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FLNA Gene
FLNA Gene
Introduction
Flna Gene is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
FLNA (Filamin A) encodes a massive actin-binding protein that forms orthogonal networks and links actin filaments to membrane glycoproteins. It serves as a scaffold for numerous proteins involved in cell signaling, mechanotransduction, and neuronal function[@stossel2001].
<div class="infobox infobox-gene">
<table>
<tr><th colspan="2" style="background:#4a90d9; color:white;">FLNA - Filamin A</th></tr>
<tr><td><strong>Gene Symbol</strong></td><td>FLNA</td></tr>
<tr><td><strong>Full Name</strong></td><td>Filamin A</td></tr>
<tr><td><strong>Chromosomal Location</strong></td><td>Xq28</td></tr>
<tr><td><strong>NCBI Gene ID</strong></td><td>[2316](https://www.ncbi.nlm.nih.gov/gene/2316)</td></tr>
<tr><td><strong>OMIM</strong></td><td>300017</td></tr>
<tr><td><strong>Ensembl ID</strong></td><td>ENSG00000196924</td></tr>
<tr><td><strong>UniProt</strong></td><td>[P21333](https://www.uniprot.org/uniprot/P21333)</td></tr>
<tr><td><strong>Associated Diseases</strong></td><td>Periventricular Heterotopia, Frontometaphyseal Dysplasia, X-linked Parkinsonism</td></tr>
</table>
</div>
Overview
...FLNA Gene
Introduction
Flna Gene is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
FLNA (Filamin A) encodes a massive actin-binding protein that forms orthogonal networks and links actin filaments to membrane glycoproteins. It serves as a scaffold for numerous proteins involved in cell signaling, mechanotransduction, and neuronal function[@stossel2001].
<div class="infobox infobox-gene">
<table>
<tr><th colspan="2" style="background:#4a90d9; color:white;">FLNA - Filamin A</th></tr>
<tr><td><strong>Gene Symbol</strong></td><td>FLNA</td></tr>
<tr><td><strong>Full Name</strong></td><td>Filamin A</td></tr>
<tr><td><strong>Chromosomal Location</strong></td><td>Xq28</td></tr>
<tr><td><strong>NCBI Gene ID</strong></td><td>[2316](https://www.ncbi.nlm.nih.gov/gene/2316)</td></tr>
<tr><td><strong>OMIM</strong></td><td>300017</td></tr>
<tr><td><strong>Ensembl ID</strong></td><td>ENSG00000196924</td></tr>
<tr><td><strong>UniProt</strong></td><td>[P21333](https://www.uniprot.org/uniprot/P21333)</td></tr>
<tr><td><strong>Associated Diseases</strong></td><td>Periventricular Heterotopia, Frontometaphyseal Dysplasia, X-linked Parkinsonism</td></tr>
</table>
</div>
Overview
FLNA (Filamin A) is a 280 kDa actin-binding protein that serves as a critical scaffold for protein-protein interactions in eukaryotic cells["@stossel2001"]. The protein forms flexible V-shaped dimers that connect actin filaments into orthogonal networks, providing mechanical stability to cells and tissues["@nakamura2007"]. In the nervous system, FLNA is essential for neuronal migration, synaptic formation, and plasticity["@deng2012"].
Function
FLNA is a large (280 kDa) actin-crosslinking protein composed of:
- N-terminal actin-binding domain: Binds to F-actin
- 24 repeat repeats: Each containing two calponin homology (CH) domains that serve as protein interaction surfaces
- C-terminal dimerization domain: Enables orthogonal network formation
Neuronal Functions
In [neurons](/entities/neurons), FLNA is enriched in [dendritic spines](/cell-types/dendritic-spines) and postsynaptic densities where it:
Non-neuronal Functions
- Cell migration and adhesion
- Mechanical stability of blood vessels
- Organ development
- Cell division and cytokinesis
Structure
FLNA contains 24 immunoglobulin-like repeats (repeats 1-23 and hinge 1-2):
| Region | Residues | Function |
|--------|----------|----------|
| Actin-binding domain | 1-274 | N-terminal F-actin binding |
| Repeats 1-9 | 275-1008 | Protein interactions (integrins, GPIbα) |
| Hinge 1 | 1009-1137 | Proteolytic cleavage site |
| Repeats 10-15 | 1138-1749 | Protein interactions (Rho GTPases) |
| Hinge 2 | 1750-1877 | Flexibility, cleavage site |
| Repeats 16-23 | 1878-2387 | Protein interactions |
| C-terminal | 2388-2647 | Dimerization |
Expression Pattern
FLNA is widely expressed throughout the brain with particularly high levels in:
- Cerebral [cortex](/brain-regions/cortex): Layers II-VI, pyramidal neurons
- [Hippocampus](/brain-regions/hippocampus): CA1-CA3 pyramidal neurons, dentate gyrus granule cells
- Basal ganglia: Striatal medium spiny neurons
- Cerebellum: Purkinje cells
- Spinal cord: Motor neurons
- Substantia nigra: Dopaminergic neurons
Expression data from Allen Brain Atlas confirms widespread neuronal expression with enrichment in regions involved in neurodegenerative processes.
Disease Associations
Periventricular Heterotopia (PVNH)
- X-linked dominant mutations in FLNA cause abnormal neuronal migration[@sheen2006]
- Characterized by nodules of gray matter lining the ventricles
- Often associated with epilepsy and developmental delays
- Female carriers may have milder phenotypes due to X-inactivation
Frontometaphyseal Dysplasia (FMD)
- FLNA mutations cause this skeletal dysplasia
- Characterized by megaencephaly, facial dysmorphism, skeletal anomalies
Parkinson's Disease
- FLNA has been implicated in PD pathogenesis through interactions with [LRRK2](/entities/lrrk2)[@gialluisi2016]
- FLNA interacts with leucine-rich repeat kinase 2 (LRRK2), a major PD gene product
- FLNA knockout in mice leads to dopaminergic neuron loss
- Variants in FLNA may modify PD risk and progression
- X-linked FLNA mutations associated with parkinsonism in some families
Alzheimer's Disease
- FLNA in [amyloid-beta](/proteins/amyloid-beta) processing and toxicity
- Synaptic FLNA loss in AD brains
- Role in [tau](/proteins/tau) phosphorylation and spread
Brain Injury
- FLNA in traumatic brain injury response
- May influence recovery and plasticity
Molecular Mechanisms
FLNA participates in multiple signaling pathways:
Therapeutic Implications
| Approach | Target | Development Stage |
|----------|--------|-------------------|
| Small molecule inhibitors | FLNA-actin binding | Preclinical |
| Peptide disrupters | Protein-protein interactions | Research |
| Gene therapy | FLNA restoration | Theoretical |
Therapeutic challenges:
- Large protein size limits traditional drug design
- Essential functions create narrow therapeutic window
- Tissue-specific targeting needed
Animal Models
- FLNA knockout mice: Embryonic lethal in males, viability in females
- Conditional knockouts: Brain-specific deletion shows neuronal migration defects
- knock-in models: Expressing patient-derived FLNA mutations
- LRRK2-FLNA double mutants: Synergistic effects on dopaminergic neurons
Research Directions
Key Publications
See Also
- [Filamin A Protein](/proteins/flna-protein)
- [LRRK2 Gene](/proteins/lrrk2-protein)
- [Periventricular Heterotopia](/diseases/periventricular-heterotopia)
- [Parkinson's Disease](/diseases/parkinsons-disease)
- [Alzheimer's Disease](/diseases/alzheimers-disease)
- [Synaptic Dysfunction Pathway](/mechanisms/synaptic-dysfunction-pathway)
External Links
- [NCBI Gene: FLNA](https://www.ncbi.nlm.nih.gov/gene/2316)
- [UniProt: P21333](https://www.uniprot.org/uniprot/P21333)
- [OMIM: 300017](https://www.omim.org/entry/300017)
- [Ensembl: FLNA](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000196924)
Research Directions
Current research on FLNA focuses on several key areas:
- Cytoskeletal Dynamics: Understanding FLNA's role in actin cross-linking
- Cell Migration: FLNA in cancer metastasis and immune cell trafficking
- Neurodevelopment: FLNA's role in neuronal migration and cortical development
Therapeutic Approaches
- Protein-Protein Interaction Inhibitors: Targeting FLNA- integrin interactions
- Gene Therapy: AAV-mediated FLNA delivery for loss-of-function
- Small Molecule Modulators: Developing compounds that modulate FLNA function
Biomarker Potential
- FLNA expression as a biomarker for certain cancers
- FLNA mutations as diagnostic markers for periventricular heterotopia
Animal Models
- FLNA Knockout Mice: Embryonic lethal, neural tube defects
- Conditional Knockouts: Tissue-specific deletion studies
- Zebrafish Models: Understanding FLNA in development
Key Publications
Background
The study of Flna Gene has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
References
Pathway Diagram
The following diagram shows the key molecular relationships involving FLNA Gene discovered through SciDEX knowledge graph analysis:
▸Metadataorigin_type: v1_polymorphic_backfill
| slug | genes-flna |
| kg_node_id | FLNA |
| entity_type | gene |
| origin_type | v1_polymorphic_backfill |
| source_table | wiki_pages |
| wiki_page_id | wp-9ed022784b25 |
| __merged_from | {'merged_at': '2026-05-13', 'unprefixed_id': 'genes-flna'} |
| _schema_version | 1 |
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