CYFIP1

Chr 15

cytoplasmic FMR1 interacting protein 1

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

NCBI Gene: 23191ENSG00000273749UniProt: Q7L576

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]

355
ClinVar variants
131
Pathogenic / LP
0.97
pLI score· haploinsufficient
0
Active trials
Clinical Summary— CYFIP1
⚡
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.
📋
ClinVar Variants
131 Pathogenic / Likely Pathogenic· 175 VUS of 355 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
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?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
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?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.19 (0.13–0.30)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.73 (0.68–0.78)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.07
0≤1.21.6
LoF obs/exp: 14 / 72.4Missense obs/exp: 567 / 774.9Syn Z: -1.01

ClinVar Variant Classifications

355 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic122
Likely Pathogenic9
VUS175
Likely Benign31
Benign17
Conflicting1
122
Pathogenic
9
Likely Pathogenic
175
VUS
31
Likely Benign
17
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
122
0
122
Likely Pathogenic
0
0
9
0
9
VUS
0
155
20
0
175
Likely Benign
0
4
5
22
31
Benign
0
3
4
10
17
Conflicting
—1
Total016216032355

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

View in ClinVar →

Protein Context — Lollipop Plot

CYFIP1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
📖
GeneReview available — CYFIP1
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
The 15q11.2 BP1-BP2 microdeletion syndrome: a review.
Cox DM et al.·Int J Mol Sci
2015Review
Prader-Willi Syndrome and Chromosome 15q11.2 BP1-BP2 Region: A Review.
Butler MG·Int J Mol Sci
2023Review
Increased CYFIP1 dosage alters cellular and dendritic morphology and dysregulates mTOR.
Oguro-Ando A et al.·Mol Psychiatry
2015
Intercorrelation of Molecular Biomarkers and Clinical Phenotype Measures in Fragile X Syndrome.
Aishworiya R et al.·Cells
2023
Microglial phagolysosome dysfunction and altered neural communication amplify phenotypic severity in Prader-Willi Syndrome with larger deletion.
Correa-da-Silva F et al.·Acta Neuropathol
2024
Intellectual Disability and Behavioral Deficits Linked to CYFIP1 Missense Variants Disrupting Actin Polymerization.
Mariano V et al.·Biol Psychiatry
2024
Beyond the Copy Number Differences: The Phenotypic Diversity of Children With 15q11.2 Microdeletions and Microduplications.
Basarir G et al.·J Child Neurol
2025
Identification of disulfidptosis-related genes and subgroups in spinal cord injury.
Tao Y et al.·Spinal Cord
2025
Low expression of Cyfip1 may be a potential biomarker in nasopharyngeal carcinoma.
Shi X et al.·Neoplasma
2018
Integrated machine learning-driven disulfidptosis profiling: CYFIP1 and EMILIN1 as therapeutic nodes in neuroblastoma.
Mengzhen Z et al.·J Cancer Res Clin Oncol
2024
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools