TK2 Gene - Thymidine Kinase 2
Mitochondrial DNA Maintenance and Disease
Gene Information Card
| Symbol | TK2 |
|---|---|
| Full Name | Thymidine Kinase 2 |
| Gene Type | Protein coding |
| Chromosomal Location | 16q21 |
| NCBI Gene ID | 7084 ncbi.nlm.nih.gov/gene/7084 |
| Ensembl ID | ENSG00000166532 |
| UniProt ID | Q00169 |
| OMIM ID | 188250 |
| HGNC ID | 11831 |
| Aliases | MTTK, TK2, TPK1, TPK2 |
Description
The TK2 gene encodes thymidine kinase 2, a mitochondrial enzyme that phosphorylates thymidine and deoxycytidine to their monophosphate forms. This is a critical step in the mitochondrial salvage pathway for deoxynucleoside triphosphate (dNTP) synthesis, essential for mitochondrial DNA replication and repair. Mutations in TK2 cause mitochondrial DNA depletion syndrome (MDS) and are associated with progressive external ophthalmoplegia and other mitochondrial disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Mitochondrial DNA depletion syndrome 2 (MTDPS2) | Loss-of-function mutations reduce dNTP pools, impairing mtDNA replication | ClinVar, OMIM |
| Progressive external ophthalmoplegia with mitochondrial DNA deletions | TK2 deficiency leads to mtDNA instability and multiple deletions | ClinVar, OMIM |
| TK2 deficiency (mitochondrial neurogastrointestinal encephalopathy-like) | Impaired thymidine phosphorylation causes mtDNA depletion in muscle and brain | OMIM, NCBI |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Skeletal muscle | 12.3 | Medium |
| Heart | 9.8 | Medium |
| Liver | 6.5 | Low |
| Brain | 5.2 | Low |
| Kidney | 4.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 8.7 | Cervical cancer cell line |
| HEK293 | 7.2 | Embryonic kidney cells |
| HepG2 | 6.0 | Hepatocellular carcinoma |
| K562 | 5.5 | Leukemia cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.323C>T (p.Thr108Met) | Missense | Common | Reduced enzyme activity, mtDNA depletion |
| c.156_157del (p.Lys53Argfs*12) | Frameshift | Rare | Loss of function, severe early-onset disease |
| c.497G>A (p.Arg166Gln) | Missense | Rare | Impaired substrate binding, mild phenotype |
Mutation functional classification
Loss of Function (LOF)
Most TK2 mutations are loss-of-function, reducing or abolishing thymidine kinase activity, leading to dNTP imbalance and mtDNA depletion.
Gain of Function (GOF)
No gain-of-function mutations reported for TK2.
Dominant Negative (DN)
No dominant-negative mechanism described; TK2 deficiency is typically autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Pyrimidine salvage pathway (Reactome: R-HSA-73621)
• Mitochondrial DNA replication (Reactome: R-HSA-159223)
Protein Summary
Thymidine kinase 2 (TK2) is a 234-amino acid mitochondrial protein that catalyzes the phosphorylation of thymidine and deoxycytidine using ATP as a phosphate donor. It is essential for maintaining balanced dNTP pools within mitochondria, supporting mtDNA replication and repair. The enzyme functions as a homodimer and is localized to the mitochondrial matrix. Deficiency leads to mtDNA depletion syndromes, often presenting with muscle weakness, ophthalmoplegia, and neurological symptoms.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PTK2B Knockout HEK293 Cell Line | EDJ-KQ992 | Human | 2185 | Details Get a Quote |
| LMTK2 Knockout HEK293 Cell Line | EDJ-KQ3648 | Human | 22853 | Details Get a Quote |
| STK24 Knockout HEK293 Cell Line | EDJ-KQ6238 | Human | 8428 | Details Get a Quote |
| STK25 Knockout HEK293 Cell Line | EDJ-KQ7062 | Human | 10494 | Details Get a Quote |
| STK26 Knockout HEK293 Cell Line | EDJ-KQ11218 | Human | 51765 | Details Get a Quote |
| TK2 Knockout HEK293 Cell Line | EDJ-KQ17908 | Human | 7084 | Details Get a Quote |
| STK24 Knockout A-549 Cell Line | EDJ-KQ30087 | Human | 8428 | Details Get a Quote |
| STK24 Knockout HCT 116 Cell Line | EDJ-KQ30088 | Human | 8428 | Details Get a Quote |
| STK24 Knockout HeLa Cell Line | EDJ-KQ30089 | Human | 8428 | Details Get a Quote |
| PTK2B Knockout A-549 Cell Line | EDJ-KQ21372 | Human | 2185 | Details Get a Quote |
| PTK2B Knockout HCT 116 Cell Line | EDJ-KQ21373 | Human | 2185 | Details Get a Quote |
| PTK2B Knockout HeLa Cell Line | EDJ-KQ21374 | Human | 2185 | Details Get a Quote |
| LMTK2 Knockout A-549 Cell Line | EDJ-KQ25613 | Human | 22853 | Details Get a Quote |
| LMTK2 Knockout HCT 116 Cell Line | EDJ-KQ25614 | Human | 22853 | Details Get a Quote |
| LMTK2 Knockout HeLa Cell Line | EDJ-KQ25615 | Human | 22853 | Details Get a Quote |
Displaying Records 1 To 15 Of 25 Records
