Mitochondrial complex I deficiency: genes and variants
Mitochondrial complex I deficiency is linked to 1 analyzed protein (ACAD9). 9 DNA variants are known to cause it; 0 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 complex I deficiency
ACAD9: Complex I assembly factor ACAD9, mitochondrial
It supports mitochondrial energy production through long-chain fatty-acid oxidation and also functions as an assembly factor for respiratory-chain complex I. Biallelic pathogenic variants can cause complex I deficiency, cardiomyopathy, exercise intolerance, and other mitochondrial disease manifestations.
9 disease-causing and 0 uncertain variants in ACAD9 are linked to Mitochondrial complex I deficiency.
Known disease-causing variants in Mitochondrial complex I deficiency
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| ACAD9 A326P | 326 | Disease-causing (★★★★) | |
| ACAD9 R414S | 414 | Disease-causing (★★) | |
| ACAD9 R417C | 417 | Disease-causing (★★) | |
| ACAD9 R266W | 266 | Disease-causing (★★) | |
| ACAD9 E413K | 413 | Disease-causing (★★) | |
| ACAD9 L98S | 98 | Disease-causing (★★) | |
| ACAD9 R532W | 532 | Disease-causing (★★) | |
| ACAD9 R518C | 518 | Disease-causing (★★) | |
| ACAD9 S602F | 602 | Disease-causing (★) |
Which prediction tools work for Mitochondrial complex I deficiency
How often each tool ranks a disease-causing variant above a harmless one (AUROC × 100).
- CADD: 96 out of 100
- REVEL: 93 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- SIFT: 93 out of 100
- CATVariant: 91 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- PolyPhen-2: 86 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- phyloP: 80 out of 100
Same protein, different disease
- Acyl-CoA dehydrogenase 9 deficiency is also caused by ACAD9 variants; they fall mostly in different places as the Mitochondrial complex I deficiency variants (24 disease-causing).
Diseases related to Mitochondrial complex I deficiency
- Hypertrophic cardiomyopathy, also linked to ACAD9
- Acyl-CoA dehydrogenase 9 deficiency, also linked to ACAD9
- Possible mitochondrial disorder - nuclear genes, also linked to ACAD9
Frequently asked questions
Which genes are linked to Mitochondrial complex I deficiency?
In CATVariant, Mitochondrial complex I deficiency is linked to 1 analyzed protein: ACAD9 (Complex I assembly factor ACAD9, mitochondrial).
How many genetic variants are linked to Mitochondrial complex I deficiency?
11 variants: 9 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 0 are of uncertain significance or have conflicting reports.
Which uncertain variants in Mitochondrial complex I deficiency look disease-causing?
None of the uncertain variants currently reaches the likely-pathogenic range on computable evidence alone.
Which variant effect predictor works best for Mitochondrial complex I deficiency?
Among tools not trained on clinical labels, CADD separates this disease's known disease-causing variants from harmless ones best (AUROC 0.96, based on 8 disease-causing and 11 harmless variants).
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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