This gene encodes a mitochondrial deoxyribonucleoside kinase that phosphorylates thymidine, deoxycytidine, and deoxyuridine, which is essential for mitochondrial DNA synthesis. Mutations cause mitochondrial DNA depletion syndrome type 2 (myopathic type) and progressive external ophthalmoplegia with mitochondrial DNA deletions, both inherited in an autosomal recessive pattern. The pathogenic mechanism involves dominant-negative effects that disrupt mitochondrial DNA replication and maintenance.

OMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
MultiplemechanismARLOEUF 1.192 OMIM phenotypes
Clinical SummaryTK2
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Gene-Disease Validity (ClinGen)
mitochondrial disease · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.19LOEUF
pLI 0.000
Z-score 1.01
OE 0.73 (0.471.19)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.15Z-score
OE missense 0.96 (0.841.11)
139 obs / 144.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.73 (0.471.19)
00.351.4
Missense OE0.96 (0.841.11)
00.61.4
Synonymous OE1.15
01.21.6
LoF obs/exp: 12 / 16.4Missense obs/exp: 139 / 144.2Syn Z: -0.89
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveTK2-related mitochondrial DNA depletion syndrome, myopathic formOTHERAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.75top 25%
GOF
0.6442th %ile
LOF
0.2774th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

TK2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold
Clinical Literature
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