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Relevance to Autism

A rare CYFIP1 deletion was found in a patient with PDD-NOS and mild intellectual disability (Leblond et al., 2012).

Molecular Function

Component of the CYFIP1-EIF4E-FMR1 complex which binds to the mRNA cap and mediates translational repression. In the CYFIP1-EIF4E-FMR1 complex this subunit is an adapter between EIF4E and FMR1. Promotes the translation repression activity of FMR1 in brain probably by mediating its association with EIF4E and mRNA. Regulates formation of membrane ruffles and lamellipodia. Plays a role in axon outgrowth. Binds to F-actin but not to RNA. Part of the WAVE complex that regulates actin filament reorganization via its interaction with the Arp2/3 complex. Actin remodeling activity is regulated by RAC1. Regulator of epithelial morphogenesis. May act as an invasion suppressor in cancers.

External Links

        

References

Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
Genetic and functional analyses of SHANK2 mutations suggest a multiple hit model of autism spectrum disorders.
ASD
ID
Positive Association
A Common CYFIP1 Variant at the 15q11.2 Disease Locus Is Associated with Structural Variation at the Language-Related Left Supramarginal Gyrus.
Inter-individual variation in surface area across
Positive Association
Common Regulatory Variants of CYFIP1 Contribute to Susceptibility for Autism Spectrum Disorder (ASD) and Classical Autism.
ASD
Positive Association
Common variants in genes of the postsynaptic FMRP signalling pathway are risk factors for autism spectrum disorders.
ASD
Support
ASD, schizophrenia
Support
Exome sequencing in multiplex autism families suggests a major role for heterozygous truncating mutations.
ASD
Support
A co-segregating microduplication of chromosome 15q11.2 pinpoints two risk genes for autism spectrum disorder.
ASD
Support
Integrating de novo and inherited variants in 42
ASD
Support
A highly conserved protein family interacting with the fragile X mental retardation protein (FMRP) and displaying selective interactions with FMRP-...
Support
Haploinsufficiency of the schizophrenia and autism risk gene Cyfip1 causes abnormal postnatal hippocampal neurogenesis through microglial and Arp2/3 mediated actin dependent mechanisms
ASD, SCZ
Support
Linking haploinsufficiency of the autism- and schizophrenia-associated gene Cyfip1 with striatal-limbic-cortical network dysfunction and cognitive inflexibility
ASD, schizophrenia
Support
Aralar Sequesters GABA into Hyperactive Mitochondria, Causing Social Behavior Deficits
Support
Impaired oxysterol-liver X receptor signaling underlies aberrant cortical neurogenesis in a stem cell model of neurodevelopmental disorder
Chromosome 15q11.2 deletion syndrome
ASD, SCZ
Support
Cytoplasmic FMRP interacting protein 1/2 (CYFIP1/2) expression analysis in autism.
Support
Intellectual Disability and Behavioral Deficits Linked to CYFIP1 Missense Variants Disrupting Actin Polymerization
DD, ID, epilepsy/seizures
Autistic features
Support
Comprehensive molecular testing in patients with high functioning autism spectrum disorder.
ASD
Recent Recommendation
Modeling a genetic risk for schizophrenia in iPSCs and mice reveals neural stem cell deficits associated with adherens junctions and polarity.
Recent Recommendation
The autism and schizophrenia associated gene CYFIP1 is critical for the maintenance of dendritic complexity and the stabilization of mature spines.
Recent Recommendation
CYFIP1 coordinates mRNA translation and cytoskeleton remodeling to ensure proper dendritic spine formation.
Recent Recommendation
Autism and Schizophrenia-Associated CYFIP1 Regulates the Balance of Synaptic Excitation and Inhibition.
Recent Recommendation
Cyfip1 Regulates Presynaptic Activity during Development.
Recent Recommendation
Reduced CYFIP1 in Human Neural Progenitors Results in Dysregulation of Schizophrenia and Epilepsy Gene Networks.
Recent Recommendation
Increased CYFIP1 dosage alters cellular and dendritic morphology and dysregulates mTOR.
Variant ID
Variant Type
Allele Change
Residue Change
Inheritance Pattern
Inheritance Association
Family Type
Author, Year
 GEN320R001 
 copy_number_loss 
  
  
 Familial 
 Paternal 
 Simplex 
 GEN320R002 
 copy_number_gain 
  
  
 Familial 
 Paternal 
 Multi-generational 
 GEN320R003 
 missense_variant 
 c.2597G>C 
 p.Arg866Pro 
 Familial 
 Maternal 
 Multiplex 
 GEN320R004 
 missense_variant 
 c.287C>T 
 p.Ala96Val 
 Familial 
 Paternal 
 Multi-generational 
 GEN320R005 
 missense_variant 
 c.1630G>A 
 p.Val544Ile 
 De novo 
  
  
 GEN320R006 
 missense_variant 
 c.3073G>A 
 p.Ala1025Thr 
 De novo 
  
  
 GEN320R007 
 intron_variant 
 c.1675-131G>C 
  
 De novo 
  
  
 GEN320R008 
 missense_variant 
 c.2867T>G 
 p.Met956Arg 
 De novo 
  
  
 GEN320R009a 
 missense_variant 
 c.1426A>G 
 p.Asn476Asp 
 Familial 
 Paternal 
 Multiplex 
 GEN320R009b 
 missense_variant 
 c.2225C>T 
 p.Pro742Leu 
 Familial 
 Maternal 
 Multiplex 
Chromosome
CNV Locus
CNV Type
# of studies
Animal Model
15
Duplication
 10
  construct
15
Duplication
 1
 
15
Duplication
 7
 
15
Duplication
 4
 
15
Duplication
 9
 
15
Duplication
 2
 
15
Duplication
 5
 
15
Deletion
 1
 
15
Deletion-Duplication
 123
 
15
Duplication
 10
 
15
Duplication
 89
  construct
15
Duplication
 10
 
15
Duplication
 21
 
15
Duplication
 3
 

Model Summary

The transgenic mice expressing Cyfip1 transgene, leading to increased production of the protein have increased mature dendritic spines and dendritic spine density.

References

Type
Title
Author, Year
Primary
Increased CYFIP1 dosage alters cellular and dendritic morphology and dysregulates mTOR.
Additional
Behavioral training rescues motor deficits in Cyfip1 haploinsufficiency mouse model of autism spectrum disorders.
Model Type: Genetic
Model Genotype: Transgenic
Mutation: Two transgenic strains (strain nos. 8 and 24) of second and third generation mice harboring a Cyfip1 spanning BAC clone generated by microinjection into fertilized C57BL/6 pronuclei, and showing a 1.5 and 2 fold increase in protein levels respectively (Fig 2E, F) in the adult hippocampus and a ~1.5 fold increase in cyfip1 transcript levels in strain number 8 in the E15 frontal cortex, P1 cerebellum, P11 hippocampus, and in adult frontal cortex and cerebellum (Fig S3).
Allele Type: Overexpression
Strain of Origin: C57BL/6
Genetic Background: C57BL/6
ES Cell Line:
Mutant ES Cell Line:
Model Source: UCLA transgenic core
Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Dendritic architecture: spine density1
Increased
 Golgi-cox staining
 2 months
Dendritic architecture: dendritic tree complexity1
Increased
 Golgi-cox staining
 2 months
Brain cytoarchitecture1
Increased
 Golgi-cox staining
 Unreported
Synapse density2
Increased
 Immunohistochemistry
 13â??15 weeks
Action potential property: amplitude2
Increased
 Whole-cell patch clamp
 3â??7 weeks
Sensory-evoked response: habituation2
Increased
 Time-lapse fluorescence microscopy
 11â??13 weeks
Sensory-evoked response: excitation2
Increased
 Time-lapse fluorescence microscopy
 11â??13 weeks
Targeted expression1
Increased
 NA
 2 months
Gene expression1
Decreased
 Quantitative pcr (qrt-pcr)
 E15
Targeted expression2
Increased
 Quantitative PCR (qRT-PCR)
 not specified
Gene expression1
Decreased
 Quantitative pcr (qrt-pcr)
 E15
Targeted expression2
Increased
 Western blot
 8â??32 weeks
Gene expression1
Decreased
 Quantitative pcr (qrt-pcr)
 E15
Regulation of translation2
Abnormal
 Co-immunoprecipitation
 not specified
Gene expression2
Increased
 Quantitative PCR (qRT-PCR)
 not specified
Brain morphology1
 No change
 Histology
 Unreported
Brain size1
 No change
 Golgi-cox staining
 Unreported
Synaptic morphology2
 No change
 Immunohistochemistry
 13â??15 weeks
Presynaptic function: paired-pulse depression (ppd)2
 No change
 Whole-cell patch clamp
 3â??7 weeks
Spontaneous post synaptic event amplitude: excitatory currents2
 No change
 Time-lapse fluorescence microscopy
 11â??13 weeks
Spontaneous post synaptic event frequency: excitatory currents2
 No change
 Time-lapse fluorescence microscopy
 11â??13 weeks
 Not Reported: Circadian sleep/wake cycle, Communications, Developmental profile, Emotion, Immune response, Learning & memory, Maternal behavior, Motor phenotype, Neurophysiology, Physiological parameters, Repetitive behavior, Seizure, Sensory, Social behavior

 

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