MAOA

Chr XXLR

monoamine oxidase A

Also known as: BRNRS, MAO-A

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.

Summary from RefSeq, OMIM, UniProt
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Primary Disease Associations & Inheritance

Brunner syndromeMIM #300615
XLR
2
Active trials
113
Pubs (1 yr)
1
P/LP submissions
P/LP missense
0.14
LOEUF· LoF intol.
LOF
Mechanism· G2P
Clinical SummaryMAOA
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Gene-Disease Validity (ClinGen)
Brunner syndrome · XLDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
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ClinVar Variants
1 unique Pathogenic / Likely Pathogenic· 12 VUS of 100 total submissions
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Clinical Trials
2 active or recruiting trials — potential therapeutic options may be available
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GeneReview available — MAOA
Authoritative clinical overview · Recommended first read
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.14LOEUF
pLI 0.999
Z-score 4.24
OE 0.00 (0.000.14)
Highly constrained

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

Missense Constraint
2.38Z-score
OE missense 0.55 (0.470.64)
119 obs / 217.9 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.00 (0.000.14)
00.351.4
Missense OE0.55 (0.470.64)
00.61.4
Synonymous OE0.83
01.21.6
LoF obs/exp: 0 / 20.9Missense obs/exp: 119 / 217.9Syn Z: 1.22

ClinVar Variant Classifications

100 submitted variants in ClinVar

Classification Summary

Pathogenic1
VUS12
Likely Benign3
1
Pathogenic
12
VUS
3
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
1
0
1
Likely Pathogenic
0
0
0
0
0
VUS
0
9
3
0
12
Likely Benign
0
1
2
0
3
Benign
0
0
0
0
0
Total0106016

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

MAOA · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold
Clinical Literature
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