OPA1
Chr 3OPA1 mitochondrial dynamin like GTPase
Dynamin-related GTPase that is essential for normal mitochondrial morphology by mediating fusion of the mitochondrial inner membranes, regulating cristae morphology and maintaining respiratory chain function (PubMed:16778770, PubMed:17709429, PubMed:20185555, PubMed:24616225, PubMed:28628083, PubMed:28746876, PubMed:31922487, PubMed:32228866, PubMed:32567732, PubMed:33130824, PubMed:33237841, PubMed:37612504, PubMed:37612506). Exists in two forms: the transmembrane, long form (Dynamin-like GTPase OPA1, long form; L-OPA1), which is tethered to the inner mitochondrial membrane, and the short soluble form (Dynamin-like GTPase OPA1, short form; S-OPA1), which results from proteolytic cleavage and localizes in the intermembrane space (PubMed:31922487, PubMed:32228866, PubMed:33237841, PubMed:37612504, PubMed:37612506). Both forms (L-OPA1 and S-OPA1) cooperate to catalyze the fusion of the mitochondrial inner membrane (PubMed:31922487, PubMed:37612504, PubMed:37612506). The equilibrium between L-OPA1 and S-OPA1 is essential: excess levels of S-OPA1, produced by cleavage by OMA1 following loss of mitochondrial membrane potential, lead to an impaired equilibrium between L-OPA1 and S-OPA1, inhibiting mitochondrial fusion (PubMed:20038677, PubMed:31922487). The balance between L-OPA1 and S-OPA1 also influences cristae shape and morphology (By similarity). Involved in remodeling cristae and the release of cytochrome c during apoptosis (By similarity). Proteolytic processing by PARL in response to intrinsic apoptotic signals may lead to disassembly of OPA1 oligomers and release of the caspase activator cytochrome C (CYCS) into the mitochondrial intermembrane space (By similarity). Acts as a regulator of T-helper Th17 cells, which are characterized by cells with fused mitochondria with tight cristae, by mediating mitochondrial membrane remodeling: OPA1 is required for interleukin-17 (IL-17) production (By similarity). Its role in mitochondrial morphology is required for mitochondrial genome maintenance (PubMed:18158317, PubMed:20974897)
Primary Disease Associations & Inheritance
Clinical highlights
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Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly LoF-intolerant (top ~10% of genes)
Mild missense constraint
ClinVar
No ClinVar data available.
Protein Context — Lollipop Plot
OPA1 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
A Longitudinal Natural History Study of OPA1-Associated Autosomal-Dominant Optic Atrophy
RECRUITINGRare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
RECRUITINGSAD of IVT PYC-001 in OPA1 Mutation-Associated Autosomal Dominant Optic Atrophy (Sundew)
ACTIVE NOT RECRUITINGSafety of Single and Repeat Dose of PYC-001 Eye Injections in People With Autosomal Dominant Optic Atrophy (Myrtle)
RECRUITINGExternal Resources
Links to major genomics databases and tools