CCNK

cyclin K, the group of Cyclins|P-TEFb complex subunits

Basic information

Region (hg38): 14:99481168-99535044

Links

ENSG00000090061 ∙ NCBI:8812 ∙ OMIM:603544 ∙ HGNC:1596 ∙ Uniprot:O75909 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• intellectual developmental disorder with hypertelorism and distinctive facies (Limited), mode of inheritance: AD
• intellectual developmental disorder with hypertelorism and distinctive facies (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Intellectual developmental disorder with hypertelorism and distinctive facies	AD	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Craniofacial; Musculoskeletal; Neurologic	30122539

ClinVar

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

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CCNK 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				8	2	10
missense			21			21
nonsense			1			1
start loss			1			1
frameshift			1			1
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				1	2	3
non coding			9	3		12
Total	0	0	33	11	2

Variants in CCNK

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

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

Position	Type	Phenotype	Significance	ClinVar
14-99492678-A-G		Intellectual developmental disorder with hypertelorism and distinctive facies	Uncertain significance (Jan 12, 2022)
14-99492710-A-G			Likely benign (Feb 01, 2023)
14-99492711-G-A		not specified	Uncertain significance (Dec 17, 2021)
14-99492820-G-A		CCNK-related disorder	Uncertain significance (Jun 24, 2023)
14-99492828-C-T			Uncertain significance (Aug 01, 2023)
14-99492837-G-A			Uncertain significance (Jul 30, 2021)
14-99495493-T-C		Intellectual developmental disorder with hypertelorism and distinctive facies • CCNK-related disorder	Benign (Jul 14, 2021)
14-99495549-A-G		Intellectual developmental disorder with hypertelorism and distinctive facies	Pathogenic (Oct 16, 2018)
14-99495579-C-T		not specified	Uncertain significance (Oct 29, 2021)
14-99500805-A-G			Uncertain significance (Dec 20, 2022)
14-99500849-A-T		CCNK-related disorder	Benign (Sep 30, 2019)
14-99500873-TAAG-T			Benign (Dec 31, 2019)
14-99501368-A-G		not specified	Uncertain significance (Apr 07, 2023)
14-99502260-T-G		not specified	Uncertain significance (Mar 28, 2024)
14-99502367-G-A		Intellectual developmental disorder with hypertelorism and distinctive facies	Uncertain significance (Apr 21, 2022)
14-99502750-A-G		CCNK-related disorder	Likely benign (Mar 28, 2019)
14-99502830-C-T		not specified	Uncertain significance (Apr 07, 2022)
14-99502851-C-T		Intellectual developmental disorder with hypertelorism and distinctive facies	Uncertain significance (Jul 01, 2023)
14-99502925-C-G		not specified	Uncertain significance (Dec 19, 2022)
14-99502929-A-G		not specified	Uncertain significance (Sep 25, 2023)
14-99502969-G-C		not specified	Uncertain significance (Jan 19, 2024)
14-99502970-G-T		not specified	Uncertain significance (Jun 17, 2024)
14-99503604-G-C			Likely benign (Jun 01, 2022)
14-99507102-A-G		not specified	Uncertain significance (Dec 09, 2023)
14-99510160-G-A		not specified	Uncertain significance (Aug 02, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CCNK	protein_coding	protein_coding	ENST00000389879	10	53876

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.000203	124564	0	4	124568	0.0000161

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.31	136	296	0.459	0.0000163	3689
Missense in Polyphen		11	70.324	0.15642		903
Synonymous	-1.10	132	117	1.13	0.00000721	1166
Loss of Function	4.79	1	28.7	0.0348	0.00000147	323

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.000106	0.0000928
European (Non-Finnish)	0.00000900	0.00000886
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.000184	0.000165

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Regulatory subunit of cyclin-dependent kinases that mediates activation of target kinases. Plays a role in transcriptional regulation via its role in regulating the phosphorylation of the C-terminal domain (CTD) of the large subunit of RNA polymerase II (POLR2A). {ECO:0000269|PubMed:10574912, ECO:0000269|PubMed:22012619, ECO:0000269|PubMed:9632813}.
• Pathway: TP53 Regulates Transcription of DNA Repair Genes;Disease;Signal Transduction;Gene expression (Transcription);HIV elongation arrest and recovery;Formation of HIV elongation complex in the absence of HIV Tat;Pausing and recovery of HIV elongation;Generic Transcription Pathway;Transcription of the HIV genome;Late Phase of HIV Life Cycle;HIV Life Cycle;HIV Infection;RNA Polymerase II Pre-transcription Events;Formation of RNA Pol II elongation complex ;RNA polymerase II transcribes snRNA genes;RNA Polymerase II Transcription;Infectious disease;RNA Polymerase II Transcription Elongation;SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription;Transcriptional activity of SMAD2/SMAD3:SMAD4 heterotrimer;TP53 Regulates Transcription of DNA Repair Genes;Transcriptional Regulation by TP53;Direct p53 effectors;Signaling by TGF-beta Receptor Complex;Signaling by TGF-beta family members (Consensus)

Recessive Scores

• pRec: 0.120

Intolerance Scores

• loftool: 0.102
• rvis_EVS: -0.36
• rvis_percentile_EVS: 28.63

Haploinsufficiency Scores

• pHI: 0.881
• hipred: Y
• hipred_score: 0.729
• ghis: 0.633

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.883

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ccnk
• Phenotype: mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span)

Zebrafish Information Network

• Gene name: ccnk
• Affected structure: Mauthner neuron
• Phenotype tag: abnormal
• Phenotype quality: absent

Gene ontology

• Biological process: regulation of cyclin-dependent protein serine/threonine kinase activity;regulation of transcription by RNA polymerase II;transcription by RNA polymerase II;transcription elongation from RNA polymerase II promoter;protein phosphorylation;cellular response to DNA damage stimulus;cell cycle;positive regulation of DNA-templated transcription, elongation;snRNA transcription by RNA polymerase II;negative regulation by host of viral genome replication;positive regulation of cyclin-dependent protein serine/threonine kinase activity;positive regulation of transcription by RNA polymerase II;cell division;negative regulation of cell cycle arrest;positive regulation of phosphorylation of RNA polymerase II C-terminal domain serine 2 residues
• Cellular component: cyclin K-CDK12 complex;cyclin K-CDK13 complex;nucleus;nucleoplasm;cyclin/CDK positive transcription elongation factor complex
• Molecular function: protein serine/threonine kinase activity;cyclin-dependent protein serine/threonine kinase activity;protein binding;RNA polymerase II CTD heptapeptide repeat kinase activity;cyclin-dependent protein serine/threonine kinase regulator activity;protein kinase binding;cyclin-dependent protein serine/threonine kinase activator activity