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GeneE
25 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
CD2AP
CD2 associated protein
Chromosome 6 Β· 6p12.3
NCBI Gene: 23607Ensembl: ENSG00000198087.8HGNC: HGNC:14258UniProt: Q9Y5K6
191PubMed Papers
21Diseases
0Drugs
17Pathogenic Variants
FUNCTIONAL ROLE
Hub Gene
RESEARCH IMPACT
Trending
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
actin filament organizationprotein bindingextracellular exosomepositive regulation of protein secretionfocal segmental glomerulosclerosisfamilial idiopathic steroid-resistant nephrotic syndromeAlzheimer diseaseAbnormality of the skeletal system
✦AI Summary

CD2AP is an adapter protein primarily functioning to link membrane proteins to the actin cytoskeleton 1. It plays critical roles in multiple biological contexts: in renal podocytes, CD2AP is expressed as a component of the slit diaphragm and anchors it to the actin cytoskeleton 2, with CD2AP mutations causing focal segmental glomerulosclerosis 3. In immune cells, CD2AP regulates cytoskeleton organization and protein trafficking 4. CD2AP is notably enriched in microglia, where it regulates phagocytic responses to amyloid-beta 4. In neuronal contexts, CD2AP facilitates endosomal-lysosomal degradation of amyloid precursor protein (APP) by promoting APP-CD2AP interaction, thereby reducing amyloid-beta generation 5. Genetic variants in CD2AP are associated with Alzheimer's disease risk 16, with evidence suggesting microglial CD2AP deficiency paradoxically protects against amyloid pathology and cognitive decline in AD models 4. This protection may occur through reduced microglial activation and altered phagocytic responses to pathological substrates. CD2AP thus represents a convergence point between kidney and brain pathophysiology, highlighting a potential kidney-brain axis in neurodegeneration 3.

Sources cited
1
CD2AP identified as genetic risk factor for late-onset Alzheimer's disease
PMID: 24951455
2
CD2AP expression in podocytes and component of slit diaphragm
PMID: 11856766
3
CD2AP polymorphisms associated with AD and focal segmental glomerulosclerosis; kidney-brain axis hypothesis
PMID: 40462155
4
CD2AP abundantly expressed in microglia; microglial CD2AP deficiency protects against AΞ² pathology and cognitive deficits in 5xFAD mice
PMID: 39695808
5
CD2AP promotes APP endosomal-lysosomal degradation, reducing AΞ² generation
PMID: 39744941
6
CD2AP linked to microglial phagocytosis and genetic risk for Alzheimer's disease
PMID: 41315858
Disease Associationsβ“˜21
focal segmental glomerulosclerosisOpen Targets
0.70Moderate
familial idiopathic steroid-resistant nephrotic syndromeOpen Targets
0.68Moderate
Alzheimer diseaseOpen Targets
0.52Moderate
Abnormality of the skeletal systemOpen Targets
0.43Moderate
dementiaOpen Targets
0.36Weak
late-onset Alzheimers diseaseOpen Targets
0.29Weak
Peyronie diseaseOpen Targets
0.25Weak
inherited focal segmental glomerulosclerosisOpen Targets
0.23Weak
genetic disorderOpen Targets
0.19Weak
Familial prostate cancerOpen Targets
0.11Weak
prostate cancerOpen Targets
0.11Weak
neoplasmOpen Targets
0.10Weak
hepatocellular carcinomaOpen Targets
0.09Suggestive
lung adenocarcinomaOpen Targets
0.09Suggestive
nephrotic syndromeOpen Targets
0.09Suggestive
skull disorderOpen Targets
0.09Suggestive
gastric cancerOpen Targets
0.08Suggestive
ulcerative colitisOpen Targets
0.08Suggestive
nephrotic syndrome, type 24Open Targets
0.08Suggestive
familial juvenile hyperuricemic nephropathy type 1Open Targets
0.07Suggestive
Focal segmental glomerulosclerosis 3UniProt
Pathogenic Variants17
NM_012120.3(CD2AP):c.764dup (p.Ser256fs)Pathogenic
Focal segmental glomerulosclerosis 3, susceptibility to|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 256
NM_012120.3(CD2AP):c.1742dup (p.Asn581fs)Pathogenic
Focal segmental glomerulosclerosis 3, susceptibility to|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 581
NM_012120.3(CD2AP):c.301del (p.Thr101fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2026β†’ Residue 101
NM_012120.3(CD2AP):c.1742del (p.Asn581fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 581
NM_012120.3(CD2AP):c.494del (p.Glu164_Leu165insTer)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 164
NM_012120.3(CD2AP):c.1386_1387del (p.Ser463fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 463
NM_012120.3(CD2AP):c.720dup (p.Pro241fs)Likely pathogenic
Focal segmental glomerulosclerosis 3, susceptibility to
β˜…β˜†β˜†β˜†2025β†’ Residue 241
NM_012120.3(CD2AP):c.330_334del (p.Arg111fs)Likely pathogenic
Focal segmental glomerulosclerosis 3, susceptibility to
β˜…β˜†β˜†β˜†2024β†’ Residue 111
NM_012120.3(CD2AP):c.865_868del (p.Thr289fs)Likely pathogenic
Focal segmental glomerulosclerosis 3, susceptibility to
β˜…β˜†β˜†β˜†2024β†’ Residue 289
NM_012120.3(CD2AP):c.865del (p.Thr289fs)Likely pathogenic
Focal segmental glomerulosclerosis 3, susceptibility to
β˜…β˜†β˜†β˜†2024β†’ Residue 289
NM_012120.3(CD2AP):c.250C>T (p.Arg84Ter)Likely pathogenic
Focal segmental glomerulosclerosis 3, susceptibility to
β˜…β˜†β˜†β˜†2024β†’ Residue 84
NM_012120.3(CD2AP):c.298C>T (p.Gln100Ter)Likely pathogenic
Focal segmental glomerulosclerosis 3, susceptibility to
β˜…β˜†β˜†β˜†2024β†’ Residue 100
NM_012120.3(CD2AP):c.30T>G (p.Tyr10Ter)Likely pathogenic
Focal segmental glomerulosclerosis 3, susceptibility to
β˜…β˜†β˜†β˜†2024β†’ Residue 10
NM_012120.3(CD2AP):c.730-1_730delinsCTPathogenic
FOCAL SEGMENTAL GLOMERULOSCLEROSIS 3|Focal segmental glomerulosclerosis 3, susceptibility to
β˜…β˜†β˜†β˜†2024
NM_012120.3(CD2AP):c.1193_1196del (p.Ala398fs)Likely pathogenic
CD2AP-related disorder
β˜…β˜†β˜†β˜†2023β†’ Residue 398
NM_012120.3(CD2AP):c.1108+1G>TLikely pathogenic
Focal segmental glomerulosclerosis 3, susceptibility to
β˜…β˜†β˜†β˜†2022
NM_012120.3(CD2AP):c.1045+1G>APathogenic
Focal segmental glomerulosclerosis 3, susceptibility to|Nonpapillary renal cell carcinoma
β˜†β˜†β˜†β˜†2017
View on ClinVar β†—
Related Genes
UBCProtein interaction99%SYNJ1Protein interaction99%CBLProtein interaction99%CBLBProtein interaction99%INPPL1Protein interaction99%BCAR1Protein interaction99%
Tissue Expression6 tissues
Bone Marrow
100%
Liver
61%
Heart
53%
Lung
53%
Brain
31%
Ovary
25%
Gene Interaction Network
Click a node to explore
CD2APUBCSYNJ1CBLCBLBINPPL1BCAR1
PROTEIN STRUCTURE
Preparing viewer…
PDB3U23 Β· 1.11 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.81LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.59 [0.44–0.81]
RankingsWhere CD2AP stands among ~20K protein-coding genes
  • #2,242of 20,598
    Most Researched191 Β· top quartile
  • #2,321of 5,498
    Most Pathogenic Variants17
  • #6,873of 17,882
    Most Constrained (LOEUF)0.81
Genes detectedCD2AP
Sources retrieved25 papers
Response timeβ€”
πŸ“„ Sources
25β–Ό
1
Alzheimer's disease risk genes and mechanisms of disease pathogenesis.
PMID: 24951455
Biol Psychiatry Β· 2015
1.00
2
Clinical efficacies, underlying mechanisms and molecular targets of Chinese medicines for diabetic nephropathy treatment and management.
PMID: 34589395
Acta Pharm Sin B Β· 2021
0.90
3
A conditionally immortalized human podocyte cell line demonstrating nephrin and podocin expression.
PMID: 11856766
J Am Soc Nephrol Β· 2002
0.80
4
Microglial CD2AP deficiency exerts protection in an Alzheimer's disease model of amyloidosis.
PMID: 39695808
Mol Neurodegener Β· 2024
0.70
5
CD2AP promotes the progression of glioblastoma multiforme via TRIM5-mediated NF-kB signaling.
PMID: 39353894
Cell Death Dis Β· 2024
0.68