OPA1
Chr 3ARADOPA1 mitochondrial dynamin like GTPase
Also known as: BERHS, MGM1, MTDPS14, MTDPS14A, MTDPS14B, NPG, NTG, largeG
OPA1 encodes a dynamin-related GTPase that mediates fusion of mitochondrial inner membranes, regulates cristae morphology, and maintains respiratory chain function. Mutations cause autosomal dominant optic atrophy type 1 with progressive visual loss, as well as autosomal recessive conditions including Behr syndrome, optic atrophy plus syndrome, and mitochondrial DNA depletion syndromes affecting the heart, brain, and muscle. The gene is highly constrained against loss-of-function variants (pLI 0.99, LOEUF 0.29), reflecting its essential role in mitochondrial function.
Moderate evidence — consider for supplementary testing
2 total gene-disease associations curated
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly LoF-intolerant (top ~10% of genes)
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to loss-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
400 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 47 | 5 | 13 | 1 | 66 |
Likely Pathogenic | 12 | 7 | 4 | 0 | 23 |
VUS | 4 | 141 | 19 | 3 | 167 |
Likely Benign | 0 | 5 | 68 | 41 | 114 |
Benign | 0 | 0 | 2 | 0 | 2 |
| Total | 63 | 158 | 106 | 45 | 372 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
OPA1 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
SAD of IVT PYC-001 in OPA1 Mutation-Associated Autosomal Dominant Optic Atrophy (Sundew)
ACTIVE NOT RECRUITINGRare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
RECRUITINGSafety of Single and Repeat Dose of PYC-001 Eye Injections in People With Autosomal Dominant Optic Atrophy (Myrtle)
RECRUITINGMITAORTA - Role of Mitochondrial Dynamic in Aneurysm and Dissection of Ascending Thoracic Aorta
ACTIVE NOT RECRUITINGExternal Resources
Links to major genomics databases and tools