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GeneE
25 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
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FLNC
filamin C
Chromosome 7 Β· 7q32.1
NCBI Gene: 2318Ensembl: ENSG00000128591.18HGNC: HGNC:3756UniProt: Q14315
250PubMed Papers
24Diseases
0Drugs
606Pathogenic Variants
FUNCTIONAL ROLE
Hub Gene
RESEARCH IMPACT
Variant-Rich
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
protein bindingcytoskeletal protein bindingankyrin bindingsarcomere organizationhypertrophic cardiomyopathy 26hypertrophic cardiomyopathymyofibrillar myopathy 5distal myopathy with posterior leg and anterior hand involvement
✦AI Summary

FLNC encodes filamin C, a muscle-specific actin-binding protein critical for sarcomere assembly and organization 1. It functions as a large actin-cross-linking protein essential for structural integrity at Z-lines and plays a central role in maintaining sarcomere stability 2. FLNC participates in reorganizing the actin cytoskeleton in response to signaling events and is crucial for both structural integrity and cell signaling of the sarcomere 3. FLNC mutations cause diverse muscle and cardiac phenotypes through distinct pathomechanisms. Truncating variants cause haploinsufficiency leading to dilated cardiomyopathy (DCM) and arrhythmogenic cardiomyopathy with high sudden cardiac death risk 34. Non-truncating missense variants, predominantly in the ROD2 domain, cause protein aggregation resulting in hypertrophic cardiomyopathy and myofibrillar myopathy 32. FLNC is classified as having definitive evidence for DCM pathogenicity 5 and is among the more prevalent genetic causes of inherited DCM 3. Additionally, FLNC variants cause distal myopathies with progressive muscle weakness in hands and feet 6. Genotype-based risk stratification using FLNC variants predicts sudden cardiac death risk more precisely than phenotype-based classification 7, emphasizing the importance of molecular diagnosis for clinical management and prognostication.

Sources cited
1
FLNC plays a central role in sarcomere assembly and organization
PMID: 34405687
2
FLNC is an actin-binding protein that participates in sarcomere stability maintenance and is crucial for structural integrity and cell signaling of the sarcomere
PMID: 34535832
3
FLNC variants are associated with myofibrillar myopathy, hypertrophic cardiomyopathy, and dilated cardiomyopathy; truncating variants cause haploinsufficiency associated with DCM and arrhythmias; missense variants in ROD2 domain cause protein aggregation and HCM/MFM
PMID: 32112656
4
FLNC is classified as having definitive evidence for dilated cardiomyopathy pathogenicity among 12 genes with strongest genetic evidence
PMID: 33947203
5
Truncating FLNC mutations are associated with high-risk dilated and arrhythmogenic cardiomyopathies with frequent sudden cardiac death and >97% penetrance in carriers older than 40 years
PMID: 27908349
6
FLNC variants cause autosomal dominant distal myopathy with prominent weakness in hands and/or feet
PMID: 33458580
7
FLNC variant carriers showed high frequency of sudden cardiac death/major ventricular arrhythmias; genotype-based classification predicted outcomes better than phenotype-based classification
PMID: 36396199
Disease Associationsβ“˜24
hypertrophic cardiomyopathy 26Open Targets
0.84Strong
hypertrophic cardiomyopathyOpen Targets
0.77Strong
myofibrillar myopathy 5Open Targets
0.76Strong
distal myopathy with posterior leg and anterior hand involvementOpen Targets
0.75Strong
dilated cardiomyopathyOpen Targets
0.70Moderate
Muscle filaminopathyOpen Targets
0.70Moderate
myopathyOpen Targets
0.69Moderate
familial restrictive cardiomyopathyOpen Targets
0.67Moderate
cardiomyopathyOpen Targets
0.62Moderate
Abnormality of the cardiovascular systemOpen Targets
0.57Moderate
autosomal dominant dilated cardiomyopathyOpen Targets
0.56Moderate
familial dilated cardiomyopathyOpen Targets
0.54Moderate
restrictive cardiomyopathyOpen Targets
0.51Moderate
myofibrillar myopathyOpen Targets
0.50Moderate
neurodegenerative diseaseOpen Targets
0.50Moderate
atrial fibrillationOpen Targets
0.41Moderate
arrhythmogenic right ventricular cardiomyopathyOpen Targets
0.38Weak
arthrogryposisOpen Targets
0.37Weak
familial isolated restrictive cardiomyopathyOpen Targets
0.37Weak
heart diseaseOpen Targets
0.34Weak
Cardiomyopathy, familial hypertrophic, 26UniProt
Cardiomyopathy, familial restrictive 5UniProt
Myopathy, distal, 4UniProt
Myopathy, myofibrillar, 5UniProt
Pathogenic Variants606
NM_001458.5(FLNC):c.5754T>A (p.Tyr1918Ter)Pathogenic
not provided|Hypertrophic cardiomyopathy 26|Distal myopathy with posterior leg and anterior hand involvement;Hypertrophic cardiomyopathy 26;not provided;Myofibrillar myopathy 5
β˜…β˜…β˜†β˜†2026β†’ Residue 1918
NM_001458.5(FLNC):c.8130G>A (p.Trp2710Ter)Pathogenic
Myofibrillar myopathy 5|not provided|Myofibrillar myopathy 5;Hypertrophic cardiomyopathy 26;not provided;Distal myopathy with posterior leg and anterior hand involvement
β˜…β˜…β˜†β˜†2026β†’ Residue 2710
NM_001458.5(FLNC):c.2971C>T (p.Arg991Ter)Pathogenic
Myofibrillar myopathy 5;Hypertrophic cardiomyopathy 26;Distal myopathy with posterior leg and anterior hand involvement|Hypertrophic cardiomyopathy 26|Primary dilated cardiomyopathy|Cardiovascular phenotype|Arrhythmogenic right ventricular cardiomyopathy|Myofibrillar myopathy 5;Hypertrophic cardiomyopathy 26;Distal myopathy with posterior leg and anterior hand involvement;not provided
β˜…β˜…β˜†β˜†2026β†’ Residue 991
NM_001458.5(FLNC):c.2119C>T (p.Gln707Ter)Pathogenic
not provided|Cardiovascular phenotype|Myofibrillar myopathy 5;Distal myopathy with posterior leg and anterior hand involvement;not provided;Hypertrophic cardiomyopathy 26
β˜…β˜…β˜†β˜†2026β†’ Residue 707
NM_001458.5(FLNC):c.5199+1G>TPathogenic
Cardiovascular phenotype|not provided|not provided;Myofibrillar myopathy 5;Distal myopathy with posterior leg and anterior hand involvement;Hypertrophic cardiomyopathy 26
β˜…β˜…β˜†β˜†2026
NM_001458.5(FLNC):c.6822C>G (p.Tyr2274Ter)Pathogenic
Cardiovascular phenotype|Distal myopathy with posterior leg and anterior hand involvement;Hypertrophic cardiomyopathy 26;not provided;Myofibrillar myopathy 5
β˜…β˜…β˜†β˜†2026β†’ Residue 2274
NM_001458.5(FLNC):c.8076C>A (p.Tyr2692Ter)Pathogenic
not provided|not provided;Hypertrophic cardiomyopathy 26;Myofibrillar myopathy 5;Distal myopathy with posterior leg and anterior hand involvement
β˜…β˜…β˜†β˜†2026β†’ Residue 2692
NM_001458.5(FLNC):c.7536_7548del (p.Pro2513fs)Pathogenic
Cardiovascular phenotype|not provided|Distal myopathy with posterior leg and anterior hand involvement;not provided;Myofibrillar myopathy 5;Hypertrophic cardiomyopathy 26
β˜…β˜…β˜†β˜†2026β†’ Residue 2513
NM_001458.5(FLNC):c.3791-1G>CPathogenic
not provided|Hypertrophic cardiomyopathy 26|Cardiovascular phenotype|FLNC-related disorder|Primary dilated cardiomyopathy|Myofibrillar myopathy 5;not provided;Distal myopathy with posterior leg and anterior hand involvement;Hypertrophic cardiomyopathy 26
β˜…β˜…β˜†β˜†2026
NM_001458.5(FLNC):c.1092dup (p.Glu365Ter)Pathogenic
Cardiovascular phenotype|Hypertrophic cardiomyopathy 26;not provided;Myofibrillar myopathy 5;Distal myopathy with posterior leg and anterior hand involvement
β˜…β˜…β˜†β˜†2026β†’ Residue 365
NM_001458.5(FLNC):c.4192A>T (p.Lys1398Ter)Pathogenic
Cardiovascular phenotype|not provided;Myofibrillar myopathy 5;Hypertrophic cardiomyopathy 26;Distal myopathy with posterior leg and anterior hand involvement|not provided|FLNC-related disorder
β˜…β˜…β˜†β˜†2026β†’ Residue 1398
NM_001458.5(FLNC):c.7581del (p.Ile2527fs)Pathogenic
Hypertrophic cardiomyopathy 26|Myofibrillar myopathy 5|Distal myopathy with posterior leg and anterior hand involvement|Primary familial dilated cardiomyopathy|Myofibrillar myopathy 5;Distal myopathy with posterior leg and anterior hand involvement;not provided;Hypertrophic cardiomyopathy 26
β˜…β˜…β˜†β˜†2026β†’ Residue 2527
NM_001458.5(FLNC):c.4926_4927insACGTCACA (p.Val1643fs)Pathogenic
Cardiovascular phenotype|Primary dilated cardiomyopathy|not provided|not provided;Hypertrophic cardiomyopathy 26;Distal myopathy with posterior leg and anterior hand involvement;Myofibrillar myopathy 5
β˜…β˜…β˜†β˜†2025β†’ Residue 1643
NM_001458.5(FLNC):c.2160del (p.Asn721fs)Pathogenic
Cardiovascular phenotype|not provided;Myofibrillar myopathy 5;Distal myopathy with posterior leg and anterior hand involvement;Hypertrophic cardiomyopathy 26
β˜…β˜…β˜†β˜†2025β†’ Residue 721
NM_001458.5(FLNC):c.671del (p.Gln224fs)Pathogenic
Cardiovascular phenotype|Myofibrillar myopathy 5;not provided;Distal myopathy with posterior leg and anterior hand involvement;Hypertrophic cardiomyopathy 26
β˜…β˜…β˜†β˜†2025β†’ Residue 224
NM_001458.5(FLNC):c.6009del (p.Ser2004fs)Pathogenic
Cardiovascular phenotype|Myofibrillar myopathy 5;not provided;Hypertrophic cardiomyopathy 26;Distal myopathy with posterior leg and anterior hand involvement
β˜…β˜…β˜†β˜†2025β†’ Residue 2004
NM_001458.5(FLNC):c.5520T>G (p.Tyr1840Ter)Pathogenic
Cardiovascular phenotype|not provided;Distal myopathy with posterior leg and anterior hand involvement;Hypertrophic cardiomyopathy 26;Myofibrillar myopathy 5
β˜…β˜…β˜†β˜†2025β†’ Residue 1840
NM_001458.5(FLNC):c.4021C>T (p.Arg1341Ter)Pathogenic
not provided|Hypertrophic cardiomyopathy 26|Cardiovascular phenotype|Primary familial dilated cardiomyopathy|Primary dilated cardiomyopathy|FLNC-related disorder|Myofibrillar myopathy 5;not provided;Hypertrophic cardiomyopathy 26;Distal myopathy with posterior leg and anterior hand involvement
β˜…β˜…β˜†β˜†2025β†’ Residue 1341
NM_001458.5(FLNC):c.4952-2A>TLikely pathogenic
Cardiovascular phenotype|not provided|Distal myopathy with posterior leg and anterior hand involvement;Myofibrillar myopathy 5;not provided;Hypertrophic cardiomyopathy 26
β˜…β˜…β˜†β˜†2025
NM_001458.5(FLNC):c.7414G>T (p.Glu2472Ter)Pathogenic
Cardiomyopathy|Myofibrillar myopathy 5;Hypertrophic cardiomyopathy 26;not provided;Distal myopathy with posterior leg and anterior hand involvement
β˜…β˜…β˜†β˜†2025β†’ Residue 2472
View on ClinVar β†—
Related Genes
PXNProtein interaction100%CRYABProtein interaction100%MYOTProtein interaction100%CFL1Protein interaction99%CFL2Protein interaction99%DMDProtein interaction99%
Tissue Expression6 tissues
Heart
100%
Lung
4%
Brain
3%
Ovary
2%
Liver
0%
Bone Marrow
0%
Gene Interaction Network
Click a node to explore
FLNCPXNCRYABMYOTCFL1CFL2DMD
PROTEIN STRUCTURE
Preparing viewer…
PDB1V05 Β· 1.43 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.42Moderately Constrained
pLIβ“˜
1.00Intolerant
Observed/Expected LoF0.36 [0.30–0.42]
RankingsWhere FLNC stands among ~20K protein-coding genes
  • #1,538of 20,598
    Most Researched250 Β· top 10%
  • #81of 5,498
    Most Pathogenic Variants606 Β· top 5%
  • #2,254of 17,882
    Most Constrained (LOEUF)0.42 Β· top quartile
Genes detectedFLNC
Sources retrieved25 papers
Response timeβ€”
πŸ“„ Sources
25β–Ό
1
A mutation update for the FLNC gene in myopathies and cardiomyopathies.
PMID: 32112656
Hum Mutat Β· 2020
1.00
2
Evidence-Based Assessment of Genes in Dilated Cardiomyopathy.
PMID: 33947203
Circulation Β· 2021
0.90
3
Filamin C in cardiomyopathy: from physiological roles to DNA variants.
PMID: 34535832
Heart Fail Rev Β· 2022
0.80
4
Late gadolinium enhancement distribution patterns in non-ischaemic dilated cardiomyopathy: genotype-phenotype correlation.
PMID: 37562008
Eur Heart J Cardiovasc Imaging Β· 2023
0.76
5
Prognostic Prediction of Genotype vs Phenotype in Genetic Cardiomyopathies.
PMID: 36396199
J Am Coll Cardiol Β· 2022
0.70