OMA1

Chr 1

OMA1 zinc metallopeptidase

Also known as: 2010001O09Rik, MPRP-1, MPRP1, YKR087C, ZMPOMA1, peptidase

NCBI Gene: 115209ENSG00000162600UniProt: Q96E52

Enables metalloendopeptidase activity. Involved in several processes, including HRI-mediated signaling; proteolysis; and regulation of mitochondrion organization. Located in mitochondrial inner membrane. Is active in mitochondrial intermembrane space. [provided by Alliance of Genome Resources, Jul 2025]

25
ClinVar variants
10
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— OMA1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
10 Pathogenic / Likely Pathogenic· 4 VUS of 25 total submissions
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

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.
1.13LOEUF
pLI 0.000
Z-score 1.04
OE 0.78 (0.55–1.13)
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.
0.49Z-score
OE missense 0.92 (0.82–1.02)
248 obs / 270.9 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.0.78 (0.55–1.13)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.92 (0.82–1.02)
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.0.91
0≤1.21.6
LoF obs/exp: 20 / 25.7Missense obs/exp: 248 / 270.9Syn Z: 0.71

ClinVar Variant Classifications

25 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic8
Likely Pathogenic2
VUS4
Likely Benign4
Benign7
8
Pathogenic
2
Likely Pathogenic
4
VUS
4
Likely Benign
7
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
8
0
8
Likely Pathogenic
0
0
2
0
2
VUS
0
0
4
0
4
Likely Benign
0
4
0
0
4
Benign
0
4
1
2
7
Total0815225

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

View in ClinVar →

Protein Context — Lollipop Plot

OMA1 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype

OMIM

No OMIM entries found.

Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
The NLRX1-SLC39A7 complex orchestrates mitochondrial dynamics and mitophagy to rejuvenate intervertebral disc by modulating mitochondrial Zn(2+) trafficking.
Song Y et al.·Autophagy
2024
Inhibition of PINK1 senses ROS signaling to facilitate neuroblastoma cell pyroptosis.
Zhu Y et al.·Autophagy
2025
Sustained OMA1-mediated integrated stress response is beneficial for spastic ataxia type 5.
Franchino CA et al.·Brain
2024
Mitochondrial quality control proteases and their modulation for cancer therapy.
Zhang J et al.·Med Res Rev
2023Review
Targeting Dio3 to enhance mitophagy and ameliorate skeletal muscle wasting in sepsis.
Wang G et al.·Redox Biol
2025
Mutant CHCHD10 disrupts cytochrome c oxidation and activates mitochondrial retrograde signaling.
Campos-Ribeiro MA et al.·EMBO Mol Med
2026
Long Noncoding RNA PCGEM1 Facilitates Tumor Growth and Metastasis of Osteosarcoma by Sponging miR-433-3p and Targeting OMA1.
Li J et al.·Orthop Surg
2023
Dual Nature of Mitochondrial Integrated Stress Response: Molecular Switches from Protection to Pathology.
Jeong J et al.·Genes (Basel)
2025Review
A Common Missense Variant in OMA1 Associated with the Prognosis of Heart Failure.
Hu D et al.·Cardiovasc Drugs Ther
2020
Pathogenic variants in the AFG3L2 proteolytic domain cause SCA28 through haploinsufficiency and proteostatic stress-driven OMA1 activation.
Tulli S et al.·J Med Genet
2019
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Stress adaptation of mitochondrial protein import by OMA1-mediated degradation of DNAJC15.
Kroczek L et al.·Nat Struct Mol Biol
2026
Cancer cells surviving cisplatin chemotherapy increase stress-induced OMA1 activity and mitochondrial fragmentation.
Li M et al.·Sci Rep
2026🔓 Open Access
Trifloxystrobin induces oxidative stress-dependent activation of the OMA1-DELE1-HRI integrated stress response leading to apoptosis in human neuroblastoma cells.
Chaabani H et al.·Environ Pollut
2026
Niujiaodihuang Detoxify Decoction Inhibits D-GalN/LPS-induced Hepatocyte Ferroptosis by Maintaining Mitochondrial Homeostasis Via OMA1-OPA1 Pathway.
Lu Y et al.·J Physiol Investig
2025
ER stress-related mitochondrial protein-coding gene risk model and in vitro experiments unveil OMA1 as a novel prognostic and therapeutic biomarker for low-grade glioma.
Qin C et al.·Life Sci
2025Functional
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