HAAO (3-Hydroxyanthranilate 3,4-Dioxygenase)
Key Enzyme in Tryptophan-Niacin Metabolism and Neuroprotection
Gene Information Card
| Symbol | HAAO |
|---|---|
| Full Name | 3-Hydroxyanthranilate 3,4-Dioxygenase |
| Gene Type | Protein coding |
| Chromosomal Location | 2p21 |
| NCBI Gene ID | 23498 ncbi.nlm.nih.gov/gene/23498 |
| Ensembl ID | ENSG00000115956 |
| UniProt ID | P46952 |
| OMIM ID | 604521 |
| HGNC ID | 4796 |
| Aliases | 3-HAO, HAO, HAD |
Description
The HAAO gene encodes 3-hydroxyanthranilate 3,4-dioxygenase, a cytosolic enzyme that catalyzes the oxidative ring cleavage of 3-hydroxyanthranilate to 2-amino-3-carboxymuconate semialdehyde in the kynurenine pathway of tryptophan degradation. This reaction is a critical step in the de novo synthesis of NAD+ from tryptophan. HAAO is expressed in liver, kidney, and brain, and its activity influences levels of neuroactive metabolites such as quinolinic acid and picolinic acid.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Neurodegenerative disorders (e.g., Huntington disease, Alzheimer disease) | Dysregulation of kynurenine pathway metabolites leads to excitotoxicity and oxidative stress | PMID: 25634563 |
| Cancer (e.g., glioblastoma, colorectal cancer) | Altered tryptophan metabolism supports immune evasion and tumor growth | PMID: 31073079 |
| NAD+ deficiency disorders | Loss-of-function mutations impair NAD+ biosynthesis, potentially contributing to pellagra-like symptoms | PMID: 28498856 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.5 | High |
| Kidney | 8.3 | Medium |
| Brain (cerebellum) | 4.1 | Low |
| Lung | 2.0 | Low |
| Heart | 1.5 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 15.2 | Hepatocellular carcinoma cell line |
| HEK293 | 6.8 | Embryonic kidney cells |
| SH-SY5Y | 3.5 | Neuroblastoma cell line |
| A549 | 2.1 | Lung carcinoma cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.457C>T (p.Arg153*) | Nonsense | Rare | Loss of function; truncation of enzyme |
| c.632G>A (p.Arg211Gln) | Missense | <0.01% | Reduced catalytic activity |
| c.1A>G (p.Met1?) | Start loss | Very rare | Complete loss of translation |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations that truncate the protein or abolish enzyme activity, leading to impaired NAD+ synthesis and accumulation of upstream metabolites.
Gain of Function (GOF)
Not reported for HAAO.
Dominant Negative (DN)
Not reported for HAAO.
View complete mutation data：
Gene Ontology (GO)
| • 4-dioxygenase activity (GO:0000334) | • iron ion binding (GO:0005506) |
| • tryptophan catabolic process (GO:0006569) | • NAD+ biosynthetic process (GO:0009435) |
| • cytosol (GO:0005829) |
Pathways
• Kynurenine pathway (Reactome: R-HSA-71240)
• Tryptophan catabolism (KEGG: hsa00380)
• NAD+ metabolism (KEGG: hsa00760)
Protein Summary
3-Hydroxyanthranilate 3,4-dioxygenase (HAAO) is a 286-amino acid cytosolic enzyme that requires Fe2+ for activity. It catalyzes the conversion of 3-hydroxyanthranilate to 2-amino-3-carboxymuconate semialdehyde, a key branch point in the kynurenine pathway. The product can spontaneously cyclize to quinolinic acid, a precursor for NAD+ synthesis, or be further metabolized to picolinic acid. HAAO is highly expressed in liver and kidney, with lower levels in brain. Its activity regulates the balance between neuroprotective and neurotoxic metabolites, and dysregulation is implicated in neurodegenerative diseases and cancer.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| HAAO Knockout HEK293 Cell Line | EDJ-KQ8031 | Human | 23498 | Details Get a Quote |
| HAAO Knockout HeLa Cell Line | EDJ-KQ55751 | Human | 23498 | Details Get a Quote |
| HAAO Knockout A-549 Cell Line | EDJ-KQ64249 | Human | 23498 | Details Get a Quote |
| HAAO Knockout HCT 116 Cell Line | EDJ-KQ72695 | Human | 23498 | Details Get a Quote |
Displaying Records 1 To 4 Of 4 Records
