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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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TWF1
twinfilin actin binding protein 1
Chromosome 12 · 12q12
NCBI Gene: 5756Ensembl: ENSG00000151239.15HGNC: HGNC:9620UniProt: Q12792
111PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
actin bindingprotein tyrosine kinase activityfocal adhesioncadherin bindingcomplex regional pain syndromemalignant renal pelvis neoplasmlung adenocarcinomaneoplasm
✦AI Summary

TWF1 (twinfilin actin binding protein 1) is an actin-binding protein that regulates cytoskeletal dynamics through multiple mechanisms. Functionally, TWF1 inhibits actin polymerization by sequestering G-actin and caps barbed ends of actin filaments, thereby controlling actin turnover and cellular motility 1. TWF1 phosphorylation at tyrosine 309 by Src kinase is essential for reelin signaling, which regulates actin remodeling and dendritic spine development; phospho-resistant mutants exhibit reduced spine density and cognitive deficits 2. Beyond developmental processes, TWF1 plays critical roles in cancer progression. In lung adenocarcinoma, TWF1 overexpression promotes migration, invasion, and autophagy through cAMP pathway suppression 3. Similarly, in hepatocellular carcinoma, TWF1 contributes to drug resistance and metastasis; miR-142-3p-mediated TWF1 suppression enhances tyrosine kinase inhibitor sensitivity by inhibiting autophagy 4. In renal cell carcinoma, miR-30a/c-5p targets TWF1 to suppress epithelial-mesenchymal transition and metastatic potential 5. TWF1 also serves as a pancreatic cancer biomarker; elevated expression in cyst fluid predicts malignancy and associates with poor prognosis 6. Additionally, TWF1 expression increases with aging and biliary injury, mediating cholangiocyte adaptation and senescence responses 7. These findings establish TWF1 as a multifunctional regulator of actin dynamics with broad implications for development, aging, and cancer pathobiology.

Sources cited
1
TWF1 controls actin depolymerization and is essential for lamellipodial dynamics and convergent extension during gastrulation
PMID: 34060614
2
Src-mediated TWF1 tyrosine 309 phosphorylation in reelin signaling regulates actin dynamics and dendritic spine development
PMID: 41075995
3
TWF1 overexpression in lung adenocarcinoma promotes migration, invasion, and autophagy through cAMP pathway inhibition
PMID: 37358822
4
TWF1 is a direct target of miR-142-3p; TWF1 knockdown inhibits autophagy and enhances tyrosine kinase inhibitor sensitivity in hepatocellular carcinoma
PMID: 40362400
5
miR-30a/c-5p directly targets TWF1 to suppress epithelial-mesenchymal transition and metastatic potential in renal cell carcinoma
PMID: 35697274
6
TWF1 is a pancreatic cancer biomarker elevated in malignant cysts and associated with poor prognosis
PMID: 40300662
7
TWF1 expression increases with aging and biliary injury, mediating cholangiocyte adaptation to aging and response to injury
PMID: 30561764
8
TWF1 is downstream of miR-486-5p in the circ_0011496-regulated cascade that promotes hepatocellular carcinoma metastasis via fibroblast activation
PMID: 38840551
Disease Associationsⓘ20
complex regional pain syndromeOpen Targets
0.11Weak
malignant renal pelvis neoplasmOpen Targets
0.10Suggestive
lung adenocarcinomaOpen Targets
0.09Suggestive
neoplasmOpen Targets
0.09Suggestive
cancerOpen Targets
0.06Suggestive
hepatocellular carcinomaOpen Targets
0.05Suggestive
septic shockOpen Targets
0.05Suggestive
glaucomaOpen Targets
0.05Suggestive
Griscelli diseaseOpen Targets
0.04Suggestive
coronary artery diseaseOpen Targets
0.04Suggestive
uncombable hair syndromeOpen Targets
0.04Suggestive
glomerulonephritisOpen Targets
0.04Suggestive
head and neck squamous cell carcinomaOpen Targets
0.03Suggestive
Griscelli disease type 1Open Targets
0.03Suggestive
Griscelli syndrome type 1Open Targets
0.03Suggestive
Griscelli disease type 3Open Targets
0.03Suggestive
Griscelli syndrome type 3Open Targets
0.03Suggestive
ProptosisOpen Targets
0.03Suggestive
Clouston syndromeOpen Targets
0.03Suggestive
hypotrichosis 8Open Targets
0.03Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
TPRNProtein interaction100%ACTA1Protein interaction98%CAPZA1Protein interaction98%CAPZA2Protein interaction98%EZRProtein interaction97%RDXProtein interaction95%
Tissue Expression6 tissues
Bone Marrow
100%
Liver
73%
Brain
55%
Ovary
39%
Lung
34%
Heart
17%
Gene Interaction Network
Click a node to explore
TWF1TPRNACTA1CAPZA1CAPZA2EZRRDX
PROTEIN STRUCTURE
Preparing viewer…
PDB7CCC · 3.20 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.60LoF Tolerant
pLIⓘ
0.85Intermediate
Observed/Expected LoF0.31 [0.17–0.60]
RankingsWhere TWF1 stands among ~20K protein-coding genes
  • #4,301of 20,598
    Most Researched111 · top quartile
  • #4,136of 17,882
    Most Constrained (LOEUF)0.60 · top quartile
Genes detectedTWF1
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Exposure of benzo[a]pyrene induces HCC exosome-circular RNA to activate lung fibroblasts and trigger organotropic metastasis.
PMID: 38840551
Cancer Commun (Lond) · 2024
1.00
2
Twinfilin-1 phosphorylation in reelin signaling regulates actin dynamics and spine development.
PMID: 41075995
Pharmacol Res · 2025
0.90
3
TWF1 induces autophagy and accelerates malignant phenotype in lung adenocarcinoma via inhibiting the cAMP signaling pathway.
PMID: 37358822
FASEB J · 2023
0.80
4
Cyst fluid proteins stratify malignant risk of intraductal papillary mucinous neoplasm of the pancreas.
PMID: 40300662
Cancer Lett · 2025
0.70
5
Aging-Related Expression of Twinfilin-1 Regulates Cholangiocyte Biological Response to Injury.
PMID: 30561764
Hepatology · 2019
0.60