GeneBe

FLNC

filamin C, the group of Filamins

Basic information

Region (hg38): 7:128830406-128859274

Previous symbols: [ "FLN2" ]

Links

ENSG00000128591 ∙ NCBI:2318 ∙ OMIM:102565 ∙ HGNC:3756 ∙ Uniprot:Q14315 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

  • hypertrophic cardiomyopathy 26 (Strong), mode of inheritance: AD
  • heart conduction disease (Limited), mode of inheritance: AD
  • distal myopathy with posterior leg and anterior hand involvement (Supportive), mode of inheritance: AD
  • familial isolated restrictive cardiomyopathy (Supportive), mode of inheritance: AD
  • myofibrillar myopathy 5 (Supportive), mode of inheritance: AD
  • distal myopathy with posterior leg and anterior hand involvement (Moderate), mode of inheritance: AD
  • hypertrophic cardiomyopathy 26 (Moderate), mode of inheritance: AD
  • dilated cardiomyopathy (Definitive), mode of inheritance: AD
  • dilated cardiomyopathy (Definitive), mode of inheritance: AD
  • myofibrillar myopathy 5 (Definitive), mode of inheritance: AD
  • hypertrophic cardiomyopathy 26 (Strong), mode of inheritance: AD
  • myofibrillar myopathy 5 (Strong), mode of inheritance: AD
  • myofibrillar myopathy 5 (Definitive), mode of inheritance: AD
  • dilated cardiomyopathy (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Cardiomyopathy, familial hypertrophic 26 (Cardiomyopthy, familial restrictive 5); Myopathy, distal, 4; Myopathy, myofibrillar, 5ADCardiovascularIndividuals (including with Distal myopathy or Myofibrillar myopathy) have been described with cardiomyopathy, and surveillance (eg, including echocardiography an electrocardiography) may allow early diagnosis and managementCardiovascular; Musculoskeletal15929027; 15824355; 19050726; 21620354; 22131542; 22806379; 23109048; 25351925; 26666891

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the FLNC gene.

  • Hypertrophic_cardiomyopathy_26 (4700 variants)
  • Distal_myopathy_with_posterior_leg_and_anterior_hand_involvement (4649 variants)
  • Myofibrillar_myopathy_5 (4645 variants)
  • Dilated_Cardiomyopathy,_Dominant (4625 variants)
  • Cardiovascular_phenotype (2173 variants)
  • not_provided (1294 variants)
  • not_specified (367 variants)
  • FLNC-related_disorder (147 variants)
  • Cardiomyopathy (129 variants)
  • Primary_dilated_cardiomyopathy (30 variants)
  • Primary_familial_dilated_cardiomyopathy (22 variants)
  • Hypertrophic_cardiomyopathy (13 variants)
  • Restrictive_cardiomyopathy (7 variants)
  • Primary_familial_hypertrophic_cardiomyopathy (3 variants)
  • Cardiomyopathy,_familial_restrictive,_5 (3 variants)
  • Arrhythmogenic_right_ventricular_cardiomyopathy (3 variants)
  • See_cases (3 variants)
  • Myofibrillar_myopathy (2 variants)
  • Wolff-Parkinson-White_pattern (2 variants)
  • Limb-girdle_muscular_dystrophy (2 variants)
  • Arrhythmogenic_right_ventricular_dysplasia,_familial,_15 (2 variants)
  • Dilated_cardiomyopathy_1A (1 variants)
  • Desmin-related_myofibrillar_myopathy (1 variants)
  • FLNC-associated_cardiomyopathy (1 variants)
  • Distal_myopathy (1 variants)
  • Inborn_genetic_diseases (1 variants)
  • Disorder_of_cardiovascular_system (1 variants)
  • Two-raphe_bicuspid_aortic_valve (1 variants)
  • Asymmetric_septal_hypertrophy (1 variants)
  • Nemaline_myopathy (1 variants)
  • Asymmetry_of_the_thorax (1 variants)
  • Episodic_vomiting (1 variants)
  • Tetralogy_of_Fallot (1 variants)
  • Patent_foramen_ovale (1 variants)
  • Muscle_weakness (1 variants)
  • Cardiomyopathy,_familial_restrictive,_1 (1 variants)
  • Facial_asymmetry (1 variants)
  • Abnormality_of_the_musculature (1 variants)
  • Conduction_disorder_of_the_heart (1 variants)
  • Cerebellar_ataxia (1 variants)
  • Arrhythmogenic_cardiomyopathy (1 variants)
  • Spastic_ataxia (1 variants)
  • SUDDEN_INFANT_DEATH_SYNDROME (1 variants)
  • Abnormal_ventricular_septum_morphology (1 variants)
  • Abnormal_morphology_of_left_ventricular_trabeculae (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the FLNC gene is commonly pathogenic or not. These statistics are base on transcript: NM_000001458.5. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
2
clinvar
30
clinvar
1331
clinvar
27
clinvar
 1390
missense
12
clinvar
37
clinvar
2283
clinvar
425
clinvar
9
clinvar
 2766
nonsense
108
clinvar
25
clinvar
4
clinvar
 137
start loss
0
frameshift
245
clinvar
62
clinvar
5
clinvar
 312
splice donor/acceptor (+/-2bp)
12
clinvar
86
clinvar
15
clinvar
 113
Total 379 210 2337 1756 36

Highest pathogenic variant AF is 0.00020144769

Loading clinvar variants...

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
FLNCprotein_codingprotein_codingENST00000325888 4828898
pLI Probability
LOF Intolerant 		pRec Probability
LOF Recessive 		Individuals with
no LOFs 		Individuals with
Homozygous LOFs 		Individuals with
Heterozygous LOFs 		Defined p
1.000.00006471256090381256470.000151
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense2.7913691.69e+30.8090.00011717582
Missense in Polyphen603860.050.701129087
Synonymous-0.6797667421.030.00005795651
Loss of Function7.96181070.1690.000005431284

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.0002370.000235
Ashkenazi Jewish0.0003980.000397
East Asian0.0002770.000273
Finnish0.000.00
European (Non-Finnish)0.0001530.000149
Middle Eastern0.0002770.000273
South Asian0.0001640.000163
Other0.000.00

dbNSFP

Source: dbNSFP

Function
FUNCTION: Muscle-specific filamin, which plays a central role in muscle cells, probably by functioning as a large actin-cross- linking protein. May be involved in reorganizing the actin cytoskeleton in response to signaling events, and may also display structural functions at the Z lines in muscle cells. Critical for normal myogenesis and for maintaining the structural integrity of the muscle fibers.;
Disease
DISEASE: Myopathy, myofibrillar, 5 (MFM5) [MIM:609524]: A form of myofibrillar myopathy, a group of chronic neuromuscular disorders characterized at ultrastructural level by disintegration of the sarcomeric Z disk and myofibrils, and replacement of the normal myofibrillar markings by small dense granules, or larger hyaline masses, or amorphous material. MFM5 is characterized by onset in adulthood, clinical features of a limb-girdle myopathy, and focal myofibrillar destruction. {ECO:0000269|PubMed:15929027}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Myopathy, distal, 4 (MPD4) [MIM:614065]: A slowly progressive muscular disorder characterized by distal muscle weakness and atrophy affecting the upper and lower limbs. Onset occurs around the third to fourth decades of life, and patients remain ambulatory even after long disease duration. Muscle biopsy shows non-specific changes with no evidence of rods, necrosis, or inflammation. {ECO:0000269|PubMed:21620354}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Cardiomyopathy, familial hypertrophic 26 (CMH26) [MIM:617047]: A hereditary heart disorder characterized by ventricular hypertrophy, which is usually asymmetric and often involves the interventricular septum. The symptoms include dyspnea, syncope, collapse, palpitations, and chest pain. They can be readily provoked by exercise. The disorder has inter- and intrafamilial variability ranging from benign to malignant forms with high risk of cardiac failure and sudden cardiac death. {ECO:0000269|PubMed:25351925}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Cardiomyopathy, familial restrictive 5 (RCM5) [MIM:617047]: A heart disorder characterized by impaired filling of the ventricles with reduced diastolic volume, in the presence of normal or near normal wall thickness and systolic function. {ECO:0000269|PubMed:26666891}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway
Focal adhesion - Homo sapiens (human);Salmonella infection - Homo sapiens (human);MAPK signaling pathway - Homo sapiens (human);Proteoglycans in cancer - Homo sapiens (human);Focal Adhesion;MAPK Signaling Pathway;Cell-extracellular matrix interactions;Cell junction organization;Cell-Cell communication (Consensus)

Recessive Scores

pRec
0.281

Intolerance Scores

loftool
0.00661
rvis_EVS
-3.64
rvis_percentile_EVS
0.29

Haploinsufficiency Scores

pHI
0.309
hipred
Y
hipred_score
0.723
ghis
0.535

Essentials

essential_gene_CRISPR
N
essential_gene_CRISPR2
N
essential_gene_gene_trap
N
gene_indispensability_pred
E
gene_indispensability_score
0.908

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

Mouse Genome Informatics

Gene name
Flnc
Phenotype
homeostasis/metabolism phenotype; muscle phenotype; growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); respiratory system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span);

Zebrafish Information Network

Gene name
flnca
Affected structure
slow muscle cell
Phenotype tag
abnormal
Phenotype quality
non-functional

Gene ontology

Biological process
cell junction assembly;muscle fiber development
Cellular component
cytoplasm;cytosol;cytoskeleton;plasma membrane;focal adhesion;sarcoplasm;Z disc;sarcolemma;costamere
Molecular function
protein binding;cytoskeletal protein binding;ankyrin binding;actin filament binding