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…

GOFmechanismLOEUF 0.94

Clinical Summary— AOX1

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

114 VUS of 170 total submissions

Explore recent and relevant literature in Research Assistant →

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

This gene — mechanism propensity

0.5968th %ile

GOF

0.72top 25%

LOF

0.3941th %ile

The highest-scoring mechanism for this gene is gain-of-function.

GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

170 submitted variants in ClinVar

ClinVar

Classification Summary

VUS114

Likely Benign17

Benign9

114

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0	0
Likely Pathogenic	0	0	0	0	0
VUS	1	113	0	0	114
Likely Benign	0	9	1	7	17
Benign	0	3	1	5	9
Total	1	125	2	12	140

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

View in ClinVar →

33 pathogenic / likely-pathogenic (of 36) ClinVar copy-number / structural variants overlap AOX1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →