CD2AP Gene: Structure, Function, and Clinical Significance
A comprehensive overview of the CD2-associated protein (CD2AP) gene, including its genomic context, protein function, associated diseases, expression patterns, and mutation landscape.
Gene Information Card
| Symbol | CD2AP |
|---|---|
| Full Name | CD2-associated protein |
| Gene Type | Protein-coding |
| Chromosomal Location | 6p12.3 |
| NCBI Gene ID | 23607 ncbi.nlm.nih.gov/gene/23607 |
| Ensembl ID | ENSG00000198087 |
| UniProt ID | Q9Y5K6 |
| OMIM ID | 604241 |
| HGNC ID | 14258 |
| Aliases | CMS; MGC10744 |
Description
CD2AP (CD2-associated protein) is a scaffold protein that plays a critical role in dynamic actin remodeling, cell polarity, endocytosis, and intracellular trafficking. It is essential for the maintenance of podocyte structure and function in the kidney, and it also participates in T-cell adhesion and immune synapse formation. Mutations in CD2AP are associated with focal segmental glomerulosclerosis (FSGS) and susceptibility to nephrotic syndrome. Additionally, CD2AP has been implicated in Alzheimer's disease pathology through its interaction with the amyloid precursor protein (APP).
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Focal segmental glomerulosclerosis (FSGS) | Loss-of-function mutations in CD2AP disrupt podocyte actin cytoskeleton and slit diaphragm integrity, leading to proteinuria and glomerular scarring. | OMIM: 604241; PMID: 12506114 |
| Nephrotic syndrome (steroid-resistant) | Homozygous or compound heterozygous mutations in CD2AP cause early-onset nephrotic syndrome due to podocyte dysfunction. | OMIM: 604241; PMID: 24035157 |
| Alzheimer's disease (late-onset) | CD2AP variants affect APP endocytosis and trafficking, contributing to amyloid-beta accumulation and neurodegeneration. | ClinVar; PMID: 21460840 |
| HIV-associated nephropathy (HIVAN) | Reduced CD2AP expression in podocytes exacerbates HIV-induced podocyte injury, leading to collapsing glomerulopathy. | PMID: 16988062 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Kidney | High (nTPM ~ 200) | High |
| Brain | Moderate (nTPM ~ 50) | Medium |
| Lung | Low (nTPM ~ 20) | Low |
| Liver | Low (nTPM ~ 10) | Low |
| Testis | Moderate (nTPM ~ 30) | Medium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Podocytes (differentiated) | High | Key cell type for CD2AP function |
| HEK 293 | Moderate | Commonly used for overexpression studies |
| HeLa | Low | Minimal expression |
| Jurkat (T-cell) | Moderate | Involved in immune synapse |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.112C>T (p.Arg38Ter) | Nonsense | Rare (0.1% in general population) | Loss of function; causes FSGS in heterozygous state with incomplete penetrance |
| c.493G>A (p.Gly165Arg) | Missense | Rare (0.05%) | Disrupts actin binding; associated with nephrotic syndrome |
| c.1249C>T (p.Arg417Ter) | Nonsense | Very rare | Loss of function; homozygous causes early-onset nephrotic syndrome |
| c.1685A>G (p.Gln562Arg) | Missense | 0.2% in East Asian populations | Alters protein stability; risk factor for Alzheimer's disease |
Mutation functional classification
Loss of Function (LOF)
Most CD2AP mutations are loss-of-function, leading to haploinsufficiency or complete loss of protein function, resulting in podocyte cytoskeletal disruption and proteinuria.
Gain of Function (GOF)
No gain-of-function mutations have been reported for CD2AP.
Dominant Negative (DN)
Some missense mutations may exert dominant-negative effects by interfering with wild-type CD2AP function in protein-protein interactions, though evidence is limited.
View complete mutation data：
Gene Ontology (GO)
| • GO:0005515 (protein binding) | • GO:0005737 (cytoplasm) |
| • GO:0005856 (cytoskeleton) | • GO:0006897 (endocytosis) |
| • GO:0007155 (cell adhesion) | • GO:0030054 (cell junction) |
| • GO:0030863 (cortical cytoskeleton) | • GO:0045202 (synapse) |
Pathways
• Regulation of actin cytoskeleton (KEGG: hsa04810)
• Endocytosis (KEGG: hsa04144)
• Adherens junction (KEGG: hsa04520)
• Fc gamma R-mediated phagocytosis (KEGG: hsa04666)
Protein Summary
CD2AP is a 639-amino-acid protein with multiple SH3 domains and a proline-rich region. It acts as an adaptor linking membrane receptors to the actin cytoskeleton. In podocytes, CD2AP is localized at the slit diaphragm and is crucial for maintaining the filtration barrier. It interacts with nephrin, podocin, and actin. In T cells, CD2AP regulates CD2-mediated adhesion and signaling. Additionally, CD2AP modulates endocytic trafficking of receptors, including EGFR and APP, thereby influencing cell growth and neurodegeneration.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CD2AP Knockout HEK293 Cell Line | EDJ-KQ8091 | Human | 23607 | Details Get a Quote |
| CD2AP Knockout A-549 Cell Line | EDJ-KQ33943 | Human | 23607 | Details Get a Quote |
| CD2AP Knockout HCT 116 Cell Line | EDJ-KQ33944 | Human | 23607 | Details Get a Quote |
| CD2AP Knockout HeLa Cell Line | EDJ-KQ33945 | Human | 23607 | Details Get a Quote |
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