OPA1

OPA1 catalogs genetic variants of the OPA1 gene and associated clinical phenotypes to support study of mitochondrial fusion defects and optic neuropathies such as Autosomal Dominant Optic Atrophy (DOA; Kjer type, MIM#165500).

Key Features:

• Gene and protein: OPA1 encodes a dynamin GTPase involved in mitochondrial fusion.
• Database scope: Contains records from 831 patients, including 697 with isolated DOA, 47 with DOA "plus" syndromes, and 83 asymptomatic or unclassified cases.
• Variant catalog: Documents 516 unique OPA1 variants.
• Pathogenic classification: Reports that 414 of the documented variants (>80%) are classified as pathogenic.
• Clinical phenotype annotation: Provides extensive clinical information for 118 patients using the Human Phenotype Ontology to standardize phenotypic descriptions.
• Data standards and infrastructure: Operates on the Global Variome shared Leiden Open-source Variation Database (LOVD) installation to enable unified nomenclature and interoperability.

Scientific Applications:

• Molecular diagnostics: Supports molecular diagnostics for OPA1-related disorders by providing a curated variant catalog.
• Gene-panel and sequencing studies: Informs gene-panel sequencing and interpretation of OPA1 variants in clinical and research sequencing data.
• Mutation-spectrum and large-scale studies: Enables large-scale mutation studies and population-level analyses of OPA1 variation.
• Genotype–phenotype correlation: Facilitates research into genotype–phenotype relationships by linking variants to standardized HPO-based clinical data.
• Study of mitochondrial dynamics and optic neuropathies: Supports research on mitochondrial fusion mechanisms and optic neuropathies, including DOA (Kjer type, MIM#165500) and related neurological disorders.

Methodology:

The database uses the Global Variome shared LOVD platform for variant data management and the Human Phenotype Ontology for standardized clinical annotation.