STING1 Gene

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STING1 Gene

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wiki page Created: 2026-04-02T07:19:20 By: crosslink-migration Quality: 50% ✓ SciDEX ID: wiki-genes-sting1

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STING1 Gene

Overview

Pathway Diagram

```mermaid
flowchart TD
STING1["STING1<br/>Stimulator of Interferon Genes"]

mtDNA["Mitochondrial DNA<br/>Damage/Stress"]
CGAS["cGAS<br/>Cyclic GMP-AMP Synthase"]
cGAMP["cGAMP<br/>Cyclic Dinucleotide"]

TYPE_I_IFN["Type I Interferon<br/>Immune Response"]
MTORC1["mTORC1<br/>Metabolic Regulator"]
AUTOPHAGY["Autophagy<br/>Cellular Clearance"]
LIPOPHAGY["Lipophagy<br/>Lipid Droplet Clearance"]

INFLAMMATION["Neuroinflammation<br/>Chronic Activation"]

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

CSNK1A1["CSNK1A1<br/>Regulatory Kinase"]
SAVI["SAVI<br/>Autoinflammatory Disease"]

mtDNA -->|"activates"| CGAS
CGAS -->|"produces"| cGAMP
cGAMP -->|"activates"| STING1
mtDNA -->|"directly activates"| STING1

STING1 -->|"activates"| TYPE_I_IFN
STING1 -->|"activates"| MTORC1
STING1 -->|"inhibits"| LIPOPHAGY
STING1 -->|"regulates"| INFLAMMATION
STING1 -->|"causes"| SAVI

AUTOPHAGY -->|"inhibits"| STING1
CSNK1A1 -->|"inhibits"| STING1

INFLAMMATION -->|"contributes to"| ALZHEIMER
INFLAMMATION -->|"contributes to"| PARKINSON
INFLAMMATION -->|"contributes to"| ALS
INFLAMMATION -->|"contributes to"| MS

style STING1 fill:#006494
style AUTOPHAGY fill:#1b5e20
style CSNK1A1 fill:#4a1a6b
style CGAS fill:#4a1a6b
style MTORC1 fill:#4a1a6b
style mtDNA fill:#ef5350
style

...

STING1 Gene

Overview

Pathway Diagram

Mermaid diagram (expand to render)

STING1 (Stimulator of Interferon Genes 1, also known as TMEM173 or MITA) encodes the STING protein, a critical adaptor in the [cGAS](/genes/cgas)-STING innate immune signaling pathway. STING detects cytosolic double-stranded DNA (dsDNA) — a danger-associated molecular pattern released from damaged mitochondria, stressed nuclei, and dying cells — and triggers type I interferon and inflammatory cytokine production. In the central nervous system, aberrant cGAS-STING activation in [microglia](/cell-types/microglia) and [astrocytes](/cell-types/astrocytes) is increasingly recognized as a driver of chronic neuroinflammation in [Alzheimer's disease](/diseases/alzheimers-disease), [Parkinson's disease](/diseases/parkinsons-disease), [ALS](/diseases/amyotrophic-lateral-sclerosis), and age-related neurodegeneration.

<div class="infobox infobox-gene"> [@sliter2018]
<div class="infobox-header">STING1</div> [@xie2023]
<table> [@jin2021]
<tr><td class="infobox-label">Full Name</td><td>Stimulator of Interferon Genes 1</td></tr> [@mccauley2020]
<tr><td class="infobox-label">Gene Symbol</td><td>STING1 (TMEM173)</td></tr> [@paul2021]
<tr><td class="infobox-label">Chromosomal Location</td><td>5q31.2</td></tr> [@ablasser2019]
<tr><td class="infobox-label">NCBI Gene ID</td><td>[340061](https://www.ncbi.nlm.nih.gov/gene/340061)</td></tr> [@gulen2023]
<tr><td class="infobox-label">Ensembl ID</td><td>[ENSG00000184584](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000184584)</td></tr>
<tr><td class="infobox-label">UniProt ID</td><td>[Q86WV6](https://www.uniprot.org/uniprot/Q86WV6)</td></tr>
<tr><td class="infobox-label">Protein</td><td>[STING Protein](/proteins/sting1-protein)</td></tr>
<tr><td class="infobox-label">Associated Diseases</td><td>[AD](/diseases/alzheimers-disease), [PD](/diseases/parkinsons-disease), [ALS](/diseases/amyotrophic-lateral-sclerosis), [FTD](/diseases/frontotemporal-dementia), SAVI</td></tr>
</table>
</div>

Function

The cGAS-STING Pathway

STING1 encodes the central signaling hub of the cytosolic DNA sensing pathway:

DNA sensing: [cGAS](/genes/cgas) (cyclic GMP-AMP synthase) binds cytosolic dsDNA from any source — mitochondrial, nuclear, microbial, or retrotransposon-derived

Second messenger synthesis: Activated cGAS catalyzes the synthesis of 2'3'-cyclic GMP-AMP (cGAMP), a cyclic dinucleotide second messenger

STING activation: cGAMP binds to the STING dimer on the endoplasmic reticulum membrane, inducing a conformational change

STING trafficking: Activated STING traffics from the ER to the Golgi via COPII vesicles

Kinase recruitment: At the Golgi, STING recruits and activates [TBK1](/genes/tbk1) (TANK-binding kinase 1)

Transcription factor activation: TBK1 phosphorylates [IRF3](/genes/irf3) and activates [NF-κB](/entities/nf-kb)

Gene induction: Phospho-IRF3 translocates to the nucleus and induces type I interferons (IFN-α, [IFN-β](/genes/ifnb1)); NF-κB induces pro-inflammatory cytokines ([TNF-α](/genes/tnf), [IL-6](/genes/il6), [IL-1β](/genes/il1b))

Autophagic degradation: STING is ultimately degraded through [autophagy](/entities/autophagy) to terminate signaling

Sources of Cytosolic DNA in Neurodegeneration

Mitochondrial DNA (mtDNA): Released through mitochondrial permeability transition pore (mPTP) opening, [BAX](/genes/bax)/[BAK](/genes/bak1) pores, and impaired mitophagy
Nuclear DNA: Released during DNA damage, chromatin remodeling defects, and micronuclei formation
Retrotransposon DNA: LINE-1 and Alu element reverse transcription products accumulate with aging and epigenetic derepression
Extracellular DNA: Released from dying [neurons](/entities/neurons) and taken up by phagocytic glia

Disease Associations

Alzheimer's Disease

cGAS-STING is activated at multiple stages of AD pathology:

[Tau](/proteins/tau) pathology induces nuclear envelope disruption and cytosolic chromatin release, activating cGAS-STING in neurons and [microglia](/cell-types/microglia-neuroinflammation)
[Amyloid-beta](/proteins/amyloid-beta)-induced mitochondrial damage releases mtDNA into the cytosol
Microglial STING activation promotes senescence-associated secretory phenotype (SASP)
Genetic variants near STING1 show nominal association with AD risk in GWAS
STING knockout in tauopathy mice (PS19) reduces neuroinflammation, brain atrophy, and [p-tau](/biomarkers/p-tau) levels
IFN-β signaling downstream of STING drives complement activation and synapse loss

Parkinson's Disease

[PINK1](/genes/pink1)/[Parkin](/genes/prkn) deficiency impairs mitophagy, leading to mtDNA accumulation in the cytosol
Pink1−/− and Prkn−/− mice show STING-dependent systemic inflammation; crossing to Sting1−/− rescues the inflammatory phenotype
[α-Synuclein](/proteins/alpha-synuclein) aggregation causes mitochondrial fragmentation and mtDNA release
[LRRK2](/genes/lrrk2) mutations enhance STING-dependent IFN-β production in macrophages and microglia
Dopaminergic neurons in the [substantia nigra](/brain-regions/substantia-nigra) show elevated cGAS and STING expression in PD postmortem tissue

Amyotrophic Lateral Sclerosis / Frontotemporal Dementia

[TDP-43](/genes/tardbp) loss of nuclear function leads to retrotransposon derepression and cytosolic DNA accumulation
[C9orf72](/genes/c9orf72) repeat expansions produce DPR aggregates that damage mitochondria and trigger mtDNA release
[SOD1](/entities/sod1) mutant motor neurons show enhanced cGAS-STING activation
STING inhibition extends survival in SOD1-G93A mice

Aging

Normal aging is associated with progressive cGAS-STING activation due to:

Accumulation of cytosolic mtDNA from age-related mitochondrial dysfunction
Derepression of retrotransposable elements (particularly LINE-1)
Increased DNA damage and micronuclei formation
This "sterile inflammation" or inflammaging contributes to age-related neurodegeneration

STING-Associated Vasculopathy (SAVI)

Gain-of-function mutations in STING1 (e.g., V155M, N154S) cause SAVI, a severe autoinflammatory disease with constitutive type I IFN production. Although primarily a systemic vasculopathy, SAVI patients can develop CNS inflammation including basal ganglia calcification.

Expression

Microglia: High STING expression; primary CNS responders to cytosolic DNA
[Astrocytes](/entities/astrocytes): Moderate expression; astrocytic STING signaling promotes A1 reactive phenotype
Neurons: Low basal expression but upregulated under stress; neuronal STING may contribute to cell-autonomous inflammatory signaling
Oligodendrocytes: Low expression
Endothelial cells: Moderate expression; relevant for [blood-brain barrier](/mechanisms/blood-brain-barrier) inflammation

Therapeutic Targeting

STING Inhibitors

H-151: Covalent small molecule STING inhibitor; blocks palmitoylation required for STING clustering and signaling; efficacious in tauopathy and PD mouse models
C-178 and C-176: Covalent STING inhibitors that block trafficking from ER to Golgi
SN-011: Non-covalent STING antagonist that competes with cGAMP binding
Astin C: Natural product STING inhibitor from Aster tataricus

Upstream Targets

cGAS inhibitors: RU.521, G150 block the DNA sensor upstream of STING
DNase delivery: Enhanced degradation of cytosolic DNA to reduce cGAS activation

Clinical Development

Several STING inhibitors are in early clinical development for autoimmune conditions. Repurposing for neurodegeneration requires demonstration of CNS penetrance and sustained target engagement.

External Links

[NCBI Gene: STING1](https://www.ncbi.nlm.nih.gov/gene/340061)
[UniProt: Q86WV6](https://www.uniprot.org/uniprot/Q86WV6)
[GeneCards: STING1](https://www.genecards.org/cgi-bin/carddisp.pl?gene=STING1)
[OMIM: TMEM173](https://www.omim.org/entry/612374)
[Allen Brain Atlas: TMEM173](https://human.brain-map.org/microarray/search/show?search_term=TMEM173)

References

[Decout A et al., The cGAS-STING pathway as a therapeutic target in inflammatory diseases (2021) (2021)](https://doi.org/10.1038/s41577-021-00524-z)

[Sliter DA et al., Parkin and PINK1 mitigate STING-induced inflammation (2018) (2018)](https://doi.org/10.1038/s41586-018-0448-9)

[Xie X et al., Activation of innate immune cGAS-STING pathway contributes to Alzheimer's pathogenesis in 5×FAD mice (2023) (2023)](https://doi.org/10.1038/s43587-023-00372-x)

[Jin M et al., Tau activates microglia via the PQBP1-cGAS-STING pathway to promote brain inflammation (2021) (2021)](https://doi.org/10.1038/s41593-021-00911-y)

[McCauley ME et al., C9orf72 in myeloid cells suppresses STING-induced inflammation (2020) (2020)](https://doi.org/10.1038/s41586-020-2625-x)

[Paul BD et al., Signaling by cGAS-STING in neurodegeneration, neuroinflammation, and aging (2021) (2021)](https://doi.org/10.1016/j.tins.2020.10.008)

[Unknown, Ablasser A & Chen ZJ, cGAS in action: expanding roles in immunity and inflammation (2019) (2019)](https://doi.org/10.1126/science.aat8657)

[Gulen MF et al., cGAS-STING drives ageing-related inflammation and neurodegeneration (2023) (2023)](https://doi.org/10.1038/s41586-023-06373-1)

From the [SciDEX Exchange](/exchange) — scored by multi-agent debate

[Senescent Cell Mitochondrial DNA Release](/hypothesis/h-1a34778f) — <span style="color:#ffd54f;font-weight:600">0.54</span> · Target: CGAS/STING1/DNASE2

Pathway Diagram

The following diagram shows the key molecular relationships involving STING1 Gene discovered through SciDEX knowledge graph analysis:

Mermaid diagram (expand to render)

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Related Entities

STING1

▸Metadataorigin_type: v1_polymorphic_backfill

slug	genes-sting1
kg_node_id	STING1
entity_type	gene
origin_type	v1_polymorphic_backfill
source_table	wiki_pages
wiki_page_id	wp-d9c12d4058be
__merged_from	{'merged_at': '2026-05-13', 'unprefixed_id': 'genes-sting1'}
_schema_version	1

📊 Evidence Profile Foundational

Evidence Balance

+0%

Certainty

100%

Debates

0

Incoming

24

Outgoing

66

0 supporting 0 contradicting 0 neutral

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📗 Cite This Artifact

STING1 Gene

STING1 Gene

Overview

Pathway Diagram

STING1 Gene

Overview

Pathway Diagram

Function

The cGAS-STING Pathway

Sources of Cytosolic DNA in Neurodegeneration

Disease Associations

Alzheimer's Disease

Parkinson's Disease

Amyotrophic Lateral Sclerosis / Frontotemporal Dementia

Aging

STING-Associated Vasculopathy (SAVI)

Expression

Therapeutic Targeting

STING Inhibitors

Upstream Targets

Clinical Development

See Also

External Links

References

Pathway Diagram

💬 Discussion

📗 Cite This Artifact

STING1 Gene

STING1 Gene

Overview

Pathway Diagram

STING1 Gene

Overview

Pathway Diagram

Function

The cGAS-STING Pathway

Sources of Cytosolic DNA in Neurodegeneration

Disease Associations

Alzheimer's Disease

Parkinson's Disease

Amyotrophic Lateral Sclerosis / Frontotemporal Dementia

Aging

STING-Associated Vasculopathy (SAVI)

Expression

Therapeutic Targeting

STING Inhibitors

Upstream Targets

Clinical Development

See Also

External Links

References

Related Hypotheses

Pathway Diagram

💬 Discussion