CCNT1
protein-codingcyclin T1, the group of P-TEFb complex subunits|Cyclins
Gene summary
This gene encodes a member of the highly conserved cyclin C subfamily. The encoded protein tightly associates with cyclin-dependent kinase 9, and is a major subunit of positive transcription elongation factor b (p-TEFb). In humans, there are multiple forms of positive transcription elongation factor b, which may include one of several different cyclins along with cyclin-dependent kinase 9. The complex containing the encoded cyclin and cyclin-dependent kinase 9 acts as a cofactor of human immunodeficiency virus type 1 (HIV-1) Tat protein, and is both necessary and sufficient for full activation of viral transcription. This cyclin and its kinase partner are also involved in triggering transcript elongation through phosphorylation of the carboxy-terminal domain of the largest RNA polymerase II subunit. Overexpression of this gene is implicated in tumor growth. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2013]
- HIVE1
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~28.5 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 CCNT1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001240.4. 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 | 1 | 2 | |||
| missense | 73 | 4 | 77 | |||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 0 | 77 | 5 | 0 | 82 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001231.2 | 9 | MANE Select | |
| Ensembl | ENSP00000261900.3 | 9 | MANE Select | |
| RefSeq | NP_001264771.1 | 7 | Standard | |
| RefSeq | NP_001400127.1 | 8 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Transcriptional misregulation in cancer - Homo sapiens (human)
- Initiation of transcription and translation elongation at the HIV-1 LTR
- 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 by RNA polymerase II
- transcription elongation from RNA polymerase II promoter
- protein phosphorylation
Molecular Function
- DNA binding
- chromatin binding
- protein serine/threonine kinase activity
- protein binding
- transcription factor binding
Cellular Component
- nucleus
- nucleoplasm
- nucleolus
- cyclin/CDK positive transcription elongation factor complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000261900
- Coding exons
- 9
- Length
- 28435
- Individuals with no LoFs
- 125733
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 15
- Defined
- 125748
- p
- 0.0000596
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.08 | 333 | 393 | 0.847 | 0.0000205 | 4768 |
| Missense (PolyPhen) | 73 | 108.01 | 0.67585 | 1305 | ||
| Synonymous | -0.277 | 144 | 140 | 1.03 | 0.00000712 | 1431 |
| Loss of Function | 3.62 | 8 | 29.0 | 0.276 | 0.00000140 | 360 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00012 | 0.00012 | rare |
| Latino/Admixed American | 0.000058 | 0.000058 | rare |
| Ashkenazi Jewish | 0.00020 | 0.00020 | rare |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.00014 | 0.000070 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Regulatory subunit of the cyclin-dependent kinase pair (CDK9/cyclin-T1) complex, also called positive transcription elongation factor B (P-TEFb), which is proposed to facilitate the transition from abortive to productive elongation by phosphorylating the CTD (carboxy-terminal domain) of the large subunit of RNA polymerase II (RNA Pol II). {ECO:0000269|PubMed:16109376, ECO:0000269|PubMed:16109377}.;
Recessive Scores
- pRec
- 0.152
Intolerance Scores
- LoFtool
- 0.314
- RVIS EVS
- -0.02
- RVIS percentile EVS
- 52.09
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.991
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |