On this page
TK2
thymidine kinase 2
TK2 is located on the long (q) arm of chromosome 16, at band 16q21. Arm ratio per GRCh38 - banding schematic.
Explore chromosome 16 in the library →Available at Jeen Health
Clinical tests that include this
Overview
TK2 is located on chromosome 16 and encodes thymidine kinase 2, an enzyme exclusive to mitochondria. Mitochondria house their own genetic material, distinct from the DNA in the cell nucleus, and rely on thymidine kinase 2 to maintain the pool of nucleotides required for mitochondrial DNA maintenance and repair.
When TK2 function is compromised through pathogenic variants, cells cannot adequately replenish mitochondrial DNA building blocks. This leads to mitochondrial DNA depletion, particularly affecting tissues with high energy demands such as skeletal muscle. The resulting condition typically manifests as progressive muscle weakness beginning in early childhood, reflecting the reliance of muscle tissue on robust mitochondrial function.
What the gene does
Thymidine kinase 2 catalyses the phosphorylation of thymidine and deoxycytidine, converting these nucleosides into nucleotides that can be incorporated into mitochondrial DNA. This salvage pathway is essential because mitochondria cannot synthesise nucleotides de novo and must recycle existing bases or import them from the cytoplasm.
The enzyme functions continuously to support mitochondrial DNA replication and repair processes. During DNA synthesis, thymidine kinase 2 ensures an adequate supply of deoxythymidine triphosphate and deoxycytidine triphosphate, both critical components of the mitochondrial genome. By maintaining balanced nucleotide pools, the enzyme prevents replication errors and allows efficient correction of DNA damage.
This activity is particularly critical in tissues with high metabolic rates and limited cell division, such as skeletal muscle and cardiac muscle, where mitochondrial turnover is constant and DNA integrity directly influences cellular energy production.
Video: Genetics 101
Chromosome location
TK2 is positioned at chromosomal band 16q21 on the long arm of chromosome 16. The gene spans approximately 30 kilobases of genomic DNA and comprises multiple exons that are transcribed and spliced to produce the messenger RNA encoding the 265-amino-acid protein. The genomic region is well characterised, facilitating variant detection and interpretation in clinical diagnostic settings.
Protein structure
The TK2 protein comprises 265 amino acids and includes a disordered region spanning amino acids 20 to 47. This disordered segment likely provides flexibility for protein-protein interactions or regulatory modifications. The catalytic core of the enzyme, located outside this disordered region, adopts a structure characteristic of nucleoside kinases, enabling substrate binding and phosphoryl transfer. Structural studies suggest that the enzyme functions as a dimer, with each subunit contributing to the active site configuration required for efficient nucleotide salvage.
Key variants
Over 30 pathogenic variants in TK2 have been documented in medical literature, with approximately two-thirds involving single amino acid substitutions. These changes typically reduce or eliminate thymidine kinase 2 enzymatic activity, impairing the cell's ability to maintain mitochondrial DNA. Loss-of-function variants are inherited in an autosomal recessive pattern, meaning that affected individuals carry pathogenic changes on both gene copies.
No pathogenic or likely-pathogenic ClinVar variants recorded yet for this gene.
Associated conditions
Pathogenic variants in TK2 cause TK2-related mitochondrial DNA depletion syndrome, myopathic form, an inherited condition characterised by progressive muscle weakness. Symptoms generally begin in early childhood, with affected individuals experiencing declining motor function as muscle tissue becomes increasingly unable to meet energy demands. The severity and age of onset can vary depending on the specific variants inherited and the degree of residual enzyme activity. Some individuals may also develop progressive external ophthalmoplegia, a condition affecting the muscles controlling eye movement, reflecting the vulnerability of extraocular muscles to mitochondrial dysfunction.
No disease links recorded for this gene in our reference set.
Inheritance pattern
Conditions caused by pathogenic TK2 variants typically follow autosomal recessive inheritance.
When both parents are carriers, each child has a 25% chance of being affected, 50% of being a carrier, and 25% of being unaffected.
UK clinical status
TK2 has been designated a green gene on multiple NHS Genomic Medicine Service panels, indicating strong evidence for its role in diagnosable conditions. These panels include Mitochondrial Disorders, Mitochondrial DNA Maintenance Disorder, Acute Rhabdomyolysis, Rhabdomyolysis and Metabolic Muscle Disorders, Likely Inborn Error of Metabolism, Undiagnosed Metabolic Disorders, Possible Mitochondrial Disorder (nuclear genes), Fetal Anomalies, and the Developmental Disorders Genotype-to-Phenotype database. This broad inclusion reflects the gene's established clinical significance in diagnosing mitochondrial myopathies and related metabolic conditions within the NHS.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What does the TK2 gene do?
TK2 provides instructions for making thymidine kinase 2, an enzyme that recycles DNA building blocks within mitochondria. This recycling process is essential for maintaining and repairing mitochondrial DNA, particularly in tissues with high energy requirements such as muscle.
How are TK2 variants inherited?
TK2-related conditions follow an autosomal recessive inheritance pattern. This means an individual must inherit a pathogenic variant from both parents to develop the condition. Carriers, who have one pathogenic variant and one typical copy, generally do not show symptoms.
What symptoms are associated with TK2 variants?
Pathogenic TK2 variants typically cause progressive muscle weakness beginning in early childhood. Affected individuals may experience difficulty with movement, feeding, and breathing as muscle function declines. Some may also develop weakness in the muscles that control eye movement.