OPTN
Chr 10ADARoptineurin
Also known as: ALS12, FIP2, GLC1E, HIP7, HYPL, NRP, TFIIIA-INTP
Optineurin functions in membrane trafficking, vesicle trafficking, autophagy, and apoptosis regulation through interactions with RAB8, huntingtin, and transcription factors. Mutations cause autosomal dominant normal-tension glaucoma, primary open-angle glaucoma, and amyotrophic lateral sclerosis type 12 with or without frontotemporal dementia, as well as autosomal recessive forms of these conditions. The pathogenic mechanism involves disruption of cellular trafficking pathways and dysregulated apoptosis.
Definitive — sufficient evidence for diagnostic panels
2 total gene-disease associations curated
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and loss-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative 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.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
OPTN · 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
Development of Targeted RNA-Seq for Amyotrophic Lateral Sclerosis Diagnosis
RECRUITINGTracking and Predicting How Brain Damage Spreads in Neurodegenerative Diseases
ENROLLING BY INVITATIONExternal Resources
Links to major genomics databases and tools