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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
OPA3
outer mitochondrial membrane lipid metabolism regulator OPA3
Chromosome 19 Β· 19q13.32
NCBI Gene: 80207Ensembl: ENSG00000125741.6HGNC: HGNC:8142UniProt: B4DK77
47PubMed Papers
22Diseases
0Drugs
38Pathogenic Variants
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
visual perceptionmitochondrionregulation of lipid metabolic process3-methylglutaconic aciduria type 3optic atrophy 3Autosomal dominant optic atrophy and cataractneurodegenerative disease
✦AI Summary

OPA3 (outer mitochondrial membrane lipid metabolism regulator OPA3) is a mitochondrial protein that plays critical roles in mitochondrial function and cellular metabolism. The protein consists of 179 amino acids and is ubiquitously expressed, with highest levels in skeletal muscle and kidney 1. OPA3 localizes to the outer mitochondrial membrane where it regulates lipid metabolism and mitochondrial dynamics 2. Functionally, OPA3 maintains mitochondrial structural integrity and prevents ferroptosis by interacting with NFS1, a key iron-sulfur cluster biogenesis protein 2. The protein also influences the cGAS-STING innate immune pathway by preventing mitochondrial DNA stress 3. Mutations in OPA3 cause autosomal dominant optic atrophy type 3 and 3-methylglutaconic aciduria type 3 (Costeff syndrome), conditions characterized by bilateral optic nerve degeneration, visual impairment, and in severe cases, multi-systemic features including cardiomyopathy and neurological dysfunction 45. OPA3 deficiency leads to retinal ganglion cell death and increased mitochondrial activity as a compensatory mechanism 5. The protein has also been implicated in cancer progression, with high expression associated with poor prognosis in ovarian and colorectal cancers 63.

Sources cited
1
OPA3 is a 179 amino acid protein ubiquitously expressed, most prominently in skeletal muscle and kidney
PMID: 11668429
2
OPA3 is a mitochondrial membrane protein that prevents ferroptosis by interacting with NFS1
PMID: 36924813
3
OPA3 influences the cGAS-STING pathway by preventing mitochondrial DNA stress
PMID: 39725842
4
OPA3 mutations cause autosomal dominant optic atrophy and affect energy metabolism and apoptosis control
PMID: 22776096
5
OPA3 deficiency leads to retinal ganglion cell loss, visual impairment, and increased mitochondrial activity
PMID: 18222992
6
High OPA3 expression is associated with poor prognosis in ovarian cancer
PMID: 35507809
7
OPA3 promotes colorectal cancer progression
PMID: 39725842
Disease Associationsβ“˜22
3-methylglutaconic aciduria type 3Open Targets
0.81Strong
optic atrophy 3Open Targets
0.81Strong
Autosomal dominant optic atrophy and cataractOpen Targets
0.69Moderate
neurodegenerative diseaseOpen Targets
0.52Moderate
autosomal dominant optic atrophyOpen Targets
0.42Moderate
Cognitive regressionOpen Targets
0.37Weak
achromatopsiaOpen Targets
0.27Weak
genetic disorderOpen Targets
0.19Weak
optic atrophyOpen Targets
0.12Weak
foveal hypoplasiaOpen Targets
0.11Weak
Hypoplasia of the foveaOpen Targets
0.11Weak
hyperpituitarismOpen Targets
0.08Suggestive
hepatocellular carcinomaOpen Targets
0.08Suggestive
placenta praeviaOpen Targets
0.08Suggestive
Abnormal pupillary functionOpen Targets
0.07Suggestive
alcohol drinkingOpen Targets
0.07Suggestive
Alzheimer diseaseOpen Targets
0.07Suggestive
ovarian dysfunctionOpen Targets
0.07Suggestive
ovarian cancerOpen Targets
0.06Suggestive
cancerOpen Targets
0.04Suggestive
3-methylglutaconic aciduria 3UniProt
Optic atrophy 3UniProt
Pathogenic Variants38
NM_025136.4(OPA3):c.143-1G>CPathogenic
3-Methylglutaconic aciduria type 3|Optic atrophy 3;3-Methylglutaconic aciduria type 3|not provided
β˜…β˜…β˜†β˜†2026
NM_025136.4(OPA3):c.313C>G (p.Gln105Glu)Pathogenic
Optic atrophy 3|Optic atrophy 3;3-Methylglutaconic aciduria type 3|not provided|3-Methylglutaconic aciduria type 3
β˜…β˜…β˜†β˜†2025β†’ Residue 105
NM_025136.4(OPA3):c.52C>T (p.Gln18Ter)Pathogenic
not provided|3-Methylglutaconic aciduria type 3|Optic atrophy 3;3-Methylglutaconic aciduria type 3
β˜…β˜…β˜†β˜†2025β†’ Residue 18
NM_025136.4(OPA3):c.1A>G (p.Met1Val)Likely pathogenic
Optic atrophy 3;3-Methylglutaconic aciduria type 3|3-Methylglutaconic aciduria type 3
β˜…β˜…β˜†β˜†2025β†’ Residue 1
NM_025136.4(OPA3):c.194del (p.Gly65fs)Likely pathogenic
not provided|3-Methylglutaconic aciduria type 3
β˜…β˜…β˜†β˜†2024β†’ Residue 65
NM_025136.4(OPA3):c.143-1G>APathogenic
3-Methylglutaconic aciduria type 3|3-Methylglutaconic aciduria type 3;Optic atrophy 3
β˜…β˜…β˜†β˜†2023
NM_025136.4(OPA3):c.13_20del (p.Ala5fs)Likely pathogenic
3-Methylglutaconic aciduria type 3
β˜…β˜†β˜†β˜†2025β†’ Residue 5
NM_025136.4(OPA3):c.142+2_142+3dupLikely pathogenic
3-Methylglutaconic aciduria type 3;Optic atrophy 3
β˜…β˜†β˜†β˜†2025
NM_025136.4(OPA3):c.140A>G (p.Gln47Arg)Likely pathogenic
3-Methylglutaconic aciduria type 3;Optic atrophy 3
β˜…β˜†β˜†β˜†2025β†’ Residue 47
NM_025136.4(OPA3):c.458_459del (p.Arg153fs)Likely pathogenic
3-Methylglutaconic aciduria type 3
β˜…β˜†β˜†β˜†2024β†’ Residue 153
NM_025136.4(OPA3):c.472_494del (p.Glu158fs)Likely pathogenic
3-Methylglutaconic aciduria type 3
β˜…β˜†β˜†β˜†2024β†’ Residue 158
NM_025136.4(OPA3):c.152G>A (p.Trp51Ter)Likely pathogenic
3-Methylglutaconic aciduria type 3;Optic atrophy 3
β˜…β˜†β˜†β˜†2024β†’ Residue 51
NM_001017989.3(OPA3):c.313C>T (p.Gln105Ter)Likely pathogenic
3-Methylglutaconic aciduria type 3|Optic atrophy 3;3-Methylglutaconic aciduria type 3
β˜…β˜†β˜†β˜†2024β†’ Residue 105
NC_000019.10:g.45529163G>ALikely pathogenic
3-Methylglutaconic aciduria type 3|Optic atrophy 3;3-Methylglutaconic aciduria type 3
β˜…β˜†β˜†β˜†2024
NM_025136.4(OPA3):c.248_251dup (p.Gly85fs)Likely pathogenic
3-Methylglutaconic aciduria type 3
β˜…β˜†β˜†β˜†2024β†’ Residue 85
NM_025136.4(OPA3):c.318_319dup (p.Gln107fs)Likely pathogenic
3-Methylglutaconic aciduria type 3
β˜…β˜†β˜†β˜†2024β†’ Residue 107
NM_025136.4(OPA3):c.217G>T (p.Glu73Ter)Likely pathogenic
3-Methylglutaconic aciduria type 3
β˜…β˜†β˜†β˜†2024β†’ Residue 73
NM_025136.4(OPA3):c.308_312del (p.Arg103fs)Likely pathogenic
Optic atrophy 3;3-Methylglutaconic aciduria type 3
β˜…β˜†β˜†β˜†2024β†’ Residue 103
NM_025136.4(OPA3):c.39C>G (p.Tyr13Ter)Pathogenic
3-Methylglutaconic aciduria type 3;Optic atrophy 3
β˜…β˜†β˜†β˜†2024β†’ Residue 13
NM_025136.4(OPA3):c.82_84delinsT (p.Ile27_Lys28insTer)Likely pathogenic
3-Methylglutaconic aciduria type 3
β˜…β˜†β˜†β˜†2024β†’ Residue 27
View on ClinVar β†—
Related Genes
TMEM126AProtein interaction93%DNAJC19Protein interaction88%AUHProtein interaction87%WFS1Protein interaction82%RPP14Protein interaction78%IMPG1Shared pathway50%
Tissue Expression6 tissues
Heart
100%
Liver
50%
Lung
39%
Brain
27%
Ovary
23%
Bone Marrow
14%
Gene Interaction Network
Click a node to explore
OPA3TMEM126ADNAJC19AUHWFS1RPP14IMPG1
PROTEIN STRUCTURE
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AlphaFoldAI-predicted Β· UniProt Q9H6K4
View on AlphaFold β†—
Constraintβ“˜
LOEUFβ“˜
1.92LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF1.42 [0.80–1.92]
RankingsWhere OPA3 stands among ~20K protein-coding genes
  • #9,248of 20,598
    Most Researched47
  • #1,602of 5,498
    Most Pathogenic Variants38
  • #17,398of 17,882
    Most Constrained (LOEUF)1.92
Genes detectedOPA3
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Expression status and prognostic significance of mitochondrial dynamics OPA3 in human ovarian cancer.
PMID: 35507809
Aging (Albany NY) Β· 2022
1.00
2
Dominant optic atrophy.
PMID: 22776096
Orphanet J Rare Dis Β· 2012
0.90
3
A missense mutation in the murine Opa3 gene models human Costeff syndrome.
PMID: 18222992
Brain Β· 2008
0.80
4
OPA3 inhibits the cGAS-STING pathway mediated by mtDNA stress to promote colorectal cancer progression.
PMID: 39725842
In Vitro Cell Dev Biol Anim Β· 2025
0.70
5
Type III 3-methylglutaconic aciduria (optic atrophy plus syndrome, or Costeff optic atrophy syndrome): identification of the OPA3 gene and its founder mutation in Iraqi Jews.
PMID: 11668429
Am J Hum Genet Β· 2001
0.60