PMID:17060380

Citation	Vatta, M, Ackerman, MJ, Ye, B, Makielski, JC, Ughanze, EE, Taylor, EW, Tester, DJ, Balijepalli, RC, Foell, JD, Li, Z, Kamp, TJ and Towbin, JA (2006) Mutant caveolin-3 induces persistent late sodium current and is associated with long-QT syndrome. Circulation 114:2104-12
Abstract	Congenital long-QT syndrome (LQTS) is a primary arrhythmogenic syndrome stemming from perturbed cardiac repolarization. LQTS, which affects approximately 1 in 3000 persons, is 1 of the most common causes of autopsy-negative sudden death in the young. Since the sentinel discovery of cardiac channel gene mutations in LQTS in 1995, hundreds of mutations in 8 LQTS susceptibility genes have been identified. All 8 LQTS genotypes represent primary cardiac channel defects (ie, ion channelopathy) except LQT4, which is a functional channelopathy because of mutations in ankyrin-B. Approximately 25% of LQTS remains unexplained pathogenetically. We have pursued a "final common pathway" hypothesis to elicit novel LQTS-susceptibility genes. With the recent observation that the LQT3-associated, SCN5A-encoded cardiac sodium channel localizes in caveolae, which are known membrane microdomains whose major component in the striated muscle is caveolin-3, we hypothesized that mutations in caveolin-3 may represent a novel pathogenetic mechanism for LQTS.
Links	PubMed Online version:10.1161/CIRCULATIONAHA.106.635268
Keywords	Amino Acid Sequence; Caveolin 3/genetics; Cell Line; DNA Mutational Analysis; Electric Conductivity; Electrocardiography; Electrophysiology; Female; Humans; Immunoprecipitation; Long QT Syndrome/diagnosis; Long QT Syndrome/genetics; Long QT Syndrome/metabolism; Long QT Syndrome/physiopathology; Male; Molecular Sequence Data; Muscle Proteins/metabolism; Mutation; Myocardium/metabolism; Sodium Channels/metabolism; Time Factors; Transfection
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HUMAN:KCNA5	colocalizes_with	GO:0005901: caveola	ECO:0000304: author statement supported by traceable reference used in manual assertion		C		Seeded From UniProt	complete
HUMAN:CAV3	enables	GO:0017080: sodium channel regulator activity	ECO:0000314: direct assay evidence used in manual assertion		F	has_input:(UniProtKB:Q14524)	Seeded From UniProt	complete
HUMAN:CAV3	located_in	GO:0005886: plasma membrane	ECO:0000314: direct assay evidence used in manual assertion		C	part_of:(CL:0002131)	Seeded From UniProt	complete
HUMAN:CAV3	involved_in	GO:2000649: regulation of sodium ion transmembrane transporter activity	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete
HUMAN:CAV3	located_in	GO:0042383: sarcolemma	ECO:0000314: direct assay evidence used in manual assertion		C		Seeded From UniProt	complete
HUMAN:CAV3	involved_in	GO:0060373: regulation of ventricular cardiac muscle cell membrane depolarization	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete
HUMAN:CAV3	involved_in	GO:0098909: regulation of cardiac muscle cell action potential involved in regulation of contraction	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
HUMAN:CAV3	involved_in	GO:0060307: regulation of ventricular cardiac muscle cell membrane repolarization	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
HUMAN:CAV3	involved_in	GO:0002027: regulation of heart rate	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
HUMAN:CAV3	enables	GO:0044325: transmembrane transporter binding	ECO:0000353: physical interaction evidence used in manual assertion	UniProtKB:Q14524	F		Seeded From UniProt	complete
HUMAN:CAV3	enables	GO:0060090: molecular adaptor activity	ECO:0000353: physical interaction evidence used in manual assertion	UniProtKB:Q14524	F		Seeded From UniProt	complete
HUMAN:SCN5A	located_in	GO:0005886: plasma membrane	ECO:0000314: direct assay evidence used in manual assertion		C	part_of:(CL:0002131)	Seeded From UniProt	complete
HUMAN:SCN5A	located_in	GO:0042383: sarcolemma	ECO:0000314: direct assay evidence used in manual assertion		C		Seeded From UniProt	complete
HUMAN:SCN5A	part_of	GO:0005886: plasma membrane	ECO:0000314: direct assay evidence used in manual assertion		C	part_of:(CL:0002131)	Seeded From UniProt	complete
HUMAN:SCN5A	enables	GO:0097110: scaffold protein binding	ECO:0000353: physical interaction evidence used in manual assertion	UniProtKB:P56539	F		Seeded From UniProt	complete
HUMAN:SCN5A	part_of	GO:0042383: sarcolemma	ECO:0000314: direct assay evidence used in manual assertion		C		Seeded From UniProt	complete
HUMAN:SCN5A	colocalizes_with	GO:0005901: caveola	ECO:0000304: author statement supported by traceable reference used in manual assertion		C		Seeded From UniProt	complete

References

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