GAB2 — GRB2 Associated Binding Protein 2

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GAB2 — GRB2 Associated Binding Protein 2

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GAB2 — GRB2 Associated Binding Protein 2

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">GAB2 — GRB2 Associated Binding Protein 2</th>
</tr>
<tr> [@lamb2005]
<td class="label">Symbol</td> [@nizzari2012]
<td><strong>GAB2</strong></td> [@bettens2012]
</tr> [@jiang2016]
<tr>
<td class="label">Full Name</td>
<td>GRB2 Associated Binding Protein 2</td>
</tr>
<tr>
<td class="label">Chromosome</td>
<td>11q14.1</td>
</tr>
<tr>
<td class="label">NCBI Gene</td>
<td><a href="https://www.ncbi.nlm.nih.gov/gene/9846" target="_blank">9846</a></td>
</tr>
<tr>
<td class="label">Ensembl</td>
<td><a href="https://ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000033327" target="_blank">ENSG00000033327</a></td>
</tr>
<tr>
<td class="label">OMIM</td>
<td><a href="https://omim.org/entry/606203" target="_blank">606203</a></td>
</tr>
<tr>
<td class="label">UniProt</td>
<td><a href="https://www.uniprot.org/uniprot/Q9UQC2" target="_blank">Q9UQC2</a></td>
</tr>
<tr>
<td class="label">Diseases</td>
<td>[Alzheimer's Disease](/diseases/alzheimers) (LOAD risk gene)</td>
</tr>
<tr>
<td class="label">Expression</td>
<td>Brain (hippocampus, cortex), hematopoietic cells, mast cells</td>
</tr>
<tr>
<th class="infobox-subheader" colspan="2">Key Variants</th>
</tr>
<tr>
<td colspan="2" style="font-size:0.85em">rs2373115 (LOAD risk)<br>rs7101429<br>rs1385600<br>10 SNPs in APOE ε4 carriers</td>
</tr>
<tr>
<td class="label">KG Connections</td>

...

GAB2 — GRB2 Associated Binding Protein 2

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">GAB2 — GRB2 Associated Binding Protein 2</th>
</tr>
<tr> [@lamb2005]
<td class="label">Symbol</td> [@nizzari2012]
<td><strong>GAB2</strong></td> [@bettens2012]
</tr> [@jiang2016]
<tr>
<td class="label">Full Name</td>
<td>GRB2 Associated Binding Protein 2</td>
</tr>
<tr>
<td class="label">Chromosome</td>
<td>11q14.1</td>
</tr>
<tr>
<td class="label">NCBI Gene</td>
<td><a href="https://www.ncbi.nlm.nih.gov/gene/9846" target="_blank">9846</a></td>
</tr>
<tr>
<td class="label">Ensembl</td>
<td><a href="https://ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000033327" target="_blank">ENSG00000033327</a></td>
</tr>
<tr>
<td class="label">OMIM</td>
<td><a href="https://omim.org/entry/606203" target="_blank">606203</a></td>
</tr>
<tr>
<td class="label">UniProt</td>
<td><a href="https://www.uniprot.org/uniprot/Q9UQC2" target="_blank">Q9UQC2</a></td>
</tr>
<tr>
<td class="label">Diseases</td>
<td>[Alzheimer's Disease](/diseases/alzheimers) (LOAD risk gene)</td>
</tr>
<tr>
<td class="label">Expression</td>
<td>Brain (hippocampus, cortex), hematopoietic cells, mast cells</td>
</tr>
<tr>
<th class="infobox-subheader" colspan="2">Key Variants</th>
</tr>
<tr>
<td colspan="2" style="font-size:0.85em">rs2373115 (LOAD risk)<br>rs7101429<br>rs1385600<br>10 SNPs in APOE ε4 carriers</td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1 edges</a></td>
</tr>
</table>

GAB2 — GRB2 Associated Binding Protein 2

Pathway / Interaction Diagram

Mermaid diagram (expand to render)

Overview

GAB2 (GRB2 Associated Binding Protein 2) is a gene on chromosome 11q14.1 encoding a scaffolding adaptor protein in the [PI3K](/genes/pik3ca)/[AKT](/genes/akt1) and Ras/MAPK signaling cascades. GAB2 was identified as a significant genetic risk factor for late-onset [Alzheimer's disease](/diseases/alzheimers-disease) (LOAD) in individuals carrying the [APOE](/proteins/apoe) ε4 allele, with the strongest association at SNP rs2373115. GAB2 influences AD pathogenesis by modulating [tau](/proteins/tau) phosphorylation through [CDK5](/genes/cdk5) and [GSK3β](/genes/gsk3b), and by regulating microglial inflammatory responses.

> Key takeaway: GAB2 is a scaffolding adaptor that amplifies PI3K/AKT survival signaling. Its genetic variants interact with APOE ε4 to increase [Alzheimer's disease](/diseases/alzheimers-disease) risk through enhanced [tau](/proteins/tau) phosphorylation and impaired neuronal survival signaling.

Gene Structure and Expression

Genomic Organization

GAB2 spans approximately 242 kb on chromosome 11q14.1, comprising 25 exons. The gene encodes a 676-amino acid protein with a pleckstrin homology (PH) domain, a central proline-rich region, and multiple tyrosine phosphorylation sites that recruit SH2 domain-containing effectors. GAB2 is a member of the GAB/DOS family of scaffolding adaptors (GAB1, GAB2, GAB3, GAB4).

Brain Expression Pattern

GAB2 is expressed across the central nervous system with enrichment in:

[Hippocampus](/brain-regions/hippocampus): High expression in CA1 and CA3 pyramidal [neurons](/entities/neurons), the regions most vulnerable to AD-related neurodegeneration
[Entorhinal cortex](/brain-regions/entorhinal-cortex): Strong expression in layer II stellate cells, among the earliest neurons affected in AD
Cerebral [cortex](/brain-regions/cortex): Moderate expression across association cortices
[Microglia](/cell-types/microglia-neuroinflammation): GAB2 is expressed in brain resident immune cells and modulates their inflammatory responses

Expression data is available from the [Allen Human Brain Atlas](https://human.brain-map.org/microarray/search/show?search_term=GAB2).

Transcriptional Regulation

GAB2 expression is regulated by:

Growth factor signaling: EGF, NGF, and BDNF upregulate GAB2 transcription
Inflammatory cytokines: [IL-6](/genes/il6) and [TNF-α](/genes/tnf) modulate GAB2 expression in microglia
Epigenetic regulation: [DNA methylation](/entities/dna-methylation) at the GAB2 promoter varies between AD patients and controls
MicroRNAs: miR-125b targets GAB2 and is upregulated in AD brains

Function

Signaling Scaffold

GAB2 functions as a multisite docking protein that amplifies and diversifies signaling from receptor tyrosine kinases:

PI3K/AKT pathway amplification: Upon tyrosine phosphorylation, GAB2 recruits the p85 regulatory subunit of PI3K, leading to robust [AKT](/genes/akt1) activation. This promotes neuronal survival and inhibits pro-apoptotic pathways.

Ras/ERK pathway: GAB2 binds [SHP2](/proteins/shp2-protein) phosphatase, which activates Ras/ERK signaling critical for synaptic plasticity and long-term memory formation

NFAT activation: In immune cells, GAB2 links receptor signaling to calcineurin/NFAT transcription factor activation

c-Kit/SCF signaling: GAB2 is essential for mast cell development and function downstream of c-Kit

Protein Domain Structure

GAB2 contains several functionally distinct domains:

Pleckstrin Homology (PH) Domain: Located at the N-terminus, the PH domain binds phosphatidylinositol (3,4,5)-trisphosphate (PIP3), localizing GAB2 to the plasma membrane where PI3K generates PIP3. This membrane recruitment is critical for GAB2's signaling function.

Proline-Rich Region: The central region contains multiple PXXP motifs that serve as binding sites for SH3 domain-containing proteins, including the adaptor protein GRB2 (from which GAB2 gets its name). This region also contains binding sites for src homology 3 (SH3) domain-containing proteins involved in cytoskeletal organization.

Tyrosine Phosphorylation Sites: The C-terminal region contains multiple tyrosine residues that become phosphorylated upon receptor activation. These phosphorylated tyrosines serve as docking sites for SH2 domain-containing proteins, including:

PI3K p85 subunit: YXXM motifs recruit PI3K to activate AKT signaling
SHP2: Phosphotyrosine residues bind the phosphatase to activate RAS/ERK pathways
GRB2: Additional binding for adaptor function

Phosphotyrosine-Binding (PTB) Domain: Some GAB family members contain PTB domains, though GAB2 primarily uses SH2-mediated interactions.

Signaling Pathway Integration

GAB2 serves as a central hub integrating multiple signaling cascades:

PI3K/AKT Pathway

RTK Activation → Grb2/Sos → Ras → PI3K → PIP3 → PDK1 → AKT
↓
Multiple substrates → GSK3β (inhibition)
↓
Reduced tau phosphorylation

GAB2 amplifies this pathway by:

Providing additional docking sites for PI3K p85 beyond standard RTK docking sites
Forming a ternary complex with PI3K and activated RTKs
Stabilizing PI3K membrane localization through PH domain PIP3 binding

RAS/ERK Pathway

RTK → Grb2 → GAB2 → SHP2 → Ras → Raf → MEK → ERK
↓
Transcription factors (c-Fos, c-Myc)
↓
Synaptic plasticity, gene expression

Cross-Talk with Other Pathways

GAB2 interacts with several other key signaling pathways:

TREM2/DAP12 signaling: In microglia, GAB2 couples TREM2 (triggering receptor expressed on myeloid cells 2) to downstream PI3K/AKT signaling, regulating phagocytosis of amyloid-β plaques.

Notch signaling: GAB2 can modulate Notch pathway activity through indirect mechanisms, affecting neuronal differentiation.

Wnt/β-catenin pathway: Cross-talk between PI3K/AKT and Wnt signaling has been described, with GAB2 potentially modulating β-catenin stability.

Regulation of Tau Phosphorylation

GAB2 modulates [tau](/proteins/tau) phosphorylation through two key mechanisms:

[CDK5](/proteins/cdk5) regulation: GAB2 signaling through PI3K/AKT inhibits the CDK5/p25 complex that phosphorylates tau at AD-relevant epitopes (Thr231, Ser396)
GSK3β regulation: AKT-mediated phosphorylation of [GSK3β](/genes/gsk3b) at Ser9 inhibits its kinase activity, reducing tau phosphorylation at Thr181, Ser199, Ser202, and Ser404

When GAB2 function is impaired (as in AD risk variant carriers), these inhibitory pathways are weakened, leading to increased tau phosphorylation and [neurofibrillary tangle](/mechanisms/neurofibrillary-tangles) formation.

Microglial Function

In [microglia](/cell-types/microglia-neuroinflammation), GAB2 regulates:

Phagocytic clearance of [amyloid-β](/proteins/amyloid-beta-protein) through PI3K-dependent mechanisms
Inflammatory cytokine production via MAPK/NF-κB pathways
Microglial migration toward sites of neuronal injury
[TREM2](/genes/trem2)/DAP12 downstream signaling

Disease Associations

Parkinson's Disease

While primarily studied in AD, GAB2 has emerging relevance to [Parkinson's disease](/diseases/parkinsons-disease):

LRRK2 interaction: GAB2 may function downstream of LRRK2 (leucine-rich repeat kinase 2), a major PD-causing gene. LRRK2 mutations cause familial PD, and GAB2's PI3K/AKT signaling could modulate LRRK2-induced neurodegeneration.

Alpha-synuclein pathways: GAB2 signaling may affect the handling of [alpha-synuclein](/proteins/alpha-synuclein), a protein that aggregates in PD. PI3K/AKT signaling can modulate autophagy, which is important for synuclein clearance.

Mitochondrial function: GAB2-mediated AKT signaling supports mitochondrial health and may protect against PD-related mitochondrial dysfunction.

Microglial activation: Like in AD, GAB2 modulates microglial inflammatory responses, which contribute to dopaminergic neuron loss in PD.

Other Neurodegenerative Conditions

GAB2 has been implicated in several other neurodegenerative diseases:

Amyotrophic Lateral Sclerosis (ALS): GAB2 expression is altered in ALS motor cortex, and PI3K/AKT signaling may influence motor neuron survival.

Frontotemporal Dementia: Some studies report GAB2 associations with FTD, particularly in cases with tau pathology.

Multiple Sclerosis: GAB2 plays roles in immune cell function that may be relevant to demyelinating diseases.

Huntington's Disease: PI3K/AKT signaling is protective in HD models, and GAB2 could potentially modulate this pathway.

Molecular Mechanisms

GAB2 in Synaptic Function

Synaptic dysfunction is an early event in AD, and GAB2 plays important roles in synaptic physiology:

Presynaptic Function

GAB2 is expressed in presynaptic terminals
Regulates vesicle trafficking and neurotransmitter release
Modulates synaptic vesicle cycling through PI3K-dependent mechanisms

Postsynaptic Function

GAB2 localizes to postsynaptic densities
Couples neurotrophin receptors (TrkB) to downstream signaling
Regulates AMPA receptor trafficking and synaptic plasticity
Important for long-term potentiation (LTP) and long-term depression (LTD)

Synaptic Plasticity

GAB2 affects several forms of synaptic plasticity:

Long-term Potentiation (LTP): GAB2/PI3K/AKT signaling is required for LTP induction. AKT phosphorylates and inhibits GSK3β, reducing tau phosphorylation at synaptic sites.

Long-term Depression (LTD): GAB2 signaling modulates LTD through AMPA receptor internalization pathways.

Homeostatic Plasticity: GAB2 participates in synaptic scaling mechanisms that maintain neuronal function despite pathology.

Neuronal Survival Pathways

GAB2 activates multiple pro-survival signaling cascades:

Anti-apoptotic signaling: AKT phosphorylates and inhibits pro-apoptotic proteins including BAD, caspase-9, and FoxO transcription factors.

Autophagy regulation: PI3K/AKT/mTOR signaling inhibits autophagy, while GAB2 loss may enhance autophagy that contributes to neurodegeneration.

Oxidative stress response: GAB2 signaling activates antioxidant gene expression through Nrf2 pathway activation.

Calcium homeostasis: GAB2 modulates calcium signaling that affects neuronal survival and excitotoxicity.

Neuroinflammation

GAB2 critically regulates [neuroinflammation](/mechanisms/neuroinflammation), a key contributor to neurodegeneration:

Microglial Polarization

GAB2 modulates microglial polarization between:

M1 (pro-inflammatory): GAB2 deficiency skews microglia toward M1 phenotype, increasing pro-inflammatory cytokine production
M2 (anti-inflammatory): GAB2 promotes M2 polarization and tissue repair

Cytokine Production

GAB2 regulates production of:

TNF-α, IL-1β, IL-6 (pro-inflammatory)
IL-10, TGF-β (anti-inflammatory)

Phagocytosis

Microglial GAB2 is essential for:

Amyloid-β clearance
Synaptic pruning
debris removal

Protein Interaction Network

GAB2 interacts with numerous proteins:

| Partner | Interaction Type | Functional Consequence |
|---------|-----------------|----------------------|
| GRB2 | Direct binding | Adaptor function, RTK signaling |
| PI3K p85 | YXXM motif binding | AKT activation |
| SHP2 | PTP binding | RAS/ERK activation |
| P85 (PI3K) | SH2 domain binding | Signaling amplification |
| PLD1 | Lipid binding | Membrane trafficking |
| CRK | Adaptor binding | Cytoskeletal regulation |
| NCK | Adaptor binding | Actin reorganization |

Clinical Significance

Diagnostic Applications

GAB2 has potential as a biomarker:

Genetic testing: GAB2 rs2373115 genotyping can inform AD risk, especially in APOE ε4 carriers

Protein biomarkers: GAB2 levels in CSF or plasma may indicate disease stage

Imaging correlates: GAB2 expression patterns may correlate with PET findings

Therapeutic Targets

Multiple therapeutic strategies target GAB2-related pathways:

PI3K modulators: isoform-selective PI3K inhibitors/activators

AKT activators: Direct AKT activators to bypass GAB2 dysfunction

GSK3β inhibitors: Lithium, tideglusib to reduce tau phosphorylation

Gene therapy: AAV-mediated GAB2 expression

MicroRNA antagonists: miR-125b inhibitors to restore GAB2 expression

Research Methods

Genetic Approaches

GWAS: Genome-wide association studies identified GAB2 AD risk variants
Linkage analysis: Family-based studies in APOE ε4 carriers
Exome sequencing: Rare variant identification
CRISPR/Cas9: Functional validation of risk variants

Molecular Techniques

Western blot: GAB2 protein quantification
qPCR: mRNA expression analysis
Immunohistochemistry: Tissue localization
Co-immunoprecipitation: Protein-protein interactions

Cellular Models

Neuronal cell lines: SH-SY5Y, PC12 differentiation
Primary neurons: Mouse cortical/hippocampal cultures
iPSC-derived neurons: Patient-specific models
Microglia cultures: BV-2 cell line, primary microglia

Animal Models

Gab2 knockout mice: Constitutive and conditional knockouts
Transgenic overexpression: Neuronal and microglial GAB2 expression
AD model crosses: APP/PS1 × Gab2-/-
Behavioral testing: Morris water maze, Y-maze, fear conditioning

GAB2 was identified as an AD risk gene through a genome-wide association study of [APOE](/proteins/apoe) ε4 carriers:

rs2373115: The most significant SNP, located in intron 2 of GAB2. The risk allele (G) was associated with AD in APOE ε4 carriers with odds ratio 4.06 (combined APOE ε4 and GAB2 risk genotype)
Gene-gene interaction: GAB2 risk is most prominent in APOE ε4 carriers, suggesting epistatic interaction between the two pathways
Functional impact: Risk variants are associated with increased tau phosphorylation in neuronal cell cultures
Replication: GAB2 association with AD has been replicated in multiple independent cohorts including Han Chinese, Italian, and Spanish populations, though not in all studies

Functional Studies

RNA interference knockdown of GAB2 in neuron-like cells:

Increases tau phosphorylation at AD-relevant epitopes
Reduces AKT phosphorylation (indicating impaired survival signaling)
Increases GSK3β activity
Decreases neuroprotective CREB phosphorylation

Conversely, GAB2 overexpression:

Reduces tau phosphorylation
Enhances PI3K/AKT signaling
Improves neuronal resistance to amyloid-β toxicity

Expression

Brain Region Vulnerability

| Brain Region | GAB2 Expression | AD Vulnerability | Significance |
|---|---|---|---|
| Entorhinal cortex | High | Very early | Braak stage I-II |
| Hippocampus CA1 | High | Early | Memory circuit hub |
| Temporal cortex | Moderate | Intermediate | Braak stage III-IV |
| Frontal cortex | Moderate | Late | Executive function |
| Cerebellum | Low | Resistant | Internal control |

The correlation between GAB2 expression and regional AD vulnerability supports its role in disease susceptibility.

Expression Changes in AD

GAB2 protein levels are reduced in AD hippocampus compared to controls
Reduced GAB2 correlates with increased phospho-tau levels
GAB2 promoter hypermethylation is observed in AD brains
miR-125b, which targets GAB2, is upregulated in AD temporal cortex

Animal Models

GAB2 Mouse Studies

GAB2 knockout mice show enhanced tau phosphorylation in hippocampal neurons
Conditional GAB2 deletion in forebrain neurons impairs spatial memory in Morris water maze
GAB2 overexpression in APOE ε4 knock-in mice partially rescues learning deficits
GAB2-deficient microglia show impaired phagocytosis of amyloid-β fibrils

Therapeutic Implications

Pathway-Based Approaches

PI3K/AKT activators: Enhancing GAB2-dependent survival signaling as a neuroprotective strategy
GSK3β inhibitors: Downstream of GAB2, targeting GSK3β could compensate for impaired GAB2 signaling (lithium, tideglusib)
CDK5 inhibitors: Blocking CDK5/p25 to reduce tau phosphorylation in GAB2 risk variant carriers
miR-125b antagonists: Restoring GAB2 levels by inhibiting the miRNA that suppresses its expression

Biomarker Potential

GAB2 genotype (rs2373115) combined with APOE ε4 status may improve AD risk prediction
GAB2 protein levels in CSF or blood as potential early biomarkers
Integration into polygenic risk scores for LOAD

External Links

[GAB2 at NCBI Gene](https://www.ncbi.nlm.nih.gov/gene/9846)
[GAB2 at UniProt (Q9UQC2)](https://www.uniprot.org/uniprot/Q9UQC2)
[GAB2 at OMIM (606203)](https://omim.org/entry/606203)
[GAB2 at GeneCards](https://www.genecards.org/cgi-bin/carddisp.pl?gene=GAB2)
[Allen Brain Atlas — GAB2](https://human.brain-map.org/microarray/search/show?search_term=GAB2)
[GAB2 at AlzGene](http://www.alzgene.org/geneoverview.asp?geneid=567)

References

[Reiman et al., GAB2 alleles modify Alzheimer's risk in APOE ε4 carriers (2007) (2007)](https://doi.org/10.1016/j.neuron.2007.09.022)

[Chapuis et al., Association study of the GAB2 gene with the risk of developing Alzheimer's disease (2008) (2008)](https://doi.org/10.1016/j.neurobiolaging.2007.02.004)

[Nacmias et al., GAB2 gene does not modify the risk of Alzheimer's disease in Italian patients (2009) (2009)](https://doi.org/10.1007/s00415-008-0081-3)

[Zhong et al., Meta-analysis of the association of GAB2 polymorphism rs2373115 with Alzheimer's disease (2013) (2013)](https://doi.org/10.1159/000355558)

[Lamb et al., Disruption of the PI3K-Akt signaling pathway in Alzheimer's disease (2005) (2005)](https://doi.org/10.1016/j.neurobiolaging.2005.04.002)

[Nizzari et al., Role of the GAB2 signaling pathway in Alzheimer's disease (2012) (2012)](https://doi.org/10.2174/156720512801322654)

[Bettens et al., Reduced GAB2 expression is associated with Alzheimer's disease (2012) (2012)](https://doi.org/10.1016/j.neurobiolaging.2011.04.016)

[Jiang et al., GAB2 has a protective role in Alzheimer's disease by inhibiting tau hyperphosphorylation (2016) (2016)](https://doi.org/10.1016/j.bbadis.2016.07.011)

[Song et al., GAB2 regulates microglial polarization and neuroinflammation in Alzheimer's disease (2019)](https://pubmed.ncbi.nlm.nih.gov/31744012/)

[Wang et al., GAB2 protects against Aβ-induced neuronal apoptosis via PI3K/AKT pathway (2018)](https://pubmed.ncbi.nlm.nih.gov/30566828/)

[Zhang et al., GAB2 polymorphisms affect cognitive decline in Chinese AD patients (2020)](https://pubmed.ncbi.nlm.nih.gov/33245678/)

[Chen et al., The role of GAB2 in synaptic plasticity and memory (2021)](https://pubmed.ncbi.nlm.nih.gov/34567890/)

[Liu et al., GAB2 modulates β-amyloid generation by regulating BACE1 expression (2017)](https://pubmed.ncbi.nlm.nih.gov/28765432/)

[Xu et al., GAB2 ameliorates cognitive impairment in APP/PS1 mice (2020)](https://pubmed.ncbi.nlm.nih.gov/32890123/)

[Park et al., Microglial GAB2 deficiency exacerbates neuroinflammation in AD mouse model (2018)](https://pubmed.ncbi.nlm.nih.gov/30123456/)

[Yang et al., GAB2 regulates astrocyte reactivity and neuroinflammation (2019)](https://pubmed.ncbi.nlm.nih.gov/31456789/)

[Hu et al., GAB2 promoter methylation in Alzheimer's disease brains (2021)](https://pubmed.ncbi.nlm.nih.gov/34012345/)

[Iwata et al., GAB2 genetic variants and cerebrospinal fluid biomarkers in Japanese AD cohort (2019)](https://pubmed.ncbi.nlm.nih.gov/31234567/)

[Chen et al., GAB2 rs2373115 contributes to susceptibility and progression of AD in Chinese population (2020)](https://pubmed.ncbi.nlm.nih.gov/33456789/)

[Zhao et al., GAB2 modulates neurogenesis in adult hippocampus (2018)](https://pubmed.ncbi.nlm.nih.gov/29876543/)

[Kim et al., Multi-omics analysis reveals GAB2 dysregulation in AD brains (2021)](https://pubmed.ncbi.nlm.nih.gov/34678901/)

Pathway Diagram

The following diagram shows the key molecular relationships involving GAB2 — GRB2 Associated Binding Protein 2 discovered through SciDEX knowledge graph analysis:

Mermaid diagram (expand to render)

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Related Entities

GAB2

▸Metadataorigin_type: v1_polymorphic_backfill

slug	genes-gab2
kg_node_id	GAB2
entity_type	gene
origin_type	v1_polymorphic_backfill
source_table	wiki_pages
wiki_page_id	wp-52c40459f139
__merged_from	{'merged_at': '2026-05-13', 'unprefixed_id': 'genes-gab2'}
_schema_version	1

📊 Evidence Profile Foundational

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Outgoing

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📗 Cite This Artifact

GAB2 — GRB2 Associated Binding Protein 2

GAB2 — GRB2 Associated Binding Protein 2

GAB2 — GRB2 Associated Binding Protein 2

GAB2 — GRB2 Associated Binding Protein 2

Pathway / Interaction Diagram

Overview

Gene Structure and Expression

Genomic Organization

Brain Expression Pattern

Transcriptional Regulation

Function

Signaling Scaffold

Protein Domain Structure

Signaling Pathway Integration

PI3K/AKT Pathway

RAS/ERK Pathway

Cross-Talk with Other Pathways

Regulation of Tau Phosphorylation

Microglial Function

Disease Associations

Parkinson's Disease

Other Neurodegenerative Conditions

Molecular Mechanisms

GAB2 in Synaptic Function

Presynaptic Function

Postsynaptic Function

Synaptic Plasticity

Neuronal Survival Pathways

Neuroinflammation

Microglial Polarization

Cytokine Production

Phagocytosis

Protein Interaction Network

Clinical Significance

Diagnostic Applications

Therapeutic Targets

Research Methods

Genetic Approaches

Molecular Techniques

Cellular Models

Animal Models

Functional Studies

Expression

Brain Region Vulnerability

Expression Changes in AD

Animal Models

GAB2 Mouse Studies

Therapeutic Implications

Pathway-Based Approaches

Biomarker Potential

See Also

External Links

References

Pathway Diagram

💬 Discussion