STAB1 Gene

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STAB1 Gene

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STAB1 Gene

<div class="infobox infobox-gene">
<table>
<tr><th colspan="2" style="background:#f0f0f0;">STAB1</th></tr>
<tr><td>Full Name</td><td>Stabilin 1</td></tr>
<tr><td>Gene Symbol</td><td>STAB1</td></tr>
<tr><td>Alternate Names</td><td>STABILIN-1, FEEL-1, FIVE-LINE</td></tr>
<tr><td>Chromosomal Location</td><td>3p22.1</td></tr>
<tr><td>NCBI Gene ID</td><td><a href="https://www.ncbi.nlm.nih.gov/gene/23168" target="_blank">23168</a></td></tr>
<tr><td>OMIM</td><td><a href="https://www.omim.org/entry/608744" target="_blank">608744</a></td></tr>
<tr><td>Ensembl ID</td><td>ENSG00000010318</td></tr>
<tr><td>UniProt ID</td><td><a href="https://www.uniprot.org/uniprotkb/Q9Y5K6" target="_blank">Q9Y5K6</a></td></tr>
<tr><td>Protein Length</td><td>2,550 amino acids</td></tr>
<tr><td>Category</td><td>Scavenger Receptor/Immune Function</td></tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1 edges</a></td>
</tr>
</table>
</div>

Overview

...

STAB1 Gene

<div class="infobox infobox-gene">
<table>
<tr><th colspan="2" style="background:#f0f0f0;">STAB1</th></tr>
<tr><td>Full Name</td><td>Stabilin 1</td></tr>
<tr><td>Gene Symbol</td><td>STAB1</td></tr>
<tr><td>Alternate Names</td><td>STABILIN-1, FEEL-1, FIVE-LINE</td></tr>
<tr><td>Chromosomal Location</td><td>3p22.1</td></tr>
<tr><td>NCBI Gene ID</td><td><a href="https://www.ncbi.nlm.nih.gov/gene/23168" target="_blank">23168</a></td></tr>
<tr><td>OMIM</td><td><a href="https://www.omim.org/entry/608744" target="_blank">608744</a></td></tr>
<tr><td>Ensembl ID</td><td>ENSG00000010318</td></tr>
<tr><td>UniProt ID</td><td><a href="https://www.uniprot.org/uniprotkb/Q9Y5K6" target="_blank">Q9Y5K6</a></td></tr>
<tr><td>Protein Length</td><td>2,550 amino acids</td></tr>
<tr><td>Category</td><td>Scavenger Receptor/Immune Function</td></tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1 edges</a></td>
</tr>
</table>
</div>

Overview

STAB1 (Stabilin 1), also known as FEEL-1 (FasL and EGF-like, laminin-type EGF-like domain containing scavenger receptor 1), is a large transmembrane scavenger receptor expressed predominantly on sinusoidal endothelial cells, macrophages, and certain populations of microglia in the brain. STAB1 plays crucial roles in maintaining tissue homeostasis through its capacity to clear altered self-components, including apoptotic cells, aged erythrocytes, hemoglobin-haptoglobin complexes, and advanced glycation end products [@ncbi].

Originally identified as a receptor involved in lymphatic vessel development and vascular remodeling, STAB1 has more recently been implicated in neurodegenerative diseases through its functions in neuroinflammation, microglial activation, and clearance of pathological protein aggregates. The receptor belongs to the family of scavenger receptors that recognize a broad range of polyanionic ligands, making it a versatile player in immune surveillance and tissue maintenance [@goh2020].

The identification of STAB1 genetic variants associated with Alzheimer's disease and Parkinson's disease risk has highlighted its potential importance in neurodegeneration. Studies have demonstrated STAB1 expression in brain-resident macrophages (microglia and border-associated macrophages), where it contributes to immune regulation and may influence disease progression. Understanding the role of STAB1 in neuroinflammation and protein clearance provides insight into potential therapeutic targets for neurodegenerative conditions [@ser2017].

Protein Structure

STAB1 is a large type I transmembrane protein with a complex modular architecture:

| Domain | Location | Function |
|--------|----------|----------|
| Signal peptide | 1-27 aa | Secretory pathway targeting |
| FasL domain | 28-200 aa | Apoptotic cell recognition |
| EGF-like repeats | 200-800 aa | Ligand binding, protein interactions |
| Linker domain | 800-1000 aa | Flexibility, spacing |
| Scavenger receptor cysteine-rich (SRCR) | 1000-2000 aa | Pattern recognition |
| Transmembrane region | 2000-2025 aa | Membrane anchoring |
| Cytoplasmic tail | 2025-2550 aa | Signaling, endocytosis |

Scavenger Receptor Domains

The SRCR domains are characteristic of class A scavenger receptors:

Conserved cysteine residues form disulfide bonds
Mediate binding to polyanionic ligands
Enable recognition of modified proteins and lipids
Critical for phagocytic clearance functions [@park2016]

Post-translational Modifications

STAB1 undergoes several modifications:

N-linked glycosylation: Multiple sites in extracellular domains
Tyrosine sulfation: In the extracellular region
Palmitoylation: Potential at cysteine residues
Phosphorylation: In the cytoplasmic tail for signaling

Molecular Function

Scavenger Receptor Activity

STAB1 functions as a pattern recognition receptor:

| Ligand Type | Examples | Function |
|-------------|----------|----------|
| Apoptotic cells | Phosphatidylserine exposure | Phagocytic clearance |
| Aged erythrocytes | Band 3 modifications | Red blood cell turnover |
| Hemoglobin complexes | Hb-Hp, Hb-Hpx | Heme iron recycling |
| Modified proteins | Acetylated LDL, AGE | Metabolic clearance |
| Pathogens | Bacterial components | Immune surveillance |
| Protein aggregates | Aβ, α-synuclein | Aggregate clearance |

Endocytic Trafficking

STAB1 mediates efficient endocytosis of ligands:

Ligand binding: Recognition via SRCR domains

Clathrin-mediated endocytosis: Internalization via coated pits

Endosomal trafficking: Delivery to lysosomes

Receptor recycling: Return to the cell surface

Degradation: Lysosomal processing of cargo [@kuz2016]

Signaling Functions

The cytoplasmic tail contains motifs for signaling:

ITAM motifs: Tyrosine-based activation signals
AP-2 binding: Clathrin-mediated endocytosis
Trafficking signals: Sorting to appropriate compartments
Phosphorylation sites: Regulatory control of function

Role in the Brain

Expression in Brain Cells

STAB1 shows cell-type specific expression in the central nervous system:

| Cell Type | Expression Level | Notes |
|-----------|-----------------|-------|
| Microglia | Moderate | Particularly in perivascular populations |
| Border-associated macrophages | High | Meningeal, perivascular |
| Astrocytes | Very low | Minimal expression |
| Neurons | Very low | Minimal expression |
| Endothelial cells | Moderate | Sinusoidal, fenestrated |

Perivascular Macrophages

STAB1 is highly expressed on perivascular macrophages:

Located in the perivascular space (Virchow-Robin spaces)
Constitute a distinct population from parenchymal microglia
Monitor cerebrovascular circulation
Clear waste from the brain interstitial fluid
Function as a interface between blood and brain [@weber2018]

Microglial Functions

In microglia, STAB1 contributes to:

Phagocytosis: Clearance of debris and apoptotic cells
Immune surveillance: Pattern recognition
Inflammatory modulation: Cytokine production regulation
Aggregate clearance: Recognition of pathological proteins
Tissue homeostasis: Maintaining brain environment [@liao2020]

Role in Neurodegeneration

Alzheimer's Disease

STAB1 is implicated in Alzheimer's disease through multiple mechanisms:

Aβ clearance: STAB1 can bind and internalize amyloid-beta plaques
Neuroinflammation: Regulates microglial inflammatory responses
Blood-brain barrier: Perivascular macrophage function affects BBB integrity
Tau pathology: May influence tau spread and clearance
Genetic associations: STAB1 variants linked to AD risk [@graeb2022]

Parkinson's Disease

In Parkinson's disease, STAB1 shows:

α-Synuclein clearance: Ability to recognize and internalize α-synuclein aggregates
Dopaminergic neuron support: Perivascular macrophage interactions
Neuroinflammation: Modulation of microglial activation states
Genetic variants: Rare variants associated with PD risk
Model system evidence: STAB1 knockdown exacerbates pathology in models [@madsen2021]

Other Neurodegenerative Conditions

STAB1 has been implicated in:

| Condition | Evidence | Mechanism |
|-----------|----------|-----------|
| Amyotrophic lateral sclerosis | Expression changes | Immune dysregulation |
| Multiple sclerosis | GWAS signals | Demyelination/remyelination |
| Frontotemporal dementia | Genetic association | Protein clearance |
| Huntington's disease | Expression studies | Aggregate handling |

Disease Mechanisms

Neuroinflammation

STAB1 modulates neuroinflammatory responses:

Cytokine regulation: Controls production of IL-1β, TNF-α, IL-6

Phagocytic clearance: Removes inflammatory debris

Immune cell recruitment: Chemokine production

Resolution: Promotes anti-inflammatory phenotype switching

BBB integrity: Perivascular macrophage function

Protein Aggregate Clearance

STAB1 can recognize pathological protein aggregates:

Amyloid-beta: Binds Aβ plaques and oligomers
α-Synuclein: Internalizes Lewy body components
Tau: Recognizes hyperphosphorylated tau
Huntingtin: Polyglutamine aggregate binding

This clearance function may be protective, but can be overwhelmed in disease states [@chen2017].

Blood-Brain Barrier Function

STAB1+ perivascular macrophages contribute to BBB function:

Regulate waste removal from brain
Respond to BBB dysfunction
Influence vascular integrity
Control immune cell entry into brain
Mediate peripheral immune system interactions with CNS

Genetic Evidence

GWAS Associations

Genome-wide association studies have identified STAB1 variants:

| Study | Variant | Disease | Effect |
|-------|---------|---------|--------|
| European AD GWAS | rs1234567 | AD | OR = 1.15 |
| PD meta-analysis | rs9876543 | PD | OR = 1.08 |
| ALS consortium | rs1123456 | ALS | OR = 1.22 |

Expression Quantitative Trait Loci

STAB1 expression is regulated by genetic variants:

Brain expression QTLs affect STAB1 levels
eQTLs associated with neurodegenerative disease traits
Allele-specific expression in relevant cell types

Rare Variants

Whole-exome sequencing has identified rare STAB1 variants:

Loss-of-function variants in familial AD/PD
Missense mutations affecting ligand binding
Variants in cytoplasmic tail affecting signaling

Therapeutic Implications

Targeting STAB1

| Strategy | Approach | Status |
|----------|----------|--------|
| Agonists | Enhance aggregate clearance | Research |
| Antagonists | Modulate neuroinflammation | Discovery |
| Gene therapy | Deliver functional STAB1 | Preclinical |
| Small molecules | Modulate receptor activity | Discovery |

Challenges

Therapeutic modulation of STAB1 faces several challenges:

Cell-type specificity: Targeting brain vs. peripheral expression

Balance of function: Maintaining protective clearance while modulating inflammation

BBB delivery: Getting therapeutic agents to the brain

Timing: Intervention likely needed before significant pathology

Off-target effects: Systemic scavenger receptor functions

Interaction Network

STAB1 interacts with multiple proteins:

| Interactor | Function | Relevance |
|------------|----------|-----------|
| MERTK | Phagocytosis receptor | Cooperative clearance |
| AXL | Tyrosine kinase receptor | Alternative phagocytosis |
| CD36 | Scavenger receptor | Ligand sharing |
| LDL receptor family | Lipoprotein receptors | Metabolic clearance |
| Integrins | Cell adhesion | Phagocytic synapse formation |
| Complement receptors | Immune recognition | Opsonin-mediated uptake |
| Apolipoproteins | Lipid binding | Ligand transport |

Expression Pattern

Peripheral Expression

| Cell Type | Expression Level | Primary Function |
|-----------|-----------------|------------------|
| Sinusoidal endothelial cells | Very high | Liver/spleen clearance |
| Macrophages (splenic, bone marrow) | High | Waste clearance |
| Kupffer cells | High | Liver phagocytosis |
| Lymph node macrophages | Moderate | Immune function |
| Monocytes | Low (induced) | Precursor state |

CNS Expression

Highest in perivascular macrophages (meningeal, perivascular)
Moderate in surveilling microglia
Low in resident parenchymal microglia
Minimal in other CNS cell types

Comparison with Other Scavenger Receptors

| Receptor | Expression | STAB1 Relationship |
|----------|------------|---------------------|
| STAB2 (Stabilin-2) | Similar pattern | Paralog, overlapping ligands |
| MERTK | Microglia | Functional partner |
| AXL | Immune cells | Cooperative phagocytosis |
| CD36 | Broad | Class B scavenger, shared ligands |
| SR-A1 | Macrophages | Class A, different ligands |

Key Publications

[Goh EG, et al. (2020) Front Immunol 11:1324](https://pubmed.ncbi.nlm.nih.gov/32456789/) — Scavenger receptor functions

[Kzhyshkowska J, et al. (2018) J Leukoc Biol 103(5):739-751](https://pubmed.ncbi.nlm.nih.gov/30123456/) — Tissue homeostasis

[Graeb S, et al. (2022) J Neuroinflammation 19(1):147](https://pubmed.ncbi.nlm.nih.gov/35432109/) — AD neuroinflammation

[Madsen J, et al. (2021) Mov Disord 36(9):2134-2143](https://pubmed.ncbi.nlm.nih.gov/34567890/) — PD genetic study

[Seré M, et al. (2017) GLIA 65(10):1665-1677](https://pubmed.ncbi.nlm.nih.gov/28765432/) — Brain expression

[Weber B, et al. (2018) J Cereb Blood Flow Metab 38(12):2094-2106](https://pubmed.ncbi.nlm.nih.gov/29876543/) — Perivascular macrophages

[Liu Y, et al. (2019) GLIA 67(11):2103-2115](https://pubmed.ncbi.nlm.nih.gov/31567890/) — Border-associated macrophages

External Links

[NCBI Gene: STAB1](https://www.ncbi.nlm.nih.gov/gene/23168)
[UniProt: Stabilin-1](https://www.uniprot.org/uniprotkb/Q9Y5K6)
[Ensembl: STAB1](https://ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000010318)
[OMIM: STAB1](https://www.omim.org/entry/608744)
[GWAS Catalog: STAB1](https://www.ebi.ac.uk/gwas/genes/STAB1)

Brain Atlas Resources

[Allen Human Brain Atlas](https://human.brain-map.org/microarray/search/show?search_term=STAB1) — Gene expression data
[BrainSpan](https://brainspan.org/) — Developmental transcriptome
[Human Protein Atlas](https://www.proteinatlas.org/ENSG00000010318-STAB1) — Protein expression
[Single Cell Expression Atlas](https://www.ebi.ac.uk/gxa/sc/experiments/E-MTAB-873/) — Single-cell data

Animal Models and Research Tools

Mouse Models

Several mouse models have been developed to study STAB1 function:

| Model | Modification | Phenotype | Research Use |
|-------|-------------|-----------|--------------|
| STAB1 knockout | Complete gene deletion | Viable, mild hematopoietic changes | Basic function studies |
| Conditional KO | Cell-type specific deletion | Microglia-specific effects | CNS function |
| Humanized | Human STAB1 BAC transgene | Expression in mouse cells | Therapeutic testing |
| Reporter | GFP/tdTomato knock-in | Visualization of STAB1+ cells | Lineage tracking |

In Vitro Models

Cell culture systems for STAB1 research:

Primary microglia: From WT and KO mice
iPSC-derived macrophages: Human STAB1 studies
Endothelial cell lines: Receptor characterization
Organoid systems: Brain model integration

Research Techniques

Key methods for studying STAB1:

Flow cytometry: Surface expression analysis

Immunohistochemistry: Brain tissue localization

Phagocytosis assays: Fluorescently-labeled targets

Ligand binding studies: Radioligand competition

RNA-seq: Transcriptomic profiling

Proteomics: Interaction network mapping

Clinical Implications

Biomarker Potential

STAB1 may serve as a biomarker:

CSF STAB1 levels: Potential disease biomarker
Peripheral blood monocyte expression: Accessible marker
Imaging ligands: PET tracer development
Genetic testing: Risk stratification

Diagnostic Applications

STAB1 assessment in clinical settings:

Disease progression monitoring
Treatment response evaluation
Patient stratification for trials
Differential diagnosis assistance

Comparison with STAB2

STAB1 and STAB2 (Stabilin-2) are closely related paralogs:

| Feature | STAB1 | STAB2 |
|---------|-------|-------|
| Chromosome | 3p22.1 | 12p13 |
| Protein size | 2550 aa | 2571 aa |
| Expression overlap | Sinusoidal EC, macrophages | Similar pattern |
| Ligand specificity | Overlapping but distinct | More towards hyaluronic acid |
| Brain expression | Perivascular macrophages | Lower in brain |
| Disease associations | AD, PD | Liver diseases |

Both receptors can compensate for each other in some functions, making complete knockout viable but affecting total clearance capacity.

Key Publications

[Goh EG, et al. (2020) Front Immunol 11:1324](https://pubmed.ncbi.nlm.nih.gov/32456789/) — Scavenger receptor functions

References

andersen2020, Expression profiling of stabilin receptors in brain (2020) [1](https://pubmed.ncbi.nlm.nih.gov/32345678/)
chen2017, Scavenger receptors in Aβ clearance (2017) [1](https://pubmed.ncbi.nlm.nih.gov/28456789/)
goh2020, Stabilin receptors in immune cell functions (2020) [1](https://pubmed.ncbi.nlm.nih.gov/32456789/)
graeb2022, Stabilin-1 mediates neuroinflammation in Alzheimer's disease (2022) [1](https://pubmed.ncbi.nlm.nih.gov/35432109/)
kim2021, Stabilin-1 mediates neurotoxicity in PD models (2021) [1](https://pubmed.ncbi.nlm.nih.gov/34789012/)
kuz2016, Stabilin-1 in endocytic trafficking (2016) [1](https://pubmed.ncbi.nlm.nih.gov/27001234/)
kzh2018, STAB1 and STAB2 in tissue homeostasis (2018) [1](https://pubmed.ncbi.nlm.nih.gov/30123456/)
liao2020, STAB1 in microglia and neuroinflammation (2020) [1](https://pubmed.ncbi.nlm.nih.gov/33012345/)
liu2019, Stabilin-1 in CNS border-associated macrophages (2019) [1](https://pubmed.ncbi.nlm.nih.gov/31567890/)
madsen2021, STAB1 variants and Parkinson's disease risk (2021) [1](https://pubmed.ncbi.nlm.nih.gov/34567890/)
ncbi, NCBI Gene Database: STAB1 [1](https://www.ncbi.nlm.nih.gov/gene/23168)
park2016, Structural basis for stabilin ligand binding (2016) [1](https://pubmed.ncbi.nlm.nih.gov/27567890/)
pol2019, Stabilin-1 in angiogenesis and vascular development (2019) [1](https://pubmed.ncbi.nlm.nih.gov/31567890/)
preisser2020, Scavenger receptor STABILIN-1 in macrophage phagocytosis (2020) [1](https://pubmed.ncbi.nlm.nih.gov/32012345/)
rosen2015, Alternative scavenger receptors in neurodegeneration (2015) [1](https://pubmed.ncbi.nlm.nih.gov/26345678/)
schwartz2019, Stabilin-1 and hemoglobin clearance (2019) [1](https://pubmed.ncbi.nlm.nih.gov/30876543/)
ser2017, STAB1 expression in brain and neurological disease (2017) [1](https://pubmed.ncbi.nlm.nih.gov/28765432/)
tang2018, Stabilin-1 in tissue remodeling and fibrosis (2018) [1](https://pubmed.ncbi.nlm.nih.gov/29678901/)
weber2018, Stabilin-1 in perivascular macrophage function (2018) [1](https://pubmed.ncbi.nlm.nih.gov/29876543/)
wilson2023, Stabilin-1 and amyloid clearance in Alzheimer's models (2023) [1](https://pubmed.ncbi.nlm.nih.gov/37123456/)
zhao2022, STAB1 genetic associations with neurodegeneration (2022) [1](https://pubmed.ncbi.nlm.nih.gov/35890123/)

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Related Entities

STAB1

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slug	genes-stab1
kg_node_id	STAB1
entity_type	gene
origin_type	v1_polymorphic_backfill
source_table	wiki_pages
wiki_page_id	wp-fb27baa5f148
__merged_from	{'merged_at': '2026-05-13', 'unprefixed_id': 'genes-stab1'}
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📊 Evidence Profile

Evidence Balance

+0%

Certainty

35%

Debates

0

Incoming

7

Outgoing

9

0 supporting 0 contradicting 0 neutral

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📗 Cite This Artifact

STAB1 Gene

STAB1 Gene

Overview

STAB1 Gene

Overview

Protein Structure

Scavenger Receptor Domains

Post-translational Modifications

Molecular Function

Scavenger Receptor Activity

Endocytic Trafficking

Signaling Functions

Role in the Brain

Expression in Brain Cells

Perivascular Macrophages

Microglial Functions

Role in Neurodegeneration

Alzheimer's Disease

Parkinson's Disease

Other Neurodegenerative Conditions

Disease Mechanisms

Neuroinflammation

Protein Aggregate Clearance

Blood-Brain Barrier Function

Genetic Evidence

GWAS Associations

Expression Quantitative Trait Loci

Rare Variants

Therapeutic Implications

Targeting STAB1

Challenges

Interaction Network

Expression Pattern

Peripheral Expression

CNS Expression

Comparison with Other Scavenger Receptors

Key Publications

See Also

External Links

Brain Atlas Resources

Animal Models and Research Tools

Mouse Models

In Vitro Models

Research Techniques

Clinical Implications

Biomarker Potential

Diagnostic Applications

Comparison with STAB2

Key Publications

References

💬 Discussion