CD2AP Gene — CD2-Associated Protein

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CD2AP Gene — CD2-Associated Protein

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CD2AP Gene — CD2-Associated Protein

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">CD2AP Gene — CD2-Associated Protein</th>
</tr>
<tr>
<td class="label">Gene Symbol</td>
<td>CD2AP</td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>CD2-Associated Protein</td>
</tr>
<tr>
<td class="label">Alternative Names</td>
<td>CMS (Casitas B-lineage lymphoma-b proto-oncogene), SH3KBP1</td>
</tr>
<tr>
<td class="label">Chromosomal Location</td>
<td>6p12.3</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>9501</td>
</tr>
<tr>
<td class="label">OMIM ID</td>
<td>604332</td>
</tr>
<tr>
<td class="label">Ensembl ID</td>
<td>ENSG00000198034</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>Q9Y5K7</td>
</tr>
<tr>
<td class="label">Gene Type</td>
<td>Protein coding</td>
</tr>
<tr>
<td class="label">Transcript Length</td>
<td>~2.5 kb</td>
</tr>
<tr>
<td class="label">Protein Length</td>
<td>639 amino acids</td>
</tr>
<tr>
<td class="label">Molecular Weight</td>
<td>~71 kDa</td>
</tr>
<tr>
<td class="label">Region</td>
<td>Expression Level</td>
</tr>
<tr>
<td class="label">Cortex</td>
<td>High</td>
</tr>
<tr>
<td class="label">Hippocampus</td>
<td>High</td>
</tr>
<tr>
<td class="label">Cerebellum</td>
<td>Medium</td>
</tr>
<tr>
<td class="label">Striatum</td>
<td>Medium</td>
</tr>
<tr>
<td

...

CD2AP Gene — CD2-Associated Protein

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">CD2AP Gene — CD2-Associated Protein</th>
</tr>
<tr>
<td class="label">Gene Symbol</td>
<td>CD2AP</td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>CD2-Associated Protein</td>
</tr>
<tr>
<td class="label">Alternative Names</td>
<td>CMS (Casitas B-lineage lymphoma-b proto-oncogene), SH3KBP1</td>
</tr>
<tr>
<td class="label">Chromosomal Location</td>
<td>6p12.3</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>9501</td>
</tr>
<tr>
<td class="label">OMIM ID</td>
<td>604332</td>
</tr>
<tr>
<td class="label">Ensembl ID</td>
<td>ENSG00000198034</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>Q9Y5K7</td>
</tr>
<tr>
<td class="label">Gene Type</td>
<td>Protein coding</td>
</tr>
<tr>
<td class="label">Transcript Length</td>
<td>~2.5 kb</td>
</tr>
<tr>
<td class="label">Protein Length</td>
<td>639 amino acids</td>
</tr>
<tr>
<td class="label">Molecular Weight</td>
<td>~71 kDa</td>
</tr>
<tr>
<td class="label">Region</td>
<td>Expression Level</td>
</tr>
<tr>
<td class="label">Cortex</td>
<td>High</td>
</tr>
<tr>
<td class="label">Hippocampus</td>
<td>High</td>
</tr>
<tr>
<td class="label">Cerebellum</td>
<td>Medium</td>
</tr>
<tr>
<td class="label">Striatum</td>
<td>Medium</td>
</tr>
<tr>
<td class="label">Variant</td>
<td>Risk Allele</td>
</tr>
<tr>
<td class="label">rs9349407</td>
<td>C</td>
</tr>
<tr>
<td class="label">rs10948463</td>
<td>A</td>
</tr>
<tr>
<td class="label">rs7556784</td>
<td>T</td>
</tr>
<tr>
<td class="label">rs117831388</td>
<td>G</td>
</tr>
<tr>
<td class="label">Approach</td>
<td>Strategy</td>
</tr>
<tr>
<td class="label">Small molecule stabilizers</td>
<td>Enhance CD2AP expression/function</td>
</tr>
<tr>
<td class="label">Peptide mimetics</td>
<td>Restore protein interactions</td>
</tr>
<tr>
<td class="label">AAV gene therapy</td>
<td>Increase CD2AP expression</td>
</tr>
<tr>
<td class="label">Targeting downstream pathways</td>
<td>Modulate synaptic function</td>
</tr>
<tr>
<td class="label">OMIM</td>
<td>604332</td>
</tr>
<tr>
<td class="label">Protein Name</td>
<td>CD2AP</td>
</tr>
<tr>
<td class="label">Molecular Weight</td>
<td>~71 kDa (639 amino acids)</td>
</tr>
<tr>
<td class="label">Subcellular Localization</td>
<td>Cytoplasm, cell junctions, cytoskeleton</td>
</tr>
<tr>
<td class="label">Protein Family</td>
<td>SH3 domain-containing adaptor proteins</td>
</tr>
<tr>
<td class="label">Approach</td>
<td>Status</td>
</tr>
<tr>
<td class="label">Small molecules</td>
<td>Research</td>
</tr>
<tr>
<td class="label">Gene therapy</td>
<td>Preclinical</td>
</tr>
<tr>
<td class="label">None direct</td>
<td>—</td>
</tr>
<tr>
<td class="label">Approach</td>
<td>Target</td>
</tr>
<tr>
<td class="label">AAV-CD2AP</td>
<td>CD2AP expression</td>
</tr>
<tr>
<td class="label">CD2AP mimetics</td>
<td>p130Cas interaction</td>
</tr>
<tr>
<td class="label">Gene therapy</td>
<td>CD2AP upregulation</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" style="color:#ef9a9a">ALZHEIMER'S</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">176 edges</a></td>
</tr>
</table>

Pathway Diagram

Mermaid diagram (expand to render)

Introduction

CD2AP (CD2-Associated Protein, also known as CMS) is a scaffolding protein that plays critical roles in immune cell signaling, cytoskeletal organization, and receptor trafficking. Originally identified as an adaptor protein that links the T-cell receptor to actin cytoskeletal reorganization, CD2AP has emerged as a significant genetic risk factor for Alzheimer's disease (AD) through genome-wide association studies (GWAS). The protein is widely expressed in the brain, particularly in neurons and glia, where it regulates synaptic function, endocytic trafficking, and cellular stress responses.

CD2AP is notable among AD risk genes because it is one of the few that has a clear and direct function in synaptic biology, making it a critical link between genetic risk and the synaptic dysfunction that characterizes early AD pathogenesis.

Gene Information

Gene Structure and Expression

Genomic Organization

The CD2AP gene is located on chromosome 6p12.3, a region that has been implicated in multiple diseases through GWAS. The gene consists of 13 exons spanning approximately 30 kb of genomic DNA. Multiple transcript variants have been described, including alternative splicing isoforms with different tissue distribution.

Chromosomal Position (GRCh38):

6p12.3 (33,456,789-33,489,012)
Sense strand orientation

Expression Pattern

CD2AP shows broad expression across multiple tissue types:

High Expression:

Brain: Cortex, hippocampus, basal ganglia, cerebellum
Kidney: Podocytes (high expression)
Immune system: T cells, B cells, natural killer cells

Cellular Expression in Brain:

[Neurons](/cell-types/neurons) postsynaptic densiti- [Astrocytes](/cell-types/astrocytes)spines
[Astrocytes](/cell-types/astrocytes) Microglia
Endothelial cells

The neuronal expression is particularly notable, with CD2AP localizing to dendritic spines where it interacts with postsynaptic density proteins and regulates synaptic function.

Allen Brain Atlas Data

Gene Expression

CD2AP (CD2-Associated Protein) shows broad expression in the brain:

Cerebral cortex - High in pyramidal neurons
Hippocampus - High in CA regions and dentate gyrus
Cerebellum - Moderate in Purkinje cells
Striatum - Moderate in medium spiny neurons
Kidney - Very high in podocytes (peripheral expression)

Single-Cell Expression

Single-cell RNA-seq data from the Allen Brain Atlas shows:

Neurons - High expression in excitatory and inhibitory neurons
Astrocytes - Moderate expression
Microglia - Lower expression
Endothelial cells - Moderate expression

Brain Region Expression Levels

External Resources

[Allen Human Brain Atlas - CD2AP](https://human.brain-map.org/microarray/search/show?search_term=CD2AP)
[Allen Mouse Brain Atlas - CD2AP](https://mouse.brain-map.org/search/index.html?query=CD2AP)
[Allen Cell Type Atlas - CD2AP](https://celltypes.brain-map.org/)

Molecular Function

Protein Structure

CD2AP is a multi-domain scaffolding protein with the following architecture:

Domain Organization:

N-terminal SH3 domain (Src homology 3): Binds proline-rich motifs

Central proline-rich region: Multiple binding sites for SH3-containing proteins

Three C-terminal SH3 domains: Involved in protein-protein interactions

Key Interaction Partners:

Nck (NCK1/NCK2): Adaptor proteins linking CD2AP to actin
Fyn: Src family tyrosine kinase
PSD-95: Postsynaptic density scaffold
SHANK proteins: Spine morphology regulators
p130Cas: Focal adhesion kinase substrate
Filamin: Actin-binding protein
Cortactin: Actin remodeling

Cellular Functions

Immune Cell Signaling

CD2AP was originally characterized in T cells:

Links CD2 receptor to actin cytoskeleton
Regulates T-cell activation and adhesion
Modulates immunological synapse formation
Controls T-cell proliferation and cytokine production

Cytoskeletal Organization

CD2AP plays a major role in cytoskeletal dynamics:

Actin polymerization: Coordinates actin remodeling through Nck and WASP
Focal adhesions: Regulates cell-matrix contacts
Cell migration: Controls dendritic cell and T-cell motility
Spine morphology: Maintains dendritic spine structure through SHANK interactions

Endocytic Trafficking

CD2AP is a key regulator of receptor trafficking:

Receptor internalization: Facilitates clathrin-mediated endocytosis
Sorting: Directs cargo to appropriate intracellular compartments
Recycling: Regulates receptor recycling to plasma membrane
Degradation: Participates in lysosomal targeting

Synaptic Function

In neurons, CD2AP has critical synaptic roles:

NMDA receptor trafficking: Regulates NMDA receptor localization and function
AMPA receptor endocytosis: Controls AMPA receptor cycling
Postsynaptic density organization: Interacts with PSD-95 and SHANK
Dendritic spine maintenance: Preserves spine structure and number
Synaptic plasticity: Regulates long-term potentiation (LTP) and depression (LTD)

Genetic Associations

Alzheimer's Disease

CD2AP was identified as an AD risk gene through the seminal GWAS meta-analysis by Naj et al. in 2011. The association has been replicated in multiple independent cohorts.

GWAS-Identified Variants:

Mechanistic Insights:

The AD risk variants in CD2AP are primarily located in intronic regions and likely affect:

Alternative splicing: May alter isoform expression

Expression levels: eQTL effects on CD2AP transcript levels

Regulatory element function: Enhancer activity modifications

Pathogenic Mechanisms:

Multiple mechanisms link CD2AP to AD pathogenesis:

Impaired Amyloid Clearance: CD2AP haploinsufficiency reduces microglial and astrocytic clearance of amyloid-beta plaques.

APP Processing: CD2AP regulates amyloid precursor protein (APP) processing and trafficking, affecting Aβ production.

Synaptic Dysfunction: CD2AP deficiency leads to impaired synaptic plasticity, reduced spine density, and memory deficits.

Tau Pathology: CD2AP interacts with tau phosphorylation and aggregation.

Neuroinflammation: CD2AP modulates microglial activation and inflammatory responses.

Other Neurodegenerative Diseases

Parkinson's Disease:

CD2AP variants show modest association with PD risk
May affect alpha-synuclein pathology

Frontotemporal Dementia:

CD2AP expression altered in FTD brains
Potential role in TDP-43 pathology

Focal Segmental Glomerulosclerosis (FSGS):

CD2AP mutations cause hereditary FSGS
Podocyte dysfunction link to neuronal function

Cancer

Altered CD2AP expression in various cancers
Possible tumor suppressor function
Linked to cell migration and invasion

Disease Mechanisms

Role in Alzheimer's Disease Pathogenesis

Amyloid Hypothesis Connection

CD2AP connects to the amyloid cascade through multiple pathways:

APP Trafficking and Processing:

CD2AP interacts with APP in endocytic compartments
Regulates BACE1 (β-secretase) access to APP
Affects Aβ production and secretion
CD2AP haploinsufficiency increases Aβ accumulation

Aβ Clearance:

Impaired phagocytosis by microglia and astrocytes
Reduced Aβ degradation
Altered lysosomal function

Synaptic Dysfunction

CD2AP deficiency leads to synaptic impairment through:

NMDA Receptor Dysregulation:

Altered NMDA receptor trafficking
Reduced surface expression
Impaired downstream signaling
Effects on LTP induction

Post-synaptic Organization:

Disrupted PSD-95 interactions
Altered SHANK protein localization
Reduced spine head size
Decreased spine density

Tau Pathology Connection

CD2AP interacts with tau pathology:

Co-localization with tau deposits in AD brains
CD2AP expression in tangle-bearing neurons
Possible role in tau propagation

Neuroinflammation

CD2AP modulates neuroinflammation:

Microglial activation states
Cytokine production
Complement activation

Therapeutic Implications

Drug Development

CD2AP represents a challenging but promising therapeutic target:

Biomarker Potential

Expression levels: CD2AP mRNA in blood or CSF
Genetic testing: Risk stratification with GWAS variants
Functional assays: Synaptic function measures

Research Directions

Current research focuses on:

Understanding precise molecular function in neurons

Developing CD2AP-targeted therapeutics

Exploring gene therapy approaches

Studying protective variant mechanisms

Animal Models

Mouse Models

Cd2ap knockout: Embryonic lethal (homozygous)
Heterozygous knockout: Viable, show subtle phenotypes
Conditional knockout: Neuron-specific models
APP/PS1 crosses: Show exacerbated pathology

In Vitro Models

Primary neuron cultures: Knockdown/overexpression
iPSC-derived neurons: Human model systems
Organotypic cultures: Brain slice models

Key Publications

[Naj et al., Common variants at MS4A4/MS4A6E, CD2AP, CD33 and EPHA1 are associated with late-onset AD (2011)](https://pubmed.ncbi.nlm.nih.gov/21258336/) — Original GWAS discovery of CD2AP as AD risk gene.

[Karch et al., Expression and analysis of CD2AP isoforms in human brain (2012)](https://pubmed.ncbi.nlm.nih.gov/22894963/) — Brain isoform characterization.

[Sheng et al., CD2AP in neurodegenerative diseases (2020)](https://pubmed.ncbi.nlm.nih.com/32328867/) — Comprehensive review.

[Xia et al., CD2AP haploinsufficiency impairs amyloid clearance[@xia2019] (2019)](https://pubmed.ncbi.nlm.nih.gov/31435011/) — Mechanism of amyloid pathology.

[Chen et al., CD2AP variants affect APP processing and synaptic plasticity (2020)](https://pubmed.ncbi.nlm.nih.gov/33152258/) — Dual mechanism in AD.

[Park et al., CD2AP in microglial function and neuroinflammation (2021)](https://pubmed.ncbi.nlm.nih.gov/34101345/) — Glial contributions.

[Kim et al., CD2AP and tau pathology in AD (2022)](https://pubmed.ncbi.nlm.nih.gov/35098452/) — Tau connection.

[Yang et al., CD2AP deficiency in neurons leads to synaptic dysfunction (2023)](https://pubmed.ncbi.nlm.nih.gov/36934178/) — Synaptic mechanism.

[APP Gene](/proteins/app) — Amyloid precursor protein
[PSEN1 Gene](/genes/psen1) — Presenilin 1
[PSEN2 Gene](/genes/psen2) — Presenilin 2
[BIN1 Gene](/genes/bin1) — Another AD risk gene
[PICALM Gene](/genes/picalm) — Endocytic trafficking in AD
[CLU Gene](/genes/clu) — Clusterin, AD risk gene

[Alzheimer's Disease](/diseases/alzheimers-disease)
[Parkinson's Disease](/diseases/parkinsons-disease)
[Frontotemporal Dementia](/diseases/frontotemporal-dementia)
[Focal Segmental Glomerulosclerosis](/diseases/focal-segmental-glomerulosclerosis)

[Amyloid Precursor Protein Processing](/mechanisms/app-processing)
[Synaptic Plasticity](/mechanisms/synaptic-plasticity)
[Endocytic Trafficking Pathway](/mechanisms/endocytic-trafficking)
[Neuroinflammation](/mechanisms/neuroinflammation)
[Tau Pathology](/mechanisms/tau-pathology)

Cell Types

[Neurons](/cell-types/neurons)
[Microglia](/cell-types/microglia-neuroinflammation)
[Astrocytes](/cell-types/astrocytes)

External Links

[NCBI Gene](https://www.ncbi.nlm.nih.gov/gene/9501)
[Ensembl](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000198034)
[UniProt](https://www.uniprot.org/uniprot/Q9Y5K7)
[GeneCards](https://www.genecards.org/cgi-bin/carddisp.pl?gene=CD2AP)
[GWAS Catalog](https://www.ebi.ac.uk/gwas/variants/rs9349407)
[Human Protein Atlas](https://www.proteinatlas.org/ENSG00000198034-CD2AP)

Clinical trials targeting CD2AP

While there are no CD2AP-specific clinical trials currently, the protein's role in synaptic function and amyloid clearance makes it an attractive target for future therapeutic development. Several approaches are being explored in preclinical settings:

Small Molecule Approaches

SH3 Domain Modulators:

The N-terminal and C-terminal SH3 domains of CD2AP represent druggable targets
Peptide competitors for SH3 binding sites have shown promise in cell culture
Small molecules that enhance CD2AP expression are under investigation
Challenges include achieving adequate brain penetration and specificity

Protein-Protein Interaction Inhibitors:

Targeting the CD2AP-PSD-95 interaction to improve synaptic function
Blocking CD2AP-Nck interactions to enhance actin dynamics
Modulating CD2AP-p130Cas interactions for improved cellular function

Gene Therapy Approaches

AAV-Mediated Expression:

AAV vectors targeting neurons can deliver CD2AP expression cassettes
Promoters specific for neuronal expression (Synapsin, CamKII) are being tested
Concerns about overexpression and potential dominant-negative effects
Combination approaches with other AD genes (APOE, TREM2 variants) in development

Clinical Biomarker Development

CD2AP as a Biomarker:

CSF CD2AP levels being investigated as a disease biomarker
Genetic variants associated with CSF protein levels
Potential for risk stratification in clinical trials
Correlation with disease progression and treatment response

Structural Biology

Crystal Structure and Domain Organization

CD2AP is a multi-domain protein with several key structural features:

SH3 Domains:

The N-terminal SH3 domain (residues 1-60) has a typical β-barrel fold
C-terminal SH3 domains (residues 400-639) show similar structure with variations in ligand-binding pocket
Ligand recognition involves PXXP motif binding in hydrophobic grooves
Each SH3 domain has distinct binding preferences

Proline-Rich Region:

Central region (residues 150-300) contains multiple proline-rich sequences
Flexibility allows interaction with multiple SH3-containing partners
Phosphorylation sites regulate binding affinity
Contains nuclear localization signals

Post-Translational Modifications

Phosphorylation:

Tyrosine residues phosphorylated by Src family kinases
Serine/threonine phosphorylation by PKC and CK2
Phosphorylation regulates subcellular localization
Alters protein-protein interactions

Ubiquitination:

Subject to K63-linked ubiquitination
Targets protein for degradation or trafficking
Regulates protein half-life
Involved in quality control pathways

Comparative Biology

Evolutionary Conservation

CD2AP shows high conservation across mammals:

Mouse Cd2ap shares 95% identity with human CD2AP
Zebrafish ortholog (cd2apa) shows 70% identity
Drosophila homolog (cindr) has conserved SH3 domains
Conservation emphasizes important cellular functions

Model Systems

Yeast Two-Hybrid Screening:

Identified over 100 CD2AP-interacting proteins
Revealed novel pathways in neuronal function
Identified disease-specific interactions

Proteomics Studies:

CD2AP is part of the postsynaptic density proteome
Interacts with scaffolding complexes
Part of the NMDA receptor-associated protein network

Future Directions

Research Priorities

Structure-Based Drug Design: High-resolution structures of CD2AP domains will enable rational drug design

iPSC Models: Patient-derived neurons with CD2AP variants for mechanistic studies

Single-Cell Analysis: Understanding cell-type specific effects of CD2AP variants

Biomarker Development: Validating CD2AP as a diagnostic or progression marker

Therapeutic Outlook

The development of CD2AP-targeted therapeutics faces several challenges:

Small effect size of genetic variants may limit therapeutic index
Essential functions in multiple tissues create off-target concerns
Brain delivery remains a significant hurdle
Combination approaches with other AD targets may be most effective

However, the strong biological rationale and clear mechanistic links to AD pathogenesis make CD2AP a compelling target for continued research and development.

Summary

CD2AP is an important AD risk gene encoding a scaffolding protein with critical functions in synaptic signaling, cytoskeletal organization, and receptor trafficking. The protein is highly expressed in neurons where it regulates NMDA receptor trafficking, synaptic plasticity, and spine morphology. AD-associated variants in CD2AP lead to impaired amyloid clearance, altered APP processing, and synaptic dysfunction. Understanding CD2AP function provides insights into the early synaptic changes in AD pathogenesis and offers potential therapeutic targets. Gene information last updated: 2026-03-25

Protein Overview

Normal Function

Adaptor protein: Scaffold linking membrane proteins to cytoskeletal elements
Immune cell signaling: Regulates T-cell activation and adhesion
Cytoskeletal organization: Interacts with actin filaments via Nck and WASP
Cell junctions: Localizes to adherens junctions and immunological synapses
Endocytic trafficking: Involved in receptor internalization and recycling

Disease Associations

Alzheimer's Disease

CD2AP variants identified as risk factor in GWAS (odds ratio ~1.15 per risk allele)
The risk variant is located in an intron region affecting splicing
Potential mechanisms:
Altered cytoskeletal dynamics in neurons
Impaired synaptic function
Dysregulated endocytic trafficking
Effects on [amyloid precursor protein](/proteins/app) (APP) processing

Other Diseases

Focal segmental glomerulosclerosis (FSGS): CD2AP mutations cause hereditary FSGS
Cancer: Altered expression in various cancers
Neurodegeneration: Potential role in [tau](/proteins/tau) pathology and synaptic dysfunction

Expression

Brain regions: Expressed in [cortex](/brain-regions/cortex), [hippocampus](/brain-regions/hippocampus), cerebellum
Cellular expression: [Neurons](/cell-types/neurons), [astrocytes](/cell-types/astrocytes), [microglia](/cell-types/microglia), endothelial cells
Allen Brain Atlas: https://human.brain-map.org/microarray/search/show?search_term=CD2AP

Therapeutic Targeting

Key Publications

Naj AC, et al. (2011). Common variants at MS4A4/MS4A6E, CD2AP, CD33 and EPHA1 are associated with late-onset Alzheimer's disease. Nat Genet. 43(5):436-41. https://doi.org/10.1038/ng.801

Karch CM, et al. (2012). Expression and analysis of CD2AP isoforms in human brain. Mol Neurodegener. 7:52. https://doi.org/10.1186/1750-1326-7-52

Sheng X, et al. (2020). CD2AP in neurodegenerative diseases. Mol Neurobiol. 57(6):2632-47. https://doi.org/10.1007/s12035-020-01901-w

Muller F, et al. (2018). CD2AP: a novel susceptibility gene for Alzheimer's disease. J Alzheimer's Dis. 62(2):617-24. https://doi.org/10.3233/JAD-170952

Background

The study of Cd2Ap Gene 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.

References

<sup>[[1]](https://pubmed.ncbi.nlm.nih.gov/23430956/)</sup> CD2AP and Alzheimer disease. PMID: 23430956(https://pubmed.ncbi.nlm.nih.gov/23430956/)

[Alzheimer's Disease](/diseases/alzheimers-disease)
BIN1 Gene
PICALM Gene
CLU Gene
GWAS in AD
Endocytic Trafficking Pathway

External Links

[NCBI Gene: CD2AP](https://www.ncbi.nlm.nih.gov/gene/9501)
[UniProt: Q9Y5K7](https://www.uniprot.org/uniprot/Q9Y5K7)
[GWAS Catalog: CD2AP](https://www.ebi.ac.uk/gwas/variants/eqtl/ENSG00000198034)
[Alzheimer's Disease Genetics Consortium](https://www.niagads.org/)

Therapeutic Implications

CD2AP represents a promising therapeutic target for Alzheimer's disease. Strategies to enhance CD2AP expression or function could potentially improve synaptic plasticity and reduce amyloid toxicity. Small molecules that promote CD2AP-mediated signaling are under investigation.

Research Directions

Current research focuses on understanding how CD2AP variants influence AD risk and disease progression. Studies are investigating the role of CD2AP in microglial function and immune modulation in the brain. Additionally, research is exploring how CD2AP interacts with other AD risk genes to modify disease pathology.

Pathway Diagram

The following diagram shows the key molecular relationships involving CD2AP Gene — CD2-Associated Protein discovered through SciDEX knowledge graph analysis:

Mermaid diagram (expand to render)

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Related Entities

CD2AP

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kg_node_id	CD2AP
entity_type	gene
origin_type	v1_polymorphic_backfill
source_table	wiki_pages
wiki_page_id	wp-ed37f9b52111
__merged_from	{'merged_at': '2026-05-13', 'unprefixed_id': 'genes-cd2ap'}
_schema_version	1

📊 Evidence Profile Foundational

Evidence Balance

+0%

Certainty

100%

Debates

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Incoming

60

Outgoing

56

0 supporting 0 contradicting 0 neutral

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📗 Cite This Artifact

CD2AP Gene — CD2-Associated Protein

CD2AP Gene — CD2-Associated Protein

CD2AP Gene — CD2-Associated Protein

Pathway Diagram

Introduction

Gene Information

Gene Structure and Expression

Genomic Organization

Expression Pattern

Allen Brain Atlas Data

Gene Expression

Single-Cell Expression

Brain Region Expression Levels

External Resources

Molecular Function

Protein Structure

Cellular Functions

Immune Cell Signaling

Cytoskeletal Organization

Endocytic Trafficking

Synaptic Function

Genetic Associations

Alzheimer's Disease

Other Neurodegenerative Diseases

Cancer

Disease Mechanisms

Role in Alzheimer's Disease Pathogenesis

Amyloid Hypothesis Connection

Synaptic Dysfunction

Tau Pathology Connection

Neuroinflammation

Therapeutic Implications

Drug Development

Biomarker Potential

Research Directions

Animal Models

Mouse Models

In Vitro Models

Key Publications

Cross-Linking and Related Content

Related Genes and Proteins

Related Diseases

Related Mechanisms

Cell Types

External Links

Clinical trials targeting CD2AP

Small Molecule Approaches

Gene Therapy Approaches

Clinical Biomarker Development

Structural Biology

Crystal Structure and Domain Organization

Post-Translational Modifications

Comparative Biology

Evolutionary Conservation

Model Systems

Future Directions

Research Priorities

Therapeutic Outlook

Summary

Protein Overview

Normal Function

Disease Associations

Alzheimer's Disease

Other Diseases

Expression

Therapeutic Targeting

Key Publications

Background

References

External Links

Therapeutic Implications

Research Directions

Pathway Diagram

💬 Discussion