ALDH9A1: Aldehyde Dehydrogenase 9 Family Member A1
A key enzyme in aldehyde metabolism, linked to neurotransmitter synthesis and metabolic disorders.
Gene Information Card
| Symbol | ALDH9A1 |
|---|---|
| Full Name | Aldehyde Dehydrogenase 9 Family Member A1 |
| Gene Type | Protein coding |
| Chromosomal Location | 1q23.1 |
| NCBI Gene ID | 223 ncbi.nlm.nih.gov/gene/223 |
| Ensembl ID | ENSG00000143149 |
| UniProt ID | P49189 |
| OMIM ID | 602733 |
| HGNC ID | 402 |
| Aliases | ALDH4, ALDH9, ALDH-E3, E3, GABALD, TMABADH |
Description
ALDH9A1 encodes a member of the aldehyde dehydrogenase superfamily, specifically the E3 isozyme. This mitochondrial enzyme catalyzes the oxidation of gamma-aminobutyraldehyde to gamma-aminobutyric acid (GABA), a major inhibitory neurotransmitter, and also metabolizes other aldehydes including betaine aldehyde and aminoaldehydes. It plays a role in carnitine biosynthesis and detoxification of reactive aldehydes. The gene is located on chromosome 1q23.1 and is expressed in multiple tissues, with highest levels in liver and kidney.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome | Potential involvement in ornithine metabolism via aldehyde intermediates; not a primary cause but may modulate phenotype | Limited; indirect evidence from metabolic pathway analysis (OMIM #602733) |
| Alcohol sensitivity / alcohol metabolism disorders | Polymorphisms may alter acetaldehyde oxidation capacity | Association studies (NCBI Gene ID 223) |
| GABAergic dysfunction (epilepsy, anxiety) | Reduced ALDH9A1 activity may impair GABA synthesis from putrescine degradation | Hypothetical; based on biochemical function (UniProt P49189) |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 18.5 | High |
| Kidney | 12.3 | Medium |
| Brain | 8.7 | Medium |
| Heart | 6.2 | Medium |
| Lung | 4.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 15.2 | Hepatocyte model |
| HEK293 | 9.8 | Embryonic kidney |
| SH-SY5Y | 7.5 | Neuroblastoma |
| K562 | 3.4 | Leukemia |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1162G>A (p.Gly388Arg) | Missense | <0.01% | Reduced enzyme activity in vitro |
| c.1456C>T (p.Arg486Trp) | Missense | <0.01% | Unknown functional effect |
| c.789_790insA | Frameshift | Rare | Predicted loss of function |
Mutation functional classification
Loss of Function (LOF)
Frameshift and certain missense variants (e.g., p.Gly388Arg) reduce catalytic activity, impairing aldehyde detoxification and GABA synthesis.
Gain of Function (GOF)
No gain-of-function mutations reported.
Dominant Negative (DN)
No evidence for dominant-negative effects.
View complete mutation data：
Gene Ontology (GO)
| • GO:0004029 - aldehyde dehydrogenase (NAD+) activity | • GO:0004028 - 3-chloroallyl aldehyde dehydrogenase activity |
| • GO:0005739 - mitochondrion | • GO:0009448 - gamma-aminobutyric acid metabolic process |
| • GO:0055114 - oxidation-reduction process |
Pathways
• Gamma-aminobutyric acid (GABA) synthesis (Reactome: R-HSA-888593)
• Betaine metabolism (Reactome: R-HSA-156590)
• Carnitine biosynthesis (Reactome: R-HSA-71291)
• Alcohol metabolism (KEGG: hsa00010)
Protein Summary
ALDH9A1 is a 494-amino acid mitochondrial aldehyde dehydrogenase (UniProt P49189). It functions as a homotetramer, catalyzing the NAD+-dependent oxidation of various aldehydes, including gamma-aminobutyraldehyde (to GABA), betaine aldehyde (to betaine), and aminoaldehydes. The enzyme is critical for neurotransmitter metabolism, osmoregulation, and detoxification. Its structure includes a Rossmann fold for NAD+ binding and a catalytic cysteine residue (Cys302).
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ALDH9A1 Knockout HEK293 Cell Line | EDJ-KQ4037 | Human | 223 | Details Get a Quote |
| ALDH9A1 Knockout HCT 116 Cell Line | EDJ-KQ25048 | Human | 223 | Details Get a Quote |
| ALDH9A1 Knockout A-549 Cell Line | EDJ-KQ26385 | Human | 223 | Details Get a Quote |
| ALDH9A1 Knockout HeLa Cell Line | EDJ-KQ26386 | Human | 223 | Details Get a Quote |
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