Methylmalonic acidemia: genes and variants
Methylmalonic acidemia is linked to 1 analyzed protein (MMUT). 32 DNA variants are known to cause it; 2 more are uncertain, and 1 of those already look disease-causing on computable evidence.
Last updated 2026-09-30. Research information, not medical advice.
Genes linked to Methylmalonic acidemia
MMUT: Methylmalonyl-CoA mutase, mitochondrial
It converts methylmalonyl-CoA to succinyl-CoA in mitochondria using adenosylcobalamin as a cofactor. Biallelic loss-of-function variants cause isolated methylmalonic acidemia, which can lead to metabolic acidosis, hyperammonemia, neurologic injury, and chronic kidney disease.
32 disease-causing and 2 uncertain variants in MMUT are linked to Methylmalonic acidemia.
Known disease-causing variants in Methylmalonic acidemia
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| MMUT R369C | 369 | Disease-causing (★★) | |
| MMUT R369H | 369 | Disease-causing (★★) | |
| MMUT Y100C | 100 | Disease-causing (★★) | |
| MMUT A141E | 141 | Disease-causing (★★) | |
| MMUT G145S | 145 | Disease-causing (★★) | |
| MMUT T230R | 230 | Disease-causing (★★) | |
| MMUT S262N | 262 | Disease-causing (★★) | |
| MMUT L305S | 305 | Disease-causing (★★) | |
| MMUT L328F | 328 | Disease-causing (★★) | |
| MMUT L358P | 358 | Disease-causing (★★) | |
| MMUT R616C | 616 | B12-binding | Disease-causing (★★) |
| MMUT R93H | 93 | Disease-causing (★★) | |
| MMUT G94V | 94 | Disease-causing (★★) | |
| MMUT R108H | 108 | Disease-causing (★★) | |
| MMUT A191E | 191 | Disease-causing (★★) | |
| MMUT N219Y | 219 | Disease-causing (★★) | |
| MMUT Y316C | 316 | Disease-causing (★★) | |
| MMUT G426R | 426 | Disease-causing (★★) | |
| MMUT G427D | 427 | Disease-causing (★★) | |
| MMUT G623R | 623 | B12-binding | Disease-causing (★★) |
| MMUT G630E | 630 | B12-binding | Disease-causing (★★) |
| MMUT G717V | 717 | B12-binding | Disease-causing (★★) |
| MMUT G203R | 203 | Disease-causing (★★) | |
| MMUT N388K | 388 | Disease-causing (★★) | |
| MMUT E432A | 432 | Disease-causing (★★) | |
| MMUT L674F | 674 | B12-binding | Disease-causing (★★) |
| MMUT A555T | 555 | Disease-causing (★★) | |
| MMUT R629G | 629 | B12-binding | Disease-causing (★★) |
| MMUT A137G | 137 | Disease-causing (★★) | |
| MMUT I200T | 200 | Disease-causing (★★) | |
| MMUT H678R | 678 | B12-binding | Disease-causing (★) |
| MMUT G703R | 703 | B12-binding | Disease-causing (★) |
Uncertain variants in Methylmalonic acidemia that look disease-causing
| Variant | Position | Protein part | Clinical label | Evidence |
|---|---|---|---|---|
| MMUT R616H | 616 | B12-binding | Conflicting reports (★) | +7: in a 3D region that tolerates change poorly (4R); R616C at the same position is pathogenic; seen in 6.8e-06 of gnomAD DNA copies; REVEL 0.957 |
Same protein, different disease
- Methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency is also caused by MMUT variants; they fall partly in the same places as the Methylmalonic acidemia variants (55 disease-causing).
- Methylmalonic aciduria due to complete methylmalonyl-CoA mutase deficiency is also caused by MMUT variants; they fall partly in the same places as the Methylmalonic acidemia variants (53 disease-causing).
Diseases related to Methylmalonic acidemia
- Methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency, also linked to MMUT
- Methylmalonic aciduria due to complete methylmalonyl-CoA mutase deficiency, also linked to MMUT
- Acute infantile liver failure due to synthesis defect of mtDNA-encoded proteins, also linked to MMUT
- Likely inborn error of metabolism, also linked to MMUT
Frequently asked questions
Which genes are linked to Methylmalonic acidemia?
In CATVariant, Methylmalonic acidemia is linked to 1 analyzed protein: MMUT (Methylmalonyl-CoA mutase, mitochondrial).
How many genetic variants are linked to Methylmalonic acidemia?
47 variants: 32 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 Methylmalonic acidemia look disease-causing?
1 uncertain variants reach the likely-pathogenic range of the ACMG/AMP points scale on computable evidence, for example MMUT R616H. These are leads for expert review, not diagnoses.
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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