ME2
Chr 18malic enzyme 2
Also known as: ODS1
The protein is a mitochondrial NAD-dependent malic enzyme that catalyzes the oxidative decarboxylation of malate to pyruvate. Mutations in this gene cause mitochondrial respiratory chain deficiency and have been associated with increased risk for idiopathic generalized epilepsy. The gene is highly constrained against loss-of-function variants, and inheritance follows an autosomal recessive pattern.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Mild missense constraint
The highest-scoring mechanism for this gene is dominant-negative.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
142 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 0 | 40 | 0 | 40 |
Likely Pathogenic | 1 | 0 | 1 | 0 | 2 |
VUS | 0 | 70 | 5 | 0 | 75 |
Likely Benign | 0 | 3 | 0 | 2 | 5 |
Benign | 0 | 1 | 1 | 1 | 3 |
| Total | 1 | 74 | 47 | 3 | 125 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
ME2 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
External Resources
Links to major genomics databases and tools