OPA1 Gene: Mitochondrial Dynamin-Like GTPase
Key regulator of mitochondrial fusion, cristae morphology, and apoptosis; mutations cause dominant optic atrophy.
Gene Information Card
| Symbol | OPA1 |
|---|---|
| Full Name | OPA1 mitochondrial dynamin like GTPase |
| Gene Type | protein coding |
| Chromosomal Location | 3q29 |
| NCBI Gene ID | 4976 ncbi.nlm.nih.gov/gene/4976 |
| Ensembl ID | ENSG00000198836 |
| UniProt ID | O60313 |
| OMIM ID | 605290 |
| HGNC ID | 8140 |
| Aliases | NPG, NTG, large GTP-binding protein, mitochondrial dynamin-like GTPase |
Description
The OPA1 gene encodes a dynamin-related GTPase protein localized to the inner mitochondrial membrane. It is essential for mitochondrial fusion, cristae organization, and maintenance of mitochondrial DNA. OPA1 also plays a role in apoptosis regulation and respiratory chain efficiency. Mutations in OPA1 are the most common cause of autosomal dominant optic atrophy (DOA), a condition characterized by progressive vision loss due to retinal ganglion cell degeneration.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Dominant optic atrophy (DOA) | Haploinsufficiency due to loss-of-function mutations leading to impaired mitochondrial fusion and cristae disorganization, causing retinal ganglion cell degeneration. | ClinVar, OMIM |
| Optic atrophy plus syndrome | Mutations affecting OPA1 protein stability or GTPase activity, leading to more severe mitochondrial dysfunction and additional neurological symptoms. | OMIM, PubMed |
| Behr syndrome | Compound heterozygous or homozygous OPA1 mutations causing early-onset optic atrophy, ataxia, and spasticity. | OMIM, PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Retina | High | High expression in retinal ganglion cells |
| Brain | Moderate | Widespread expression, especially in neurons |
| Muscle | Moderate | Skeletal and cardiac muscle |
| Liver | Low | Low expression |
| Kidney | Low | Low expression |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | Moderate | Cervical cancer cell line |
| SH-SY5Y | High | Neuroblastoma cell line |
| HepG2 | Low | Hepatocellular carcinoma |
| MCF7 | Moderate | Breast cancer cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.2708_2711delTTAG | Frameshift | Rare | Loss of function, causes DOA |
| c.985A>G (p.Lys329Glu) | Missense | Rare | Dominant negative effect, impairs GTPase activity |
| c.1496C>T (p.Ala499Val) | Missense | Rare | Pathogenic, associated with DOA plus |
| c.1212+1G>A | Splice site | Rare | Exon skipping, loss of function |
Mutation functional classification
Loss of Function (LOF)
Most OPA1 mutations are loss-of-function, leading to haploinsufficiency. This reduces OPA1 protein levels, impairing mitochondrial fusion and cristae maintenance, resulting in mitochondrial fragmentation and apoptosis.
Gain of Function (GOF)
No clear gain-of-function mutations have been reported for OPA1.
Dominant Negative (DN)
Some missense mutations in the GTPase domain exert dominant-negative effects, interfering with the function of the wild-type allele and causing more severe phenotypes.
View complete mutation data：
Gene Ontology (GO)
| • GTPase activity | • mitochondrial fusion |
| • mitochondrial cristae organization | • apoptotic process |
| • regulation of mitochondrial membrane potential | • protein homodimerization activity |
Pathways
• Mitochondrial fusion
• Apoptosis
• Mitochondrial dynamics
Protein Summary
OPA1 is a nuclear-encoded mitochondrial protein that is imported into mitochondria and processed into multiple isoforms. It contains an N-terminal mitochondrial targeting sequence, a transmembrane domain, and a C-terminal GTPase domain. OPA1 exists in long and short forms; long forms mediate mitochondrial fusion, while short forms are involved in cristae remodeling and apoptosis. The protein is essential for maintaining mitochondrial network integrity and cellular energy production.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| OPA1 Knockout HEK293 Cell Line | EDJ-KQ50491 | Human | 4976 | Details Get a Quote |
| OPA1 Knockout HeLa Cell Line | EDJ-KQ54044 | Human | 4976 | Details Get a Quote |
| OPA1 Knockout A-549 Cell Line | EDJ-KQ62532 | Human | 4976 | Details Get a Quote |
| OPA1 Knockout HCT 116 Cell Line | EDJ-KQ71004 | Human | 4976 | Details Get a Quote |
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