MAOA (Monoamine Oxidase A Mitochondrial Flavoenzyme Gene)
MAOA (monoamine oxidase A; HGNC:6833, NCBI Gene ID 4128) is a human locus mapped to chromosome band Xp11.3 that encodes mitochondrial outer-membrane monoamine oxidase A (527 aa; EC 1.4.3.4). MAOA acts in oxidative deamination of serotonin, norepinephrine & dopamine, together with COMT (Catechol-O-Methyltransferase Gene), SLC6A4 (Serotonin Transporter SERT Gene), and Serotonin. Encodes the X-linked mitochondrial enzyme monoamine oxidase A catabolizing serotonin and norepinephrine.
Approved Symbol
MAOA
Chromosomal Locus
Xp11.3
Encoded Product
Mitochondrial outer-membrane monoamine oxidase A (527 aa; EC 1.4.3.4)
Primary Pathway
Oxidative deamination of serotonin, norepinephrine & dopamine
Genomic Organization & Cytogenetic Locus: 15-exon X-linked gene at Xp11.3 positioned in tail-to-tail orientation with its paralog MAOB, featuring a polymorphic 30-bp variable number tandem repeat (uVNTR, 2 to 5 copies) 1.2 kb upstream of the transcription start site that modulates basal transcriptional efficiency.
Cellular & Tissue Expression Profile: Anchored to the outer mitochondrial membrane via a C-terminal transmembrane helix in central noradrenergic (locus coeruleus) and serotonergic (dorsal raphe) neurons, cardiomyocytes, placental syncytiotrophoblasts, intestinal enterocytes, and hepatocytes.
Molecular Function & Pathways
Biochemical & Physiological Mechanism: Uses a covalently bound flavin adenine dinucleotide (FAD) cofactor (linked to Cys406) to catalyze the O2-dependent oxidative deamination of primary and secondary biogenic monoamines—preferentially serotonin (5-HT), norepinephrine, epinephrine, and tyramine—producing an aldehyde intermediate, ammonia, and hydrogen peroxide.
Clinical & Therapeutic Significance
Human Genetic Variants & Disease Phenotypes: Hemizygous truncating loss-of-function mutations in males cause Brunner syndrome, a rare X-linked disorder characterized by markedly elevated urinary serotonin and normetanephrine, mild intellectual disability, episodic impulsive aggression, and autistic-like features.
Therapeutic & Clinical Pharmacology: Pharmacologically targeted by irreversible non-selective monoamine oxidase inhibitors (phenelzine, tranylcypromine, isocarboxazid) and reversible inhibitors of MAO-A (RIMAs such as moclobemide) for treatment-resistant major depressive disorder and panic disorder.