CCNK
protein-codingcyclin K, the group of Cyclins|P-TEFb complex subunits
Gene summary
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. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~53.9 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0029143
Submitter: G2P
Inheritance Pattern: AD
Disease ID:MONDO:0029143
Submitter: Ambry Genetics
Inheritance Pattern: Unknown
Disease ID:MONDO:0029143
Submitter: Labcorp Genetics (formerly Invitae)
Clinical Genomic Database (CGD)
Manifestation: Craniofacial; Musculoskeletal; Neurologic
Intervention: General
Rationale: 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
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to CCNK variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001099402.2. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 3 | 25 | 1 | 29 | ||
| missense | 1 | 72 | 6 | 79 | ||
| nonsense | 2 | 2 | ||||
| start loss | 1 | 1 | ||||
| frameshift | 3 | 3 | ||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 1 | 83 | 31 | 1 | 116 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001092872.1 | 10 | MANE Select | |
| Ensembl | ENSP00000374529.5 | 10 | MANE Select | |
| Ensembl | ENSP00000452307.1 | 10 | Standard | |
| Ensembl | ENSP00000452307.1 | 10 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| ccnk | Danio rerio | Structure: Mauthner neuron Quality: absent abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- TP53 Regulates Transcription of DNA Repair Genes
- Disease
- Signal Transduction
- Gene expression (Transcription)
- HIV elongation arrest and recovery
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
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
Cellular Component
- cyclin K-CDK12 complex
- cyclin K-CDK13 complex
- nucleus
- nucleoplasm
- cyclin/CDK positive transcription elongation factor complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000389879
- Coding exons
- 10
- Length
- 53876
- Individuals with no LoFs
- 124564
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 4
- Defined
- 124568
- p
- 0.0000161
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 3.31 | 136 | 296 | 0.459 | 0.0000163 | 3689 |
| Missense (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 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0.00011 | 0.000093 | rare |
| European (Non-Finnish) | 0.0000090 | 0.0000089 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0.00018 | 0.00017 | rare |
dbNSFP Gene Annotations
Source:
- 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}.;
Recessive Scores
- pRec
- 0.120
Intolerance Scores
- LoFtool
- 0.102
- RVIS EVS
- -0.36
- RVIS percentile EVS
- 28.63
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- E
- Essential (gene trap)
- E
- Indispensability pred.
- E
- Indispensability score
- 0.883
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |