AOC3

Chr 17

amine oxidase copper containing 3

Also known as: HPAO, SSAO, VAP-1, VAP1

NCBI Gene: 8639UniProt: Q16853

This gene encodes a member of the semicarbazide-sensitive amine oxidase family. Copper amine oxidases catalyze the oxidative conversion of amines to aldehydes in the presence of copper and quinone cofactor. The encoded protein is localized to the cell surface, has adhesive properties as well as monoamine oxidase activity, and may be involved in leukocyte trafficking. Alterations in levels of the encoded protein may be associated with many diseases, including diabetes mellitus. A pseudogene of this gene has been described and is located approximately 9-kb downstream on the same chromosome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2013]

156
ClinVar variants
6
Pathogenic / LP
0.00
pLI score
0.5
Missense Z
1.03
LOEUF
1
Active trials
Clinical Summary— AOC3
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
6 Pathogenic / Likely Pathogenic· 127 VUS of 156 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
Some data sources returned errors (1)

ensembl: TimeoutError: The operation was aborted due to timeout

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.03LOEUF
pLI 0.000
Z-score 1.42
OE 0.71 (0.50–1.03)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.47Z-score
OE missense 0.94 (0.86–1.02)
426 obs / 454.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.71 (0.50–1.03)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.94 (0.86–1.02)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.17
0≤1.21.6
LoF obs/exp: 20 / 28.1Missense obs/exp: 426 / 454.3Syn Z: -1.87

ClinVar Variant Classifications

156 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic6
VUS127
Likely Benign18
Benign5
6
Pathogenic
127
VUS
18
Likely Benign
5
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
6
0
6
Likely Pathogenic
0
0
0
0
0
VUS
0
127
0
0
127
Likely Benign
0
15
0
3
18
Benign
0
4
0
1
5
Total014664156

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

View in ClinVar →

Protein Context — Lollipop Plot

AOC3 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Vascular adhesion protein-1 (VAP-1) in vascular inflammatory diseases.
Danielli M et al.·Vasa
2022Review
Amine oxidase activity regulates the development of pulmonary fibrosis.
Marttila-Ichihara F et al.·FASEB J
2017
Zinc-α2-glycoprotein as an inhibitor of amine oxidase copper-containing 3.
Romauch M·Open Biol
2020
A randomised Phase IIa trial of amine oxidase copper-containing 3 (AOC3) inhibitor BI 1467335 in adults with non-alcoholic steatohepatitis.
Newsome PN et al.·Nat Commun
2023Clinical trial
AOC3 Loss Promotes Imatinib Resistance in GIST by Stabilizing HK2 and Enhancing H3K18la-Driven Myc Transcription.
Guo Z et al.·Mol Carcinog
2026
Crosstalk of cell death pathways unveils an autophagy-related gene AOC3 as a critical prognostic marker in colorectal cancer.
Xu H et al.·Commun Biol
2024
Evaluation of the Expression of Amine Oxidase Proteins in Breast Cancer.
Sun WY et al.·Int J Mol Sci
2017
Expression of amine oxidase-related proteins in breast phyllodes tumor.
Kim HM et al.·Histol Histopathol
2025
Comminuted AO-C3 fractures of the patella: good outcome using anatomically contoured locking plate fixation.
Buschbeck S et al.·Int Orthop
2022
Oral therapies for diabetic retinopathy: Addressing an unmet need or a distant prospect?
Empeslidis T et al.·J Int Med Res
2025Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Amine oxidase copper-containing 3 (AOC3) inhibition: a potential novel target for the management of diabetic retinopathy
Boyer DS et al.·Int J Retina Vitreous
2021
Increased atherosclerotic plaque in AOC3 knock-out in ApoE-/- mice and characterization of AOC3 in atherosclerotic human coronary arteries
Filip A et al.·Front Cardiovasc Med
2022
Screening and identification of novel protein markers of early-stage lung cancer and construction and application of screening models
Yuan H et al.·Front Oncol
2025Functional
Amine oxidase copper-containing 3 aggravates cardiac remodelling by generating hydrogen peroxide after myocardial infarction.
Zhong C et al.·J Pathol
2023Functional
Identification of AOC3 and LRRC17 as Colonic Fibroblast Activation Markers and Their Potential Roles in Colorectal Cancer Progression
Ahmad Zawawi SS et al.·Asian Pac J Cancer Prev
2023
Proteomic analysis of premature umbilical cord blood and its relationship with bronchopulmonary dysplasia
Chen J et al.·Ital J Pediatr
2025
ROBIN: a randomised, double-masked, placebo-controlled Phase IIa study of the AOC3 inhibitor BI 1467335 in diabetic retinopathy
Dong Nguyen Q et al.·Eye (Lond)
2024
Top 7 full-text resultsSearch PubTator3 ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Giant Cell ArteritisPolymyalgia Rheumatica

Assessing Biomarker in Giant Cell Arteritis and Polymyalgia Rheumatic

RECRUITING
NCT06460142University of BonnStarted 2023-09-01
Aortic/ cardiac magnetic resonance imagingVascular ultrasoundTransorbital Ultrasound

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients