The TK2 gene has been mapped to chromosome 16q21, where it encodes an enzyme called deoxyribonucleoside kinase. This mitochondrial enzyme comprises of 265 amino acids and weighs approximately 31 kDa. Deoxyribonucleoside kinase enzyme is required for mitochondrial DNA synthesis; it phosphorylates thymidine, deoxycytidine, and deoxyuridine.
Defects in the deoxyribonucleoside kinase enzyme are the cause of mitochondrial DNA depletion syndrome 2, also known as TK2-related mitochondrial DNA depletion syndrome, myopathic form. This is an autosomal recessive disorder due to mitochondrial dysfunction characterized by childhood onset of muscle weakness, and associated with depletion of mtDNA in skeletal muscle.
The TK2 gene spans a length of about 45 kb in length and contains 16 exons that are subject to extensive alternative splicing. At least 30 different mutations in this gene have been identified in patients with mitochondrial DNA depletion syndrome 2. All these mutations result in a decrease of deoxyribonucleoside kinase enzyme activity, which impairs mtDNA synthesis, in turn causing mtDNA depletion in muscle tissues. Patients with TK2-MDS have very low amounts of mtDNA, ranging from 5% to 30% of normal values.