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GeneE
50 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
FLNA
filamin A
Chromosome X Β· Xq28
NCBI Gene: 2316Ensembl: ENSG00000196924.19HGNC: HGNC:3754UniProt: P21333
712PubMed Papers
30Diseases
1Drugs
334Pathogenic Variants
FUNCTIONAL ROLE
Highly ConstrainedHub Gene
RESEARCH IMPACT
Highly StudiedTrendingVariant-Rich
CLINICAL
Clinical TrialsOMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
semaphorin-plexin signaling pathwaynucleuscytoplasmcytosolMelnick-Needles syndromeotopalatodigital syndrome type 2otopalatodigital syndrome type 1heterotopia, periventricular, X-linked dominant
✦AI Summary

FLNA (filamin A) is an X-linked actin-binding protein that serves as a critical scaffolding molecule linking the actin cytoskeleton to membrane proteins and facilitating cellular signaling 1. The protein plays essential roles in neurodevelopment, particularly in neuronal migration and brain organization, with mutations causing periventricular nodular heterotopia and other neurodevelopmental disorders 21. FLNA functions as a key regulator of cardiovascular development and remodeling, with mutations associated with cardiac valvular dysplasia, aortic stenosis, and vascular malformations 34. In pathological contexts, FLNA contributes to disease progression through multiple mechanisms: it promotes pathological angiogenesis in moyamoya disease via AKT/GSK-3Ξ²/Ξ²-catenin signaling 5, modulates tumor immunity and metastasis in colorectal cancer through disulfidptosis regulation 6, and drives seizure activity in focal cortical malformations 7. Therapeutically, FLNA represents a promising target, with small molecule inhibitor PTI-125 showing efficacy in reducing seizures and tumor progression 76. The protein's involvement spans from developmental biology to cancer and neurological diseases, highlighting its fundamental importance in cellular organization and disease pathogenesis.

Sources cited
1
FLNA is a key actin-binding protein involved in neurodevelopment and neuronal migration
PMID: 40613361
2
FLNA mutations cause X-linked epilepsies and neuronal migration disorders
PMID: 38612920
3
FLNA participates in cardiovascular development and remodeling
PMID: 34207234
4
Novel FLNA mutations associate with cardiac valve stenosis and brain heterotopia
PMID: 33852449
5
FLNA promotes pathological angiogenesis in moyamoya disease via AKT/GSK-3Ξ²/Ξ²-catenin signaling
PMID: 37886851
6
FLNA modulates tumor immunity and progression in colorectal cancer through disulfidptosis
PMID: 40713509
7
FLNA inhibition with PTI-125 reduces seizure activity in focal cortical malformation models
PMID: 32075941
Disease Associationsβ“˜30
Melnick-Needles syndromeOpen Targets
0.82Strong
otopalatodigital syndrome type 2Open Targets
0.81Strong
otopalatodigital syndrome type 1Open Targets
0.81Strong
heterotopia, periventricular, X-linked dominantOpen Targets
0.80Strong
frontometaphyseal dysplasia 1Open Targets
0.80Strong
cardiac valvular dysplasia, X-linkedOpen Targets
0.77Strong
terminal osseous dysplasia-pigmentary defects syndromeOpen Targets
0.75Strong
Genetic intestinal diseaseOpen Targets
0.74Strong
frontometaphyseal dysplasiaOpen Targets
0.74Strong
Terminal osseous dysplasia - pigmentary defectsOpen Targets
0.73Strong
congenital short bowel syndromeOpen Targets
0.73Strong
periventricular nodular heterotopiaOpen Targets
0.72Strong
FG syndrome 2Open Targets
0.70Strong
Osteodysplasty, Melnick-Needles typeOpen Targets
0.70Moderate
Neuronal intestinal pseudoobstructionOpen Targets
0.62Moderate
Epileptic encephalopathyOpen Targets
0.55Moderate
familial thoracic aortic aneurysm and aortic dissectionOpen Targets
0.55Moderate
MacrothrombocytopeniaOpen Targets
0.54Moderate
Rare disease with thoracic aortic aneurysm and aortic dissectionOpen Targets
0.53Moderate
otopalatodigital syndrome spectrum disorderOpen Targets
0.42Moderate
Cardiac valvular dysplasia, X-linkedUniProt
Congenital short bowel syndrome, X-linkedUniProt
FG syndrome 2UniProt
Frontometaphyseal dysplasia 1UniProt
Intestinal pseudoobstruction, neuronal, chronic idiopathic, X-linkedUniProt
Melnick-Needles syndromeUniProt
Otopalatodigital syndrome 1UniProt
Otopalatodigital syndrome 2UniProt
Periventricular nodular heterotopia 1UniProt
Terminal osseous dysplasiaUniProt
Pathogenic Variants334
NM_001110556.2(FLNA):c.3562G>A (p.Ala1188Thr)Pathogenic
Melnick-Needles syndrome|not provided|Heterotopia, periventricular, X-linked dominant;Melnick-Needles syndrome;Frontometaphyseal dysplasia;Oto-palato-digital syndrome, type II
β˜…β˜…β˜†β˜†2026β†’ Residue 1188
NM_001110556.2(FLNA):c.257AGA[2] (p.Lys88del)Pathogenic
not provided|Heterotopia, periventricular, X-linked dominant;Melnick-Needles syndrome;Frontometaphyseal dysplasia;Oto-palato-digital syndrome, type II
β˜…β˜…β˜†β˜†2026β†’ Residue 88
NM_001110556.2(FLNA):c.3596C>T (p.Ser1199Leu)Pathogenic
Melnick-Needles syndrome|Heterotopia, periventricular, X-linked dominant;Melnick-Needles syndrome;Frontometaphyseal dysplasia;Oto-palato-digital syndrome, type II|Melnick-Needles syndrome;Oto-palato-digital syndrome, type I;Oto-palato-digital syndrome, type II|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 1199
NM_001110556.2(FLNA):c.5217G>A (p.Thr1739=)Pathogenic
Terminal osseous dysplasia-pigmentary defects syndrome|not provided|Heterotopia, periventricular, X-linked dominant;Melnick-Needles syndrome;Frontometaphyseal dysplasia;Oto-palato-digital syndrome, type II|Heterotopia, periventricular, X-linked dominant|Thyroid cancer, nonmedullary, 1|Familial thoracic aortic aneurysm and aortic dissection
β˜…β˜…β˜†β˜†2025β†’ Residue 1739
NM_001110556.2(FLNA):c.6245del (p.Leu2082fs)Pathogenic
not provided|Familial thoracic aortic aneurysm and aortic dissection
β˜…β˜…β˜†β˜†2025β†’ Residue 2082
NM_001110556.2(FLNA):c.5417-2A>GLikely pathogenic
Frontometaphyseal dysplasia;Heterotopia, periventricular, X-linked dominant;Melnick-Needles syndrome;Oto-palato-digital syndrome, type II|not provided
β˜…β˜…β˜†β˜†2025
NM_001110556.2(FLNA):c.4726G>A (p.Gly1576Arg)Pathogenic
Cardiac valvular dysplasia, X-linked|Oto-palato-digital syndrome, type II;Frontometaphyseal dysplasia;Melnick-Needles syndrome;Heterotopia, periventricular, X-linked dominant|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 1576
NM_001110556.2(FLNA):c.2020_2021del (p.Arg674fs)Pathogenic
FLNA related lung disease|Melnick-Needles syndrome;Oto-palato-digital syndrome, type II;Frontometaphyseal dysplasia;Heterotopia, periventricular, X-linked dominant
β˜…β˜…β˜†β˜†2025β†’ Residue 674
NM_001110556.2(FLNA):c.7255C>T (p.Arg2419Ter)Pathogenic
not provided|Oto-palato-digital syndrome, type II;Heterotopia, periventricular, X-linked dominant;Frontometaphyseal dysplasia;Melnick-Needles syndrome
β˜…β˜…β˜†β˜†2025β†’ Residue 2419
NM_001110556.2(FLNA):c.5162del (p.Val1721fs)Pathogenic
Oto-palato-digital syndrome, type I|FLNA-related disorder
β˜…β˜…β˜†β˜†2025β†’ Residue 1721
NM_001110556.2(FLNA):c.3557C>T (p.Ser1186Leu)Pathogenic
Frontometaphyseal dysplasia 1|not provided|Heterotopia, periventricular, X-linked dominant;Melnick-Needles syndrome;Frontometaphyseal dysplasia;Oto-palato-digital syndrome, type II|Oto-palato-digital syndrome, type II
β˜…β˜…β˜†β˜†2025β†’ Residue 1186
NM_001110556.2(FLNA):c.6724C>T (p.Arg2242Ter)Pathogenic
not provided|Heterotopia, periventricular, X-linked dominant;Melnick-Needles syndrome;Oto-palato-digital syndrome, type II;Frontometaphyseal dysplasia
β˜…β˜…β˜†β˜†2025β†’ Residue 2242
NM_001110556.2(FLNA):c.7941_7942del (p.Ter2648SerextTer?)Pathogenic
not provided|Heterotopia, periventricular, X-linked dominant|Oto-palato-digital syndrome, type II;Melnick-Needles syndrome;Heterotopia, periventricular, X-linked dominant;Frontometaphyseal dysplasia
β˜…β˜…β˜†β˜†2025β†’ Residue 2648
NM_001110556.2(FLNA):c.4598+1G>APathogenic
Heterotopia, periventricular, X-linked dominant;Frontometaphyseal dysplasia;Oto-palato-digital syndrome, type II;Melnick-Needles syndrome|9 conditions
β˜…β˜…β˜†β˜†2025
NM_001110556.2(FLNA):c.5930_5942del (p.Glu1977fs)Pathogenic
not provided|Periventricular nodular heterotopia
β˜…β˜…β˜†β˜†2025β†’ Residue 1977
NM_001110556.2(FLNA):c.6425_6428del (p.Glu2142fs)Likely pathogenic
Frontometaphyseal dysplasia;Oto-palato-digital syndrome, type II;Heterotopia, periventricular, X-linked dominant;Melnick-Needles syndrome|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 2142
NM_001110556.2(FLNA):c.620C>T (p.Pro207Leu)Pathogenic
Oto-palato-digital syndrome, type I|Cleft palate;Conductive hearing impairment;Short stature|not specified|Familial thoracic aortic aneurysm and aortic dissection|not provided|Heterotopia, periventricular, X-linked dominant;Melnick-Needles syndrome;Frontometaphyseal dysplasia;Oto-palato-digital syndrome, type II|FLNA-related disorder|Gastric cancer|Thyroid cancer, nonmedullary, 1
β˜…β˜…β˜†β˜†2025β†’ Residue 207
NM_001110556.2(FLNA):c.4660G>A (p.Gly1554Arg)Pathogenic
Cardiac valvular dysplasia, X-linked|not provided|Familial thoracic aortic aneurysm and aortic dissection|Heterotopia, periventricular, X-linked dominant;Oto-palato-digital syndrome, type II;Melnick-Needles syndrome;Frontometaphyseal dysplasia
β˜…β˜…β˜†β˜†2025β†’ Residue 1554
NM_001110556.2(FLNA):c.2527dup (p.Ala843fs)Pathogenic
Heterotopia, periventricular, X-linked dominant|Familial thoracic aortic aneurysm and aortic dissection
β˜…β˜…β˜†β˜†2025β†’ Residue 843
NM_001110556.2(FLNA):c.862G>A (p.Gly288Arg)Pathogenic
Cardiac valvular dysplasia, X-linked|Heterotopia, periventricular, X-linked dominant|Heterotopia, periventricular, X-linked dominant;Melnick-Needles syndrome;Frontometaphyseal dysplasia;Oto-palato-digital syndrome, type II
β˜…β˜…β˜†β˜†2024β†’ Residue 288
View on ClinVar β†—
Drug Targets1
SIMUFILAMPhase III
Filamin-A positive modulator
Alzheimer disease
Related Genes
PXNProtein interaction100%FBLIM1Protein interaction100%ACTA1Protein interaction100%CFL1Protein interaction100%CFL2Protein interaction100%DMDProtein interaction100%
Tissue Expression6 tissues
Lung
100%
Ovary
69%
Bone Marrow
33%
Heart
21%
Brain
13%
Liver
8%
Gene Interaction Network
Click a node to explore
FLNAPXNFBLIM1ACTA1CFL1CFL2DMD
PROTEIN STRUCTURE
Preparing viewer…
PDB3CNK Β· 1.65 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.08Highly Constrained
pLIβ“˜
1.00Intolerant
Observed/Expected LoF0.04 [0.03–0.08]
RankingsWhere FLNA stands among ~20K protein-coding genes
  • #300of 20,598
    Most Researched712 Β· top 5%
  • #178of 5,498
    Most Pathogenic Variants334 Β· top 5%
  • #30of 17,882
    Most Constrained (LOEUF)0.08 Β· top 1%
Genes detectedFLNA
Sources retrieved50 papers
Response timeβ€”
πŸ“„ Sources
50β–Ό
1
X-Linked Epilepsies: A Narrative Review.
PMID: 38612920
Int J Mol Sci Β· 2024
1.00
2
GPIbΞ±-filamin A interaction regulates megakaryocyte localization and budding during platelet biogenesis.
PMID: 37922495
Blood Β· 2024
0.90
3
FOXA1 regulates alternative splicing in prostate cancer.
PMID: 36170835
Cell Rep Β· 2022
0.90
4
The clinical and imaging features of FLNA positive and negative periventricular nodular heterotopia.
PMID: 35660364
Biomed J Β· 2022
0.84
5
Pulmonary hypertension in patients carrying
PMID: 39510553
Eur Respir J Β· 2025
0.82