AOX1

Chr 2

aldehyde oxidase 1

Also known as: AO, AOH1

NCBI Gene: 316 ENSG00000138356 UniProt: Q06278 OMIM: 602841

Aldehyde oxidase is a metabolic enzyme that oxidizes aromatic compounds and aldehydes, playing a key role in xenobiotic and drug metabolism while also participating in reactive oxygen species homeostasis. Mutations cause autosomal recessive cutis laxa with severe pulmonary, gastrointestinal, and genitourinary anomalies, typically presenting in the neonatal period. This gene shows very low constraint against loss-of-function variants.

OMIM ResearchSummary from RefSeq, UniProt

Aldehyde oxidase produces hydrogen peroxide and, under certain conditions, can catalyze the formation of superoxide. Aldehyde oxidase is a candidate gene for amyotrophic lateral sclerosis. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.94

LOEUF

GOF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.94LOEUF

pLI 0.000

Z-score 2.02

OE 0.75 (0.61–0.94)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.18Z-score

OE missense 0.98 (0.92–1.04)

731 obs / 744.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.75 (0.61–0.94)

0≤0.351.4

Missense OE?0.98 (0.92–1.04)

0≤0.61.4

Synonymous OE?1.01

0≤1.21.6

LoF obs/exp: 59 / 78.3Missense obs/exp: 731 / 744.8Syn Z: -0.12

Background carrier burden — how many people carry a rare variant somewhere in AOX1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 35

1,799 rare PASS variants

Rare truncating (LoF)

1 in 420

304 rare PASS variants

Rare synonymous (reference)

1 in 73

620 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for AOX1. 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)	~556k	1 in 53	1 in 590
South Asian	~43k	1 in 28	1 in 180
Remaining (unassigned)	~30k	1 in 37	1 in 260
European (Finnish)	~27k	1 in 180	1 in 890
Admixed American	~22k	1 in 29	1 in 260
African / African American	~21k	1 in 29	1 in 210
East Asian	~20k	1 in 29	1 in 180
Ashkenazi Jewish	~13k	1 in 99	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 30	1 in 260

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): 32 of 35 coding exons well covered in gnomAD exomes; exons 8, 10, 27 marginal. Genomes: all 35.? see exons ↓