CFL1

Chr 11

cofilin 1

Also known as: CFL, HEL-S-15, cofilin

NCBI Gene: 1072ENSG00000172757UniProt: P23528

The protein encoded by this gene can polymerize and depolymerize F-actin and G-actin in a pH-dependent manner. Increased phosphorylation of this protein by LIM kinase aids in Rho-induced reorganization of the actin cytoskeleton. Cofilin is a widely distributed intracellular actin-modulating protein that binds and depolymerizes filamentous F-actin and inhibits the polymerization of monomeric G-actin in a pH-dependent manner. It is involved in the translocation of actin-cofilin complex from cytoplasm to nucleus.[supplied by OMIM, Apr 2004]

23
ClinVar variants
10
Pathogenic / LP
0.56
pLI score
0
Active trials
Clinical Summary— CFL1
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.56) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
10 Pathogenic / Likely Pathogenic· 12 VUS of 23 total submissions
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
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.
0.72LOEUF
pLI 0.556
Z-score 2.03
OE 0.15 (0.05–0.72)
Moderately constrained

Typical tolerance to LoF variation

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.
2.80Z-score
OE missense 0.21 (0.15–0.30)
21 obs / 99.6 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.0.15 (0.05–0.72)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.21 (0.15–0.30)
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.1.60
0≤1.21.6
LoF obs/exp: 1 / 6.6Missense obs/exp: 21 / 99.6Syn Z: -3.09

ClinVar Variant Classifications

23 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic8
Likely Pathogenic2
VUS12
Benign1
8
Pathogenic
2
Likely Pathogenic
12
VUS
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
8
0
8
Likely Pathogenic
0
0
2
0
2
VUS
0
8
4
0
12
Likely Benign
0
0
0
0
0
Benign
0
0
0
1
1
Total0814123

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

View in ClinVar →

Protein Context — Lollipop Plot

CFL1 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype

OMIM

No OMIM entries found.

Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Oncogenic β-catenin stimulation of cofilin 1-mediated macropinocytosis is druggable for cancer.
Zhang B et al.·Theranostics
2025
Estradiol inhibits HIV-1(BaL) infection and induces CFL1 expression in peripheral blood mononuclear cells and endocervical mucosa.
Verma N et al.·Sci Rep
2022
Identification of proteomic signatures associated with lung cancer and COPD.
Pastor MD et al.·J Proteomics
2013Clinical trial
Genetic variants affecting mitochondrial function provide further insights for kidney disease.
Cañadas-Garre M et al.·BMC Genomics
2024
Multi-omics and machine learning identify novel biomarkers and therapeutic targets of COVID-19.
Zhou Y et al.·Front Immunol
2025
The expression of CFL1 and N-WASP in esophageal squamous cell carcinoma and its correlation with clinicopathological features.
Wang WS et al.·Dis Esophagus
2010
Hypoxia-induced cofilin 1 promotes hepatocellular carcinoma progression by regulating the PLD1/AKT pathway.
Yao B et al.·Clin Transl Med
2021
Lower expression of MMP2, FLNA, and CFL1 is correlated with favorable prognosis in invasive micropapillary breast cancer.
Wang Y et al.·Gene
2025
Progress and challenges in the use of Cofilin-1 as a prognostic and predictive biomarker for cancer management.
Branco MA et al.·Gene
2025Review
Remodeling Serine Synthesis and Metabolism via Nanoparticles (NPs)-Mediated CFL1 Silencing to Enhance the Sensitivity of Hepatocellular Carcinoma to Sorafenib.
Li S et al.·Adv Sci (Weinh)
2023Functional
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