MAOA

Chr XXLR

monoamine oxidase A

Also known as: BRNRS, MAO-A

NCBI Gene: 4128 ENSG00000189221 UniProt: P21397 OMIM: 309850

This mitochondrial enzyme catalyzes the oxidative deamination of neurotransmitters including serotonin, dopamine, and norepinephrine. Mutations cause Brunner syndrome, an X-linked recessive disorder characterized by intellectual disability and behavioral abnormalities. The gene is highly constrained against loss-of-function variants, indicating that complete loss of enzyme activity has severe consequences.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Brunner syndromeMIM #300615

XLR

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · Brunner syndrome · XL · ClinGen 2026

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

168

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.14

LOEUF· LoF intol.

LOF

Mechanism· G2P

📖

GeneReview available — MAOA

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — X-linked: males carry a single copy

LoF Constraint?

0.14LOEUF

pLI 0.999

Z-score 4.24

OE 0.00 (0.00–0.14)

Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint?

2.38Z-score

OE missense 0.55 (0.47–0.64)

119 obs / 217.9 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.00 (0.00–0.14)

0≤0.351.4

Missense OE?0.55 (0.47–0.64)

0≤0.61.4

Synonymous OE?0.83

0≤1.21.6

LoF obs/exp: 0 / 20.9Missense obs/exp: 119 / 217.9Syn Z: 1.22

Background carrier burden — how many people carry a rare variant somewhere in MAOA?

gnomAD v4 · ~732k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 310

275 rare PASS variants

Rare truncating (LoF)

1 in 8,100

14 rare PASS variants

Rare synonymous (reference)

1 in 560

147 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for MAOA. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~561k	1 in 430	1 in 7,400
South Asian	~36k	1 in 270	none seen
Remaining (unassigned)	~31k	1 in 190	≈ 1 in 27,000
European (Finnish)	~27k	1 in 1,100	none seen
Admixed American	~23k	1 in 230	none seen
African / African American	~21k	1 in 150	≈ 1 in 9,200
East Asian	~20k	1 in 350	≈ 1 in 6,600
Ashkenazi Jewish	~13k	≈ 1 in 3,200	none seen
Middle Eastern	~2,758	1 in 310	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 14 of 15 coding exons well covered in gnomAD exomes; exon 10 marginal. Genomes: all 15.? see exons ↓