Glutaric acidemia IIc: genes and variants
Glutaric acidemia IIc is linked to 1 analyzed protein (ETFDH). 51 DNA variants are known to cause it; 17 more are uncertain, and 2 of those already look disease-causing on computable evidence.
Last updated 2026-09-30. Research information, not medical advice.
Also known as: Glutaric acidemia type 2C
Genes linked to Glutaric acidemia IIc
ETFDH: Electron transfer flavoprotein-ubiquinone oxidoreductase, mitochondrial
It transfers electrons from electron-transfer flavoprotein to ubiquinone in the inner mitochondrial membrane, linking several dehydrogenases to the respiratory chain. Biallelic deficiency causes multiple acyl-CoA dehydrogenase deficiency, often with a riboflavin-responsive late-onset myopathic form.
51 disease-causing and 16 uncertain variants in ETFDH are linked to Glutaric acidemia IIc.
Weakly linked (only a few uncertain records): ETFB.
Where Glutaric acidemia IIc variants cluster
- ETFDH Intramembrane (positions 460–484): 4 of 51 disease-causing changes, 1.9× more than its size predicts.
Known disease-causing variants in Glutaric acidemia IIc
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| ETFDH L127H | 127 | Disease-causing (★★) | |
| ETFDH L127P | 127 | Disease-causing (★★) | |
| ETFDH R175L | 175 | Disease-causing (★★) | |
| ETFDH R175H | 175 | Disease-causing (★★) | |
| ETFDH G611R | 611 | Disease-causing (★★) | |
| ETFDH R175C | 175 | Disease-causing (★★) | |
| ETFDH G611E | 611 | Disease-causing (★★) | |
| ETFDH S82P | 82 | Disease-causing (★★) | |
| ETFDH R358K | 358 | Disease-causing (★★) | |
| ETFDH Y361C | 361 | Disease-causing (★★) | |
| ETFDH M404T | 404 | Disease-causing (★★) | |
| ETFDH G467R | 467 | Intramembrane | Disease-causing (★★) |
| ETFDH H529R | 529 | Disease-causing (★★) | |
| ETFDH D130V | 130 | Disease-causing (★★) | |
| ETFDH L138R | 138 | Disease-causing (★★) | |
| ETFDH L334P | 334 | Disease-causing (★★) | |
| ETFDH P456S | 456 | Disease-causing (★★) | |
| ETFDH P456L | 456 | Disease-causing (★★) | |
| ETFDH G472R | 472 | Intramembrane | Disease-causing (★★) |
| ETFDH P483L | 483 | Intramembrane | Disease-causing (★★) |
| ETFDH W484R | 484 | Intramembrane | Disease-causing (★★) |
| ETFDH G610R | 610 | Disease-causing (★★) | |
| ETFDH M1I | 1 | Disease-causing (★★) | |
| ETFDH M1T | 1 | Disease-causing (★★) | |
| ETFDH V174A | 174 | Disease-causing (★★) | |
| ETFDH L176F | 176 | Disease-causing (★★) | |
| ETFDH P227T | 227 | Disease-causing (★★) | |
| ETFDH Y333C | 333 | Disease-causing (★★) | |
| ETFDH G356E | 356 | Disease-causing (★★) | |
| ETFDH L377P | 377 | Disease-causing (★★) | |
| ETFDH L409F | 409 | Disease-causing (★★) | |
| ETFDH T485S | 485 | Disease-causing (★★) | |
| ETFDH S35P | 35 | Disease-causing (★★) | |
| ETFDH R99C | 99 | Disease-causing (★★) | |
| ETFDH R155G | 155 | Intramembrane | Disease-causing (★★) |
| ETFDH A215T | 215 | Disease-causing (★★) | |
| ETFDH Y257C | 257 | Disease-causing (★★) | |
| ETFDH G272R | 272 | Disease-causing (★★) | |
| ETFDH G362R | 362 | Disease-causing (★★) | |
| ETFDH V451L | 451 | Disease-causing (★★) | |
| ETFDH Y553H | 553 | Disease-causing (★★) | |
| ETFDH E557K | 557 | Disease-causing (★★) | |
| ETFDH E567K | 567 | Disease-causing (★★) | |
| ETFDH E185K | 185 | Disease-causing (★★) | |
| ETFDH Q222P | 222 | Disease-causing (★★) | |
| ETFDH E246K | 246 | Disease-causing (★★) | |
| ETFDH V291G | 291 | Disease-causing (★★) | |
| ETFDH S307C | 307 | Disease-causing (★★) | |
| ETFDH P27S | 27 | Disease-causing (★★) | |
| ETFDH E193K | 193 | Disease-causing (★) | |
| ETFDH A84T | 84 | Disease-causing |
Uncertain variants in Glutaric acidemia IIc that look disease-causing
| Variant | Position | Protein part | Clinical label | Evidence |
|---|---|---|---|---|
| ETFDH P227S | 227 | Conflicting reports (★) | +7: in a 3D region that tolerates change poorly (1R); P227T at the same position is pathogenic; seen in 6.6e-06 of gnomAD DNA copies; REVEL 0.782 | |
| ETFDH G610A | 610 | Uncertain | +6: 3 other pathogenic changes within 3 positions; G610R at the same position is pathogenic; seen in 6.8e-07 of gnomAD DNA copies; REVEL 0.704 |
Which prediction tools work for Glutaric acidemia IIc
How often each tool ranks a disease-causing variant above a harmless one (AUROC × 100).
- SIFT: 98 out of 100
Same protein, different disease
- Multiple acyl-CoA dehydrogenase deficiency is also caused by ETFDH variants; they fall partly in the same places as the Glutaric acidemia IIc variants (90 disease-causing).
Diseases related to Glutaric acidemia IIc
- Multiple acyl-CoA dehydrogenase deficiency, also linked to ETFDH
Frequently asked questions
Which genes are linked to Glutaric acidemia IIc?
In CATVariant, Glutaric acidemia IIc is linked to 1 analyzed protein: ETFDH (Electron transfer flavoprotein-ubiquinone oxidoreductase, mitochondrial).
How many genetic variants are linked to Glutaric acidemia IIc?
71 variants: 51 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 17 are of uncertain significance or have conflicting reports.
Which uncertain variants in Glutaric acidemia IIc look disease-causing?
2 uncertain variants reach the likely-pathogenic range of the ACMG/AMP points scale on computable evidence, for example ETFDH P227S and ETFDH G610A. These are leads for expert review, not diagnoses.
Which variant effect predictor works best for Glutaric acidemia IIc?
Among tools not trained on clinical labels, SIFT separates this disease's known disease-causing variants from harmless ones best (AUROC 0.98, based on 44 disease-causing and 8 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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