CYFIP1

Chr 15

cytoplasmic FMR1 interacting protein 1

Also known as: P140SRA-1, SHYC, SRA-1, SRA1

NCBI Gene: 23191 ENSG00000273749 UniProt: Q7L576 OMIM: 606322

CYFIP1 encodes a protein that regulates actin cytoskeleton dynamics and inhibits protein translation by forming complexes with EIF4E and FMR1 protein. Deletions encompassing this highly constrained gene (pLI 0.97) cause neurodevelopmental disorders including intellectual disability, autism spectrum disorder, epilepsy, and schizophrenia with autosomal dominant inheritance. The gene plays critical roles in neuronal development, axon outgrowth, and synaptic function.

GeneReviews OMIM ResearchSummary from RefSeq, UniProt

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]

GeneReviews OMIM ResearchGenerating clinical summary…

LOEUF 0.30

Clinical Summary— CYFIP1

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Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.97). One damaged copy is likely sufficient to cause disease.

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ClinVar Variants

2 unique Pathogenic / Likely Pathogenic· 164 VUS of 255 total submissions

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GeneReview available — CYFIP1

Authoritative clinical overview · Recommended first read

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.30LOEUF

pLI 0.968

Z-score 6.36

OE 0.19 (0.13–0.30)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

2.65Z-score

OE missense 0.73 (0.68–0.78)

567 obs / 774.9 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.19 (0.13–0.30)

0≤0.351.4

Missense OE?0.73 (0.68–0.78)

0≤0.61.4

Synonymous OE?1.07

0≤1.21.6

LoF obs/exp: 14 / 72.4Missense obs/exp: 567 / 774.9Syn Z: -1.01

ClinVar Variant Classifications

255 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic1

Likely Pathogenic1

VUS164

Likely Benign31

Benign17

Conflicting1

Pathogenic

Likely Pathogenic

164

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	1	0	1
Likely Pathogenic	0	0	1	0	1
VUS	0	155	9	0	164
Likely Benign	0	4	5	22	31
Benign	0	3	4	10	17
Conflicting	—				1
Total	0	162	20	32	215

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

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215 pathogenic / likely-pathogenic (of 338) ClinVar copy-number / structural variants overlap CYFIP1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →