CCT8
protein-codingchaperonin containing TCP1 subunit 8, the group of Chaperonins
Gene summary
This gene encodes the theta subunit of the CCT chaperonin, which is abundant in the eukaryotic cytosol and may be involved in the transport and assembly of newly synthesized proteins. Alternative splicing results in multiple transcript variants of this gene. A pseudogene related to this gene is located on chromosome 1. [provided by RefSeq, Sep 2013]
- C21orf112
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~18.0 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0700092
Submitter: Ambry Genetics
Inheritance Pattern: AD
Disease ID:MONDO:0100038
Submitter: G2P
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to CCT8 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_006585.4. 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 | 72 | 2 | 1 | 75 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 0 | 76 | 3 | 1 | 80 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_006576.2 | 15 | MANE Select | |
| Ensembl | ENSP00000286788.4 | 15 | MANE Select | |
| RefSeq | NP_001269836.1 | 15 | Standard | |
| RefSeq | NP_001269837.1 | 13 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| cct8 | Danio rerio | Structure: skeletal muscle cell Quality: decreased amount abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Neutrophil degranulation
- Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding
- Metabolism of proteins
- Chaperonin-mediated protein folding
- TCR
Biological Process
- protein folding
- binding of sperm to zona pellucida
- positive regulation of telomere maintenance via telomerase
- neutrophil degranulation
- pore complex assembly
Molecular Function
- protein binding
- ATP binding
- ATPase activity, coupled
- cadherin binding
- unfolded protein binding
Cellular Component
- zona pellucida receptor complex
- extracellular region
- nucleoplasm
- cytoplasm
- centrosome
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000286788
- Coding exons
- 15
- Length
- 17993
- Individuals with no LoFs
- 125723
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 8
- Defined
- 125731
- p
- 0.0000318
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.07 | 235 | 286 | 0.822 | 0.0000140 | 3580 |
| Missense (PolyPhen) | 43 | 91.16 | 0.4717 | 1208 | ||
| Synonymous | 0.333 | 93 | 97.2 | 0.957 | 0.00000503 | 1059 |
| Loss of Function | 4.19 | 4 | 27.9 | 0.144 | 0.00000139 | 364 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000058 | 0.000058 | rare |
| Ashkenazi Jewish | 0.00010 | 0.000099 | rare |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000027 | 0.000026 | rare |
| South Asian | 0.000074 | 0.000065 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Component of the chaperonin-containing T-complex (TRiC), a molecular chaperone complex that assists the folding of proteins upon ATP hydrolysis (PubMed:25467444). The TRiC complex mediates the folding of WRAP53/TCAB1, thereby regulating telomere maintenance (PubMed:25467444). As part of the TRiC complex may play a role in the assembly of BBSome, a complex involved in ciliogenesis regulating transports vesicles to the cilia (PubMed:20080638). The TRiC complex plays a role in the folding of actin and tubulin (Probable). {ECO:0000269|PubMed:20080638, ECO:0000269|PubMed:25467444, ECO:0000305}.;
Recessive Scores
- pRec
- 0.476
Intolerance Scores
- LoFtool
- 0.143
- RVIS EVS
- -0.25
- RVIS percentile EVS
- 36.07
Essentials
- Essential (CRISPR)
- E
- Essential (gene trap)
- E
- Indispensability pred.
- E
- Indispensability score
- 0.892
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |