MDH1

Chr 2

malate dehydrogenase 1

Also known as: DEE88, EIEE88, HEL-S-32, KAR, MDH-s, MDHA, MGC:1375, MOR2

This gene encodes an enzyme that catalyzes the NAD/NADH-dependent, reversible oxidation of malate to oxaloacetate in many metabolic pathways, including the citric acid cycle. Two main isozymes are known to exist in eukaryotic cells: one is found in the mitochondrial matrix and the other in the cytoplasm. This gene encodes the cytosolic isozyme, which plays a key role in the malate-aspartate shuttle that allows malate to pass through the mitochondrial membrane to be transformed into oxaloacetate for further cellular processes. Alternatively spliced transcript variants have been found for this gene. A recent study showed that a C-terminally extended isoform is produced by use of an alternative in-frame translation termination codon via a stop codon readthrough mechanism, and that this isoform is localized in the peroxisomes. Pseudogenes have been identified on chromosomes X and 6. [provided by RefSeq, Feb 2016]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtDevelopmental and epileptic encephalopathy 88

Clinical highlights

Interpreting a novel variant
This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.
0
Active trials
57
Pubs (1 yr)
P/LP submissions
P/LP missense
0.37
LOEUF
Mechanism
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint?
0.37LOEUF
pLI 0.928
Z-score 3.40
OE 0.12 (0.050.37)
Highly constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?
1.18Z-score
OE missense 0.76 (0.660.87)
141 obs / 186.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.12 (0.050.37)
00.351.4
Missense OE?0.76 (0.660.87)
00.61.4
Synonymous OE?0.91
01.21.6
LoF obs/exp: 2 / 17.2Missense obs/exp: 141 / 186.3Syn Z: 0.60

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

MDH1 · 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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