Mitochondrial DNA maintenance disorder: genes and variants
Mitochondrial DNA maintenance disorder is linked to 2 analyzed proteins (POLG and SPG7). 4 DNA variants are known to cause it; 2 more are uncertain, and 0 of those already look disease-causing on computable evidence.
Last updated 2026-09-30. Research information, not medical advice.
Genes linked to Mitochondrial DNA maintenance disorder
POLG: DNA polymerase subunit gamma-1
It replicates and repairs mitochondrial DNA and is therefore essential for maintaining mitochondrial genome copy number and integrity. Pathogenic variants cause a broad spectrum including Alpers syndrome, progressive external ophthalmoplegia, epilepsy, ataxia, neuropathy, and liver disease.
2 disease-causing and 1 uncertain variants in POLG are linked to Mitochondrial DNA maintenance disorder.
SPG7: Mitochondrial inner membrane m-AAA protease component paraplegin
It participates in mitochondrial inner-membrane protein quality control and respiratory homeostasis as part of the m-AAA protease machinery. Biallelic pathogenic variants cause SPG7-related disease, commonly presenting with spastic ataxia, optic neuropathy, or progressive gait impairment.
2 disease-causing and 0 uncertain variants in SPG7 are linked to Mitochondrial DNA maintenance disorder.
Weakly linked (only a few uncertain records): MFN2.
Known disease-causing variants in Mitochondrial DNA maintenance disorder
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| SPG7 A510V | 510 | Mitochondrial matrix | Disease-causing (★★★★) |
| POLG E1136K | 1136 | Pol C | Disease-causing (★★) |
| POLG G848S | 848 | Disease-causing (★★) | |
| SPG7 A510L | 510 | Mitochondrial matrix | Disease-causing (★★) |
Same protein, different disease
- Progressive sclerosing poliodystrophy is also caused by POLG variants; they fall mostly in different places as the Mitochondrial DNA maintenance disorder variants (77 disease-causing).
- Mitochondrial DNA depletion syndrome is also caused by POLG variants; they fall mostly in different places as the Mitochondrial DNA maintenance disorder variants (26 disease-causing).
- Progressive external ophthalmoplegia with mitochondrial DNA deletions is also caused by POLG variants; they fall mostly in different places as the Mitochondrial DNA maintenance disorder variants (17 disease-causing).
- Mitochondrial disease is also caused by POLG variants; they fall mostly in different places as the Mitochondrial DNA maintenance disorder variants (6 disease-causing).
- Sensory ataxic neuropathy, dysarthria, and ophthalmoparesis is also caused by POLG variants; they fall mostly in different places as the Mitochondrial DNA maintenance disorder variants (6 disease-causing).
- Hereditary spastic paraplegia is also caused by SPG7 variants; they fall mostly in different places as the Mitochondrial DNA maintenance disorder variants (26 disease-causing).
Diseases related to Mitochondrial DNA maintenance disorder
- Hereditary spastic paraplegia, also linked to POLG and SPG7
- Mitochondrial disease, also linked to POLG and SPG7
- Possible mitochondrial disorder - nuclear genes, also linked to POLG and SPG7
- Progressive sclerosing poliodystrophy, also linked to POLG
- Mitochondrial DNA depletion syndrome, also linked to POLG
- Fanconi anemia, also linked to POLG
- Progressive external ophthalmoplegia with mitochondrial DNA deletions, also linked to POLG
- Hereditary pancreatitis, also linked to SPG7
- Spastic ataxia, also linked to SPG7
- Sensory ataxic neuropathy, dysarthria, and ophthalmoparesis, also linked to POLG
- Autosomal recessive spastic paraplegia type 78, also linked to SPG7
- Hereditary ataxia, also linked to SPG7
Frequently asked questions
Which genes are linked to Mitochondrial DNA maintenance disorder?
In CATVariant, Mitochondrial DNA maintenance disorder is linked to 2 analyzed proteins: POLG (DNA polymerase subunit gamma-1) and SPG7 (Mitochondrial inner membrane m-AAA protease component paraplegin).
How many genetic variants are linked to Mitochondrial DNA maintenance disorder?
6 variants: 4 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 2 are of uncertain significance or have conflicting reports.
Which uncertain variants in Mitochondrial DNA maintenance disorder look disease-causing?
None of the uncertain variants currently reaches the likely-pathogenic range on computable evidence alone.
About this data
Variant–disease links come from ClinVar, Open Targets and UniProt, pooled from the latest public CATVariant analysis of each human protein. Evidence scores use the ACMG/AMP Bayesian points scale with computable criteria only (position among known disease variants, rarity in gnomAD, calibrated predictors, deep mutational scanning); there is no family or patient data, so they prioritise variants for expert review and never classify them.
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