CYFIP1

protein-coding

cytoplasmic FMR1 interacting protein 1, the group of SCAR/WAVE complex

Gene summary

This gene encodes a protein that regulates cytoskeletal dynamics and protein translation. The encoded protein is a component of the WAVE regulatory complex (WRC), which promotes actin polymerization. This protein also interacts with the synaptic functional regulator FMR1 protein and translation initiation factor 4E to inhibit protein translation. A large chromosomal deletion including this gene is associated with increased risk of schizophrenia and epilepsy in human patients. Reduced expression of this gene has been observed in various human cancers and the encoded protein may inhibit tumor invasion. [provided by RefSeq, Mar 2022]

MANE transcript

NM_014608.6

Inheritance

—

ClinVar variants

U:174B:37

Top phenotype

CYFIP1-related disorder

Max pathogenic AF

—

Genomic locus

chr15:22,867,052-22,981,063

External References & Databases

Ensembl (ENSG00000273749)

Transcript & Mutation Effects

hg38 • Region Span ~114.0 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CYFIP1 variants in ClinVar

9 Conditions Cataloged

not specifiedTotal: 157

not providedTotal: 43

CYFIP1-related disorderTotal: 3

AutismTotal: 2

StrabismusTotal: 2

Cognitive impairmentTotal: 2

Delayed speech and language developmentTotal: 2

Autistic behaviorTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_014608.6. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			3 clinvar	20 clinvar	10 clinvar	33
missense			164 clinvar	4 clinvar	3 clinvar	171
nonsense			1 clinvar			1
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			5 clinvar			5
Total	0	0	174	24	13	211

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 83 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_014608.6	RefSeq	NP_055423.1	30	MANE Select
ENST00000617928.5	Ensembl	ENSP00000481038.1	30	MANE Select
NM_001033028.3	RefSeq	NP_001028200.1	16	Standard
NM_001287810.4	RefSeq	NP_001274739.1	30	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

RNA transport - Homo sapiens (human)
Regulation of actin cytoskeleton - Homo sapiens (human)
Brain-Derived Neurotrophic Factor (BDNF) signaling pathway
Prader-Willi and Angelman Syndrome
G13 Signaling Pathway

Biological Process

cell morphogenesis
regulation of translation
axon guidance
regulation of cell shape
Rac protein signal transduction

Molecular Function

RNA 7-methylguanosine cap binding
protein binding
translation regulator activity
Rac GTPase binding
actin filament binding

Cellular Component

ruffle
extracellular region
cytosol
mRNA cap binding complex
focal adhesion

dbNSFP Gene Annotations

Source: dbNSFP

Function: 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 (By similarity). 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. As component of the WAVE1 complex, required for BDNF-NTRK2 endocytic trafficking and signaling from early endosomes (By similarity). May act as an invasion suppressor in cancers. {ECO:0000250|UniProtKB:Q7TMB8, ECO:0000269|PubMed:16260607, ECO:0000269|PubMed:19524508, ECO:0000269|PubMed:21107423, ECO:0000269|PubMed:9417078}.;

Recessive Scores

pRec: 0.141

Intolerance Scores

LoFtool: 0.520
RVIS EVS: -1.3
RVIS percentile EVS: 4.99

Essentials

Essential (CRISPR): N
Essential (CRISPR2): E
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.722

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	High
Cancer	Medium	Medium	Medium