OMA1
protein-codingOMA1 zinc metallopeptidase, the group of M48 metallopeptidase family
Gene summary
Enables metalloendopeptidase activity. Involved in several processes, including HRI-mediated signaling; mitochondrial protein processing; and regulation of mitochondrion organization. Located in mitochondrial inner membrane. Is active in mitochondrial intermembrane space. [provided by Alliance of Genome Resources, Jun 2026]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~131.4 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to OMA1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_145243.5. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 2 | 2 | 4 | |||
| missense | 3 | 4 | 3 | 10 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 6 | 4 | 5 | 15 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_660286.1 | 8 | MANE Select | |
| Ensembl | ENSP00000360270.3 | 8 | MANE Select | |
| Ensembl | ENSP00000409589.1 | 3 | Standard | |
| Ensembl | ENSP00000391941.1 | 8 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| oma1 | Danio rerio | Structure: head Quality: decreased size abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Regulation of Apoptosis
- Apoptosis
- Programmed Cell Death
Biological Process
- diet induced thermogenesis
- glucose metabolic process
- protein quality control for misfolded or incompletely synthesized proteins
- lipid metabolic process
- negative regulation of mitochondrial fusion
Molecular Function
- metalloendopeptidase activity
- metal ion binding
Cellular Component
- mitochondrial inner membrane
- integral component of membrane
- mitochondrial membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000371226
- Coding exons
- 8
- Length
- 131419
- Individuals with no LoFs
- 125697
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 46
- Defined
- 125743
- p
- 0.000183
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.494 | 248 | 271 | 0.916 | 0.0000130 | 3466 |
| Missense (PolyPhen) | 55 | 69.703 | 0.78906 | 903 | ||
| Synonymous | 0.715 | 89 | 98.0 | 0.908 | 0.00000486 | 974 |
| Loss of Function | 1.04 | 20 | 25.7 | 0.779 | 0.00000145 | 284 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00012 | 0.00012 | rare |
| Latino/Admixed American | 0.00029 | 0.00020 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00022 | 0.00022 | rare |
| Finnish | 0.00023 | 0.00023 | rare |
| European (Non-Finnish) | 0.00017 | 0.00017 | rare |
| South Asian | 0.00030 | 0.00029 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Metalloprotease that is part of the quality control system in the inner membrane of mitochondria. Following stress conditions that induce loss of mitochondrial membrane potential, mediates cleavage of OPA1 at S1 position, leading to OPA1 inactivation and negative regulation of mitochondrial fusion. May also cleave UQCC3 under these conditions. Its role in mitochondrial quality control is essential for regulating lipid metabolism as well as to maintain body temperature and energy expenditure under cold-stress conditions. {ECO:0000250|UniProtKB:Q9D8H7, ECO:0000269|PubMed:20038677}.;
Recessive Scores
- pRec
- 0.0909
Intolerance Scores
- LoFtool
- 0.915
- RVIS EVS
- 1.24
- RVIS percentile EVS
- 93.42
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.324
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |