FLNA (Filamin A): Genetics, Function, and Associated Diseases
A comprehensive overview of the FLNA gene, its protein product, expression patterns, clinical significance, and molecular mechanisms.
Gene Information Card
| Symbol | FLNA |
|---|---|
| Full Name | Filamin A |
| Gene Type | Protein coding |
| Chromosomal Location | Xq28 |
| NCBI Gene ID | 2316 ncbi.nlm.nih.gov/gene/2316 |
| Ensembl ID | ENSG00000196924 |
| UniProt ID | P21333 |
| OMIM ID | 300017 |
| HGNC ID | 3754 |
| Aliases | ABP-280, ABPX, FLN, FLN-A, FMD, MNS, NHBP |
Description
The FLNA gene encodes filamin A, a large actin-binding protein that crosslinks actin filaments into orthogonal networks and links them to cellular membranes. This protein plays a critical role in cell motility, signaling, and maintaining cell shape. Mutations in FLNA are primarily associated with a spectrum of X-linked dominant and recessive disorders, most notably periventricular heterotopia (PH), a neuronal migration disorder. The gene is highly conserved and expressed in most tissues, with particularly high levels in the brain, muscle, and endothelial cells.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Periventricular Heterotopia (PH) | Loss-of-function mutations (e.g., frameshift, nonsense) lead to haploinsufficiency, disrupting neuronal migration during cortical development. | OMIM #300049; Multiple case studies and cohort analyses confirm the causal link. |
| Filamin A-related skeletal dysplasia (e.g., Otopalatodigital syndrome spectrum, Melnick-Needles syndrome) | Specific missense mutations in the actin-binding domain or repeat segments cause gain-of-function or dominant-negative effects, altering bone development. | OMIM #311300 (Otopalatodigital syndrome type 1); OMIM #309350 (Melnick-Needles syndrome). |
| Cardiac valvular dysplasia | Mutations affecting the C-terminal region can disrupt signaling pathways (e.g., TGF-β) leading to abnormal valve development. | OMIM #314400; Reported in familial cases with specific FLNA variants. |
| Intestinal pseudo-obstruction | Mutations in FLNA can affect smooth muscle function and enteric neuron development, leading to chronic intestinal dysmotility. | Case reports and small cohort studies in ClinVar and literature. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain (Cerebellum) | 24.8 | High |
| Skeletal Muscle | 22.1 | High |
| Heart | 19.5 | High |
| Lung | 15.2 | Medium |
| Liver | 8.3 | Low |
| Kidney | 12.4 | Medium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Endothelial Cells (HUVEC) | 28.5 | High expression; critical for vascular integrity. |
| Fibroblasts (Lung) | 25.0 | High expression; involved in cytoskeletal organization. |
| Smooth Muscle Cells (Aorta) | 20.3 | High expression; essential for contractile function. |
| Hepatocytes | 9.8 | Low to medium expression. |
| T-lymphocytes (Jurkat) | 15.1 | Medium expression; involved in immune synapse formation. |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.739G>T (p.Glu247Ter) | Nonsense | Rare (found in PH families) | Loss-of-function; leads to premature truncation and haploinsufficiency. |
| c.472C>T (p.Arg158Cys) | Missense | Recurrent in skeletal dysplasias | Gain-of-function; alters actin-binding affinity and disrupts bone development. |
| c.541C>T (p.Arg181Cys) | Missense | Rare (found in PH) | Loss-of-function; affects protein stability and actin crosslinking. |
| c.739G>A (p.Gly247Arg) | Missense | Rare (found in valvular dysplasia) | Dominant-negative; disrupts interaction with integrins and signaling molecules. |
Mutation functional classification
Loss of Function (LOF)
Predominant mechanism for periventricular heterotopia (PH). Nonsense, frameshift, and splice-site mutations lead to mRNA decay or truncated proteins, resulting in haploinsufficiency. This disrupts the actin cytoskeleton dynamics necessary for proper neuronal migration.
Gain of Function (GOF)
Observed in certain skeletal dysplasias (e.g., Otopalatodigital syndrome). Missense mutations in the actin-binding domain (ABD) can increase actin-binding affinity or alter the conformation of the protein, leading to abnormal bone development.
Dominant Negative (DN)
Some missense mutations, particularly in the C-terminal region, produce a mutant protein that interferes with the function of the wild-type allele. This is seen in some cases of cardiac valvular dysplasia and intestinal pseudo-obstruction, where the mutant protein disrupts signaling complexes.
View complete mutation data：
Gene Ontology (GO)
| • actin binding | • actin filament binding |
| • protein homodimerization activity | • identical protein binding |
| • integrin binding | • signal transducer activity |
| • cytoskeletal protein binding | • structural constituent of cytoskeleton |
Pathways
• Actin cytoskeleton regulation
• Cell adhesion (integrin signaling)
• Cell migration
• Neuronal migration
• TGF-beta signaling pathway (modulation)
Protein Summary
Filamin A is a 280 kDa homodimeric protein composed of an N-terminal actin-binding domain (ABD) followed by 24 immunoglobulin-like repeats. It crosslinks actin filaments into orthogonal networks and connects them to various cellular structures, including membranes and signaling proteins. The protein is essential for cell motility, maintaining cell shape, and mechanotransduction. It also serves as a scaffold for over 90 binding partners, including ion channels, receptors, and signaling molecules, thereby integrating multiple cellular pathways. Its expression is ubiquitous but particularly high in tissues with high mechanical stress, such as muscle and endothelium.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| FLNA Knockout HEK293 Cell Line | EDJ-KQ171 | Human | 2316 | Details Get a Quote |
| RFLNA Knockout HEK293 Cell Line | EDJ-KQ10412 | Human | 144347 | Details Get a Quote |
| FLNA Knockout A-549 Cell Line | EDJ-KQ19185 | Human | 2316 | Details Get a Quote |
| FLNA Knockout HCT 116 Cell Line | EDJ-KQ19187 | Human | 2316 | Details Get a Quote |
| FLNA Knockout HeLa Cell Line | EDJ-KQ19188 | Human | 2316 | Details Get a Quote |
| RFLNA Knockout HeLa Cell Line | EDJ-KQ58506 | Human | 144347 | Details Get a Quote |
| RFLNA Knockout A-549 Cell Line | EDJ-KQ66994 | Human | 144347 | Details Get a Quote |
| RFLNA Knockout HCT 116 Cell Line | EDJ-KQ75394 | Human | 144347 | Details Get a Quote |
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