OPA3 Gene

Name	optic atrophy 3 (autosomal recessive, with chorea and spastic paraplegia)
Description	The mouse ortholog of this protein co-purifies with the mitochondrial inner membrane. Mutations in this gene have been shown to result in 3-methylglutaconic aciduria type III and autosomal dominant optic atrophy and cataract. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2009]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nOPA3 was first identified through studies of 3‐methylglutaconic aciduria type III (also known as Costeff syndrome), a neuro‐ophthalmologic disorder marked by early bilateral optic atrophy, spasticity, extrapyramidal dysfunction, and mild cognitive deficits. The OPA3 gene, consisting of two exons and encoding a small peptide of 179 amino acids, is broadly expressed—with prominent expression in skeletal muscle, kidney, and select brain regions—and its mutation leads to loss of mRNA expression in affected individuals. These findings established an essential link between aberrant OPA3 and the clinical phenotype of optic atrophy with additional neurological abnormalities."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nFurther functional studies have elucidated that OPA3 is an integral protein of the mitochondrial outer membrane, possessing an N‐terminal mitochondrial targeting domain and a C‐terminal region exposed to the cytosol. Manipulation of OPA3 expression levels revealed that overexpression prompts significant mitochondrial fragmentation, whereas its knockdown results in an elongation of the mitochondrial network. Moreover, while normal OPA3‐induced fragmentation does not trigger spontaneous apoptosis, certain familial mutations (for example, the G93S variant) can promote mitochondrial fission to the extent of sensitizing cells to apoptotic stimuli or even triggering cell death, thereby suggesting a potential gain‐of‐function mechanism in pathogenic states."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nExtensive genetic screening across diverse patient cohorts with suspected hereditary optic neuropathies has further underscored the clinical relevance of OPA3. In several studies, mutations in OPA3—though representing a smaller fraction compared to OPA1 alterations—have been identified in cases of both autosomal dominant and recessive optic atrophy. These investigations not only expanded the mutation spectrum but also highlighted distinct clinical phenotypes, wherein dominant mutations may associate with cataract formation, while recessive changes are linked to the broader manifestations of Costeff syndrome. Complementary proteomic and molecular approaches have reinforced the mitochondrial localization of OPA3, emerging as a critical regulator of mitochondrial morphology and, consequently, of optic nerve integrity."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "12"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Y Anikster, R Kleta, A Shaag, et al. "}, {"type": "b", "children": [{"type": "t", "text": "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."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2001)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1086/324651"}], "href": "https://doi.org/10.1086/324651"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11668429"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11668429"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Noam Fink, Meir Mouallem "}, {"type": "b", "children": [{"type": "t", "text": "[Costeff syndrome: a syndrome that was described in Israel and the responsible gene discovered by an Israeli doctor]."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Harefuah (2006)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16838891"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16838891"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Seung-Wook Ryu, Hyeon Joo Jeong, Myunghwan Choi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Optic atrophy 3 as a protein of the mitochondrial outer membrane induces mitochondrial fragmentation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Mol Life Sci (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00018-010-0365-z"}], "href": "https://doi.org/10.1007/s00018-010-0365-z"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20372962"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20372962"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Marjan Huizing, Heidi Dorward, Lien Ly, et al. "}, {"type": "b", "children": [{"type": "t", "text": "OPA3, mutated in 3-methylglutaconic aciduria type III, encodes two transcripts targeted primarily to mitochondria."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Genet Metab (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ymgme.2010.03.005"}], "href": "https://doi.org/10.1016/j.ymgme.2010.03.005"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20350831"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20350831"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Marc Ferré, Dominique Bonneau, Dan Milea, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Molecular screening of 980 cases of suspected hereditary optic neuropathy with a report on 77 novel OPA1 mutations."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mutat (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/humu.21025"}], "href": "https://doi.org/10.1002/humu.21025"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19319978"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19319978"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Patrick Yu-Wai-Man, Suma P Shankar, Valérie Biousse, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genetic screening for OPA1 and OPA3 mutations in patients with suspected inherited optic neuropathies."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Ophthalmology (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ophtha.2010.07.029"}], "href": "https://doi.org/10.1016/j.ophtha.2010.07.029"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21036400"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21036400"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Tanja Grau, Lena F Burbulla, Gertraud Engl, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A novel heterozygous OPA3 mutation located in the mitochondrial target sequence results in altered steady-state levels and fragmented mitochondrial network."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Med Genet (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1136/jmedgenet-2013-101774"}], "href": "https://doi.org/10.1136/jmedgenet-2013-101774"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24136862"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24136862"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Eric D Gaier, Inderneel Sahai, Janey L Wiggs, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Novel homozygous "}, {"type": "a", "children": [{"type": "t", "text": "i"}], "href": "i"}, {"type": "t", "text": "OPA3"}, {"type": "a", "children": [{"type": "t", "text": "/i"}], "href": "/i"}, {"type": "t", "text": " mutation in an Afghani family with 3-methylglutaconic aciduria type III and optic atrophy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Ophthalmic Genet (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1080/13816810.2019.1711428"}], "href": "https://doi.org/10.1080/13816810.2019.1711428"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31928268"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31928268"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Beenish Arif, Kishore R Kumar, Philip Seibler, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A novel OPA3 mutation revealed by exome sequencing: an example of reverse phenotyping."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "JAMA Neurol (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1001/jamaneurol.2013.1174"}], "href": "https://doi.org/10.1001/jamaneurol.2013.1174"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23700088"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23700088"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Jieqiong Chen, Ke Xu, Xiaohui Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mutation screening of mitochondrial DNA as well as OPA1 and OPA3 in a Chinese cohort with suspected hereditary optic atrophy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Invest Ophthalmol Vis Sci (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1167/iovs.14-14953"}], "href": "https://doi.org/10.1167/iovs.14-14953"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25205859"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25205859"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "David J Pagliarini, Sarah E Calvo, Betty Chang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A mitochondrial protein compendium elucidates complex I disease biology."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cell.2008.06.016"}], "href": "https://doi.org/10.1016/j.cell.2008.06.016"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18614015"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18614015"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Sandrine Da Cruz, Ioannis Xenarios, James Langridge, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Proteomic analysis of the mouse liver mitochondrial inner membrane."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M304940200"}], "href": "https://doi.org/10.1074/jbc.M304940200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12865426"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12865426"}]}]}]}
Synonyms	MGA3
Proteins	OPA3_HUMAN
NCBI Gene ID	80207
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

OPA3 has 7,238 functional associations with biological entities spanning 9 categories (molecular profile, organism, chemical, disease, phenotype or trait, functional term, phrase or reference, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 120 datasets.

Click the + buttons to view associations for OPA3 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

OPA3 Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Achilles Cell Line Gene Essentiality Profiles	cell lines with fitness changed by OPA3 gene knockdown relative to other cell lines from the Achilles Cell Line Gene Essentiality Profiles dataset.
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of OPA3 gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of OPA3 gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles	tissue samples with high or low expression of OPA3 gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of OPA3 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq	tissue samples with high or low expression of OPA3 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of OPA3 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of OPA3 gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of OPA3 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of OPA3 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	Carcinogenome Chemical Perturbation Carcinogenicity Signatures	small molecule perturbations changing expression of OPA3 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of OPA3 gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of OPA3 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with OPA3 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with OPA3 gene from the CellMarker Gene-Cell Type Associations dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of OPA3 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of OPA3 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of OPA3 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	ClinVar Gene-Phenotype Associations	phenotypes associated with OPA3 gene from the curated ClinVar Gene-Phenotype Associations dataset.
	ClinVar Gene-Phenotype Associations 2025	phenotypes associated with OPA3 gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	CM4AI U2OS Cell Map Protein Localization Assemblies	assemblies containing OPA3 protein from integrated AP-MS and IF data from the CM4AI U2OS Cell Map Protein Localization Assemblies dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of OPA3 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing OPA3 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing OPA3 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing OPA3 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores 2025	cellular components containing OPA3 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with OPA3 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with OPA3 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of OPA3 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with OPA3 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Disease Associations	diseases associated with OPA3 gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with OPA3 gene in GWAS and other genetic association datasets from the dbGAP Gene-Trait Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of OPA3 protein relative to other small molecule perturbations from the DeepCoverMOA Drug Mechanisms of Action dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by OPA3 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores	diseases involving OPA3 gene from the DISEASES Curated Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving OPA3 gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores	diseases associated with OPA3 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with OPA3 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with OPA3 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with OPA3 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.