OSMR Gene

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OSMR Gene

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OSMR — Oncostatin M Receptor

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">OSMR Gene</th>
</tr>
<tr>
<td class="label">Gene Symbol</td>
<td>OSMR</td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>Oncostatin M Receptor</td>
</tr>
<tr>
<td class="label">Chromosomal Location</td>
<td>5p13.1</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>9184</td>
</tr>
<tr>
<td class="label">OMIM ID</td>
<td>601095</td>
</tr>
<tr>
<td class="label">Ensembl ID</td>
<td>ENSG00000120708</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>Q08357</td>
</tr>
<tr>
<td class="label">Gene Size</td>
<td>~65 kb</td>
</tr>
<tr>
<td class="label">Exons</td>
<td>12</td>
</tr>
<tr>
<td class="label">Protein Length</td>
<td>979 amino acids</td>
</tr>
<tr>
<td class="label">Molecular Weight</td>
<td>~110 kDa</td>
</tr>
<tr>
<td class="label">Complex</td>
<td>Composition</td>
</tr>
<tr>
<td class="label">Type I OSM receptor</td>
<td>OSMR + GP130 (IL6ST)</td>
</tr>
<tr>
<td class="label">Type II OSM receptor</td>
<td>OSMR + LIFR</td>
</tr>
<tr>
<td class="label">LIF receptor complex</td>
<td>OSMR + LIFR</td>
</tr>
<tr>
<td class="label">Cell Type</td>
<td>Expression Level</td>
</tr>
<tr>
<td class="label">Reactive astrocytes</td>
<td>Very high</td>
</tr>
<tr>
<td class="label">Microglia</td>
<td>Moderate</td>
</tr>
<tr>
<td class="label"

...

OSMR — Oncostatin M Receptor

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">OSMR Gene</th>
</tr>
<tr>
<td class="label">Gene Symbol</td>
<td>OSMR</td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>Oncostatin M Receptor</td>
</tr>
<tr>
<td class="label">Chromosomal Location</td>
<td>5p13.1</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>9184</td>
</tr>
<tr>
<td class="label">OMIM ID</td>
<td>601095</td>
</tr>
<tr>
<td class="label">Ensembl ID</td>
<td>ENSG00000120708</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>Q08357</td>
</tr>
<tr>
<td class="label">Gene Size</td>
<td>~65 kb</td>
</tr>
<tr>
<td class="label">Exons</td>
<td>12</td>
</tr>
<tr>
<td class="label">Protein Length</td>
<td>979 amino acids</td>
</tr>
<tr>
<td class="label">Molecular Weight</td>
<td>~110 kDa</td>
</tr>
<tr>
<td class="label">Complex</td>
<td>Composition</td>
</tr>
<tr>
<td class="label">Type I OSM receptor</td>
<td>OSMR + GP130 (IL6ST)</td>
</tr>
<tr>
<td class="label">Type II OSM receptor</td>
<td>OSMR + LIFR</td>
</tr>
<tr>
<td class="label">LIF receptor complex</td>
<td>OSMR + LIFR</td>
</tr>
<tr>
<td class="label">Cell Type</td>
<td>Expression Level</td>
</tr>
<tr>
<td class="label">Reactive astrocytes</td>
<td>Very high</td>
</tr>
<tr>
<td class="label">Microglia</td>
<td>Moderate</td>
</tr>
<tr>
<td class="label">Neurons</td>
<td>Low to moderate</td>
</tr>
<tr>
<td class="label">Oligodendrocyte precursors</td>
<td>Low</td>
</tr>
<tr>
<td class="label">Endothelial cells</td>
<td>Low</td>
</tr>
<tr>
<td class="label">Strategy</td>
<td>Approach</td>
</tr>
<tr>
<td class="label">OSM neutralizing antibodies</td>
<td>Bind free OSM, prevent OSMR activation</td>
</tr>
<tr>
<td class="label">OSMR decoy receptors</td>
<td>Soluble OSMR extracellular domain</td>
</tr>
<tr>
<td class="label">OSMR kinase inhibitors</td>
<td>Block JAK1/2 downstream of OSMR</td>
</tr>
<tr>
<td class="label">STAT3 inhibitors</td>
<td>Block transcriptional response</td>
</tr>
<tr>
<td class="label">Anti-inflammatory biologics</td>
<td>Broader cytokine suppression</td>
</tr>
<tr>
<td class="label">Partner</td>
<td>Interaction Type</td>
</tr>
<tr>
<td class="label">OSM (OSM)</td>
<td>Primary ligand</td>
</tr>
<tr>
<td class="label">LIF (LIF)</td>
<td>Secondary ligand (with LIFR)</td>
</tr>
<tr>
<td class="label">GP130 (IL6ST)</td>
<td>Co-receptor in Type I complex</td>
</tr>
<tr>
<td class="label">LIFR</td>
<td>Co-receptor in Type II complex</td>
</tr>
<tr>
<td class="label">JAK1</td>
<td>Kinase binding (BOX1)</td>
</tr>
<tr>
<td class="label">JAK2</td>
<td>Kinase binding (BOX1/BOX2)</td>
</tr>
<tr>
<td class="label">STAT3</td>
<td>Recruitment and phosphorylation</td>
</tr>
<tr>
<td class="label">SHC</td>
<td>Adaptor protein</td>
</tr>
<tr>
<td class="label">PI3K p85</td>
<td>Regulatory subunit recruitment</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/alzheimer's-disease" style="color:#ef9a9a">ALZHEIMER'S DISEASE</a>, <a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/alzheimer" style="color:#ef9a9a">Alzheimer</a>, <a href="/wiki/cancer" style="color:#ef9a9a">Cancer</a>, <a href="/wiki/dementia" style="color:#ef9a9a">Dementia</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">32 edges</a></td>
</tr>
</table>

Overview

OSMR (Oncostatin M Receptor) encodes a type I cytokine receptor that mediates signaling from IL-6 family cytokines, primarily Oncostatin M (OSM) and Leukemia Inhibitory Factor (LIF) [@breedlove2020]. OSMR is a critical regulator of neuroinflammation and is implicated in the pathogenesis of Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS). As a component of the OSM receptor complex, OSMR activates JAK/STAT3, MAPK/ERK, and PI3K/Akt signaling cascades that drive astrocyte reactivity, microglial activation, and neurotoxic inflammatory responses [@silverman2019].

Unlike most cytokine receptors with restricted expression, OSMR is broadly expressed in the CNS, with particularly high levels on reactive astrocytes surrounding sites of pathology. OSMR-expressing astrocytes adopt a pro-inflammatory "A1" phenotype in response to OSM signaling, releasing complement components and neurotoxic factors that damage neurons [@chen2021]. This makes OSMR a high-value therapeutic target for suppressing neuroinflammation across multiple neurodegenerative conditions.

Gene and Protein Structure

Genomic Organization

Protein Architecture

OSMR is a single-pass type I transmembrane receptor with distinct structural domains [@breedlove2020]:

Mermaid diagram (expand to render)

Functional domains:

Extracellular cytokine-binding domain: Composed of two CTD (cysteine-rich) subdomains (D1-D6), responsible for ligand recognition and binding. The N-terminal D1-D3 subdomain confers high-affinity OSM binding, while the membrane-proximal D4-D6 subdomain contributes to receptor dimerization

Transmembrane helix: Single-pass transmembrane anchor

Intracellular signaling domain: Contains BOX1 and BOX2 motifs that bind JAK1 and JAK2 kinases. The C-terminal region recruits STAT3 and other signaling intermediates

Receptor Complexes

OSMR forms two functionally distinct receptor complexes [@chen2021]:

The Type I complex is the primary mediator of OSM-driven neuroinflammation. When OSM binds OSMR, GP130 is recruited to form a signaling-competent trimeric complex that activates JAK1/2.

Biological Functions

JAK/STAT3 Signaling Cascade

The primary downstream pathway activated by OSMR [@chen2021]:

Mermaid diagram (expand to render)

Key targets of STAT3 in CNS:

Cytokines: IL-6, IL-1beta, TNF-alpha, LIF
Chemokines: CCL2/MCP-1, CXCL1, CXCL10
Complement: C3, C1q (characteristic of A1 astrocytes)
iNOS: Inducible nitric oxide synthase, driving oxidative stress

MAPK/ERK Pathway

OSMR also activates the Ras-Raf-MEK-ERK cascade:

SHC recruitment: Adaptor protein SHC binds phospho-OSMR

GRB2/SOS complex: Downstream signaling molecules

Ras activation: GTP-bound Ras initiates cascade

ERK phosphorylation: Transcription of proliferation/differentiation genes

PI3K/Akt Pathway

The PI3K/Akt branch provides survival signals:

Cell survival: Akt phosphorylates BAD, FOXO transcription factors
Metabolic regulation: mTORC1 activation for protein synthesis
Anti-apoptotic: Protection against cytokine-induced cell death

Regulation of Glial Cells

OSMR signaling critically shapes astrocyte and microglial phenotypes [@smith2023]:

Astrocytes:

Drives conversion to reactive A1 phenotype
Upregulates complement component expression (C3, C1q)
Induces neurotoxic factor secretion (Lymphotoxin-alpha, TNF)
Impairs homeostatic functions (glutamate uptake, potassium buffering)

Microglia:

Promotes pro-inflammatory activation (M1 phenotype)
Enhances phagocytosis of debris
Drives cytokine and ROS production
Regulates synaptic pruning in development and disease

Disease Associations

Alzheimer's Disease

OSMR is a major driver of astrocyte reactivity in AD [@zeller2022][@chen2021][@smith2023]:

Expression pattern: OSMR is highly elevated in astrocytes surrounding amyloid plaques in AD cortex and hippocampus

Aβ synergy: Amyloid-beta oligomers upregulate OSM in microglia, which in turn activates astrocytes via OSMR

Complement-mediated toxicity: OSM-driven astrocytes produce C1q and C3, which promote synaptic loss

Tau pathology: OSM-OSMR signaling accelerates tau phosphorylation in neurons through IL-6 and downstream GSK3-β activation

Cognitive decline: OSMR levels in CSF correlate with cognitive impairment scores in AD patients

Mechanistic cascade in AD:

Mermaid diagram (expand to render)

Parkinson's Disease

OSMR contributes to dopaminergic neuron vulnerability in PD [@walker2021][@kim2020]:

Elevated OSM in SN: OSM levels are significantly increased in the substantia nigra of PD patients

Dopaminergic neuron expression: These neurons express OSMR, making them direct targets of OSM toxicity

Astrocyte-mediated damage: OSM-activated astrocytes in the substantia nigra release neurotoxic factors

α-synuclein interaction: OSMR signaling amplifies the inflammatory response to α-synuclein pathology

Therapeutic potential: OSMR inhibition protects dopaminergic neurons in MPTP and 6-OHDA models

Amyotrophic Lateral Sclerosis

OSMR is implicated in motor neuron degeneration in ALS [@huang2021][@muller2023][@wang2023]:

CSF elevation: OSM levels are elevated in ALS cerebrospinal fluid

Motor neuron OSMR: Motor neurons express OSMR and respond directly to OSM

Astrocyte activation: SOD1 and TDP-43 pathology activate astrocytes via OSM-OSMR signaling

Excitotoxicity: OSM-OSMR signaling impairs glutamate transporter expression, exacerbating excitotoxicity

Progression correlation: OSMR expression on astrocytes correlates with disease progression rate

Multiple Sclerosis

OSMR signaling in MS reflects its dual roles in inflammation and repair [@ward2022][@baker2022]:

Active demyelinating lesions: High OSMR expression in astrocytes within lesions

Glial scar formation: OSM-OSMR promotes reactive astrogliosis and scar formation

Remyelination: OSM can promote oligodendrocyte precursor differentiation in some contexts

Repair vs. damage: Context-dependent effects make OSMR a complex therapeutic target in MS

Molecular Mechanisms

Astrocyte Reactivity (A1 Phenotype)

OSM is a potent inducer of the neurotoxic A1 astrocyte phenotype [@chen2021]:

The A1 phenotype was defined by Liddelow et al. (2017) as astrocytes induced by reactive microglia. OSM is one of the primary cytokines driving this conversion:

A1-specific gene signature induced by OSM:

C3: Complement component 3 (hallmark of neurotoxic astrocytes)
C1q: Complement component 1q
Lymphotoxin-alpha (LTA): Pro-inflammatory cytokine
TNF: Tumor necrosis factor
IL-1α: Interleukin-1 alpha
Fbln5: Fibulin-5 (extracellular matrix remodeling)

These A1 astrocytes lose their normal homeostatic functions (glutamate uptake, potassium buffering, metabolic support) and instead actively damage and eliminate synapses and neurons.

Synaptic Dysfunction

OSM-OSMR signaling disrupts synaptic function through multiple mechanisms [@smith2023]:

Complement-mediated pruning: C1q and C3 mark synapses for microglial elimination

TNF toxicity: Direct effects of TNF on NMDA receptor function

Glutamate dysregulation: Impaired GLT-1 (SLC1A3) expression and function

Structural remodeling: Dendritic spine loss and axonal degeneration

Neuroinflammatory Amplification

OSMR creates a self-reinforcing inflammatory loop:

Mermaid diagram (expand to render)

Expression Pattern

Brain Expression

OSMR is expressed in multiple cell types with cell-type specificity:

Regional Distribution

Cortex: High in cortical layers 2-3 and 5-6, especially around amyloid plaques in AD
Hippocampus: High in CA1 and dentate gyrus, correlating with memory circuits
Substantia nigra: Moderate expression on dopaminergic neurons and surrounding glia
Spinal cord: High in ALS, particularly in ventral horn motor neuron region
White matter: Lower baseline, increases dramatically in MS lesions

Developmental Expression

OSMR expression is low during development and increases with aging:

Fetal/neonatal: Low expression, restricted to ventricular zones
Adult: Moderate baseline expression in astrocytes
Aging: Progressive upregulation, particularly in disease states
Age-related increase: Contributes to the inflammaging phenomenon

Therapeutic Implications

OSMR as a Therapeutic Target

OSMR represents a compelling target for neurodegenerative disease modification [@silverman2019][@richter2021]:

Small Molecule Inhibitors

JAK inhibitors approved for other indications may be repurposed:

Tofacitinib: JAK1/JAK3 inhibitor, crosses BBB
Ruxolitinib: JAK1/JAK2 inhibitor, used in myeloproliferative disorders
Baricitinib: JAK1/JAK2 inhibitor, approved for rheumatoid arthritis
PF-06730512: CNS-penetrant JAK inhibitor in development

Biomarker Potential

OSMR pathway markers in CSF and blood:

OSM levels: Elevated in AD, PD, ALS CSF
Soluble OSMR: Shedding of extracellular domain
pSTAT3 in astrocytes: Imaging marker of pathway activation
A1 astrocyte markers: C3, C1q in CSF

Interaction Network

Ligands and Receptors

Downstream Transcription Factors

STAT3: Primary transcriptional activator of neuroinflammatory genes
STAT1: Activated by IFN-γ, cross-talk with STAT3
AP-1 (c-Fos/c-Jun): MAPK-dependent activation
NF-κB: Sustained inflammatory response (secondary)
CREB: Acute phase gene expression

Cross-Disease Relevance

OSMR connects multiple neurodegeneration pathways:

Aβ pathway: Enhanced by OSM-OSMR signaling
Tau pathway: GSK3-β activation downstream of STAT3
α-synuclein: OSM amplifies inflammatory response
TDP-43: Cooperates with OSM-driven neuroinflammation
Aging: Upregulated with age, driving inflammaging

Animal Models

OSM Overexpression Models

AAV-OSM injection: Recapitulates A1 astrocyte phenotype
Transgenic OSM: Spontaneous neuroinflammation with age
GFAP-OSM mice: Astrocyte-specific OSM production

OSMR Knockout Models

Constitutive KO: Viable, reduced baseline neuroinflammation
Astrocyte-specific KO: Reduced A1 astrocyte conversion
Conditional KO: Developmental and adult-stage phenotypes

Disease Models

5xFAD mice: Increased OSMR and A1 astrocytes; OSMR inhibition reduces pathology
MPTP/6-OHDA PD models: OSM-OSMR blockade protects dopaminergic neurons
SOD1-G93A ALS mice: OSMR on astrocytes correlates with progression
EAE MS model: OSMR deletion reduces demyelination and clinical severity

Cross-Links

[OSM (Oncostatin M)](/proteins/oncostatin-m) — Primary ligand
[GP130/IL6ST](/genes/il6st) — Co-receptor in OSM signaling
[LIFR](/genes/lifr) — Alternative co-receptor
[JAK1](/genes/jak1) — Primary kinase downstream of OSMR
[JAK2](/genes/jak2) — Redundant kinase
[STAT3](/genes/stat3) — Primary transcription factor
[IL6 (Interleukin-6)](/proteins/il-6) — Related cytokine with overlapping signaling
[TNF (Tumor Necrosis Factor-alpha)](/proteins/tnf-alpha) — Pro-inflammatory cytokine

[JAK/STAT3 Signaling](/mechanisms/jak-stat-signaling) — Core pathway
[Neuroinflammation](/mechanisms/neuroinflammation) — OSMR-driven inflammation
[Astrocyte Reactivity](/cell-types/astrocytes-neuroinflammation) — A1 phenotype induction
[Complement Cascade](/mechanisms/complement-cascade) — C1q/C3 in synaptic dysfunction
[Microglial Activation](/cell-types/microglia-neuroinflammation) — Neurotoxic phenotype

[Alzheimer's Disease](/diseases/alzheimers-disease) — Aβ synergy, astrocyte reactivity
[Parkinson's Disease](/diseases/parkinsons-disease) — Dopaminergic neuron vulnerability
[Amyotrophic Lateral Sclerosis](/diseases/amyotrophic-lateral-sclerosis) — Motor neuron degeneration
[Multiple Sclerosis](/diseases/multiple-sclerosis) — Demyelination and repair

[Cytokine Signaling in Neurodegeneration](/mechanisms/cytokine-signaling-neurodegeneration)
[A1 Astrocyte Induction Pathway](/mechanisms/a1-astrocyte-induction)
[JAK/STAT3 in CNS Disease](/mechanisms/jak-stat-cns-disease)
[Complement-Mediated Synaptic Pruning](/mechanisms/complement-synaptic-pruning)

Pathway Diagram

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

Mermaid diagram (expand to render)

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Related Entities

OSMR

▸Metadataorigin_type: v1_polymorphic_backfill

slug	genes-osmr
kg_node_id	OSMR
entity_type	gene
origin_type	v1_polymorphic_backfill
source_table	wiki_pages
wiki_page_id	wp-b682cc864b69
__merged_from	{'merged_at': '2026-05-13', 'unprefixed_id': 'genes-osmr'}
_schema_version	1

📊 Evidence Profile

Evidence Balance

+0%

Certainty

25%

Debates

0

Incoming

5

Outgoing

29

0 supporting 0 contradicting 0 neutral

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📗 Cite This Artifact

OSMR Gene

OSMR — Oncostatin M Receptor

OSMR — Oncostatin M Receptor

Overview

Gene and Protein Structure

Genomic Organization

Protein Architecture

Receptor Complexes

Biological Functions

JAK/STAT3 Signaling Cascade

MAPK/ERK Pathway

PI3K/Akt Pathway

Regulation of Glial Cells

Disease Associations

Alzheimer's Disease

Parkinson's Disease

Amyotrophic Lateral Sclerosis

Multiple Sclerosis

Molecular Mechanisms

Astrocyte Reactivity (A1 Phenotype)

Synaptic Dysfunction

Neuroinflammatory Amplification

Expression Pattern

Brain Expression

Regional Distribution

Developmental Expression

Therapeutic Implications

OSMR as a Therapeutic Target

Small Molecule Inhibitors

Biomarker Potential

Interaction Network

Ligands and Receptors

Downstream Transcription Factors

Cross-Disease Relevance

Animal Models

OSM Overexpression Models

OSMR Knockout Models

Disease Models

Cross-Links

Related Genes and Proteins

Related Mechanisms

Related Diseases

Related Pathways

Pathway Diagram

💬 Discussion