LDHA (Lactate Dehydrogenase A) - Glycolysis, Cancer Metabolism, and Genetic Variants
A comprehensive biomedical overview of the LDHA gene, including its genomic context, protein function, expression patterns, associated diseases, and clinical significance.
Gene Information Card
| Symbol | LDHA |
|---|---|
| Full Name | Lactate Dehydrogenase A |
| Gene Type | Protein coding |
| Chromosomal Location | 11p15.1 |
| NCBI Gene ID | 3939 ncbi.nlm.nih.gov/gene/3939 |
| Ensembl ID | ENSG00000134333 |
| UniProt ID | P00338 |
| OMIM ID | 150000 |
| HGNC ID | 6535 |
| Aliases | LDH-A, LDHM, GSD11, PIG19 |
Description
The LDHA gene encodes the A subunit of lactate dehydrogenase (LDH), a tetrameric enzyme that catalyzes the reversible conversion of pyruvate to lactate, coupled with the oxidation of NADH to NAD+. This reaction is the final step of anaerobic glycolysis. LDHA is predominantly expressed in skeletal muscle and is strongly induced by hypoxia via HIF1A. It plays a central role in the 'Warburg effect' in cancer cells, promoting aerobic glycolysis. Mutations in LDHA cause Glycogen Storage Disease XI (GSD11), characterized by exercise intolerance and myoglobinuria. Elevated LDHA expression is a poor prognostic marker in many cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Glycogen Storage Disease XI (GSD11) | Loss-of-function mutations in LDHA lead to a deficiency of the LDHA subunit, impairing the conversion of pyruvate to lactate in skeletal muscle during anaerobic exercise. This results in an inability to sustain high-intensity exercise and leads to muscle damage and myoglobinuria. | OMIM #612933; ClinVar; PMID: 12838515 |
| Cancer (Multiple Types) | LDHA is overexpressed in many cancers (e.g., pancreatic, breast, lung, colorectal). It drives the Warburg effect, promoting glycolysis and lactate production, which supports tumor growth, invasion, and immune evasion. High LDHA expression correlates with poor prognosis and metastasis. | COSMIC; PMID: 27378309; PMID: 29622463 |
| Exertional Myoglobinuria | As a key symptom of GSD11, LDHA deficiency leads to exercise-induced rhabdomyolysis and myoglobinuria due to impaired muscle energy metabolism. | OMIM #612933; PMID: 12838515 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Skeletal Muscle | High | Very High |
| Heart | Moderate | Medium |
| Liver | Low | Low |
| Kidney | Moderate | Medium |
| Brain | Low | Low |
| Pancreas | Low | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa (Cervical Cancer) | High | Cancer cell line with high glycolytic activity |
| A549 (Lung Cancer) | High | Overexpressed in lung adenocarcinoma |
| MCF7 (Breast Cancer) | Moderate | Expression varies with subtype |
| HepG2 (Liver Cancer) | Low | Lower expression compared to muscle-derived lines |
| K562 (Leukemia) | Moderate | Expressed in hematopoietic lineage |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.860G>A (p.Arg287Gln) | Missense | Rare | Loss of enzymatic activity; associated with GSD11 |
| c.112G>A (p.Gly38Arg) | Missense | Rare | Loss of function; reported in GSD11 patients |
| c.733C>T (p.Arg245Cys) | Missense | Rare | Reduced enzyme activity; linked to exertional myoglobinuria |
| c.1040A>G (p.Tyr347Cys) | Missense | Rare | Impaired tetramer formation; pathogenic in GSD11 |
Mutation functional classification
Loss of Function (LOF)
Most pathogenic LDHA mutations are loss-of-function, leading to reduced or absent enzymatic activity. This causes GSD11, characterized by muscle glycogenosis and exercise intolerance.
Gain of Function (GOF)
Gain-of-function mutations are not commonly reported in germline settings. However, somatic copy number gains and transcriptional upregulation (not point mutations) are frequent in cancers, leading to increased LDHA activity.
Dominant Negative (DN)
Some missense mutations may exert a dominant-negative effect by disrupting the tetrameric assembly of the LDH enzyme, although this is less well-documented compared to recessive loss-of-function alleles.
View complete mutation data：
Gene Ontology (GO)
| • L-lactate dehydrogenase activity | • NAD binding |
| • identical protein binding | • glycolytic process |
| • response to hypoxia | • cytosol |
| • extracellular exosome |
Pathways
• Glycolysis / Gluconeogenesis
• HIF-1 signaling pathway
• Central carbon metabolism in cancer
• Pyruvate metabolism
Protein Summary
The LDHA protein (UniProt P00338) is a 332-amino acid enzyme that forms homo- or heterotetramers with LDHB to create various LDH isozymes. The LDHA homotetramer (LDH-5) has a high affinity for pyruvate and is specialized for anaerobic glycolysis. It is localized in the cytoplasm. The protein is regulated by allosteric effectors and post-translational modifications, including acetylation and phosphorylation. Its expression is strongly induced by HIF1A under hypoxic conditions, and it is a key mediator of the Warburg effect in tumors.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| LDHAL6A Knockout HEK293 Cell Line | EDJ-KQ918 | Human | 160287 | Details Get a Quote |
| LDHAL6B Knockout HEK293 Cell Line | EDJ-KQ1517 | Human | 92483 | Details Get a Quote |
| LDHA Knockout HEK293 Cell Line | EDJ-KQ1518 | Human | 3939 | Details Get a Quote |
| LDHA Knockout A-549 Cell Line | EDJ-KQ21153 | Human | 3939 | Details Get a Quote |
| LDHA Knockout HCT 116 Cell Line | EDJ-KQ21154 | Human | 3939 | Details Get a Quote |
| LDHA Knockout HeLa Cell Line | EDJ-KQ21155 | Human | 3939 | Details Get a Quote |
| LDHA Knockout Huh-7 Cell Line | EDJ-KZ326 | Human | 3939 | Details Get a Quote |
| LDHA Knockout ZR-75-1 Cell Line | EDJ-KZ327 | Human | 3939 | Details Get a Quote |
| LDHAL6B Knockout HeLa Cell Line | EDJ-KQ57841 | Human | 92483 | Details Get a Quote |
| LDHAL6A Knockout HeLa Cell Line | EDJ-KQ58810 | Human | 160287 | Details Get a Quote |
| LDHAL6B Knockout A-549 Cell Line | EDJ-KQ66337 | Human | 92483 | Details Get a Quote |
| LDHAL6A Knockout A-549 Cell Line | EDJ-KQ67294 | Human | 160287 | Details Get a Quote |
| LDHAL6B Knockout HCT 116 Cell Line | EDJ-KQ74763 | Human | 92483 | Details Get a Quote |
| LDHAL6A Knockout HCT 116 Cell Line | EDJ-KQ75693 | Human | 160287 | Details Get a Quote |
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