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Target intelligence / Profile preview
FERM domain-containing protein 4A (FRMD4A)
- Target
- FRMD4A
- Molecular classification
- Scaffolding protein, FERM domain-containing protein, Cytoskeletal adaptor, Other (not a receptor, enzyme, transporter, or transcription factor)
01
Overview
FERM domain-containing protein 4A (FRMD4A) is a scaffolding adaptor protein belonging to the FERM domain superfamily. It regulates epithelial cell polarity by connecting ARF6 activation with the Par complex, supporting cytoskeletal remodeling and membrane trafficking. FRMD4A is required for normal neuronal and epithelial cell structure and function, and loss-of-function mutations are associated with neurodevelopmental disorders. Overexpression of FRMD4A promotes tumor progression and metastasis in head and neck squamous cell carcinoma and tongue cancer, with its presence correlating with advanced disease stages and poor prognosis. FRMD4A also modulates tau secretion in neurons via ARF6 signaling and is implicated by genetic studies as a risk factor for Alzheimer’s disease, nicotine dependence, and other cognitive disorders. Therapeutic intervention via siRNA targeting FRMD4A inhibits cancer cell proliferation, migration, and invasion, suggesting its potential as a future cancer therapy target[1][2][3][4].
- Other names
- FERM domain containing 4AFRMD4AFRMD4KIAA1294FLJ10210bA295P9.4CCAFCA
02
Mechanism of action
Gene silencing (siRNA to FRMD4A inhibits proliferation and migration of cancer cells); Interference with ARF6 signaling and cell polarity pathways
03
Biological functions
Regulation of epithelial cell polarityRemodeling of adherens junctionsActin cytoskeleton dynamicsMembrane traffickingSignal transductionRegulation of cell cycle progressionCell migration and invasion
04
Disease associations
Cancer (head and neck squamous cell carcinoma, tongue squamous cell carcinoma, general carcinogenesis and metastasis)Neurodevelopmental disorders (Corpus callosum agenesis, intellectual disability, cortical dysplasia)Neurodegenerative disease (late-onset Alzheimer’s disease)Nicotine dependenceAlcohol dependenceCognitive impairment
05
Safety considerations
No specific safety concerns are documented regarding direct inhibition of FRMD4A, but therapeutic challenges may arise from its fundamental role in cell polarity and cytoskeletal dynamics, which are critical for multiple tissues[3].
06
Biomarkers
Overexpression of FRMD4A correlates with tumor progression, lymph node metastasis, and advanced clinical stage in squamous cell carcinomaGenetic polymorphisms associated with risk for Alzheimer's disease and nicotine dependence
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