AOPEP

Chr 9AR

aminopeptidase O (putative)

Also known as: AP-O, APO, C90RF3, C9orf3, DYT31, ONPEP

NCBI Gene: 84909ENSG00000148120UniProt: Q8N6M6

This gene encodes a member of the M1 zinc aminopeptidase family. The encoded protein is a zinc-dependent metallopeptidase that catalyzes the removal of an amino acid from the amino terminus of a protein or peptide. This protein may play a role in the generation of angiotensin IV. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Oct 2010]

Primary Disease Associations & Inheritance

Dystonia 31MIM #619565
AR
574
ClinVar variants
52
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— AOPEP
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
52 Pathogenic / Likely Pathogenic· 314 VUS of 574 total submissions

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.
0.94LOEUF
pLI 0.000
Z-score 1.87
OE 0.69 (0.51–0.94)
Tolerant

Typical tolerance to LoF variation

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.
0.46Z-score
OE missense 0.94 (0.86–1.02)
411 obs / 438.2 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.0.69 (0.51–0.94)
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.0.95
0≤1.21.6
LoF obs/exp: 29 / 42.1Missense obs/exp: 411 / 438.2Syn Z: 0.49

ClinVar Variant Classifications

574 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic29
Likely Pathogenic23
VUS314
Likely Benign199
Benign1
Conflicting8
29
Pathogenic
23
Likely Pathogenic
314
VUS
199
Likely Benign
1
Benign
8
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
19
0
10
0
29
Likely Pathogenic
15
2
6
0
23
VUS
1
295
14
4
314
Likely Benign
0
14
66
119
199
Benign
0
0
1
0
1
Conflicting
—8
Total3531197123574

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

View in ClinVar →

Protein Context — Lollipop Plot

AOPEP · 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
AMINOPEPTIDASE O; AOPEP
MIM #619600 · *

Dystonia 31

MIM #619565

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — AOPEP
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
AOPEP-related autosomal recessive dystonia: update on Zech-Boesch syndrome.
Boesch S et al.·J Med Genet
2025Review
Genome sequencing reanalysis increases the diagnostic yield in dystonia.
Fellner A et al.·Parkinsonism Relat Disord
2024
Spiking Patterns in the Globus Pallidus Highlight Convergent Neural Dynamics across Diverse Genetic Dystonia Syndromes.
Kaymak A et al.·Ann Neurol
2025
A renal biopsy-anchored multi-marker signature involving AOPEP SNP-driven splicing, miR-27b-3p and glycated albumin for stratifying renal damage in type 2 diabetes.
Conserva F et al.·Diabetes Res Clin Pract
2025
AOPEP variants as a novel cause of recessive dystonia: Generalized dystonia and dystonia-parkinsonism.
Garavaglia B et al.·Parkinsonism Relat Disord
2022
Mutation screening of AOPEP variants in a large dystonia cohort.
Lin J et al.·J Neurol
2023Cohort
Biallelic AOPEP Loss-of-Function Variants Cause Progressive Dystonia with Prominent Limb Involvement.
Zech M et al.·Mov Disord
2022
Generalized dystonia unraveled: Molecular mechanisms, diagnostic strategies, and treatment paradigms.
Yarahmadi F et al.·Neurol Sci
2025Review
AOPEP Homozygous Loss-of-Function Variant in an Indian Patient with Early-Onset Generalized Dystonia.
Fevga C et al.·Mov Disord
2022
Suicide Related Phenotypes in a Bipolar Sample: Genetic Underpinnings.
Lybech LKM et al.·Genes (Basel)
2021
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools