MDH2

Chr 7AR

malate dehydrogenase 2

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

Malate dehydrogenase catalyzes the reversible oxidation of malate to oxaloacetate, utilizing the NAD/NADH cofactor system in the citric acid cycle. The protein encoded by this gene is localized to the mitochondria and may play pivotal roles in the malate-aspartate shuttle that operates in the metabolic coordination between cytosol and mitochondria. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2013]

OMIMResearchGenerating clinical summary…
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.

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 OE?0.41 (0.220.81)
00.351.4
Missense OE?1.00 (0.891.12)
00.61.4
Synonymous OE?1.07
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

This gene — mechanism propensity

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.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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