Mitochondrial disease: genes and variants
Mitochondrial disease is linked to 3 analyzed proteins (POLG, COQ8A and SPG7). 7 DNA variants are known to cause it; 5 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 disease
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.
6 disease-causing and 4 uncertain variants in POLG are linked to Mitochondrial disease.
COQ8A: Atypical kinase COQ8A, mitochondrial
It supports coenzyme Q biosynthesis and mitochondrial respiratory function, particularly in neurons and cerebellar tissue. Biallelic pathogenic variants cause primary coenzyme Q10 deficiency with cerebellar ataxia and variable seizures, neuropathy, or developmental impairment.
1 disease-causing and 0 uncertain variants in COQ8A are linked to Mitochondrial disease.
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.
0 disease-causing and 0 uncertain variants in SPG7 are linked to Mitochondrial disease.
Weakly linked (only a few uncertain records): OPA1 and IDH2.
Known disease-causing variants in Mitochondrial disease
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| POLG A1105T | 1105 | Disease-causing (★★★) | |
| POLG A1105P | 1105 | Disease-causing (★★★) | |
| POLG D1184N | 1184 | Disease-causing (★★★) | |
| POLG K1191N | 1191 | Disease-causing (★★★) | |
| POLG R1096C | 1096 | Disease-causing (★★★) | |
| POLG G888D | 888 | Pol A | Disease-causing (★★) |
| COQ8A A339T | 339 | Protein kinase | Disease-causing (★★) |
Same protein, different disease
- Progressive sclerosing poliodystrophy is also caused by POLG variants; they fall mostly in different places as the Mitochondrial disease variants (77 disease-causing).
- Mitochondrial DNA depletion syndrome is also caused by POLG variants; they fall mostly in different places as the Mitochondrial disease 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 disease variants (17 disease-causing).
- Sensory ataxic neuropathy, dysarthria, and ophthalmoparesis is also caused by POLG variants; they fall mostly in different places as the Mitochondrial disease variants (6 disease-causing).
- Autosomal recessive ataxia due to ubiquinone deficiency is also caused by COQ8A variants; they fall mostly in different places as the Mitochondrial disease variants (23 disease-causing).
Diseases related to Mitochondrial disease
- Hereditary spastic paraplegia, also linked to POLG and SPG7
- Possible mitochondrial disorder - nuclear genes, also linked to POLG and SPG7
- Mitochondrial DNA maintenance disorder, also linked to POLG and SPG7
- Progressive sclerosing poliodystrophy, also linked to POLG
- Mitochondrial DNA depletion syndrome, also linked to POLG
- Autosomal recessive ataxia due to ubiquinone deficiency, also linked to COQ8A
- 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
Frequently asked questions
Which genes are linked to Mitochondrial disease?
In CATVariant, Mitochondrial disease is linked to 3 analyzed proteins: POLG (DNA polymerase subunit gamma-1), COQ8A (Atypical kinase COQ8A, mitochondrial) and SPG7 (Mitochondrial inner membrane m-AAA protease component paraplegin).
How many genetic variants are linked to Mitochondrial disease?
21 variants: 7 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 5 are of uncertain significance or have conflicting reports.
Which uncertain variants in Mitochondrial disease 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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