DDO (D-Aspartate Oxidase) Gene
DDO: A key enzyme in D-aspartate metabolism and potential biomarker in human diseases
Gene Information Card
| Symbol | DDO |
|---|---|
| Full Name | D-aspartate oxidase |
| Gene Type | protein-coding |
| Chromosomal Location | 6q21 |
| NCBI Gene ID | 8528 ncbi.nlm.nih.gov/gene/8528 |
| Ensembl ID | ENSG00000112297 |
| UniProt ID | Q99489 |
| OMIM ID | 124450 |
| HGNC ID | 2728 |
| Aliases | DASOX, DDO-1, DDO-2 |
Description
The DDO gene encodes D-aspartate oxidase (EC 1.4.3.1), a flavin adenine dinucleotide (FAD)-dependent enzyme that catalyzes the oxidative deamination of D-aspartate and N-methyl-D-aspartate (NMDA) to produce oxaloacetate, ammonia, and hydrogen peroxide. This enzyme is primarily expressed in the kidney, brain, and liver, and plays a critical role in regulating D-aspartate levels, which modulate NMDA receptor signaling. Altered DDO expression and activity have been implicated in neurological disorders (e.g., schizophrenia, Alzheimer disease) and various cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Schizophrenia | Reduced DDO activity leads to elevated D-aspartate levels, which may dysregulate NMDA receptor function and contribute to glutamatergic hypofunction. | PMID: 22968150; NCBI GeneRIF |
| Alzheimer disease | Increased DDO expression in brain regions correlates with amyloid-beta pathology and oxidative stress. | PMID: 25634563; NCBI GeneRIF |
| Renal cell carcinoma | DDO is downregulated in clear cell renal cell carcinoma; loss of DDO may promote tumor growth via altered D-aspartate metabolism. | PMID: 29348629; COSMIC |
| Colorectal cancer | DDO expression is reduced in colorectal tumors compared to normal tissue; associated with poor prognosis. | PMID: 31065109; COSMIC |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Kidney | 28.5 | High |
| Liver | 12.3 | Medium |
| Brain (cerebellum) | 8.7 | Medium |
| Brain (cortex) | 6.2 | Medium |
| Testis | 4.1 | Low |
| Heart | 1.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 15.2 | High expression |
| HepG2 | 10.5 | Medium expression |
| SH-SY5Y | 7.8 | Medium expression |
| A549 | 3.4 | Low expression |
| MCF7 | 2.1 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.101C>T (p.Thr34Met) | Missense | <0.01% | Reduced enzyme activity; associated with altered D-aspartate levels |
| c.457G>A (p.Gly153Ser) | Missense | <0.01% | Unknown functional effect; reported in ClinVar |
| c.832C>T (p.Arg278Trp) | Missense | <0.01% | Potential loss of function; observed in cancer samples (COSMIC) |
| c.1120_1121insA | Frameshift | <0.01% | Predicted loss of function; rare in population databases |
Mutation functional classification
Loss of Function (LOF)
Missense variants (e.g., p.Thr34Met) and frameshift mutations that reduce or abolish DDO enzymatic activity, leading to elevated D-aspartate.
Gain of Function (GOF)
No gain-of-function mutations have been reported for DDO.
Dominant Negative (DN)
No dominant-negative mutations have been characterized for DDO.
View complete mutation data：
Gene Ontology (GO)
| • D-aspartate oxidase activity (GO:0003884) | • oxidoreductase activity (GO:0016491) |
| • oxidation-reduction process (GO:0055114) | • cytoplasm (GO:0005737) |
| • cytosol (GO:0005829) | • mitochondrion (GO:0005739) |
| • cellular amino acid catabolic process (GO:0009063) | • D-aspartate catabolic process (GO:0042403) |
Pathways
• D-aspartate degradation
• Amino acid metabolism
• Reactive oxygen species production
Protein Summary
D-aspartate oxidase (DDO) is a 37.5 kDa FAD-dependent enzyme that catalyzes the oxidative deamination of D-aspartate and N-methyl-D-aspartate (NMDA). The protein is localized to the cytoplasm and mitochondria, with highest expression in kidney and liver. DDO regulates D-aspartate levels, which act as an endogenous agonist of NMDA receptors. Structural studies show a conserved FAD-binding domain and a substrate-binding pocket specific for dicarboxylic D-amino acids. Post-translational modifications include phosphorylation at Ser-308, which may modulate activity. DDO deficiency leads to D-aspartate accumulation and has been linked to neurological and oncological conditions.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| DDO Knockout HEK293 Cell Line | EDJ-KQ5576 | Human | 8528 | Details Get a Quote |
| DDO Knockout HeLa Cell Line | EDJ-KQ54930 | Human | 8528 | Details Get a Quote |
| DDO Knockout A-549 Cell Line | EDJ-KQ63416 | Human | 8528 | Details Get a Quote |
| DDO Knockout HCT 116 Cell Line | EDJ-KQ71880 | Human | 8528 | Details Get a Quote |
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