CDK13

cyclin dependent kinase 13, the group of Cyclin dependent kinases

Basic information

Region (hg38): 7:39950120-40099580

Previous symbols: [ "CDC2L5" ]

Links

ENSG00000065883 ∙ NCBI:8621 ∙ OMIM:603309 ∙ HGNC:1733 ∙ Uniprot:Q14004 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• congenital heart defects, dysmorphic facial features, and intellectual developmental disorder (Strong), mode of inheritance: AD
• congenital heart defects, dysmorphic facial features, and intellectual developmental disorder (Strong), mode of inheritance: AD
• syndromic intellectual disability (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Congenital heart defects, dysmorphic facial features, and intellectual developmental disorder	AD	Cardiovascular	The condition can involve congenital cardiac anomalies, and awareness may allow early management	Cardiovascular; Craniofacial; Musculoskeletal; Neurologic	27479907

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CDK13 gene.

• not provided (429 variants)
• Inborn genetic diseases (87 variants)
• Congenital heart defects, dysmorphic facial features, and intellectual developmental disorder (73 variants)
• CDK13-related condition (16 variants)
• not specified (5 variants)
• Global developmental delay (3 variants)
• See cases (3 variants)
• - (2 variants)
• Intellectual disability (2 variants)
• Wolfram-like disorder (1 variants)
• Neurodevelopmental disorder (1 variants)
• Neurodevelopmental delay (1 variants)
• Autism spectrum disorder (1 variants)
• CDK13-Related Disorder (1 variants)
• Seizure;Intellectual disability (1 variants)
• Marfanoid habitus and intellectual disability (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CDK13 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	107	14	122
missense	6	20	228	37	18	309
nonsense	5	5	5			15
start loss						0
frameshift	6	7	9			22
inframe indel		1	15			16
splice donor/acceptor (+/-2bp)			1			1
splice region			5	5	1	11
non coding			1	17	20	38
Total	17	33	260	161	52

Highest pathogenic variant AF is 0.0000199

Variants in CDK13

This is a list of pathogenic ClinVar variants found in the CDK13 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
7-39950654-T-C			Uncertain significance (Nov 03, 2022)
7-39950659-C-A			Uncertain significance (Sep 10, 2022)
7-39950659-C-G		CDK13-related disorder	Uncertain significance (Jun 08, 2023)
7-39950661-C-T		CDK13-related disorder	Uncertain significance (Nov 17, 2022)
7-39950682-G-A		Inborn genetic diseases	Uncertain significance (Dec 14, 2023)
7-39950688-G-C			Benign (Jan 24, 2023)
7-39950689-C-G			Uncertain significance (Jun 29, 2023)
7-39950692-G-A		Congenital heart defects, dysmorphic facial features, and intellectual developmental disorder	Uncertain significance (Aug 10, 2022)
7-39950701-G-A			Likely benign (Oct 04, 2023)
7-39950711-G-T		Congenital heart defects, dysmorphic facial features, and intellectual developmental disorder	Uncertain significance (Oct 13, 2022)
7-39950735-C-G			Benign (Jul 17, 2023)
7-39950735-C-T		CDK13-related disorder	Likely benign (Sep 20, 2023)
7-39950738-T-C			Uncertain significance (Nov 10, 2023)
7-39950740-C-T			Likely benign (Aug 04, 2023)
7-39950741-C-T			Benign (Jul 17, 2023)
7-39950756-C-T			Benign (Jan 17, 2024)
7-39950759-C-T			Likely benign (Apr 18, 2023)
7-39950766-C-CGCTCCTGCAGCCGCA			Uncertain significance (Dec 07, 2023)
7-39950774-C-A			Uncertain significance (Jan 02, 2022)
7-39950776-G-GCCGCAGCTCCTGCAA			Uncertain significance (Dec 12, 2022)
7-39950783-C-T			Uncertain significance (Jan 22, 2024)
7-39950785-C-T			Likely benign (Oct 03, 2023)
7-39950787-T-C			Uncertain significance (May 05, 2021)
7-39950790-A-C			Uncertain significance (May 08, 2023)
7-39950791-A-ACCGCCGCCGCCC			Likely pathogenic (May 11, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CDK13	protein_coding	protein_coding	ENST00000181839	14	147098

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.908	0.0925	125733	0	14	125747	0.0000557

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.35	510	683	0.747	0.0000357	9669
Missense in Polyphen		158	309.35	0.51075		3862
Synonymous	-1.51	292	261	1.12	0.0000137	3100
Loss of Function	5.58	11	56.2	0.196	0.00000328	720

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000120	0.000120
Ashkenazi Jewish	0.000199	0.000198
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000628	0.0000615
Middle Eastern	0.00	0.00
South Asian	0.0000659	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: 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. Required during hematopoiesis. In case of infection by HIV-1 virus, interacts with HIV-1 Tat protein acetylated at 'Lys-50' and 'Lys- 51', thereby increasing HIV-1 mRNA splicing and promoting the production of the doubly spliced HIV-1 protein Nef. {ECO:0000269|PubMed:16721827, ECO:0000269|PubMed:1731328, ECO:0000269|PubMed:18480452, ECO:0000269|PubMed:20952539}.
• Disease: DISEASE: Congenital heart defects, dysmorphic facial features, and intellectual developmental disorder (CHDFIDD) [MIM:617360]: An autosomal dominant syndrome characterized by atrial and/or ventricular septal congenital heart defects, facial dysmorphism with hypertelorism, upslanted palpebral fissures, epicanthal folds, ptosis, strabismus, posteriorly rotated ears, thin upper lip, and small mouth. Patients manifest global developmental delay, delayed walking and speech acquisition, and intellectual disability. Some patients have mild microcephaly, a small cerebral cortex, and agenesis of corpus callosum. More variable features include clinodactyly and/or camptodactyly of the fingers, hypotonia, and joint hypermobility. {ECO:0000269|PubMed:27479907, ECO:0000269|PubMed:28807008}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Neutrophil degranulation;Gene expression (Transcription);Generic Transcription Pathway;RNA Polymerase II Transcription;Innate Immune System;Immune System;TP53 Regulates Transcription of DNA Repair Genes;Transcriptional Regulation by TP53 (Consensus)

Recessive Scores

• pRec: 0.226

Intolerance Scores

• loftool: 0.569
• rvis_EVS: -1.08
• rvis_percentile_EVS: 7.28

Haploinsufficiency Scores

• pHI: 0.258
• hipred: Y
• hipred_score: 0.682
• ghis: 0.675

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: K
• gene_indispensability_pred: E
• gene_indispensability_score: 0.731

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Cdk13

Gene ontology

• Biological process: alternative mRNA splicing, via spliceosome;transcription elongation from RNA polymerase II promoter;protein phosphorylation;regulation of mitotic nuclear division;multicellular organism development;positive regulation of cell population proliferation;viral process;hemopoiesis;positive regulation of transcription elongation from RNA polymerase II promoter;neutrophil degranulation;positive regulation of transcription by RNA polymerase II;phosphorylation of RNA polymerase II C-terminal domain;negative regulation of stem cell differentiation
• Cellular component: cyclin-dependent protein kinase holoenzyme complex;nuclear chromatin;cyclin K-CDK13 complex;extracellular region;extracellular space;nucleus;nucleoplasm;chromosome;Golgi apparatus;cytosol;cyclin/CDK positive transcription elongation factor complex;nuclear speck;nuclear cyclin-dependent protein kinase holoenzyme complex;ficolin-1-rich granule lumen
• Molecular function: RNA binding;protein kinase activity;cyclin-dependent protein serine/threonine kinase activity;protein binding;ATP binding;transcription factor binding;RNA polymerase II CTD heptapeptide repeat kinase activity;protein kinase binding;cyclin binding;transcription regulatory region DNA binding