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.
Primary Disease Associations & Inheritance
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 (loss-of-function and dominant-negative). The Badonyi & Marsh model scores dominant-negative highest among its predictions, but genomic evidence (constraint, ClinVar variant spectrum, and literature) most strongly supports loss-of-function (haploinsufficiency). 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
330 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 | 9 | 2 | 26 | 0 | 37 |
Likely Pathogenic | 14 | 1 | 8 | 0 | 23 |
VUS | 2 | 142 | 25 | 2 | 171 |
Likely Benign | 0 | 1 | 33 | 42 | 76 |
Benign | 0 | 1 | 9 | 1 | 11 |
Conflicting | — | 11 | |||
| Total | 25 | 147 | 101 | 45 | 329 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View 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.
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
External Resources
Links to major genomics databases and tools