TTK
protein-codingTTK protein kinase
Gene summary
This gene encodes a dual specificity protein kinase with the ability to phosphorylate tyrosine, serine and threonine. Associated with cell proliferation, this protein is essential for chromosome alignment at the centromere during mitosis and is required for centrosome duplication. It has been found to be a critical mitotic checkpoint protein for accurate segregation of chromosomes during mitosis. Tumorigenesis may occur when this protein fails to degrade and produces excess centrosomes resulting in aberrant mitotic spindles. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2009]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~38.6 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 TTK variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_003318.5. 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 | 2 | 2 | 1 | 5 | ||
| missense | 103 | 7 | 1 | 111 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 6 | 6 | ||||
| Total | 0 | 0 | 111 | 9 | 2 | 122 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_003309.2 | 21 | MANE Select | |
| Ensembl | ENSP00000358813.2 | 21 | MANE Select | |
| RefSeq | NP_001160163.1 | 21 | Standard | |
| RefSeq | NP_001424819.1 | 21 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| ttk | Danio rerio | Structure: nervous system Quality: quality abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Cell cycle - Homo sapiens (human)
- Retinoblastoma (RB) in Cancer
Biological Process
- spindle organization
- mitotic spindle organization
- mitotic spindle assembly checkpoint
- positive regulation of cell population proliferation
- positive regulation of pathway-restricted SMAD protein phosphorylation
Molecular Function
- protein serine/threonine kinase activity
- protein serine/threonine/tyrosine kinase activity
- protein tyrosine kinase activity
- protein binding
- ATP binding
Cellular Component
- kinetochore
- cytoplasm
- spindle
- membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000369798
- Coding exons
- 21
- Length
- 38641
- Individuals with no LoFs
- 125697
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 23
- Defined
- 125720
- p
- 0.0000915
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.722 | 382 | 424 | 0.901 | 0.0000206 | 5673 |
| Missense (PolyPhen) | 57 | 95.85 | 0.59468 | 1304 | ||
| Synonymous | 1.05 | 128 | 144 | 0.889 | 0.00000722 | 1496 |
| Loss of Function | 4.58 | 15 | 49.9 | 0.301 | 0.00000246 | 635 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00013 | 0.00012 | rare |
| Latino/Admixed American | 0.00015 | 0.00014 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000056 | 0.000054 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000082 | 0.000079 | rare |
| South Asian | 0.00019 | 0.00016 | rare |
| Other | 0.00017 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Phosphorylates proteins on serine, threonine, and tyrosine. Probably associated with cell proliferation. Essential for chromosome alignment by enhancing AURKB activity (via direct CDCA8 phosphorylation) at the centromere, and for the mitotic checkpoint. {ECO:0000269|PubMed:18243099}.;
Recessive Scores
- pRec
- 0.169
Intolerance Scores
- LoFtool
- 0.339
- RVIS EVS
- -0.29
- RVIS percentile EVS
- 33.47
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- E
- Essential (gene trap)
- E
- Indispensability pred.
- E
- Indispensability score
- 0.964
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |