TK1
protein-codingthymidine kinase 1, the group of Deoxyribonucleoside kinases
Gene summary
The protein encoded by this gene is a cytosolic enzyme that catalyzes the addition of a gamma-phosphate group to thymidine. This creates dTMP and is the first step in the biosynthesis of dTTP, which is one component required for DNA replication. The encoded protein, whose levels fluctuate depending on the cell cycle stage, can act as a low activity dimer or a high activity tetramer. High levels of this protein have been used as a biomarker for diagnosing and categorizing many types of cancers. [provided by RefSeq, Oct 2016]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~13.1 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 TK1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_003258.5. 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 | 1 | 1 | 2 | |||
| missense | 37 | 1 | 38 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 39 | 1 | 1 | 41 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_003249.3 | 7 | MANE Select | |
| Ensembl | ENSP00000301634.6 | 7 | MANE Select | |
| RefSeq | NP_001333592.1 | 7 | Standard | |
| RefSeq | NP_001350777.1 | 6 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Pyrimidine metabolism - Homo sapiens (human)
- Drug metabolism - other enzymes - Homo sapiens (human)
- Fluoropyrimidine Pathway, Pharmacokinetics
- Zidovudine Pathway, Pharmacokinetics/Pharmacodynamics
- Pyrimidine Metabolism
Biological Process
- nucleobase-containing compound metabolic process
- DNA metabolic process
- deoxyribonucleoside monophosphate biosynthetic process
- nucleotide biosynthetic process
- phosphorylation
Molecular Function
- thymidine kinase activity
- protein binding
- ATP binding
- zinc ion binding
- nucleoside kinase activity
Cellular Component
- cytosol
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000301634
- Coding exons
- 7
- Length
- 13155
- Individuals with no LoFs
- 125596
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 9
- Defined
- 125605
- p
- 0.0000358
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.31 | 101 | 146 | 0.694 | 0.00000927 | 1499 |
| Missense (PolyPhen) | 24 | 52.197 | 0.4598 | 513 | ||
| Synonymous | 0.645 | 54 | 60.4 | 0.894 | 0.00000419 | 459 |
| Loss of Function | 2.04 | 3 | 9.92 | 0.302 | 4.19e-7 | 125 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00020 | 0.00018 | rare |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0.00010 | 0.000099 | rare |
| East Asian | 0.000067 | 0.000054 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000028 | 0.000026 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
Recessive Scores
- pRec
- 0.444
Intolerance Scores
- LoFtool
- 0.442
- RVIS EVS
- -0.21
- RVIS percentile EVS
- 38.58
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.999
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |