

Reports Added
[Excess of de novo variants in genes involved in chromatin remodelling in patients with marfanoid habitus and intellectual disability2020]
10/1/2019
S
icon
S

Score remained at S

New Scoring Scheme
Description

Heterozygous mutations in the CDK13 gene are associated with congenital heart defects, dysmorphic facial features, and intellectual developmental disorder (CHDFIDD; OMIM 617360) (Sifrim et al., 2016; Bostwick et al., 2017). Phenotypic characterization of 16 individuals with heterozygous CDK13 variants in Hamilton et al., 2017 demonstrated that, in addition to previously identified phenotypes such as developmental delay, structural cardiac anomalies, and dysmorphic features, six patients had a diagnosis of autism spectrum disorder, while an additional two patients displayed autistic traits or stereotypies. A de novo missense variant that was predicted to be damaging was identified in an ASD proband from the Simons Simplex Collection in Iossifov et al., 2014. A clinical evaluation of fifteen previously unreported individuals with CDK13 variants in van den Akker et al., 2018 demonstrated that autism spectrum disorders were observed in five of these individuals.

Reports Added
[New Scoring Scheme]
7/1/2019
S
icon
S

Score remained at S

Description

Heterozygous mutations in the CDK13 gene are associated with congenital heart defects, dysmorphic facial features, and intellectual developmental disorder (CHDFIDD; OMIM 617360) (Sifrim et al., 2016; Bostwick et al., 2017). Phenotypic characterization of 16 individuals with heterozygous CDK13 variants in Hamilton et al., 2017 demonstrated that, in addition to previously identified phenotypes such as developmental delay, structural cardiac anomalies, and dysmorphic features, six patients had a diagnosis of autism spectrum disorder, while an additional two patients displayed autistic traits or stereotypies. A de novo missense variant that was predicted to be damaging was identified in an ASD proband from the Simons Simplex Collection in Iossifov et al., 2014. A clinical evaluation of fifteen previously unreported individuals with CDK13 variants in van den Akker et al., 2018 demonstrated that autism spectrum disorders were observed in five of these individuals.

Reports Added
[Variantrecurrence in neurodevelopmental disorders: the use of publicly available genomic data identifies clinically relevant pathogenic missense v...2019] [Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks.2019]
7/1/2018
S
icon
S

Score remained at S

Description

Heterozygous mutations in the CDK13 gene are associated with congenital heart defects, dysmorphic facial features, and intellectual developmental disorder (CHDFIDD; OMIM 617360) (Sifrim et al., 2016; Bostwick et al., 2017). Phenotypic characterization of 16 individuals with heterozygous CDK13 variants in Hamilton et al., 2017 demonstrated that, in addition to previously identified phenotypes such as developmental delay, structural cardiac anomalies, and dysmorphic features, six patients had a diagnosis of autism spectrum disorder, while an additional two patients displayed autistic traits or stereotypies. A de novo missense variant that was predicted to be damaging was identified in an ASD proband from the Simons Simplex Collection in Iossifov et al., 2014. A clinical evaluation of fifteen previously unreported individuals with CDK13 variants in van den Akker et al., 2018 demonstrated that autism spectrum disorders were observed in five of these individuals.

Reports Added
[Structural and Functional Analysis of the Cdk13/Cyclin K Complex.2016]
Krishnan Probability Score

Score 0.49582288880268

Ranking 2792/25841 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 0.75125053815132

Ranking 4206/18225 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 0.82552103555306

Ranking 2737/18665 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 0.30107334410736

Ranking 2726/20870 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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