MDH2

Chr 7AR

malate dehydrogenase 2

Also known as: DEE51, EIEE51, M-MDH, MDH, MGC:3559, MOR1

Malate dehydrogenase 2 catalyzes the reversible oxidation of malate to oxaloacetate using NAD/NADH in the mitochondrial citric acid cycle and participates in the malate-aspartate shuttle for metabolic coordination between cytosol and mitochondria. Autosomal recessive mutations cause developmental and epileptic encephalopathy 51. The pathogenic mechanism appears to involve a dominant-negative effect despite the recessive inheritance pattern.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
LOFmechanismARLOEUF 0.811 OMIM phenotype
Clinical SummaryMDH2
Population Constraint (gnomAD)
Low constraint (pLI 0.01) — loss-of-function variants are relatively tolerated in the population.
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GeneReview available — MDH2
Authoritative clinical overview · Recommended first read
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.81LOEUF
pLI 0.007
Z-score 2.10
OE 0.41 (0.220.81)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.03Z-score
OE missense 1.00 (0.891.12)
208 obs / 209.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.41 (0.220.81)
00.351.4
Missense OE1.00 (0.891.12)
00.61.4
Synonymous OE1.07
01.21.6
LoF obs/exp: 6 / 14.7Missense obs/exp: 208 / 209.0Syn Z: -0.52
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongMDH2-related early-onset severe encephalopathyLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.7230th %ile
GOF
0.4579th %ile
LOF
0.3843th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

MDH2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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