MDH1 (Malate Dehydrogenase 1)
A key enzyme in the malate-aspartate shuttle and tricarboxylic acid cycle, implicated in metabolic disorders and cancer.
Gene Information Card
| Symbol | MDH1 |
|---|---|
| Full Name | Malate Dehydrogenase 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 2p23.3 |
| NCBI Gene ID | 4190 ncbi.nlm.nih.gov/gene/4190 |
| Ensembl ID | ENSG00000114646 |
| UniProt ID | P40925 |
| OMIM ID | 154200 |
| HGNC ID | 6919 |
| Aliases | MDH, MDH-s, MOR2, MGC:1375 |
Description
MDH1 encodes cytosolic malate dehydrogenase, an NAD-dependent enzyme that catalyzes the reversible conversion of oxaloacetate to malate. It plays a critical role in the malate-aspartate shuttle, facilitating NADH transfer from the cytosol to mitochondria, and contributes to the tricarboxylic acid (TCA) cycle. MDH1 is involved in cellular metabolism, redox balance, and is implicated in various cancers and metabolic disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (multiple types) | Altered MDH1 expression and activity affect NAD+/NADH ratio and metabolic reprogramming, promoting tumor growth. | COSMIC; NCBI PubMed |
| Metabolic syndrome | Dysregulation of MDH1 may disrupt the malate-aspartate shuttle, impacting insulin secretion and lipid metabolism. | OMIM; NCBI PubMed |
| Neurodegenerative disorders | Impaired MDH1 function can lead to oxidative stress and mitochondrial dysfunction, contributing to neuronal damage. | NCBI PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.5 | Medium |
| Heart | 18.3 | High |
| Skeletal Muscle | 15.7 | High |
| Kidney | 10.2 | Medium |
| Brain | 8.9 | Medium |
| Lung | 6.4 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 14.2 | High expression |
| HeLa | 11.8 | Medium expression |
| HepG2 | 13.5 | High expression |
| A549 | 9.1 | Medium expression |
| MCF7 | 7.6 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.419A>G (p.Asn140Ser) | Missense | <0.01% | Reported in cancer; potential impact on enzyme activity |
| c.728C>T (p.Thr243Met) | Missense | <0.01% | Found in metabolic disorder cases; reduced catalytic efficiency |
| c.1A>G (p.Met1?) | Start loss | <0.01% | Likely loss of function; associated with developmental delay |
Mutation functional classification
Loss of Function (LOF)
Mutations leading to reduced or absent MDH1 activity, such as start-loss or severe missense variants, impair the malate-aspartate shuttle and cellular redox balance.
Gain of Function (GOF)
No well-characterized gain-of-function mutations reported in MDH1.
Dominant Negative (DN)
No evidence of dominant-negative effects for MDH1 mutations.
View complete mutation data：
Gene Ontology (GO)
| • malate metabolic process (GO:0006108) | • tricarboxylic acid cycle (GO:0006099) |
| • oxidoreductase activity (GO:0016616) | • cytoplasm (GO:0005737) |
| • cytosol (GO:0005829) |
Pathways
• Malate-aspartate shuttle (Reactome: R-HSA-70263)
• Tricarboxylic acid cycle (KEGG: hsa00020)
• Metabolic reprogramming in cancer (KEGG: hsa05230)
Protein Summary
MDH1 is a 334-amino acid cytosolic enzyme that forms homodimers. It catalyzes the NADH-dependent reduction of oxaloacetate to malate, a key step in the malate-aspartate shuttle and TCA cycle. The protein is highly conserved and expressed in metabolically active tissues. Structural studies reveal a Rossmann fold for NAD binding. MDH1 activity is regulated by substrate availability and post-translational modifications, and its dysregulation is linked to cancer metabolism and metabolic diseases.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| MDH1 Knockout HEK293 Cell Line | EDJ-KQ4417 | Human | 4190 | Details Get a Quote |
| MDH1B Knockout HEK293 Cell Line | EDJ-KQ9250 | Human | 130752 | Details Get a Quote |
| MDH1 Knockout A-549 Cell Line | EDJ-KQ28178 | Human | 4190 | Details Get a Quote |
| MDH1 Knockout HCT 116 Cell Line | EDJ-KQ28180 | Human | 4190 | Details Get a Quote |
| MDH1 Knockout HeLa Cell Line | EDJ-KQ28181 | Human | 4190 | Details Get a Quote |
| MDH1B Knockout HeLa Cell Line | EDJ-KQ34601 | Human | 130752 | Details Get a Quote |
| MDH1B Knockout A-549 Cell Line | EDJ-KQ35846 | Human | 130752 | Details Get a Quote |
| MDH1B Knockout HCT 116 Cell Line | EDJ-KQ35847 | Human | 130752 | Details Get a Quote |
Displaying Records 1 To 8 Of 8 Records
