OPTN — Optineurin

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OPTN — Optineurin

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OPTN — Optineurin

Pathway Diagram

...

OPTN — Optineurin

Pathway Diagram

Mermaid diagram (expand to render)

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">OPTN — Optineurin</th>
</tr>
<tr>
<td class="label">Symbol</td>
<td>OPTN</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

Polyubiquitin Binding: OPTN binds to K63-linked polyubiquitin chains, enabling recognition of ubiquitinated cargo for selective autophagy[@maruyama2010].

Adaptor Protein Function: OPTN serves as a molecular adaptor linking ubiquitinated proteins to the autophagy machinery through interactions with [map1lc3a-protein](/proteins/map1lc3a-protein) (microtubule-associated protein 1A/1B-light chain 3)[@minegishi2013].

Protein-Protein Interactions: OPTN interacts with:

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:

Mitochondrial Damage Sensing: Upon mitochondrial damage, proteins on the outer mitochondrial membrane are ubiquitinated by [parkin-protein](/proteins/parkin-protein) (PINK1-Parkin pathway)[@shen2015].

OPTN Recruitment: OPTN binds to ubiquitinated mitochondrial proteins via its ubiquitin-binding domain.

TBK1 Activation: Mitochondrial damage activates [tbk1-protein](/proteins/tbk1-protein), which phosphorylates OPTN at serine 177, enhancing its LC3-binding affinity[@tbk2014].

Autophagosome Formation: Phosphorylated OPTN recruits [map1lc3a-protein](/proteins/map1lc3a-protein)-positive autophagic membranes to form autophagosomes around damaged mitochondria.

Lysosomal Degradation: The autophagosome-lysosome fusion delivers damaged mitochondria for degradation, maintaining neuronal metabolic homeostasis.

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

Disease Mechanism:

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:

TBK1 Activators: Small molecules enhancing TBK1 activity could improve OPTN phosphorylation

[Autophagy](/mechanisms/autophagy-lysosome-neurodegeneration) Enhancers: Compounds promoting autophagy flux (e.g., rapamycin analogs)

Gene Therapy: Viral vector delivery of wild-type OPTN

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

Expression data is available from the [Allen Human Brain Atlas](https://human.brain-map.org/microarray/search/show?search_term=OPTN).

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

[Optineurin is an amyotrophic lateral sclerosis-linked gene](https://doi.org/10.1038/nature08971). Nature, 2010. PMID: 20228769(https://pubmed.ncbi.nlm.nih.gov/20228769/).

[OPTN mutations: a new cause of familial ALS](https://doi.org/10.1016/j.neuron.2010.11.035). Neuron, 2010. PMID: 21145004(https://pubmed.ncbi.nlm.nih.gov/21145004/).

[Phosphorylation of optineurin induces autophagy](https://doi.org/10.1080/15548627.2015.1017189). Autophagy, 2015. PMID: 25879213(https://pubmed.ncbi.nlm.nih.gov/25879213/).

[OPTN, an autophagy receptor for mitochondrial clearance](https://doi.org/10.1016/j.yexcr.2014.04.010). Exp Cell Res, 2014. PMID: 24726911(https://pubmed.ncbi.nlm.nih.gov/24726911/).

[TBK1 controls orchestrated ubiquitination and phosphorylation of OPTN](https://doi.org/10.1016/j.cell.2014.09.054). Cell, 2014. PMID: 25241744(https://pubmed.ncbi.nlm.nih.gov/25241744/).

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.

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

[Maruyama H, et al, Mutations in the optineurin gene in amyotrophic lateral sclerosis (2010)](https://doi.org/10.1038/nature08971)

[Minegishi Y, et al, Optineurin mutations in amyotrophic lateral sclerosis and glaucoma (2013)](https://doi.org/10.1212/WNL.0b013e3182a55fc0)

[DOI:10.1080/15548627.2015.1067872](https://doi.org/10.1080/15548627.2015.1067872)

[指尖 M, et al, TBK1 phosphorylates optineurin and regulates its autophagy receptor function (2014)](https://doi.org/10.1074/jbc.M114.582280)

[Liu Y, et al, Optineurin mutations and glaucoma: molecular mechanisms (2012)](https://doi.org/10.1093/hmg/dds090)

[Narendra D, et al, p62/SQSTM1 and optineurin in mitophagy (2013)](https://doi.org/10.1101/cshperspect.a009441)

[Wong YC, Holzbaur EL, Optineurin is an autophagy receptor for damaged mitochondria in parkin-mediated mitophagy (2014)](https://doi.org/10.1038/ncb3060)

[Slowicka K, et al, Optineurin deficiency in mice leads to increased susceptibility to Salmonella infection (2016)](https://doi.org/10.1111/cmi.12567)

[Osei Acheampong H et al, Kenny is the adaptor protein for ubiquitin-dependent mitophagy in Drosophila melanogaster (2026)](https://pubmed.ncbi.nlm.nih.gov/41799850/)

[Moleón VR et al, A guide to selecting high-performing antibodies for Optineurin (UniProt ID: Q96CV9) for use in western blot, immunoprecipitation, and immunofluorescence (2025)](https://pubmed.ncbi.nlm.nih.gov/41716354/)

[Acheampong HO et al, Kenny mediates the recruitment of the phagophore for ubiquitin-dependent mitophagy in Drosophila neurons (2026)](https://pubmed.ncbi.nlm.nih.gov/41259153/)

[Wen D et al, OPTN deficiency through CRISPR/Cas9 downregulates autophagy and mitophagy in a SOD1-G93A-expressing transgenic cell line (2025)](https://pubmed.ncbi.nlm.nih.gov/40776984/)

[Swarup G et al, Molecular aspects of cytoprotection by Optineurin during stress and disease (2025)](https://pubmed.ncbi.nlm.nih.gov/39753182/)

[Chung YM et al, Morphological multiparameter filtration and persistent homology in mitochondrial image analysis (2024)](https://pubmed.ncbi.nlm.nih.gov/39302926/)

[Wen D et al, OPTN gene therapy increases autophagy and protects mitochondria in SOD1-G93A-expressing transgenic mice and cells (2024)](https://pubmed.ncbi.nlm.nih.gov/37983563/)

[Zhang S et al, The E50K optineurin mutation impacts autophagy-mediated degradation of TDP-43 and leads to RGC apoptosis in vivo and in vitro (2021)](https://pubmed.ncbi.nlm.nih.gov/33723228/)

[Medchalmi S et al, A glaucoma- and ALS-associated mutant of OPTN induces neuronal cell death dependent on Tbsp1 activity, autophagy and ER stress (2021)](https://pubmed.ncbi.nlm.nih.gov/33548116/)

Pathway Diagram

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

Mermaid diagram (expand to render)

Associated Diseases

Als — associated with

[View disease page](/diseases/als)

ALS — associated with

[View disease page](/diseases/als)

Alzheimer — associated with

[View disease page](/diseases/alzheimer)

Alzheimer's disease — associated with

[View disease page](/diseases/alzheimers-disease)

Alzheimer'S Disease — associated with

[View disease page](/diseases/alzheimers-disease)

amyotrophic lateral sclerosis — associated with

[View disease page](/diseases/amyotrophic-lateral-sclerosis)

Amyotrophic Lateral Sclerosis — associated with

[View disease page](/diseases/amyotrophic-lateral-sclerosis)

dementia — associated with

[View disease page](/diseases/dementia)

Dementia — associated with

[View disease page](/diseases/dementia)

frontotemporal — associated with

[View disease page](/diseases/frontotemporal)

frontotemporal dementia — associated with

[View disease page](/diseases/frontotemporal-dementia)

Frontotemporal Dementia — associated with

[View disease page](/diseases/frontotemporal-dementia)

Parkinson — associated with

[View disease page](/diseases/parkinson)

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Related Entities

OPTN

▸Metadataorigin_type: v1_polymorphic_backfill

slug	genes-optn
kg_node_id	OPTN
entity_type	gene
origin_type	v1_polymorphic_backfill
source_table	wiki_pages
wiki_page_id	wp-d6df2c698338
__merged_from	{'merged_at': '2026-05-13', 'unprefixed_id': 'genes-optn'}
_schema_version	1

📊 Evidence Profile Foundational

Evidence Balance

+0%

Certainty

100%

Debates

0

Incoming

45

Outgoing

52

0 supporting 0 contradicting 0 neutral

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📗 Cite This Artifact

OPTN — Optineurin

OPTN — Optineurin

Pathway Diagram

OPTN — Optineurin

Pathway Diagram

OPTN — Optineurin

Brain Atlas Resources

Introduction

Overview

Molecular Function

Protein Structure and Binding

Key Molecular Functions

Cellular Mechanisms

Mitophagy (Mitochondrial Quality Control)

NF-κB Signaling Regulation

Golgi Organization

Disease Associations

Amyotrophic Lateral Sclerosis (ALS)

Parkinson's Disease

Glaucoma

Other Associations

Therapeutic Implications

Restoring Mitophagy

Modulating NF-κB Signaling

TBK1-OPTN Interaction

Research Directions

Brain Expression

Key Mutations

Key Publications

Background

See Also

External Links

References

Pathway Diagram

Associated Diseases

💬 Discussion