ALDOA Gene (Aldolase, Fructose-Bisphosphate A)
Key Glycolytic Enzyme and Disease-Associated Gene
Gene Information Card
| Symbol | ALDOA |
|---|---|
| Full Name | Aldolase, Fructose-Bisphosphate A |
| Gene Type | Protein coding |
| Chromosomal Location | 16p11.2 |
| NCBI Gene ID | 226 ncbi.nlm.nih.gov/gene/226 |
| Ensembl ID | ENSG00000149925 |
| UniProt ID | P04075 |
| OMIM ID | 103850 |
| HGNC ID | 414 |
| Aliases | ALDA, GSD12, HEL-S-87p |
Description
The ALDOA gene encodes aldolase A, one of three isozymes (A, B, C) of fructose-bisphosphate aldolase. This enzyme catalyzes the reversible cleavage of fructose-1,6-bisphosphate into dihydroxyacetone phosphate (DHAP) and glyceraldehyde-3-phosphate (G3P) in glycolysis. Aldolase A is predominantly expressed in muscle, erythrocytes, and brain. Mutations in ALDOA cause glycogen storage disease type XII (GSD XII) and hereditary hemolytic anemia. The gene is also implicated in cancer metabolism and is a target for therapeutic intervention.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Glycogen Storage Disease Type XII | Deficiency of aldolase A leads to impaired glycolysis, accumulation of fructose-1,6-bisphosphate, and glycogen storage in muscle and erythrocytes. | OMIM #611881; ClinVar |
| Hereditary Hemolytic Anemia | Reduced aldolase A activity in erythrocytes causes ATP depletion and increased hemolysis. | OMIM #103850; ClinVar |
| Cancer (various) | Overexpression of ALDOA supports aerobic glycolysis (Warburg effect) in tumor cells. | COSMIC; NCBI Gene |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Skeletal muscle | 78.3 | High |
| Heart | 45.6 | High |
| Brain | 32.1 | Medium |
| Liver | 8.9 | Low |
| Erythrocytes | N/A | High (protein level) |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 62.4 | High expression |
| K562 | 55.2 | High expression |
| HepG2 | 40.1 | Medium expression |
| A549 | 35.8 | Medium expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.113G>A (p.Arg38His) | Missense | Rare | Reduced enzyme activity; associated with GSD XII |
| c.617G>A (p.Arg206Gln) | Missense | Rare | Impaired catalytic function; hemolytic anemia |
| c.1039C>T (p.Arg347Cys) | Missense | Rare | Loss of activity; GSD XII |
Mutation functional classification
Loss of Function (LOF)
Missense mutations (e.g., p.Arg38His, p.Arg206Gln, p.Arg347Cys) reduce or abolish aldolase A enzymatic activity, leading to metabolic disorders.
Gain of Function (GOF)
Not reported in germline; somatic overexpression in cancers may confer a metabolic advantage.
Dominant Negative (DN)
Not documented for ALDOA; disease inheritance is autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
| • GO:0004332 (fructose-bisphosphate aldolase activity) | • GO:0006096 (glycolytic process) |
| • GO:0016853 (isomerase activity) | • GO:0005829 (cytosol) |
| • GO:0005737 (cytoplasm) | • GO:0005515 (protein binding) |
Pathways
• Glycolysis / Gluconeogenesis (KEGG: hsa00010)
• Carbon metabolism (KEGG: hsa01200)
• Fructose and mannose metabolism (KEGG: hsa00051)
• Metabolic pathways (KEGG: hsa01100)
Protein Summary
Aldolase A (UniProt P04075) is a homotetrameric enzyme of 364 amino acids (molecular weight ~39.4 kDa). It catalyzes the fourth step of glycolysis. The protein is highly expressed in muscle, erythrocytes, and brain. Structural analysis reveals a TIM barrel fold. Post-translational modifications include acetylation and phosphorylation. Deficiency leads to metabolic myopathy and hemolytic anemia.
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