CCNC
protein-codingcyclin C, the group of Cyclins|Mediator complex
Gene summary
The protein encoded by this gene is a member of the cyclin family of proteins. The encoded protein interacts with cyclin-dependent kinase 8 and induces the phophorylation of the carboxy-terminal domain of the large subunit of RNA polymerase II. The level of mRNAs for this gene peaks in the G1 phase of the cell cycle. Two transcript variants encoding different isoforms have been found for this gene. [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 ~26.4 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to CCNC variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_005190.4. 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 | 1 | 2 | 3 | |||
| missense | 16 | 16 | ||||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 4 | 4 | ||||
| Total | 0 | 0 | 22 | 2 | 0 | 24 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_005181.2 | 12 | MANE Select | |
| Ensembl | ENSP00000428982.1 | 12 | MANE Select | |
| RefSeq | NP_001013417.1 | 9 | Standard | |
| RefSeq | NP_001350466.1 | 12 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| ccnc | Danio rerio | Structure: pronephric podocyte Quality: malformed abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Vitamin D Receptor Pathway
- Developmental Biology
- Disease
- Signal Transduction
- Gene expression (Transcription)
Biological Process
- regulation of cyclin-dependent protein serine/threonine kinase activity
- regulation of transcription by RNA polymerase II
- transcription initiation from RNA polymerase II promoter
- protein phosphorylation
- positive regulation of transcription by RNA polymerase II
Molecular Function
- protein serine/threonine kinase activity
- protein binding
- cyclin-dependent protein serine/threonine kinase regulator activity
Cellular Component
- nucleus
- nucleoplasm
- mediator complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000520429
- Coding exons
- 12
- Length
- 26594
- Individuals with no LoFs
- 125235
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 1
- Defined
- 125236
- p
- 0.00000399
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.25 | 63 | 137 | 0.459 | 0.00000618 | 1870 |
| Missense (PolyPhen) | 19 | 47.837 | 0.39718 | 641 | ||
| Synonymous | 0.402 | 42 | 45.4 | 0.924 | 0.00000219 | 467 |
| Loss of Function | 4.19 | 0 | 20.4 | 0.00 | 8.62e-7 | 278 |
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 | 0.0 | absent |
| European (Non-Finnish) | 0 | 0.0 | absent |
| South Asian | 0.000033 | 0.000033 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Component of the Mediator complex, a coactivator involved in regulated gene transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. Mediator is recruited to promoters by direct interactions with regulatory proteins and serves as a scaffold for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors. Binds to and activates cyclin-dependent kinase CDK8 that phosphorylates the CTD (C-terminal domain) of the large subunit of RNA polymerase II (RNAp II), which may inhibit the formation of a transcription initiation complex. {ECO:0000269|PubMed:16595664, ECO:0000269|PubMed:8700522}.;
Recessive Scores
- pRec
- 0.194
Intolerance Scores
- LoFtool
- 0.537
- RVIS EVS
- -0.1
- RVIS percentile EVS
- 46.2
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- H
- Indispensability pred.
- E
- Indispensability score
- 0.967
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Low | Low | Low |
| Primary Immunodeficiency | Low | Low | Low |
| Cancer | Low | Low | Low |