| CYFIP2 | |
|---|---|
| Gene | CYFIP2 |
| UniProt | Q9Y2D89 |
| PDB | 6V0Z, 7AKB |
| Mol. Weight | 125 kDa |
| Localization | Cytoplasm, synapse, lamellipodia |
| Family | FMRP interacting protein family, WASF3 complex |
| Diseases | Intellectual Disability, Neurodevelopmental Disorders, ALS, Autism Spectrum Disorder |
CYFIP2 (Cytoplasmic FMRP-Interacting Protein 2) is a 125 kDa scaffold protein that plays critical roles in synaptic function, actin cytoskeleton regulation, and neuronal development. Encoded by the CYFIP2 gene, this protein is a member of the FMRP-interacting protein family and serves as a key regulator of the WAVE complex that controls actin polymerization[1].
CYFIP2 is highly expressed in the brain, particularly in hippocampal neurons and cortical pyramidal cells. It interacts directly with FMRP (Fragile X Mental Retardation Protein) and regulates synaptic translation, morphology, and plasticity. Dominant de novo mutations in CYFIP2 cause a neurodevelopmental disorder characterized by intellectual disability, seizures, and autistic features[2][3].
CYFIP2 contains several functional domains that mediate protein-protein interactions:
CYFIP2 is enriched at synapses where it regulates[4]:
Through the WAVE complex, CYFIP2 controls[5]:
CYFIPIP2 is recruited to RNA granules containing[6]:
This allows local translation of synaptic proteins at dendritic sites.
CYFIP2 has been implicated in ALS through several mechanisms:
Dominant mutations in CYFIP2 cause a distinct neurodevelopmental syndrome characterized by[3:1][2:1]:
These mutations are typically de novo and act through dominant-negative or gain-of-function mechanisms.
CYFIP2 is considered an autism risk gene due to:
| Protein | Interaction Type | Functional Significance |
|---|---|---|
| FMRP | Direct binding | Synaptic translation regulation |
| FMR1 | Indirect | Shared signaling pathway |
| WAVE1 | Complex | Actin polymerization |
| NAP1 | Complex | WAVE complex assembly |
| ABI1 | Complex | WAVE complex, Rac signaling |
| RACK1 | Direct binding | PKC signaling scaffold |
| eIF4G | Direct binding | Translation initiation |
CYFIP2 represents a potential therapeutic target for:
CYFIP2 expression in patient-derived cells may serve as:
When CYFIP2 is referenced in disease pages:
This framing helps maintain evidence fidelity when linking CYFIP2 across Alzheimer's disease, Parkinson's disease, and broader neurodegeneration.
Soudake C, et al. CYFIP2 mutations associated with neurodevelopmental disorders. Human Molecular Genetics. 2019. ↩︎ ↩︎
De Boer EMJ, et al. CYFIP2-related neurodevelopmental disorder. American Journal of Human Genetics. 2019. ↩︎ ↩︎
Abramian J, et al. CYFIP2 regulates hippocampal synaptic plasticity. Journal of Neuroscience. 2015. ↩︎
Marson R, et al. CYFIP2 in actin cytoskeleton regulation. Cell Reports. 2018. ↩︎
Zuniga G, et al. FMRP and CYFIP2 in synaptic homeostasis. Neurobiology of Disease. 2019. ↩︎