Affinage

CYFIP1

Cytoplasmic FMR1-interacting protein 1 · UniProt Q7L576

Length
1253 aa
Mass
145.2 kDa
Annotated
2026-06-09
52 papers in source corpus 28 papers cited in narrative 28 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CYFIP1 is a dual-function scaffold protein that couples activity-dependent mRNA translation to actin cytoskeletal remodeling, integrating these outputs at synapses and other cellular interfaces through a single Rac1-gated conformational switch (PMID:9417078, PMID:24050404). It directly binds the translation initiation factor eIF4E via a domain structurally related to 4E-BP inhibitors, repressing cap-dependent translation as part of an FMRP complex; BDNF or DHPG stimulation dissociates CYFIP1 from eIF4E to license local protein synthesis (PMID:18805096). Independently, CYFIP1 is a core subunit of the WAVE regulatory complex (WRC) and binds GTP-loaded Rac1 through its N-terminal domain, co-sedimenting with F-actin to drive Arp2/3-dependent actin polymerization (PMID:9417078, PMID:26676744). These two states are mutually exclusive: Rac1-GTP drives a butterfly-like conformational change that shifts CYFIP1 from the eIF4E-repressor complex into the WRC, thereby co-regulating translation and actin dynamics for proper dendritic spine morphology (PMID:24050404, PMID:26575774), with MNK-dependent eIF4E phosphorylation tuning the eIF4E–CYFIP1 interaction (PMID:25588502). Through these activities CYFIP1 governs synaptic structure and function — controlling dendritic complexity, AMPA receptor mobility, presynaptic release, and excitatory/inhibitory balance (PMID:24667445, PMID:26843638, PMID:30784587) — and acts as an RNA-binding regulator that stabilizes voltage-gated calcium channel mRNAs to support axon growth and mitochondrial function (PMID:41315480) and controls translation of NMDA receptor complex mRNAs (PMID:34247782). Beyond neurons, the CYFIP1-WRC-Arp2/3 axis shapes microglial morphology, surveillance, and synaptic pruning (PMID:37573007, PMID:41818151), regulates neural stem cell fate and white matter myelination (PMID:31988061, PMID:31371763), and as part of the WASF3/NCKAP1 complex suppresses cancer cell invasion and metastasis downstream of RAC1 (PMID:19524508, PMID:27432794). Biallelic CYFIP1 missense variants disrupting WRC interactions cause intellectual disability and ASD with impaired actin polymerization (PMID:37704042).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1998 High

    Established CYFIP1 as a Rac1 effector, defining its first molecular function by linking it specifically to active Rac1 signaling and the actin cytoskeleton.

    Evidence Affinity purification from brain cytosol, GST-pulldown with nucleotide-loaded GTPases, and F-actin co-sedimentation with domain mapping

    PMID:9417078

    Open questions at the time
    • Did not identify CYFIP1 as a WRC subunit or define how Rac1 binding alters CYFIP1 activity
    • No translational function known at this stage
  2. 2008 High

    Revealed CYFIP1's second, unexpected function as a translational repressor that mimics 4E-BP, recasting it as a bifunctional protein bridging translation control and the FMRP pathway.

    Evidence Co-IP, in vitro binding, structural homology analysis, and BDNF/DHPG-stimulated protein synthesis after RNAi in neurons

    PMID:18805096

    Open questions at the time
    • How translational repression is mechanistically reconciled with the actin/WRC role was not yet defined
    • Identity of repressed mRNA targets not established
  3. 2009 High

    Demonstrated that CYFIP1 acts as a WAVE-complex-dependent invasion suppressor, extending its actin-regulatory role into epithelial morphogenesis and tumorigenesis.

    Evidence RNAi knockdown with morphogenesis assays, in vivo Ras cooperation xenografts, and genomic deletion analysis

    PMID:19524508

    Open questions at the time
    • Did not resolve the molecular interface between CYFIP1 and other WRC subunits
    • Relationship to translational function untested
  4. 2013 High

    Unified the two CYFIP1 functions into a single switch model, showing Rac1-driven conformational change toggles CYFIP1 between eIF4E-repressor and WRC states to co-coordinate translation and actin dynamics.

    Evidence Intramolecular FRET, reciprocal Co-IP, interactome mass spectrometry, and CYFIP1 knockdown with spine morphology readouts in neurons

    PMID:24050404

    Open questions at the time
    • Structural basis of the conformational switch not directly resolved at atomic level
    • Kinetics of the switch in vivo unknown
  5. 2015 Medium

    Provided structural and regulatory detail for the switch — defining a butterfly-like conformational change, mutual exclusivity of eIF4E vs WRC binding, and MNK-dependent control of the eIF4E interaction.

    Evidence Molecular dynamics simulation grounded in the WRC crystal structure plus FRET data; reciprocal Co-IP in Mnk1/2 knockout and inhibitor-treated fibroblasts

    PMID:25588502 PMID:26575774

    Open questions at the time
    • MD model and MNK regulation rest largely on a single lab each
    • Direct atomic structure of the eIF4E-bound CYFIP1 conformation not solved
  6. 2016 High

    Defined the WASF3-NCKAP1-CYFIP1 complex as a RAC1-dependent metastasis driver, and showed disrupting subunit interfaces suppresses invasion, validating the complex as a druggable unit.

    Evidence siRNA knockdown across cancer cell lines, in vivo metastasis models, RAC1-complex Co-IP, and stapled-peptide interface disruption

    PMID:26676744 PMID:27432794

    Open questions at the time
    • Whether CYFIP1's translational function contributes to invasion not addressed
    • Specificity of peptide effects beyond the WASF3 complex not fully delimited
  7. 2016 High

    Established CYFIP1 dosage as a determinant of synaptic structure and function in vivo, linking haploinsufficiency to dendritic, spine, AMPA receptor, and presynaptic phenotypes via the WRC-Rac1 axis.

    Evidence Cyfip1 heterozygous mice, shRNA with mutant rescue, single-particle AMPA receptor tracking, electrophysiology, and Rac1 inhibitor rescue

    PMID:24667445 PMID:26843638

    Open questions at the time
    • Relative contribution of translational vs actin functions to each phenotype not separated
    • Cell-type-specific origins of presynaptic effects partly unresolved
  8. 2017 Medium

    Showed CYFIP1 and FMRP antagonistically modulate mTOR signaling and that NOTCH1 transcriptionally controls CYFIP1, situating CYFIP1 within broader growth-signaling and gene-regulatory networks.

    Evidence Drosophila NMJ and mouse olfactory neurogenesis epistasis with mTOR immunoblotting; ChIP and pathway manipulation in keratinocytes

    PMID:25311365 PMID:28183735 PMID:28410392

    Open questions at the time
    • Mechanism connecting CYFIP1 to mTOR is indirect and not biochemically resolved
    • NOTCH1 regulation shown in keratinocytes, not neurons
  9. 2019 High

    Expanded CYFIP1's role beyond synapses to circuit-level connectivity and white matter, showing haploinsufficiency disrupts myelination and bilateral connectivity across species.

    Evidence Cyfip1 heterozygous mice and rats with fMRI/DTI, electron microscopy, MBP immunohistochemistry, and electrophysiology

    PMID:31371726 PMID:31371763

    Open questions at the time
    • Whether myelin defects are oligodendrocyte-autonomous vs axon-driven not fully resolved
    • Molecular mechanism linking CYFIP1 to MBP distribution unknown
  10. 2019 High

    Identified CYFIP1 as a regulator of synaptic excitatory/inhibitory balance enriched at inhibitory postsynaptic sites, distinguishing its role from paralog CYFIP2.

    Evidence Bidirectional manipulation (overexpression and conditional knockout) with electrophysiology and immunoblotting for GABAA subunits and neuroligin 3

    PMID:30784587

    Open questions at the time
    • Molecular route by which CYFIP1 controls GABAA/neuroligin 3 levels not defined
    • Whether effect is translational or structural unresolved
  11. 2021 High

    Identified specific in vivo mRNA targets of CYFIP1 — NMDAR complex and SynGAP1-associated synaptic components — and microglial/Arp2/3-dependent control of adult neurogenesis, deepening the translational-regulator and actin roles.

    Evidence RIP-seq, bidirectional genetic models with electrophysiology and pharmacological rescue; subcellular fractionation and Rac1/CaMKII activity assays; BrdU/TUNEL with Arp2/3 inhibition

    PMID:33613257 PMID:34031371 PMID:34247782

    Open questions at the time
    • How target-mRNA selectivity is achieved not defined
    • Some downstream signaling claims rest on single-lab correlative measurements
  12. 2022 High

    Defined a CYFIP1-specific interactome distinct from CYFIP2, including astrocytic focal adhesion proteins, establishing non-redundant and non-neuronal cellular contexts for CYFIP1.

    Evidence Reciprocal Co-IP from knock-in mice with mass spectrometry, size-exclusion chromatography, immunocytochemistry, and proximity ligation assay

    PMID:35567753

    Open questions at the time
    • Functional consequences of focal-adhesion association not tested
    • Whether astrocytic CYFIP1 uses WRC or translational functions unknown
  13. 2023 Medium

    Linked CYFIP1 directly to disease and to microglial function, showing biallelic WRC-disrupting variants cause ID/ASD and that CYFIP1 loss impairs microglial synaptic pruning and motility.

    Evidence Patient fibroblast and Drosophila knockin actin assays; CRISPR knockout in patient- and iPSC-derived microglia-like cells with phagocytosis and motility readouts

    PMID:37545882 PMID:37573007 PMID:37704042

    Open questions at the time
    • Causality of variants supported by model systems but limited human genetic replication
    • Microglial findings in vitro; in vivo confirmation pending
  14. 2025 High

    Established a new RNA-stabilization function — CYFIP1 binds and stabilizes voltage-gated calcium channel mRNAs to control intracellular calcium, axon growth, and mitochondrial health.

    Evidence RIP, calcium imaging, in vivo axon tracing, mitochondrial imaging, and calcium-elevation rescue in Cyfip1 heterozygous neurons

    PMID:41315480

    Open questions at the time
    • Mechanism distinguishing mRNA stabilization from translational repression not resolved
    • Whether stabilization requires the WRC or eIF4E conformations unknown
  15. 2026 High

    Confirmed in vivo microglial roles, showing CYFIP1 maintains microglial surveillance, morphological complexity, and homeostatic state while restraining presynapse engulfment.

    Evidence Conditional microglial Cyfip1 knockout with two-photon live imaging, CD68 lysosome immunostaining, and synapse engulfment assays

    PMID:41818151

    Open questions at the time
    • Whether engulfment phenotype is WRC/Arp2/3-mediated not directly demonstrated in this model
    • Circuit-level consequences of altered pruning not assessed

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how CYFIP1 selects between its mutually exclusive translational-repressor, mRNA-stabilizing, and WRC actin-nucleating functions in a given cell type and whether a single molecular hierarchy governs all phenotypes.
  • No unifying quantitative model partitioning translation vs actin functions across cell types
  • Atomic structure of the eIF4E-bound conformation unsolved
  • Mechanism of target-mRNA recognition undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0045182 translation regulator activity 3 GO:0003723 RNA binding 2 GO:0008092 cytoskeletal protein binding 2 GO:0060089 molecular transducer activity 2 GO:0060090 molecular adaptor activity 2 GO:0098772 molecular function regulator activity 2
Localization
GO:0005856 cytoskeleton 2 GO:0005886 plasma membrane 2 GO:0005829 cytosol 1
Pathway
R-HSA-112316 Neuronal System 4 R-HSA-1266738 Developmental Biology 4 R-HSA-162582 Signal Transduction 3 R-HSA-1643685 Disease 3 R-HSA-392499 Metabolism of proteins 3 R-HSA-168256 Immune System 2
Partners
EIF4EFAM49BFMR1GAS7NCKAP1NRXN1RAC1WASF3
Complex memberships
FMRP-eIF4E translational repressor complexWASF3-NCKAP1-CYFIP1 complexWAVE regulatory complex (WRC)

Evidence

Reading pass · 28 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 CYFIP1 (p140Sra-1/KIAA0068) was identified as a specific binding partner of GTP-bound Rac1 small GTPase but not GDP-Rac1, Cdc42, or RhoA. The N-terminal domain (amino acids 1-407) mediates Rac1 interaction. CYFIP1 also directly co-sediments with F-actin and co-localizes with dominant-active Rac1 and cortical actin at membrane ruffling areas. Affinity purification from bovine brain cytosol, GST-pulldown with GTPγS/GDP-loaded GTPases, co-sedimentation with F-actin, co-localization in KB cells The Journal of biological chemistry High 9417078
2008 CYFIP1 directly binds the translation initiation factor eIF4E through a domain structurally related to 4E-BP translational inhibitors, thereby repressing translation initiation as part of the FMRP complex. BC1 RNA (another FMRP binding partner) increases the affinity of FMRP for the CYFIP1-eIF4E complex. BDNF or DHPG stimulation causes CYFIP1 to dissociate from eIF4E at synapses, triggering protein synthesis in an activity-dependent manner. Co-immunoprecipitation, in vitro binding assays, structural homology analysis, neuronal stimulation (BDNF/DHPG) with protein level measurements after CYFIP1 reduction by RNAi Cell High 18805096
2009 CYFIP1, as a subunit of the WAVE complex regulating cytoskeletal dynamics, functions as an invasion suppressor in epithelial cancers. Silencing of CYFIP1 disturbs normal epithelial morphogenesis in vitro and cooperates with oncogenic Ras to produce invasive carcinomas in vivo by impairing WAVE-regulated actin dynamics and cell-cell adhesion and cell-ECM interactions. RNAi knockdown in epithelial cells, in vitro morphogenesis assays, in vivo xenograft cooperation with oncogenic Ras, genomic deletion analysis Cell High 19524508
2013 BDNF-driven synaptic signaling releases CYFIP1 from the translational inhibitory eIF4E complex, triggering mRNA translation, and simultaneously shifts CYFIP1 into the WAVE regulatory complex. Active Rac1 alters CYFIP1 conformation (demonstrated by intramolecular FRET), and is key in changing the equilibrium between the two complexes, coordinating protein translation and actin polymerization for correct dendritic spine morphology. Intramolecular FRET to detect conformational change, co-immunoprecipitation, CYFIP1 knockdown in neurons with spine morphology readout, BDNF stimulation assays, interactome mass spectrometry Neuron High 24050404
2014 CYFIP1 is highly enriched at synapses and regulates dendritic complexity, spine morphology, spine actin dynamics, and AMPA receptor lateral diffusion. Cyfip1 haploinsufficiency in mice leads to reduced dendritic complexity, increased mobile F-actin, enhanced GluA2-containing AMPA receptor mobility at synapses, and an altered immature-to-mature spine ratio in hippocampal CA1 neurons in vivo. In vitro neuronal overexpression and shRNA knockdown, live imaging (F-actin dynamics), single-particle tracking of AMPA receptors, in vivo analysis of Cyfip1 heterozygous mice (dendritic morphology, spine ratios) Translational psychiatry High 24667445
2014 CYFIP1 overexpression activates mTOR signaling, as confirmed at the protein level in neuronal progenitors and in post-mortem brain from 15q11-13 duplication patients with ASD. mTOR inhibitor rapamycin rescues morphological abnormalities (cellular hypertrophy, dendritic spine changes) resulting from CYFIP1 overexpression. BAC transgenic mouse overexpressing Cyfip1, neuronal progenitor overexpression, gene expression profiling, western blot for mTOR pathway components, rapamycin rescue experiment Molecular psychiatry Medium 25311365
2015 MNK kinases (Mnk1/Mnk2) regulate the binding of eIF4E to CYFIP1; inhibition or genetic knockout of Mnks increases eIF4E-CYFIP1 binding, suggesting that MNK-dependent eIF4E phosphorylation promotes release of CYFIP1-mediated translational repression of FMRP-bound mRNAs. Co-immunoprecipitation of eIF4E-CYFIP1 in fibroblasts from Mnk1/2 knockout mice and with Mnk inhibitor Mnk-I1 The Biochemical journal Medium 25588502
2015 CYFIP1 undergoes a butterfly-like conformational change (bringing N- and C-termini closer together) when released from WAVE regulatory complex partners, enabling interaction with eIF4E. The interaction of CYFIP1 with eIF4E and with the WRC are mutually exclusive, and Rac1-GTP directly promotes the switch from eIF4E-bound to WRC-bound CYFIP1 conformation. Molecular dynamics simulation on CYFIP1 extracted from known WRC crystal structure, supported by intramolecular FRET data and published structural/biochemical data showing mutual exclusivity Journal of chemical theory and computation Medium 26575774
2015 Stapled peptides targeting the α-helical interface between WASF3 and CYFIP1 (WAHM peptides) destabilize the WASF3 complex, suppress RAC1 binding to the WASF3 complex, and inhibit cancer cell invasion. Genetic knockdown of CYFIP1 also destabilizes the WASF3 complex and suppresses invasion. Structure-based stapled peptide design, CYFIP1 RNAi knockdown, invasion assays, co-immunoprecipitation of RAC1 with WASF3 complex Cancer research Medium 26676744
2016 The WASF3-NCKAP1-CYFIP1 complex is required for breast cancer metastasis. NCKAP1 silencing destabilizes the WASF3 complex, preventing RAC1 association with the complex and suppressing invasion in vitro and spontaneous metastasis in vivo. Stapled peptides targeting the NCKAP1-CYFIP1 interface suppress RAC1 binding and invasion. siRNA knockdown of NCKAP1 in breast/prostate/colon cancer cells, in vivo metastasis model in immunocompromised mice, co-immunoprecipitation of RAC1 with WASF3 complex, stapled peptide treatment Cancer research High 27432794
2016 Cyfip1 haploinsufficiency in juvenile mice increases presynaptic terminal size and enhances vesicle release probability, decreasing paired-pulse facilitation and increasing mEPSC frequency. These presynaptic alterations are caused by dysregulation of the WAVE regulatory complex downstream of Rac1, as shown by shRNA knockdown combined with expression of Cyfip1 mutants, and rescued by acute Rac1 inhibition. Cyfip1 heterozygous mice, shRNA knockdown with Cyfip1 mutant rescue constructs, electrophysiology (PPF, mEPSC), Rac1 inhibitor treatment in culture and hippocampal slices The Journal of neuroscience High 26843638
2017 CYFIP1 and FMRP antagonize each other's function during neuromuscular junction growth in Drosophila and during new neuronal differentiation in adult mouse olfactory bulb. Mechanistically, FMRP and CYFIP1 modulate mTOR signaling in an antagonistic manner via independent pathways. Drosophila NMJ morphology analysis in cyfip/fmr1 mutants, adult mouse olfactory bulb neurogenesis assay, western blot for mTOR signaling components in double mutants Disease models & mechanisms Medium 28183735
2017 NOTCH1 directly controls CYFIP1 expression in keratinocytes. ChIP confirmed direct binding of NOTCH1 to the CYFIP1 promoter, and manipulation of the NOTCH1 pathway in keratinocytes altered CYFIP1 mRNA levels. Chromatin immunoprecipitation (ChIP) for NOTCH1 at CYFIP1 promoter, NOTCH1 overexpression and pathway manipulation in keratinocytes with RT-PCR/qPCR readout PloS one Medium 28410392
2018 GAS7b associates with CYFIP1 and WAVE2 complex to suppress breast cancer metastasis by blocking CYFIP1-Rac1 protein interaction, actin polymerization, and β1-integrin/FAK/Src signaling. Co-immunoprecipitation of GAS7-CYFIP1 complex, functional invasion/metastasis assays with GAS7 knockdown/overexpression, Rac1-CYFIP1 interaction assays, actin polymerization readouts Oncogene Medium 29706651
2019 Cyfip1 heterozygous mice have reduced functional connectivity, defects in white matter architecture, decreased myelination in callosal axons, and altered presynaptic function in callosal connections. Cyfip1 deficiency leads to impaired bilateral connectivity. Cyfip1 heterozygous mouse model, functional MRI connectivity, diffusion tensor imaging, electron microscopy of axon myelination, electrophysiology for presynaptic function Nature communications High 31371726
2019 Cyfip1 haploinsufficiency in rats produces extensive white matter changes with myelin sheath thinning in the corpus callosum, independent of changes in axon number or diameter, associated with aberrant intracellular distribution of myelin basic protein in mature oligodendrocytes. Novel rat Cyfip1 heterozygous model, diffusion tensor imaging, transmission electron microscopy, immunohistochemistry for myelin basic protein in oligodendrocytes Nature communications High 31371763
2019 CYFIP1 and its paralog CYFIP2 are enriched at inhibitory postsynaptic sites. CYFIP1 upregulation increases excitatory synapse number/mEPSC frequency but decreases inhibitory synapse size and mIPSC amplitude. Conditional knockout of CYFIP1 in neocortical principal cells increases GABAA receptor β2/3-subunits and neuroligin 3 expression, enhancing synaptic inhibition. CYFIP1/2 overexpression in neurons (electrophysiology, immunostaining), conditional Cyfip1 knockout mice with immunoblot for GABAA subunits and neuroligin 3, mIPSC/mEPSC recordings Cell reports High 30784587
2020 CYFIP1 expression is preferentially localized to B1 neural stem cells (NSCs) in the adult mouse subventricular zone (SVZ). Acute deletion of Cyfip1 in adult NSCs causes rapid changes in adherens junction proteins and increased B1 cell proliferation and symmetric renewal at the ventricular surface, indicating CYFIP1 regulates NSC fate decisions. Immunofluorescence for CYFIP1 in adult SVZ, conditional Cyfip1 deletion in adult NSCs (Cre-lox), BrdU/EdU proliferation assays, immunostaining for adherens junction proteins The Journal of neuroscience Medium 31988061
2021 Cyfip1 haploinsufficiency leads to increased numbers of adult-born hippocampal neurons due to reduced apoptosis (not altered proliferation), caused by a cell-autonomous failure of microglia to secrete appropriate pro-apoptotic factors. Additionally, adult-born neuron migration is abnormal due to altered Arp2/3-mediated actin dynamics. Cyfip1 heterozygous mice, BrdU/TUNEL assays for proliferation and apoptosis, microglia conditional experiments, pharmacological Arp2/3 inhibition, cell migration assays Translational psychiatry Medium 34031371
2021 CYFIP1 regulates protein translation of NMDA receptor complex components at synapses. RNA immunoprecipitation sequencing (RIP-seq) identified NMDAR complex mRNAs as in vivo CYFIP1 targets. Loss- and gain-of-function mouse models show diametric changes in synaptic NMDAR levels due to dysregulated translation, resulting in bidirectional alteration of NMDAR-mediated signaling, rescuable by pharmacological normalization of NMDAR signaling. RIP-seq in mouse brain, electrophysiology for NMDAR-mediated signaling, western blot for synaptic NMDAR subunits in Cyfip1 LOF and GOF mice, pharmacological rescue Biological psychiatry High 34247782
2021 Cyfip1 haploinsufficiency reduces synaptic (but not total) SynGAP1 levels during early postnatal development and in adults, associated with reduced Cdk5 levels and maintained CaMKII activation, increased Rac1 activity, elevated synaptic F-actin, and increased WAVE regulatory complex activity. Decreased synaptic SynGAP1 is associated with elevated synaptic GluA2, increased AMPA receptor-mediated responses, and increased synaptic mGluR1/5. Cyfip1 heterozygous mouse hippocampus, subcellular fractionation for synaptic vs total protein levels, kinase activity assays (Rac1 activity, CaMKII activation), F-actin sedimentation, electrophysiology Frontiers in synaptic neuroscience Medium 33613257
2022 CYFIP1 (but not CYFIP2) associates with astrocytic focal adhesion proteins. Mass spectrometry-based interactome of CYFIP1 from knock-in mouse brains identified 131 CYFIP1-specific interactors with only 8 shared with CYFIP2 interactome. CYFIP1 was detected in both neurons and astrocytes by immunostaining and proximity ligation assay confirmed co-localization with focal adhesion proteins in astrocytes. CYFIP1 and CYFIP2 are not significantly co-immunoprecipitated with each other. Reciprocal co-IP from CYFIP1-2xMyc and CYFIP2-3xFlag knock-in mice, mass spectrometry interactome, size-exclusion chromatography, single-cell RNA-seq database analysis, immunocytochemistry, proximity ligation assay Journal of neurochemistry High 35567753
2023 CYFIP1 loss-of-function in human microglia-like cells (derived from PBMCs and iPSCs) decreases synaptic vesicle phagocytosis (synaptic pruning), shifts microglial morphology toward a more ramified profile, and significantly reduces motility. CYFIP1-KO microglia retain the ability to differentiate but show functional deficits in synaptic engulfment. CRISPR knockout of CYFIP1 in patient-derived microglia-like cells and iPSC-derived microglia-like cells, synaptosome phagocytosis assay, morphological analysis, motility assay, multiple isogenic line pairs Biological psychiatry High 37573007
2023 Two biallelic CYFIP1 missense variants in probands with intellectual disability and ASD are located in protein domains responsible for maintaining interactions within the WAVE regulatory complex, causing deficits in actin polymerization in patient skin fibroblasts and abnormal brain morphology and F-actin loss in Drosophila knockin mutants. Patient fibroblast actin polymerization assays, Drosophila knockin mutants for corresponding variants, brain morphology analysis in flies, behavioral assays Biological psychiatry Medium 37704042
2023 CYFIP1 overexpression enhances localization of synaptic organizer neurexin 1 (NRXN1) at climbing fiber synaptic input sites on Purkinje cell primary dendrites and concomitantly enhances climbing fiber synaptic transmission (CF-EPSCs) in cerebellar Purkinje cells. CYFIP1 overexpressing mice, immunostaining for NRXN1 at climbing fiber synapses, whole-cell patch-clamp recordings of CF-EPSCs, two-photon GCaMP6f imaging of climbing fiber signals in vivo Frontiers in cellular neuroscience Medium 37545882
2024 CYFIP1 (as part of the WAVE regulatory complex) is required for platelet lamellipodia formation. Platelet-specific Cyfip1 knockout mice fail to form lamellipodia on fibrinogen-coated surfaces and show enhanced spreading in structured micropatterns, demonstrating that CYFIP1-WRC-ARP2/3 axis controls platelet morphology. FAM49b (CYRI-B) negatively regulates WRC by competing for RAC1 binding, and its inhibitory effect requires functional CYFIP1-WRC. Platelet-specific Cyfip1-/-, Fam49b-/-, and double-knockout mice, platelet spreading assays on fibrinogen-coated surfaces and 2D micropatterns, morphology analysis Cells Medium 38391912
2025 CYFIP1 binds and stabilizes mRNAs of specific voltage-gated calcium channel subunits, explaining reduced intracellular calcium in Cyfip1-deficient cortical neurons and axons. Cyfip1 heterozygosity delays callosal axon growth and arborization in vivo, associated with impaired mitochondria morphology, activity, and motility. Elevating intracellular calcium rescues both delayed axonal growth and mitochondrial defects in Cyfip1-deficient neurons. Cyfip1 heterozygous mice (in vivo axon tracing), calcium imaging in neurons, mitochondrial morphology/motility imaging, RNA immunoprecipitation for voltage-gated calcium channel mRNAs, calcium elevation rescue experiments Nature communications High 41315480
2026 Conditional deletion of Cyfip1 in mouse microglia reduces microglial morphological complexity and surveillance of the brain parenchyma (without affecting chemotaxis), increases CD68-positive lysosome volume, and enhances engulfment of presynapses, shifting microglia away from a homeostatic state. Conditional Cyfip1 knockout in microglia (Cre-lox), two-photon live imaging for microglial surveillance and chemotaxis, immunostaining for CD68 lysosomes, synapse engulfment assays Proceedings of the National Academy of Sciences of the United States of America High 41818151

Source papers

Stage 0 corpus · 52 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2008 The fragile X syndrome protein represses activity-dependent translation through CYFIP1, a new 4E-BP. Cell 492 18805096
2013 CYFIP1 coordinates mRNA translation and cytoskeleton remodeling to ensure proper dendritic spine formation. Neuron 244 24050404
1998 p140Sra-1 (specifically Rac1-associated protein) is a novel specific target for Rac1 small GTPase. The Journal of biological chemistry 194 9417078
2014 The autism and schizophrenia associated gene CYFIP1 is critical for the maintenance of dendritic complexity and the stabilization of mature spines. Translational psychiatry 160 24667445
2014 Increased CYFIP1 dosage alters cellular and dendritic morphology and dysregulates mTOR. Molecular psychiatry 98 25311365
2019 Autism and Schizophrenia-Associated CYFIP1 Regulates the Balance of Synaptic Excitation and Inhibition. Cell reports 90 30784587
2012 Haploinsufficiency of Cyfip1 produces fragile X-like phenotypes in mice. PloS one 88 22900020
2009 Cyfip1 is a putative invasion suppressor in epithelial cancers. Cell 77 19524508
2019 The autism- and schizophrenia-associated protein CYFIP1 regulates bilateral brain connectivity and behaviour. Nature communications 76 31371726
2016 The WASF3-NCKAP1-CYFIP1 Complex Is Essential for Breast Cancer Metastasis. Cancer research 66 27432794
2019 Cyfip1 haploinsufficient rats show white matter changes, myelin thinning, abnormal oligodendrocytes and behavioural inflexibility. Nature communications 57 31371763
2015 The MAP kinase-interacting kinases regulate cell migration, vimentin expression and eIF4E/CYFIP1 binding. The Biochemical journal 57 25588502
2016 Cyfip1 Regulates Presynaptic Activity during Development. The Journal of neuroscience : the official journal of the Society for Neuroscience 52 26843638
2015 Targeting the WASF3-CYFIP1 Complex Using Stapled Peptides Suppresses Cancer Cell Invasion. Cancer research 52 26676744
2017 New insights into the regulatory function of CYFIP1 in the context of WAVE- and FMRP-containing complexes. Disease models & mechanisms 51 28183735
2018 Wild-type p53 upregulates an early onset breast cancer-associated gene GAS7 to suppress metastasis via GAS7-CYFIP1-mediated signaling pathway. Oncogene 41 29706651
2015 Common Regulatory Variants of CYFIP1 Contribute to Susceptibility for Autism Spectrum Disorder (ASD) and Classical Autism. Annals of human genetics 34 26094621
2016 Reduced CYFIP1 in Human Neural Progenitors Results in Dysregulation of Schizophrenia and Epilepsy Gene Networks. PloS one 30 26824476
2015 MD and Docking Studies Reveal That the Functional Switch of CYFIP1 is Mediated by a Butterfly-like Motion. Journal of chemical theory and computation 30 26575774
2021 Haploinsufficiency of the schizophrenia and autism risk gene Cyfip1 causes abnormal postnatal hippocampal neurogenesis through microglial and Arp2/3 mediated actin dependent mechanisms. Translational psychiatry 28 34031371
2019 Differential cell-type-expression of CYFIP1 and CYFIP2 in the adult mouse hippocampus. Animal cells and systems 26 31853374
2020 FMRP and CYFIP1 at the Synapse and Their Role in Psychiatric Vulnerability. Complex psychiatry 25 34883502
2019 Behavioral training rescues motor deficits in Cyfip1 haploinsufficiency mouse model of autism spectrum disorders. Translational psychiatry 21 30664619
2015 Parental origin impairment of synaptic functions and behaviors in cytoplasmic FMRP interacting protein 1 (Cyfip1) deficient mice. Brain research 21 26474913
2021 Treadmill exercise enhances synaptic plasticity in the ischemic penumbra of MCAO mice by inducing the expression of Camk2a via CYFIP1 upregulation. Life sciences 20 33497737
2019 CYFIP1 overexpression increases fear response in mice but does not affect social or repetitive behavioral phenotypes. Molecular autism 19 31198525
2019 Cyfip1 Haploinsufficiency Increases Compulsive-Like Behavior and Modulates Palatable Food Intake in Mice: Dependence on Cyfip2 Genetic Background, Parent-of Origin, and Sex. G3 (Bethesda, Md.) 19 31324746
2023 Loss of Function in the Neurodevelopmental Disease and Schizophrenia-Associated Gene CYFIP1 in Human Microglia-like Cells Supports a Functional Role in Synaptic Engulfment. Biological psychiatry 14 37573007
2021 CYFIP1 Dosages Exhibit Divergent Behavioral Impact via Diametric Regulation of NMDA Receptor Complex Translation in Mouse Models of Psychiatric Disorders. Biological psychiatry 13 34247782
2018 Cytoplasmic FMRP interacting protein 1/2 (CYFIP1/2) expression analysis in autism. Metabolic brain disease 13 29752658
2020 Persistent Cyfip1 Expression Is Required to Maintain the Adult Subventricular Zone Neurogenic Niche. The Journal of neuroscience : the official journal of the Society for Neuroscience 12 31988061
2018 Prenatal diagnosis of a familial 15q11.2 (BP1-BP2) microdeletion encompassing TUBGCP5, CYFIP1, NIPA2 and NIPA1 in a fetus with ventriculomegaly, microcephaly and intrauterine growth restriction on prenatal ultrasound. Taiwanese journal of obstetrics & gynecology 12 30342661
2016 A Common CYFIP1 Variant at the 15q11.2 Disease Locus Is Associated with Structural Variation at the Language-Related Left Supramarginal Gyrus. PloS one 12 27351196
2019 Domain-Specific Cognitive Impairments in Humans and Flies With Reduced CYFIP1 Dosage. Biological psychiatry 11 31202490
2019 Evidence for a Contribution of the Nlgn3/Cyfip1/Fmr1 Pathway in the Pathophysiology of Autism Spectrum Disorders. Neuroscience 11 31705895
2023 Intellectual Disability and Behavioral Deficits Linked to CYFIP1 Missense Variants Disrupting Actin Polymerization. Biological psychiatry 10 37704042
2017 CYFIP1 is directly controlled by NOTCH1 and down-regulated in cutaneous squamous cell carcinoma. PloS one 10 28410392
2016 Cyfip1 is downregulated in acute lymphoblastic leukemia and may be a potential biomarker in acute lymphoblastic leukemia. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 10 26779626
2022 Protein interactome and cell-type expression analyses reveal that cytoplasmic FMR1-interacting protein 1 (CYFIP1), but not CYFIP2, associates with astrocytic focal adhesion. Journal of neurochemistry 9 35567753
2023 Overexpression of the autism candidate gene Cyfip1 pathologically enhances olivo-cerebellar signaling in mice. Frontiers in cellular neuroscience 7 37545882
1998 Identification of shyc, a novel gene expressed in the murine developing and adult nervous system. Neuroscience letters 7 9756361
2018 Expression Analysis of CYFIP1 and CAMKK2 Genes in the Blood of Epileptic and Schizophrenic Patients. Journal of molecular neuroscience : MN 6 29992499
2024 Integrated machine learning-driven disulfidptosis profiling: CYFIP1 and EMILIN1 as therapeutic nodes in neuroblastoma. Journal of cancer research and clinical oncology 5 38427078
2024 Linking haploinsufficiency of the autism- and schizophrenia-associated gene Cyfip1 with striatal-limbic-cortical network dysfunction and cognitive inflexibility. Translational psychiatry 5 38876996
2021 Cyfip1 Regulates SynGAP1 at Hippocampal Synapses. Frontiers in synaptic neuroscience 5 33613257
2025 CYFIP1 coordinate with RNMT to induce osteosarcoma cuproptosis via AURKAIP1 m7G modification. Molecular medicine (Cambridge, Mass.) 4 39984834
2023 Different dysregulations of CYFIP1 and CYFIP2 in distinct types of dementia. Brain research bulletin 4 38128786
2018 Low expression of Cyfip1 may be a potential biomarker in nasopharyngeal carcinoma. Neoplasma 4 29534591
2024 Differential Role of the RAC1-Binding Proteins FAM49b (CYRI-B) and CYFIP1 in Platelets. Cells 3 38391912
2019 Cyfip1 Haploinsufficiency Does Not Alter GABAA Receptor δ-Subunit Expression and Tonic Inhibition in Dentate Gyrus PV+ Interneurons and Granule Cells. eNeuro 3 31209152
2026 Control of microglial dynamics by the Arp2/3 complex and the autism- and schizophrenia-associated protein CYFIP1. Proceedings of the National Academy of Sciences of the United States of America 0 41818151
2025 CYFIP1 governs the development of cortical axons by modulating calcium availability. Nature communications 0 41315480

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