MAOA
protein-codingmonoamine oxidase A
Gene summary
This gene is one of two neighboring gene family members that encode mitochondrial enzymes which catalyze the oxidative deamination of amines, such as dopamine, norepinephrine, and serotonin. Mutation of this gene results in Brunner syndrome. This gene has also been associated with a variety of other psychiatric disorders, including antisocial behavior. Alternatively spliced transcript variants encoding multiple isoforms have been observed. [provided by RefSeq, Jul 2012]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~91.9 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: XL
Disease ID:MONDO:0010379
Submitter: Orphanet
Inheritance Pattern: XL
Disease ID:MONDO:0010379
Submitter: G2P
Inheritance Pattern: XL
Disease ID:MONDO:0010379
Submitter: ClinGen
*MAOA* is located at Xp11.3 and encodes monoamine oxidase A, an enzyme crucial for the degradation of biogenic amines, including the neurotransmitters serotonin, dopamine, and norepinephrine. *MAOA* was first reported in relation to X-linked recessive Brunner syndrome in 1993 in a large Dutch family with 14 affected males (Brunner et al., PMID: 8211186). Brunner syndrome is characterized by borderline or mild intellectual disability, prominent behavioral abnormalities including aggressive and violent behavior, and deficiency of monoamine oxidase A enzymatic activity (Brunner et al. 1993, PMIDs: 8211186, 8503438). Seven variants (1 nonsense, 1 splice, 1 frameshift, and 4 missense) that have been reported in 7 male probands in 6 publications (PMIDs: 8211186, 24169519, 25969726, 25807999, 33728254, 37750385) are included in this curation. Variants in this gene segregated with disease in 9 additional male relatives (PMIDs: 8211186, 24169519, 25969726, 25807999). The mechanism of pathogenicity is loss of function. Biochemical analyses in blood and urine show elevated levels of MAOA substrates (serotonin, metanephrine and normetanephrine), and low levels of breakdown products (vanillylmandelic acid, homovanillic acid and 5-hydroxyindoleacetic acid), consistent with defective MAOA enzymatic activity. This gene-disease relationship is also supported by mouse models (PMIDs: 7792602, 22850464). In summary, there is definitive evidence supporting the relationship between *MAOA* and X-linked Brunner syndrome. Although Brunner syndrome is rare, this gene-disease relationship has been demonstrated in multiple reports and has been upheld over time. This gene-disease pair was originally evaluated by the ClinGen Intellectual Disability and Autism Gene Curation Expert Panel on January 15, 2020. It was reevaluated on June 29, 2026 (SOP Version 12). Although 2 new cases were added (PMIDs: 33728254, 37750385), the classification did not change.
Inheritance Pattern: XL
Disease ID:MONDO:0010379
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: XL
Disease ID:MONDO:0010379
Submitter: PanelApp Australia
Clinical Genomic Database (CGD)
Manifestation: Neurologic
Intervention: General
Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to MAOA variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_000240.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 10 | 32 | 1 | 43 | ||
| missense | 1 | 3 | 158 | 15 | 1 | 178 |
| nonsense | 2 | 2 | 7 | 11 | ||
| start loss | 3 | 3 | ||||
| frameshift | 3 | 5 | 8 | |||
| splice donor/acceptor (+/-2bp) | 1 | 3 | 30 | 34 | ||
| Total | 7 | 13 | 208 | 47 | 2 | 277 |
Highest pathogenic variant AF is 9.1262524e-7
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_000231.1 | 15 | MANE Select | |
| Ensembl | ENSP00000340684.3 | 15 | MANE Select | |
| RefSeq | NP_001257387.1 | 12 | Standard | |
| Ensembl | ENSP00000440846.1 | 12 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Tryptophan metabolism - Homo sapiens (human)
- Arginine and proline metabolism - Homo sapiens (human)
- Serotonergic synapse - Homo sapiens (human)
- Dopaminergic synapse - Homo sapiens (human)
- Phenylalanine metabolism - Homo sapiens (human)
Biological Process
- cellular biogenic amine metabolic process
- cytokine-mediated signaling pathway
- neurotransmitter metabolic process
- neurotransmitter catabolic process
- dopamine catabolic process
Molecular Function
- primary amine oxidase activity
Cellular Component
- mitochondrion
- mitochondrial outer membrane
- integral component of membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000338702
- Coding exons
- 15
- Length
- 90602
- Individuals with no LoFs
- 0
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 0
- Defined
- 0
- p
- 0.00
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.38 | 119 | 218 | 0.546 | 0.0000173 | 3442 |
| Missense (PolyPhen) | 16 | 75.015 | 0.21329 | 1141 | ||
| Synonymous | 1.22 | 66 | 79.9 | 0.826 | 0.00000652 | 997 |
| Loss of Function | 4.24 | 0 | 20.9 | 0.00 | 0.00000146 | 366 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0 | 0.0 | absent |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Catalyzes the oxidative deamination of biogenic and xenobiotic amines and has important functions in the metabolism of neuroactive and vasoactive amines in the central nervous system and peripheral tissues. MAOA preferentially oxidizes biogenic amines such as 5-hydroxytryptamine (5-HT), norepinephrine and epinephrine.;
- Disease
- DISEASE: Brunner syndrome (BRNRS) [MIM:300615]: A form of X-linked non-dysmorphic mild mental retardation. Male patients are affected by borderline mental retardation and exhibit abnormal behavior, including disturbed regulation of impulsive aggression. Obligate female carriers have normal intelligence and behavior. {ECO:0000269|PubMed:8211186}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Intolerance Scores
- RVIS EVS
- -0.14
- RVIS percentile EVS
- 43.29
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.965
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |