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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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TWF2
twinfilin actin binding protein 2
Chromosome 3 · 3p21.2
NCBI Gene: 11344Ensembl: ENSG00000247596.11HGNC: HGNC:9621UniProt: Q6IBS0
72PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
RNA bindingprotein kinase C bindingprotein bindingATP bindingschizophreniabipolar disorderneurodegenerative diseasediverticular disease
✦AI Summary

TWF2 (twinfilin actin binding protein 2) is an actin-binding protein that inhibits actin polymerization by sequestering G-actin monomers and capping barbed ends of filaments 1. This dual mechanism regulates cellular motility and cytoskeletal dynamics, with roles in clathrin-mediated endocytosis and dendritic spine morphology 2. In cancer biology, TWF2 has emerged as an important oncogenic driver. In renal cell carcinoma (RCC), TWF2 is markedly upregulated in sunitinib-resistant cells and promotes tumor progression, invasion, and metastasis by suppressing Hippo signaling 3. Mechanistically, TWF2 stabilizes Yes-associated protein (YAP) by preventing its ubiquitination and degradation, with critical binding occurring at M99 residue 3. TWF2 is part of a broader pan-cancer oncogenic program across multiple malignancies 4. In hepatocellular carcinoma, TWF2 expression is significantly downregulated following CHAF1B knockdown, correlating with reduced tumor growth 5. Clinically, TWF2 methylation status serves as a prognostic marker for clear cell RCC survival, independent of standard clinical factors 6. Additionally, TWF2 has been identified as a potential biomarker for cytokine release syndrome in CAR-T therapy 7. In platelet biology, TWF2-mediated actin dynamics regulate platelet reactivity and hemostasis through n-cofilin and profilin 1 pathways 1.

Sources cited
1
TWF2 inhibits actin filament assembly by sequestering actin monomers and capping filament barbed ends; regulates platelet reactivity through actin dynamics
PMID: 28743718
2
TWF2 modulates dendritic spine length in entorhinal cortex; altered in Alzheimer's disease pathology
PMID: 37055180
3
TWF2 promotes RCC tumor progression and sunitinib resistance by inhibiting Hippo signaling; stabilizes YAP through M99 binding residue
PMID: 40948085
4
TWF2 has oncogenic roles across multiple human cancer types in pan-cancer analysis
PMID: 36128444
5
TWF2 expression is downregulated in hepatocellular carcinoma following CHAF1B knockdown, correlating with reduced tumor growth
PMID: 29767268
6
TWF2 methylation status correlates with prognosis and overall survival in clear cell renal cell carcinoma
PMID: 26515236
7
TWF2 is a potential biomarker for cytokine release syndrome prediction in CAR-T therapy
PMID: 41125014
Disease Associationsⓘ20
schizophreniaOpen Targets
0.30Weak
bipolar disorderOpen Targets
0.23Weak
neurodegenerative diseaseOpen Targets
0.20Weak
diverticular diseaseOpen Targets
0.16Weak
neoplasmOpen Targets
0.09Suggestive
renal cell carcinomaOpen Targets
0.07Suggestive
Crohn's diseaseOpen Targets
0.06Suggestive
cancerOpen Targets
0.06Suggestive
obesityOpen Targets
0.04Suggestive
osteoarthritis, kneeOpen Targets
0.04Suggestive
medical procedureOpen Targets
0.04Suggestive
AnxietyOpen Targets
0.04Suggestive
Abnormality of the skeletal systemOpen Targets
0.04Suggestive
nonpapillary renal cell carcinomaOpen Targets
0.03Suggestive
colon carcinomaOpen Targets
0.02Suggestive
lung adenocarcinomaOpen Targets
0.01Suggestive
pancreatic adenocarcinomaOpen Targets
0.00Suggestive
prostate adenocarcinomaOpen Targets
0.00Suggestive
type 1 diabetes mellitusOpen Targets
0.00Suggestive
type 2 diabetes mellitusOpen Targets
0.00Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
EPS8L2Protein interaction95%MYO15AProtein interaction94%CFL1Protein interaction94%ESPNProtein interaction93%EPS8Protein interaction92%WHRNProtein interaction92%
Tissue Expression6 tissues
Heart
100%
Lung
85%
Ovary
50%
Liver
43%
Brain
37%
Bone Marrow
25%
Gene Interaction Network
Click a node to explore
TWF2EPS8L2MYO15ACFL1ESPNEPS8WHRN
PROTEIN STRUCTURE
Preparing viewer…
PDB2VAC · 1.70 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.53Moderately Constrained
pLIⓘ
0.95Intolerant
Observed/Expected LoF0.34 [0.23–0.53]
RankingsWhere TWF2 stands among ~20K protein-coding genes
  • #6,595of 20,598
    Most Researched72
  • #3,266of 17,882
    Most Constrained (LOEUF)0.53 · top quartile
Genes detectedTWF2
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Oncogenic role of TWF2 in human tumors: A pan-cancer analysis.
PMID: 36128444
Open Med (Wars) · 2022
1.00
2
TWF2 Drives Tumor Progression and Sunitinib Resistance in Renal Cell Carcinoma through Hippo Signaling Suppression.
PMID: 40948085
Adv Sci (Weinh) · 2025
0.90
3
Cross-Platform Synaptic Network Analysis of Human Entorhinal Cortex Identifies TWF2 as a Modulator of Dendritic Spine Length.
PMID: 37055180
J Neurosci · 2023
0.80
4
CHAF1B knockdown blocks migration in a hepatocellular carcinoma model.
PMID: 29767268
Oncol Rep · 2018
0.70
5
Multi-omics analysis reveals dynamic proteomic remodeling and metabonomic dysregulation underlying cytokine release syndrome in CAR-T-treated B-ALL.
PMID: 41125014
Int Immunopharmacol · 2025
0.60