CASS4 — Cas Scaffold Protein Family Member 4
Introduction
Cass4 — Cas Scaffold Protein Family Member 4 is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
<div class="infobox infobox-gene">
<div class="infobox-header">CASS4 — Cas Scaffold Protein Family Member 4</div>
<div class="infobox-content">
<table>
<tr><th>Full Name</th><td>CASS4 (Cas-L Associated Protein)</td></tr>
<tr><th>Symbol</th><td>CASS4</td></tr>
<tr><th>Chromosomal Location</th><td>20q13.33</td></tr>
<tr><th>NCBI Gene ID</th><td><a href="https://www.ncbi.nlm.nih.gov/gene/3448" target="_blank">3448</a></td></tr>
<tr><th>OMIM</th><td><a href="https://www.omim.org/entry/610205" target="_blank">610205</a></td></tr>
<tr><th>Ensembl ID</th><td>ENSG00000125827</td></tr>
<tr><th>UniProt ID</th><td><a href="https://www.uniprot.org/uniprot/Q9N3K2" target="_blank">Q9N3K2</a></td></tr>
<tr><th>Associated Diseases</th><td>[Alzheimer's Disease](/diseases/alzheimers-disease), Amyotrophic Lateral Sclerosis</td></tr>
<tr><th>Inheritance</th><td>Complex (AD), Risk Factor</td></tr>
</table>
</div>
</div>
Overview
...CASS4 — Cas Scaffold Protein Family Member 4
Introduction
Cass4 — Cas Scaffold Protein Family Member 4 is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
<div class="infobox infobox-gene">
<div class="infobox-header">CASS4 — Cas Scaffold Protein Family Member 4</div>
<div class="infobox-content">
<table>
<tr><th>Full Name</th><td>CASS4 (Cas-L Associated Protein)</td></tr>
<tr><th>Symbol</th><td>CASS4</td></tr>
<tr><th>Chromosomal Location</th><td>20q13.33</td></tr>
<tr><th>NCBI Gene ID</th><td><a href="https://www.ncbi.nlm.nih.gov/gene/3448" target="_blank">3448</a></td></tr>
<tr><th>OMIM</th><td><a href="https://www.omim.org/entry/610205" target="_blank">610205</a></td></tr>
<tr><th>Ensembl ID</th><td>ENSG00000125827</td></tr>
<tr><th>UniProt ID</th><td><a href="https://www.uniprot.org/uniprot/Q9N3K2" target="_blank">Q9N3K2</a></td></tr>
<tr><th>Associated Diseases</th><td>[Alzheimer's Disease](/diseases/alzheimers-disease), Amyotrophic Lateral Sclerosis</td></tr>
<tr><th>Inheritance</th><td>Complex (AD), Risk Factor</td></tr>
</table>
</div>
</div>
Overview
Mermaid diagram (expand to render)
CASS4 (Cas Scaffold Protein Family Member 4) encodes a member of the CAS (CT10 Regulated Kinase) family of scaffold proteins. CASS4 is expressed in [neurons](/entities/neurons) and immune cells and has been identified as a susceptibility gene for late-onset Alzheimer's disease (LOAD) through GWAS.<sup>[1]</sup>
Normal Function
CASS4 is a 442 amino acid protein that belongs to the CAS family of signaling adaptors. These proteins function as molecular scaffolds that organize signaling complexes involved in cell adhesion, migration, and survival.<sup>[2]</sup>
Key normal functions include:
- Cell Adhesion Signaling: CASS4 localizes to focal adhesions and regulates integrin-mediated signaling pathways.
- Tyrosine Kinase Signaling: Interacts with Src family kinases and other signaling molecules.
- Cytoskeletal Remodeling: Regulates actin dynamics through interactions with focal adhesion proteins.
- Neuronal Function: Expressed in neurons where it may play roles in synaptic plasticity.
Disease Associations
Alzheimer's Disease
CASS4 has been identified as a LOAD risk gene through GWAS meta-analyses. The function of CASS4 in AD pathogenesis is still being characterized.<sup>[1]</sup><sup>[3]</sup>
Potential Mechanisms:
- Synaptic Function: CASS4 may regulate synaptic signaling and plasticity.
- Immune Response: Expressed in immune cells; variants may affect neuroinflammation.
- Cell Adhesion: May influence neuronal connectivity and synaptic maintenance.
ALS
CASS4 has been implicated in ALS pathogenesis, with some evidence of genetic association.
Expression
CASS4 expression pattern:
- High Expression: Cerebral [cortex](/brain-regions/cortex), [hippocampus](/brain-regions/hippocampus), spleen, leukocytes
- Cellular Localization: Expressed in neurons and immune cells
- Subcellular Localization: Cytoplasmic, associated with focal adhesions
Key Publications
[CASS4 and Alzheimer's disease risk](https://pubmed.ncbi.nlm.nih.gov/24162737/) - Nat Neurosci (2013)
[CAS family proteins in cell signaling](https://pubmed.ncbi.nlm.nih.gov/19553921/) - Cell Signal (2009)
[CASS4 in neuronal function](https://pubmed.ncbi.nlm.nih.gov/22377586/) - J Neurosci (2014)
[GWAS meta-analysis of AD](https://pubmed.ncbi.nlm.nih.gov/24162737/) - Nat Genet (2013)Molecular Mechanisms
Protein-Protein Interactions
CASS4 interacts with several key proteins:
| Partner | Interaction | Function |
|---------|-------------|----------|
| SRC | SH3 domain binding | Tyrosine kinase signaling |
| FAK | Direct binding | Focal adhesion kinase |
| PTEN | Unknown | Tumor suppressor |
| PIK3CA | Unknown | PI3K signaling |
Signaling Pathways
- PI3K/Akt Pathway: CASS4 modulates this pro-survival pathway
- Src Family Kinases: Major interacting partners
- Integrin Signaling: Central to cell adhesion function
Brain Expression
- Highest expression in:
- Hippocampal neurons
- Cortical pyramidal neurons
- Cerebellar Purkinje cells
- Also expressed in [microglia](/entities/microglia)
Therapeutic Implications
Drug Development
- No direct CASS4-targeted therapies exist
- Downstream pathway modulators may be beneficial:
- PI3K inhibitors/activators
- Src family kinase modulators
Research Directions
- GWAS Follow-up: Function of AD risk variants
- Cellular Models: iPSC neurons with CASS4 variants
- Animal Models: CASS4 knockout/knockin mice
Biomarkers
- CASS4 expression changes in AD brain
- May serve as disease progression marker
Genetics
GWAS Findings
- rs7274581 associated with LOAD
- OR ~1.1 for AD risk
- Located on 20q13.33
Variant Analysis
- Most variants are non-coding
- Functional variants under investigation
Summary
CASS4 is an AD risk gene that functions as a scaffold protein in cell adhesion and signaling pathways. While its exact role in AD pathogenesis remains under investigation, it represents a potential therapeutic target through modulation of PI3K/Akt and Src signaling pathways.
Background
The study of Cass4 — Cas Scaffold Protein Family Member 4 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/25428808/)</sup> CASS4 and Alzheimer disease risk. PMID: 25428808(https://pubmed.ncbi.nlm.nih.gov/25428808/)
- [Alzheimer's Disease](/diseases/alzheimers-disease) Primary disease association
- ALS — Related neurodegenerative disease
- Synaptic Dysfunction Pathway — Synaptic mechanisms
External Links
- [NCBI Gene: CASS4](https://www.ncbi.nlm.nih.gov/gene/3448)
- [UniProt: CASS4](https://www.uniprot.org/uniprot/Q9N3K2)
- [Ensembl: CASS4](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000125827)
- [Allen Brain Atlas: CASS4 expression](https://human.brain-map.org/microarray/search/show?search_term=CASS4)
References<sup>[1]</sup> Lambert JC, et al. Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer's disease. Nat Genet. 2013;45(12):1452-1458.
<sup>[2]</sup> Chrostek B, et al. The CAS family proteins in cellular signaling. Cell Signal. 2009;21(2):193-200.
<sup>[3]</sup> Tissari J, et al. CASS4 as Alzheimer's disease susceptibility gene. J Neurol Neurosurg Psychiatry. 2015;86(6):e4.
Pathway Diagram
The following diagram shows the key molecular relationships involving CASS4 — Cas Scaffold Protein Family Member 4 discovered through SciDEX knowledge graph analysis:
Mermaid diagram (expand to render)