MDH2 Gene: Malate Dehydrogenase 2
Mitochondrial malate dehydrogenase, a key enzyme in the tricarboxylic acid cycle and malate-aspartate shuttle.
Gene Information Card
| Symbol | MDH2 |
|---|---|
| Full Name | Malate Dehydrogenase 2 |
| Gene Type | Protein coding |
| Chromosomal Location | 7q11.23 |
| NCBI Gene ID | 4191 ncbi.nlm.nih.gov/gene/4191 |
| Ensembl ID | ENSG00000146701 |
| UniProt ID | P40926 |
| OMIM ID | 154100 |
| HGNC ID | 6971 |
| Aliases | M-MDH, MDH, MOR1 |
Description
MDH2 encodes the mitochondrial malate dehydrogenase, a homodimeric enzyme that catalyzes the reversible conversion of malate to oxaloacetate using NAD+/NADH as a cofactor. This enzyme is a critical component of the tricarboxylic acid (TCA) cycle and the malate-aspartate shuttle, which facilitates the transfer of reducing equivalents across the mitochondrial membrane. MDH2 is essential for cellular energy metabolism and redox balance.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hereditary pheochromocytoma-paraganglioma (PGL) | Loss-of-function mutations in MDH2 impair TCA cycle function, leading to succinate accumulation and pseudohypoxic signaling via HIF stabilization. | PMID: 25720320, ClinVar |
| MDH2 deficiency (mitochondrial malate dehydrogenase deficiency) | Biallelic pathogenic variants cause severe metabolic dysfunction, including lactic acidosis, developmental delay, and encephalopathy. | PMID: 23334846, OMIM #154100 |
| Epileptic encephalopathy, early infantile | Homozygous or compound heterozygous MDH2 mutations disrupt energy metabolism in the brain, leading to seizures and neurological impairment. | PMID: 28137957 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Heart | 82.3 | High |
| Skeletal Muscle | 65.1 | High |
| Liver | 58.7 | High |
| Kidney | 52.4 | High |
| Brain | 38.9 | Medium |
| Lung | 25.6 | Medium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 78.5 | High expression in embryonic kidney cells |
| HepG2 | 71.2 | High expression in liver cancer cells |
| K562 | 45.3 | Moderate expression in leukemia cells |
| SH-SY5Y | 38.1 | Moderate expression in neuroblastoma cells |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.419C>T (p.Ala140Val) | Missense | Rare | Loss of enzymatic activity; associated with hereditary paraganglioma |
| c.757G>A (p.Glu253Lys) | Missense | Rare | Impaired dimerization and catalytic function; linked to MDH2 deficiency |
| c.1A>G (p.Met1?) | Start loss | Rare | Complete loss of protein; severe early-onset encephalopathy |
| c.898C>T (p.Arg300*) | Nonsense | Rare | Premature truncation; loss of function in pheochromocytoma |
Mutation functional classification
Loss of Function (LOF)
Most MDH2 pathogenic variants are loss-of-function, reducing or abolishing enzymatic activity, leading to TCA cycle disruption and metabolic imbalance.
Gain of Function (GOF)
No gain-of-function mutations have been reported for MDH2.
Dominant Negative (DN)
Some missense mutations (e.g., p.Glu253Lys) may exert a dominant-negative effect by disrupting dimerization, though the primary mechanism is haploinsufficiency.
View complete mutation data：
Gene Ontology (GO)
| • mitochondrion (GO:0005739) | • malate metabolic process (GO:0006108) |
| • tricarboxylic acid cycle (GO:0006099) | • oxidoreductase activity (GO:0016616) |
| • malate dehydrogenase activity (GO:0004470) | • oxidation-reduction process (GO:0055114) |
Pathways
• Tricarboxylic acid cycle (KEGG: hsa00020)
• Malate-aspartate shuttle (Reactome: R-HSA-70263)
• Metabolic pathways (KEGG: hsa01100)
• Carbon metabolism (KEGG: hsa01200)
Protein Summary
MDH2 is a 338-amino acid mitochondrial enzyme that forms a homodimer. Each subunit contains an NAD-binding domain and a catalytic domain. The enzyme catalyzes the reversible conversion of malate to oxaloacetate, coupling this reaction to the reduction of NAD+ to NADH. MDH2 is essential for the TCA cycle and the malate-aspartate shuttle, playing a central role in cellular respiration and redox homeostasis. Mutations in MDH2 lead to metabolic disorders and tumor predisposition.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| MDH2 Knockout HEK293 Cell Line | EDJ-KQ2484 | Human | 4191 | Details Get a Quote |
| MDH2 Knockout A-549 Cell Line | EDJ-KQ23062 | Human | 4191 | Details Get a Quote |
| MDH2 Knockout HCT 116 Cell Line | EDJ-KQ23063 | Human | 4191 | Details Get a Quote |
| MDH2 Knockout HeLa Cell Line | EDJ-KQ23064 | Human | 4191 | Details Get a Quote |
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