OPTN — Optineurin

OPTN — Optineurin

Pathway Diagram

```mermaid
flowchart TD
OPTN["OPTN<br/>(Optineurin)"]
RIPK1["RIPK1<br/>(Receptor Interacting<br/>Protein Kinase 1)"]
Autophagy["Autophagy<br/>Pathway"]
NFkB["NF-kappaB<br/>Signaling"]
Inflammation["Neuroinflammation"]

ALS["Amyotrophic<br/>Lateral Sclerosis"]
Parkinson["Parkinson's<br/>Disease"]
Alzheimer["Alzheimer's<br/>Disease"]
MS["Multiple<br/>Sclerosis"]
Dementia["Dementia"]
Neurodegeneration["Neurodegeneration"]

ProteinAggregation["Protein<br/>Aggregation"]
CellDeath["Neuronal<br/>Cell Death"]
MotorNeuronLoss["Motor Neuron<br/>Degeneration"]

OPTN -->|"inhibits"| RIPK1
OPTN -->|"regulates"| Autophagy
OPTN -->|"inhibits"| NFkB
OPTN -->|"regulates"| Inflammation

RIPK1 -->|"promotes"| NFkB
NFkB -->|"activates"| Inflammation
Inflammation -->|"leads to"| CellDeath

OPTN -->|"mutations cause"| ALS
OPTN -->|"associated with"| Parkinson
OPTN -->|"associated with"| Alzheimer
OPTN -->|"associated with"| MS
OPTN -->|"associated with"| Dementia

ALS -->|"characterized by"| MotorNeuronLoss
Autophagy -->|"clears"| ProteinAggregation
ProteinAggregation -->|"promotes"| Neurodegeneration
CellDeath -->|"leads to"| Neurodegeneration

style OPTN fill:#006494
style Autophagy fill:#1b5e20
style RIPK1 fill:#4a1a6b
style NFkB fill:#4a1a6b
style Inflammation fill:#ef5350
style ALS fill:#5d4400
style Parkinson fill:#5d4400
style Alzheimer fill:#5d4400
style MS fill:#5d

OPTN — Optineurin

Pathway Diagram

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">OPTN — Optineurin</th>
</tr>
<tr>
<td class="label">Symbol</td>
<td><strong>OPTN</strong></td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>Optineurin</td>
</tr>
<tr>
<td class="label">Chromosome</td>
<td>10p13</td>
</tr>
<tr>
<td class="label">NCBI Gene</td>
<td><a href="https://www.ncbi.nlm.nih.gov/gene/10133" target="_blank">10133</a></td>
</tr>
<tr>
<td class="label">Ensembl</td>
<td><a href="https://ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000123240" target="_blank">ENSG00000123240</a></td>
</tr>
<tr>
<td class="label">OMIM</td>
<td><a href="https://omim.org/entry/602432" target="_blank">602432</a></td>
</tr>
<tr>
<td class="label">UniProt</td>
<td><a href="https://www.uniprot.org/uniprot/Q96CV9" target="_blank">Q96CV9</a></td>
</tr>
<tr>
<td class="label">Diseases</td>
<td>[ALS](/diseases/als), [Parkinson's disease](/diseases/parkinsons-disease), Glaucoma</td>
</tr>
<tr>
<td class="label">Expression</td>
<td>Motor cortex, Spinal cord, Retina, Brain</td>
</tr>
<tr>
<th class="infobox-subheader" colspan="2">Key Mutations</th>
</tr>
<tr>
<td colspan="2" style="font-size:0.85em">E478G, Q398X, D474N, M98K, 691-692insAG</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/ad" style="color:#ef9a9a">AD</a>, <a href="/wiki/ali" style="color:#ef9a9a">ALI</a>, <a href="/wiki/als" style="color:#ef9a9a">ALS</a>, <a href="/wiki/alzheimer" style="color:#ef9a9a">ALZHEIMER</a>, <a href="/wiki/alzheimer's-disease" style="color:#ef9a9a">ALZHEIMER'S DISEASE</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1444 edges</a></td>
</tr>
</table>

OPTN — Optineurin

Brain Atlas Resources

• [Allen Human Brain Atlas search: OPTN](https://human.brain-map.org/search?searchText=OPTN)
• [Allen Mouse Brain Atlas search: OPTN](https://mouse.brain-map.org/search/index.html?query=OPTN)
• [Allen Brain Map portal search: OPTN](https://portal.brain-map.org/search?query=OPTN)
• [BrainSpan developmental transcriptome search: OPTN](https://www.brainspan.org/search/index.html?search=OPTN)

Introduction

Optn — Optineurin is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.

Overview

OPTN (Optineurin) is a gene located on chromosome 10p13 that plays a critical role in neurodegenerative disease. Mutations in OPTN are associated with [als](/diseases/als), [parkinson](/diseases/parkinsons-disease), and glaucoma. The gene is catalogued as NCBI Gene ID [10133](https://www.ncbi.nlm.nih.gov/gene/10133) and OMIM [602432](https://omim.org/entry/602432).

OPTN encodes a coiled-coil containing protein that functions as a critical adaptor protein involved in multiple cellular processes including [autophagy](/entities/autophagy), mitophagy, [NF-κB](/entities/nf-kb) signaling, and Golgi organization. Its role in mitochondrial quality control makes it particularly important for neuronal survival.

Molecular Function

Protein Structure and Binding

OPTN encodes a 577-amino acid protein with multiple functional domains. The protein contains:

• Coiled-coil domains: Mediate protein-protein interactions
• Ubiquitin-binding domain (UBD): Enables binding to K63-linked polyubiquitin chains
• Zinc finger (ZZ) domain: Facilitates zinc ion binding

Key Molecular Functions

• RAB8: Vesicle trafficking and membrane transport
• [Huntingtin](/proteins/huntingtin): Transcription activation and protein aggregates
• [tbk1](/genes/tbk1): TANK-binding kinase 1 - critical for OPTN phosphorylation and mitophagy activation
• [parkin](/proteins/parkin): E3 ubiquitin ligase in mitophagy pathway

Cellular Mechanisms

Mitophagy (Mitochondrial Quality Control)

OPTN is a critical receptor for mitophagy, the selective autophagy of damaged mitochondria. The mechanism involves:

NF-κB Signaling Regulation

OPTN negatively regulates canonical [nf-kb-signaling](/nf-kb-signaling-pathway-in-neurodegeneration), a key pathway in neuroinflammation:

• OPTN interacts with NF-κB signaling components
• Loss of OPTN function leads to increased NF-κB activation
• Dysregulated NF-κB signaling contributes to neuroinflammation in ALS and PD

Golgi Organization

OPTN plays a role in Golgi apparatus organization and protein trafficking:

• Maintains Golgi ribbon formation
• Facilitates vesicular transport
• Disruption affects protein secretion and membrane protein trafficking

Disease Associations

Amyotrophic Lateral Sclerosis (ALS)

OPTN mutations cause ALS type 12 (ALS12), accounting for approximately 1-3% of familial ALS cases[@liu2012]:

• E478G mutation: Most common pathogenic mutation, located in the ubiquitin-binding domain
• Q398X nonsense mutation: Produces truncated protein lacking functional domains
• Deletions: Frameshift mutations causing loss of function

• Loss of mitophagy function leads to accumulation of damaged mitochondria
• Impaired clearance of protein aggregates
• Increased oxidative stress and neuronal death
• Some mutations cause both ALS and frontotemporal dementia (FTD)

Parkinson's Disease

OPTN variants are associated with [parkinson](/diseases/parkinsons-disease):

• OPTN mutations can cause a PSP (Progressive Supranuclear Palsy)-CBS (Corticobasal Syndrome)-like phenotype
• Altered mitophagy may contribute to dopaminergic neuron vulnerability
• Interaction with [pink1](/proteins/pink1-protein) and [parkin](/proteins/parkin) pathways

Glaucoma

OPTN was first identified as a glaucoma gene:

• M98K polymorphism: Associated with normal-tension glaucoma, sensitizes retinal cells to endoplasmic reticulum stress
• Primary open-angle glaucoma: OPTN variants increase susceptibility
• Retinal ganglion cell death involves similar mechanisms to neuronal degeneration

Other Associations

• Paget's disease of bone: GWAS-identified susceptibility locus
• Inflammatory diseases: Altered immune response due to NF-κB dysregulation

Therapeutic Implications

Restoring Mitophagy

Therapeutic strategies targeting OPTN-mediated mitophagy:

Modulating NF-κB Signaling

• NF-κB inhibitors: Reduce neuroinflammation in OPTN-deficient [neurons](/entities/neurons)
• Anti-inflammatory approaches: Target microglial activation

TBK1-OPTN Interaction

• Kinase inhibitors: TBK1 activators to compensate for impaired OPTN function
• Phosphomimetic approaches: Develop compounds that enhance OPTN-LC3 binding

Research Directions

• OPTN knockout mouse models show neurodegeneration
• iPSC-derived neurons from ALS patients with OPTN mutations
• High-throughput screening for mitophagy-enhancing compounds

Brain Expression

OPTN is expressed in multiple brain regions relevant to neurodegeneration:

• Motor [cortex](/brain-regions/cortex): Affected in ALS
• Spinal cord: Site of motor neuron degeneration in ALS
• Substantia nigra: Dopaminergic neurons affected in PD
• Retina: Glaucoma relevance

Key Mutations

| Mutation | Type | Domain | Associated Phenotype |
|----------|------|--------|---------------------|
| E478G | Missense | UBD | ALS, glaucoma |
| Q398X | Nonsense | Coiled-coil | ALS |
| D474N | Missense | UBD | Glaucoma |
| M98K | Missense | N-terminus | Glaucoma |
| 691-692insAG | Frameshift | C-terminus | ALS |

Key Publications

Background

The study of Optn — Optineurin has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.

Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.

See Also

• [Amyotrophic Lateral Sclerosis](/diseases/amyotrophic-lateral-sclerosis) — ALS
• [Parkinson's Disease](/diseases/parkinsons-disease-disease) — PD
• [TBK1](/genes/tbk1) — TANK-binding kinase 1
• [Parkin](/genes/parkin) — PRKN
• [PINK1](/genes/pink1) — PTEN-induced kinase 1
• [Mitophagy](/mechanisms/mitophagy)
• [NF-κB Signaling](/mechanisms/nf-kb-signaling)
• [Mitochondrial Dynamics](/mechanisms/mitochondrial-dynamics)

External Links

• NCBI Gene: [https://www.ncbi.nlm.nih.gov/gene/10133](https://www.ncbi.nlm.nih.gov/gene/10133)
• Ensembl: [https://ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000123240](https://ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000123240)
• OMIM: [https://omim.org/entry/602432](https://omim.org/entry/602432)
• UniProt: [https://www.uniprot.org/uniprot/Q96CV9](https://www.uniprot.org/uniprot/Q96CV9)
• PubMed: [https://pubmed.ncbi.nlm.nih.gov/?term=OPTN+optineurin+ALS](https://pubmed.ncbi.nlm.nih.gov/?term=OPTN+optineurin+ALS)

References

Pathway Diagram

The following diagram shows the key molecular relationships involving OPTN — Optineurin discovered through SciDEX knowledge graph analysis:

Associated Diseases

• Als — associated with

• ALS — associated with

• Alzheimer — associated with

• Alzheimer's disease — associated with

• Alzheimer'S Disease — associated with

• amyotrophic lateral sclerosis — associated with

• Amyotrophic Lateral Sclerosis — associated with

• dementia — associated with

• Dementia — associated with

• frontotemporal — associated with

• frontotemporal dementia — associated with

• Frontotemporal Dementia — associated with

• Parkinson — associated with