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Q14524 (SCN5A_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 157. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Sodium channel protein type 5 subunit alpha
Alternative name(s):
HH1
Sodium channel protein cardiac muscle subunit alpha
Sodium channel protein type V subunit alpha
Voltage-gated sodium channel subunit alpha Nav1.5
Gene names
Name:SCN5A
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length2016 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

This protein mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which Na+ ions may pass in accordance with their electrochemical gradient. It is a tetrodotoxin-resistant Na+ channel isoform. This channel is responsible for the initial upstroke of the action potential. Channel inactivation is regulated by intracellular calcium levels. Ref.21

Subunit structure

Interacts with the PDZ domain of the syntrophin SNTA1, SNTB1 and SNTB2 By similarity. Interacts with NEDD4, NEDD4L, WWP2 and GPD1L. Interacts with CALM. Interacts with FGF13; the interaction is direct and may regulate SNC5A density at membranes and function. Ref.11 Ref.12 Ref.14 Ref.18 Ref.22

Subcellular location

Membrane; Multi-pass membrane protein Ref.21.

Tissue specificity

Found in jejunal circular smooth muscle cells (at protein level). Expressed in human atrial and ventricular cardiac muscle but not in adult skeletal muscle, brain, myometrium, liver, or spleen. Isoform 4 is expressed in brain. Ref.2 Ref.15

Domain

The sequence contains 4 internal repeats, each with 5 hydrophobic segments (S1,S2,S3,S5,S6) and one positively charged segment (S4). Segments S4 are probably the voltage-sensors and are characterized by a series of positively charged amino acids at every third position.

The IQ domain mediates association with calmodulin.

Post-translational modification

Regulated through phosphorylation by CaMK2D By similarity.

Ubiquitinated by NEDD4L; which promotes its endocytosis. Does not seem to be ubiquitinated by NEDD4 or WWP2. Ref.11 Ref.12

Phosphorylation at Ser-1503 by PKC in a highly conserved cytoplasmic loop slows inactivation of the sodium channel and reduces peak sodium currents By similarity.

Involvement in disease

Progressive familial heart block 1A (PFHB1A) [MIM:113900]: A cardiac bundle branch disorder characterized by progressive alteration of cardiac conduction through the His-Purkinje system, with a pattern of a right bundle-branch block and/or left anterior hemiblock occurring individually or together. It leads to complete atrio-ventricular block causing syncope and sudden death.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.37 Ref.46 Ref.48 Ref.58 Ref.60 Ref.92

Long QT syndrome 3 (LQT3) [MIM:603830]: A heart disorder characterized by a prolonged QT interval on the ECG and polymorphic ventricular arrhythmias. They cause syncope and sudden death in response to exercise or emotional stress, and can present with a sentinel event of sudden cardiac death in infancy.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.4 Ref.24 Ref.25 Ref.26 Ref.27 Ref.28 Ref.29 Ref.30 Ref.32 Ref.34 Ref.36 Ref.37 Ref.39 Ref.41 Ref.42 Ref.43 Ref.45 Ref.49 Ref.51 Ref.55 Ref.59 Ref.68 Ref.72 Ref.74 Ref.76 Ref.84 Ref.85 Ref.87 Ref.94

Brugada syndrome 1 (BRGDA1) [MIM:601144]: A tachyarrhythmia characterized by right bundle branch block and ST segment elevation on an electrocardiogram (ECG). It can cause the ventricles to beat so fast that the blood is prevented from circulating efficiently in the body. When this situation occurs, the individual will faint and may die in a few minutes if the heart is not reset.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.31 Ref.33 Ref.35 Ref.37 Ref.38 Ref.43 Ref.47 Ref.50 Ref.52 Ref.54 Ref.62 Ref.64 Ref.65 Ref.66 Ref.67 Ref.69 Ref.70 Ref.71 Ref.73 Ref.75 Ref.77 Ref.78 Ref.79 Ref.80 Ref.92 Ref.93

Sick sinus syndrome 1 (SSS1) [MIM:608567]: The term 'sick sinus syndrome' encompasses a variety of conditions caused by sinus node dysfunction. The most common clinical manifestations are syncope, presyncope, dizziness, and fatigue. Electrocardiogram typically shows sinus bradycardia, sinus arrest, and/or sinoatrial block. Episodes of atrial tachycardias coexisting with sinus bradycardia ('tachycardia-bradycardia syndrome') are also common in this disorder. SSS occurs most often in the elderly associated with underlying heart disease or previous cardiac surgery, but can also occur in the fetus, infant, or child without heart disease or other contributing factors. SSS1 onset is in utero, infancy, or early childhood.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.37 Ref.44 Ref.61 Ref.95

Familial paroxysmal ventricular fibrillation 1 (VF1) [MIM:603829]: A cardiac arrhythmia marked by fibrillary contractions of the ventricular muscle due to rapid repetitive excitation of myocardial fibers without coordinated contraction of the ventricle and by absence of atrial activity.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.37 Ref.40

Sudden infant death syndrome (SIDS) [MIM:272120]: SIDS is the sudden death of an infant younger than 1 year that remains unexplained after a thorough case investigation, including performance of a complete autopsy, examination of the death scene, and review of clinical history. Pathophysiologic mechanisms for SIDS may include respiratory dysfunction, cardiac dysrhythmias, cardiorespiratory instability, and inborn errors of metabolism, but definitive pathogenic mechanisms precipitating an infant sudden death remain elusive.
Note: Disease susceptibility is associated with variations affecting the gene represented in this entry. Ref.37 Ref.89 Ref.91

Atrial standstill (ATST) [MIM:108770]: A rare arrhythmia characterized by the absence of electrical and mechanical activity in the atria. Electrocardiographically, it is characterized by bradycardia, the absence of P waves, and a junctional narrow complex escape rhythm.
Note: The disease may be caused by mutations affecting distinct genetic loci, including the gene represented in this entry. A mutation in SCN5A has been detected in combination with a rare GJA5 genotype in a large family with atrial standstill. Ref.37 Ref.57

Cardiomyopathy, dilated 1E (CMD1E) [MIM:601154]: A disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.37 Ref.63

Atrial fibrillation, familial, 10 (ATFB10) [MIM:614022]: A familial form of atrial fibrillation, a common sustained cardiac rhythm disturbance. Atrial fibrillation is characterized by disorganized atrial electrical activity and ineffective atrial contraction promoting blood stasis in the atria and reduces ventricular filling. It can result in palpitations, syncope, thromboembolic stroke, and congestive heart failure.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.37 Ref.82 Ref.83

Miscellaneous

Na+ channels in mammalian cardiac membrane have functional properties quite distinct from Na+ channels in nerve and skeletal muscle.

Sequence similarities

Belongs to the sodium channel (TC 1.A.1.10) family. Nav1.5/SCN5A subfamily. [View classification]

Contains 1 IQ domain.

Ontologies

Keywords
   Biological processIon transport
Sodium transport
Transport
   Cellular componentMembrane
   Coding sequence diversityAlternative splicing
Polymorphism
   DiseaseAtrial fibrillation
Brugada syndrome
Cardiomyopathy
Disease mutation
Long QT syndrome
   DomainRepeat
Transmembrane
Transmembrane helix
   LigandCalmodulin-binding
Sodium
   Molecular functionIon channel
Sodium channel
Voltage-gated channel
   PTMGlycoprotein
Methylation
Phosphoprotein
Ubl conjugation
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processAV node cell to bundle of His cell communication

Inferred from mutant phenotype Ref.37Ref.78. Source: BHF-UCL

SA node cell to atrial cardiac muscle cell communication

Inferred from mutant phenotype Ref.78. Source: BHF-UCL

brainstem development

Inferred from sequence or structural similarity. Source: BHF-UCL

bundle of His cell to Purkinje myocyte communication

Inferred from mutant phenotype PubMed 18065446. Source: BHF-UCL

cardiac muscle cell action potential involved in contraction

Inferred from mutant phenotype PubMed 21895525. Source: BHF-UCL

cardiac muscle contraction

Inferred from mutant phenotype PubMed 18065446PubMed 21895525PubMed 22529811. Source: BHF-UCL

cardiac ventricle development

Inferred from sequence or structural similarity. Source: BHF-UCL

cellular response to calcium ion

Inferred from direct assay Ref.21. Source: UniProtKB

cerebellum development

Inferred from sequence or structural similarity. Source: BHF-UCL

membrane depolarization

Inferred from direct assay Ref.3PubMed 21051419PubMed 21895525. Source: BHF-UCL

membrane depolarization during SA node cell action potential

Inferred from sequence or structural similarity. Source: BHF-UCL

membrane depolarization during action potential

Inferred from direct assay Ref.3PubMed 18065446PubMed 22529811. Source: BHF-UCL

membrane depolarization during cardiac muscle cell action potential

Inferred from mutant phenotype PubMed 21895525. Source: BHF-UCL

odontogenesis of dentin-containing tooth

Inferred from sequence or structural similarity. Source: BHF-UCL

positive regulation of action potential

Inferred from sequence or structural similarity. Source: BHF-UCL

positive regulation of epithelial cell proliferation

Inferred from sequence or structural similarity. Source: BHF-UCL

positive regulation of sodium ion transport

Inferred from direct assay Ref.3PubMed 18065446PubMed 19808477PubMed 22529811. Source: BHF-UCL

regulation of atrial cardiac muscle cell membrane depolarization

Inferred from mutant phenotype PubMed 19167345PubMed 22247482. Source: BHF-UCL

regulation of atrial cardiac muscle cell membrane repolarization

Inferred from mutant phenotype PubMed 19167345. Source: BHF-UCL

regulation of cardiac muscle cell contraction

Inferred from mutant phenotype PubMed 22529811. Source: BHF-UCL

regulation of heart rate

Inferred from mutant phenotype Ref.37PubMed 18065446Ref.78PubMed 21895525PubMed 22529811. Source: BHF-UCL

regulation of heart rate by cardiac conduction

Inferred from mutant phenotype PubMed 21895525. Source: BHF-UCL

regulation of sodium ion transmembrane transport

Inferred from direct assay PubMed 18591664. Source: BHF-UCL

regulation of ventricular cardiac muscle cell membrane depolarization

Inferred from mutant phenotype PubMed 18065446PubMed 22529811Ref.24. Source: BHF-UCL

regulation of ventricular cardiac muscle cell membrane repolarization

Inferred from mutant phenotype Ref.24. Source: BHF-UCL

response to denervation involved in regulation of muscle adaptation

Inferred from sequence or structural similarity. Source: BHF-UCL

sodium ion transmembrane transport

Inferred from direct assay Ref.3PubMed 21051419. Source: BHF-UCL

sodium ion transport

Inferred from direct assay Ref.21. Source: UniProtKB

telencephalon development

Inferred from sequence or structural similarity. Source: BHF-UCL

ventricular cardiac muscle cell action potential

Inferred from mutant phenotype PubMed 18065446PubMed 22529811. Source: BHF-UCL

   Cellular_componentT-tubule

Inferred from direct assay Ref.65. Source: BHF-UCL

caveola

Inferred from direct assay PubMed 23420830. Source: BHF-UCL

cell surface

Inferred from direct assay Ref.3Ref.14. Source: BHF-UCL

endoplasmic reticulum

Inferred from direct assay PubMed 22529811. Source: BHF-UCL

integral component of membrane

Inferred from direct assay Ref.21. Source: UniProtKB

intercalated disc

Inferred from direct assay Ref.65. Source: BHF-UCL

lateral plasma membrane

Traceable author statement PubMed 21164104. Source: BHF-UCL

plasma membrane

Inferred from direct assay PubMed 16728661PubMed 17060380PubMed 22529811. Source: BHF-UCL

sarcolemma

Inferred from direct assay PubMed 17060380. Source: BHF-UCL

voltage-gated sodium channel complex

Inferred from direct assay PubMed 19808477PubMed 20042427PubMed 21051419. Source: BHF-UCL

   Molecular_functionankyrin binding

Inferred from direct assay Ref.65. Source: BHF-UCL

calmodulin binding

Inferred from physical interaction Ref.22. Source: BHF-UCL

enzyme binding

Inferred from physical interaction Ref.14. Source: BHF-UCL

fibroblast growth factor binding

Inferred from physical interaction PubMed 12401812. Source: BHF-UCL

ion channel binding

Inferred from physical interaction PubMed 17592081PubMed 20042427. Source: BHF-UCL

nitric-oxide synthase binding

Inferred from physical interaction PubMed 18591664. Source: BHF-UCL

scaffold protein binding

Inferred from physical interaction PubMed 17060380. Source: BHF-UCL

ubiquitin protein ligase binding

Inferred from physical interaction Ref.11. Source: BHF-UCL

voltage-gated sodium channel activity

Inferred from direct assay Ref.21. Source: UniProtKB

voltage-gated sodium channel activity involved in cardiac muscle cell action potential

Inferred from direct assay PubMed 18065446. Source: BHF-UCL

Complete GO annotation...

Alternative products

This entry describes 6 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q14524-1)

Also known as: CAG-inclusive variant; Nav1.5c;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Note: Most abundant isoform in heart.
Isoform 2 (identifier: Q14524-2)

Also known as: Nav1.5b;

The sequence of this isoform differs from the canonical sequence as follows:
     1076-1076: Missing.
Note: Very abundant isoform.
Isoform 3 (identifier: Q14524-3)

The sequence of this isoform differs from the canonical sequence as follows:
     206-211: TTEFVD → VSENIK
     1076-1076: Missing.
     1573-1604: Missing.
Isoform 4 (identifier: Q14524-4)

Also known as: Nav1.5e; neonatal;

The sequence of this isoform differs from the canonical sequence as follows:
     206-211: TTEFVD → VSENIK
Note: Abundantly expressed in neonatal brain and heart, slower kinetics of activation and inactivation.
Isoform 5 (identifier: Q14524-5)

Also known as: Ex18del; Nav1.5a;

The sequence of this isoform differs from the canonical sequence as follows:
     206-211: TTEFVD → VSENIK
     1077-1130: Missing.
Note: Only detected in neuroblastoma in humans.
Isoform 6 (identifier: Q14524-6)

Also known as: Ex24del; Nav1.5f;

The sequence of this isoform differs from the canonical sequence as follows:
     206-211: TTEFVD → VSENIK
     1416-1433: Missing.
Note: High expression in brain where it accounts for nearly 50% of the total transcripts. Non-functional channel, may exist to limit the number of undesired functional Nav1.5 channels.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 20162016Sodium channel protein type 5 subunit alpha
PRO_0000048497

Regions

Topological domain1 – 126126Cytoplasmic Potential
Transmembrane127 – 15024Helical; Name=S1 of repeat I; Potential
Topological domain151 – 1588Extracellular Potential
Transmembrane159 – 17820Helical; Name=S2 of repeat I; Potential
Topological domain179 – 19113Cytoplasmic Potential
Transmembrane192 – 21019Helical; Name=S3 of repeat I; Potential
Topological domain211 – 2166Extracellular Potential
Transmembrane217 – 23620Helical; Voltage-sensor; Name=S4 of repeat I; Potential
Topological domain237 – 25216Cytoplasmic Potential
Transmembrane253 – 27624Helical; Name=S5 of repeat I; Potential
Topological domain277 – 389113Extracellular Potential
Transmembrane390 – 41526Helical; Name=S6 of repeat I; Potential
Topological domain416 – 711296Cytoplasmic Potential
Transmembrane712 – 73625Helical; Name=S1 of repeat II; Potential
Topological domain737 – 74711Extracellular Potential
Transmembrane748 – 77124Helical; Name=S2 of repeat II; Potential
Topological domain772 – 7798Cytoplasmic Potential
Transmembrane780 – 79920Helical; Name=S3 of repeat II; Potential
Topological domain800 – 8056Extracellular Potential
Transmembrane806 – 82520Helical; Voltage-sensor; Name=S4 of repeat II; Potential
Topological domain826 – 84116Cytoplasmic Potential
Transmembrane842 – 86221Helical; Name=S5 of repeat II; Potential
Topological domain863 – 91351Extracellular Potential
Transmembrane914 – 93926Helical; Name=S6 of repeat II; Potential
Topological domain940 – 1200261Cytoplasmic Potential
Transmembrane1201 – 122424Helical; Name=S1 of repeat III; Potential
Topological domain1225 – 123713Extracellular Potential
Transmembrane1238 – 126326Helical; Name=S2 of repeat III; Potential
Topological domain1264 – 12696Cytoplasmic Potential
Transmembrane1270 – 129122Helical; Name=S3 of repeat III; Potential
Topological domain1292 – 12954Extracellular Potential
Transmembrane1296 – 131722Helical; Voltage-sensor; Name=S4 of repeat III; Potential
Topological domain1318 – 133619Cytoplasmic Potential
Transmembrane1337 – 135923Helical; Name=S5 of repeat III; Potential
Topological domain1360 – 144384Extracellular Potential
Transmembrane1444 – 147027Helical; Name=S6 of repeat III; Potential
Topological domain1471 – 152353Cytoplasmic Potential
Transmembrane1524 – 154724Helical; Name=S1 of repeat IV; Potential
Topological domain1548 – 155811Extracellular Potential
Transmembrane1559 – 158224Helical; Name=S2 of repeat IV; Potential
Topological domain1583 – 15886Cytoplasmic Potential
Transmembrane1589 – 161224Helical; Name=S3 of repeat IV; Potential
Topological domain1613 – 162210Extracellular Potential
Transmembrane1623 – 164422Helical; Voltage-sensor; Name=S4 of repeat IV; Potential
Topological domain1645 – 165915Cytoplasmic Potential
Transmembrane1660 – 168223Helical; Name=S5 of repeat IV; Potential
Topological domain1683 – 174765Extracellular Potential
Transmembrane1748 – 177225Helical; Name=S6 of repeat IV; Potential
Topological domain1773 – 2016244Cytoplasmic Potential
Domain1901 – 193030IQ
Region1839 – 190163Interaction with FGF13
Region1974 – 19774Interaction with NEDD4, NEDD4L and WWP2

Amino acid modifications

Modified residue361Phosphoserine Ref.20
Modified residue381Phosphothreonine Ref.20
Modified residue4571Phosphoserine Ref.20
Modified residue4601Phosphoserine Ref.20
Modified residue4831Phosphoserine Ref.20
Modified residue4841Phosphoserine
Modified residue4971Phosphoserine Ref.20
Modified residue5101Phosphoserine Ref.20
Modified residue5131Dimethylated arginine; alternate Ref.19
Modified residue5131Omega-N-methylarginine; alternate Ref.19
Modified residue5261Dimethylated arginine; alternate Ref.19
Modified residue5261Omega-N-methylarginine; alternate Ref.19
Modified residue5711Phosphoserine Ref.20
Modified residue6641Phosphoserine Ref.20
Modified residue6671Phosphoserine Ref.20
Modified residue6801Dimethylated arginine; alternate Ref.19
Modified residue6801Omega-N-methylarginine; alternate Ref.19
Modified residue15031Phosphoserine; by PKC By similarity
Glycosylation2141N-linked (GlcNAc...) Potential
Glycosylation2831N-linked (GlcNAc...) Potential
Glycosylation2881N-linked (GlcNAc...) Potential
Glycosylation2911N-linked (GlcNAc...) Potential
Glycosylation3181N-linked (GlcNAc...) Potential
Glycosylation3281N-linked (GlcNAc...) Potential
Glycosylation7401N-linked (GlcNAc...) Potential
Glycosylation8031N-linked (GlcNAc...) Potential
Glycosylation8641N-linked (GlcNAc...) Potential
Glycosylation13651N-linked (GlcNAc...) Potential
Glycosylation13741N-linked (GlcNAc...) Potential
Glycosylation13801N-linked (GlcNAc...) Potential
Glycosylation13881N-linked (GlcNAc...) Potential
Glycosylation17361N-linked (GlcNAc...) Potential

Natural variations

Alternative sequence206 – 2116TTEFVD → VSENIK in isoform 3, isoform 4, isoform 5 and isoform 6.
VSP_037477
Alternative sequence10761Missing in isoform 2 and isoform 3.
VSP_037478
Alternative sequence1077 – 113054Missing in isoform 5.
VSP_037479
Alternative sequence1416 – 143318Missing in isoform 6.
VSP_037480
Alternative sequence1573 – 160432Missing in isoform 3.
VSP_037481
Natural variant91G → V in LQT3. Ref.72
VAR_036660
Natural variant181R → W in LQT3. Ref.68
VAR_068325
Natural variant271R → H in BRGDA1. Ref.50
VAR_026341
Natural variant341R → C. Ref.51 Ref.82
Corresponds to variant rs6791924 [ dbSNP | Ensembl ].
VAR_026342
Natural variant431R → Q in LQT3; does not affect baseline kinetics of sodium currents; causes an unusual hyperpolarizing shift of the activation kinetics after lidocaine treatment. Ref.85
VAR_055159
Natural variant951V → I in BRGDA1. Ref.73
VAR_055160
Natural variant1251V → L in LQT3. Ref.68
VAR_068326
Natural variant1261K → E in BRGDA1. Ref.54
VAR_026343
Natural variant1381M → I in ATFB10. Ref.82
VAR_055161
Natural variant1611E → K in BRGDA1 and PFHB1A. Ref.47 Ref.92
VAR_026344
Natural variant1871T → I in BRGDA1; loss of function. Ref.69
VAR_026345
Natural variant2121L → P in PFHB1A.
VAR_055162
Natural variant2161S → L Rare variant found in patients with atrial fibrillation; unknown pathological significance. Ref.82
Corresponds to variant rs41276525 [ dbSNP | Ensembl ].
VAR_055163
Natural variant2201T → I in SSS1. Ref.61
Corresponds to variant rs45620037 [ dbSNP | Ensembl ].
VAR_017670
Natural variant2251R → Q in LQT3. Ref.72
VAR_036661
Natural variant2251R → W in PFHB1A. Ref.58
VAR_055164
Natural variant2261A → V in BRGDA1. Ref.50
VAR_026346
Natural variant2301I → V in BRGDA1. Ref.50
VAR_026347
Natural variant2321V → I. Ref.81
Corresponds to variant rs45471994 [ dbSNP | Ensembl ].
VAR_055165
Natural variant2451Q → K in LQT3. Ref.68
VAR_068327
Natural variant2821R → H in BRGDA1. Ref.50
VAR_026348
Natural variant2941V → M in BRGDA1. Ref.50
VAR_026349
Natural variant2981G → S in PFHB1A; also in irritable bowel syndrome; results in reduction of whole cell current density and a delay in channel activation kinetics without a change in single-channel conductance. Ref.48 Ref.90
VAR_017671
Natural variant3191G → S in BRGDA1. Ref.50
VAR_026350
Natural variant3251L → R in BRGDA1.
VAR_055166
Natural variant3361P → L in BRGDA1; detected in a compound heterozygote also carrying V-1660; the presence of both mutations is necessary for the phenotypic expression of the disease; severe reduction of sodium currents. Ref.6 Ref.71
VAR_055167
Natural variant3511G → V in BRGDA1; 7-fold current reduction. Ref.54
VAR_026351
Natural variant3531T → I in BRGDA1. Ref.75
VAR_055168
Natural variant3561D → N in BRGDA1; loss of function. Ref.69
VAR_026352
Natural variant3671R → C in BRGDA1; express no current. Ref.47 Ref.92
Corresponds to variant rs28937318 [ dbSNP | Ensembl ].
VAR_026353
Natural variant3671R → H in BRGDA1; express no current. Ref.52 Ref.92
Corresponds to variant rs28937318 [ dbSNP | Ensembl ].
VAR_017672
Natural variant3691M → K in BRGDA1. Ref.47
VAR_026354
Natural variant3761R → H Found in patients with atrial fibrillation. Ref.82
VAR_055169
Natural variant3931Missing in BRGDA1. Ref.50
VAR_026355
Natural variant4041L → Q in LQT3. Ref.68
VAR_068328
Natural variant4061N → K in LQT3. Ref.68
VAR_055170
Natural variant4061N → S in BRGDA1.
VAR_055171
Natural variant4111V → M in LQT3. Ref.68
VAR_068329
Natural variant4281E → K in ATFB10. Ref.82
VAR_055172
Natural variant4451H → D in ATFB10. Ref.82
VAR_055173
Natural variant4611L → V Found in patients with atrial fibrillation. Ref.82
Corresponds to variant rs41313697 [ dbSNP | Ensembl ].
VAR_055174
Natural variant4621E → K in LQT3. Ref.68
VAR_068330
Natural variant4701N → K in ATFB10. Ref.82
VAR_055175
Natural variant4811R → W Found in patients with atrial fibrillation. Ref.82
VAR_055176
Natural variant5121T → I in PFHB1A; voltage-dependent activation and inactivation of the Ile-512 channel is shifted negatively by 8 to 9 mV and had enhanced slow activation and slower recovery from inactivation commpared to the wild-type channel; the double mutant Arg-558/Ile-512 channel shows that Arg-558 eliminates the negative shift induced by Ile-512 but only partially restores the kinetic abnormalities. Ref.60
VAR_036662
Natural variant5141G → C in BRGDA1 and PFHB1A. Ref.46 Ref.92
VAR_017673
Natural variant5241S → Y Found in patients with atrial fibrillation. Ref.82
Corresponds to variant rs41313691 [ dbSNP | Ensembl ].
VAR_036663
Natural variant5321F → C in SIDS. Ref.89
VAR_055177
Natural variant5521G → R. Ref.1 Ref.2 Ref.70
Corresponds to variant rs3918389 [ dbSNP | Ensembl ].
VAR_026356
Natural variant5581H → R Channels properties are similar to wild-type; the double mutant Arg-558/Ile-512 channel shows that Arg-558 eliminates the negative shift induced by Ile-512 but only partially restores the kinetic abnormalities; can modulate the gating defects caused by Ala-2006 and other mutations. Ref.3 Ref.4 Ref.9 Ref.51 Ref.54 Ref.60 Ref.82 Ref.88 Ref.94
Corresponds to variant rs1805124 [ dbSNP | Ensembl ].
VAR_008955
Natural variant5671L → Q in BRGDA1. Ref.50
VAR_026357
Natural variant5721A → D in LQT3 and ATFB10. Ref.68 Ref.82
Corresponds to variant rs36210423 [ dbSNP | Ensembl ].
VAR_055178
Natural variant586 – 5872Missing in LQT3.
VAR_055179
Natural variant6151G → E in LQT3; drug-induced LQT syndrome. Ref.51 Ref.68
Corresponds to variant rs12720452 [ dbSNP | Ensembl ].
VAR_026358
Natural variant6181L → F in drug-induced LQT syndrome; also found in patients with atrial fibrillation. Ref.68 Ref.82
Corresponds to variant rs45488304 [ dbSNP | Ensembl ].
VAR_047360
Natural variant6191L → F in LQT3. Ref.51 Ref.59
VAR_015682
Natural variant6371P → L in LQT3. Ref.68
VAR_068331
Natural variant6391G → R in LQT3. Ref.72
VAR_036664
Natural variant6481P → L in LQT3. Ref.68
VAR_068332
Natural variant6551E → K in ATFB10. Ref.82
VAR_055180
Natural variant6801R → H in LQT3.
VAR_055181
Natural variant6811H → P in BRGDA1. Ref.50
VAR_026359
Natural variant7351A → E in BRGDA1. Ref.50
VAR_026360
Natural variant7351A → V in BRGDA1 and SSS1; expresses currents with steady state activation voltage shifted to more positive potentials and exhibit reduced sodium channel current at the end of phase I of the action potential. Ref.52 Ref.95
VAR_017674
Natural variant7521G → R in BRGDA1 and PFHB1A. Ref.47 Ref.92
VAR_026361
Natural variant8141R → Q in BRGDA1.
VAR_055182
Natural variant8511F → L in BRGDA1. Ref.50
VAR_026362
Natural variant8781R → C in BRGDA1. Ref.78
VAR_055183
Natural variant8921F → I in BRGDA1. Ref.50
VAR_026363
Natural variant8961C → S in BRGDA1. Ref.50
VAR_026364
Natural variant9101S → L in BRGDA1. Ref.50
VAR_026365
Natural variant9411S → N in LQT3; also in SIDS. Ref.41
VAR_017675
Natural variant9651R → C in BRGDA1; steady state inactivation shifted to a more negative potential; slower recovery from inactivation. Ref.50 Ref.93
VAR_026366
Natural variant9711R → C in LQT3. Ref.68
VAR_068333
Natural variant9971A → S in LQT3; also found in patients with atrial fibrillation; sodium current characterized by slower decay and a 2- to 3-fold increase in late sodium current. Ref.45 Ref.82
VAR_017676
Natural variant10231R → H in BRGDA1.
VAR_055184
Natural variant10271R → Q. Ref.1 Ref.6 Ref.70
VAR_026367
Natural variant10411D → N.
Corresponds to variant rs45491996 [ dbSNP | Ensembl ].
VAR_047361
Natural variant10531E → K in BRGDA1 and ATFB10; abolishes binding to ANK3 and also prevents accumulation of SCN5A at cell surface sites in ventricular cardiomyocytes. Ref.50 Ref.65 Ref.82
VAR_026368
Natural variant10691T → M in LQT3. Ref.68
VAR_068334
Natural variant10841G → S in SIDS; may be a rare polymorphism. Ref.89
VAR_055185
Natural variant10901P → L. Ref.88
Corresponds to variant rs1805125 [ dbSNP | Ensembl ].
VAR_014464
Natural variant11031S → Y May confer susceptibility to acquired arrhythmia. Ref.3 Ref.53 Ref.56 Ref.82
Corresponds to variant rs7626962 [ dbSNP | Ensembl ].
VAR_017677
Natural variant11141D → N in LQT3. Ref.39
VAR_009935
Natural variant11311T → I in ATFB10. Ref.82
VAR_055186
Natural variant11801A → V.
Corresponds to variant rs41310765 [ dbSNP | Ensembl ].
VAR_047362
Natural variant11931R → Q in BRGDA1 and LQT3; also found in patients with atrial fibrillation; accelerates the inactivation of the sodium channel current and exhibit reduced sodium channel current at the end of phase I of the action potential. Ref.52 Ref.82
Corresponds to variant rs41261344 [ dbSNP | Ensembl ].
VAR_017678
Natural variant12251E → K in BRGDA1 and LQT3. Ref.47 Ref.68
VAR_026369
Natural variant12311E → K in LQT3. Ref.68
VAR_068335
Natural variant12321R → W in BRGDA1 and PFHB1A. Ref.31 Ref.92
VAR_017679
Natural variant12361K → N in BRGDA1. Ref.50
VAR_026370
Natural variant12401E → Q in BRGDA1. Ref.50
VAR_026371
Natural variant12501F → L in LQT3; drug-induced LQT syndrome. Ref.51
Corresponds to variant rs45589741 [ dbSNP | Ensembl ].
VAR_026372
Natural variant12621G → S in BRGDA1. Ref.64
VAR_036665
Natural variant12751D → N in CMD1E, BRGDA1, PFHB1A and ATST; in familial atrial standstill is found in association with polymorphisms in the regulatory region of GJA5. Ref.57 Ref.63 Ref.92
VAR_026373
Natural variant12931F → S in BRGDA1. Ref.50
Corresponds to variant rs41311127 [ dbSNP | Ensembl ].
VAR_026374
Natural variant12951E → K in LQT3; causes significant positive shifts in the half-maximal voltage of steady-state inactivation and activation. Ref.42
VAR_055187
Natural variant12981P → L in SSS1. Ref.61
Corresponds to variant rs28937319 [ dbSNP | Ensembl ].
VAR_017680
Natural variant13041T → M in LQT3. Ref.32
VAR_008956
Natural variant13081L → F Associated with I-232 in a case of lidocaine-induced Brugada syndrome. Ref.81
Corresponds to variant rs41313031 [ dbSNP | Ensembl ].
VAR_055188
Natural variant13191G → V in BRGDA1. Ref.47 Ref.92
VAR_026375
Natural variant13251N → S in LQT3. Ref.68
Corresponds to variant rs28937317 [ dbSNP | Ensembl ].
VAR_001577
Natural variant13301A → P in LQT3.
VAR_055189
Natural variant13301A → T in LQT3.
VAR_055190
Natural variant13321P → L in LQT3.
VAR_055191
Natural variant13331S → Y in LQT3 and SIDS. Ref.72 Ref.91
VAR_036666
Natural variant13441F → S in BRGDA1. Ref.70
VAR_026376
Natural variant13821S → I in BRGDA1. Ref.47
VAR_026377
Natural variant14051V → L in BRGDA1. Ref.47
VAR_026378
Natural variant14061G → R in BRGDA1. Ref.47
VAR_026379
Natural variant14081G → R in SSS1 and BRGDA1; also in cardiac conduction defect. Ref.44 Ref.61 Ref.92
Corresponds to variant rs28936971 [ dbSNP | Ensembl ].
VAR_017681
Natural variant14321R → G in BRGDA1.
VAR_055192
Natural variant14381P → L in BRGDA1.
VAR_055193
Natural variant14581S → Y in LQT3. Ref.68
VAR_068336
Natural variant14731F → C in LQT3. Ref.76
VAR_055194
Natural variant14791Missing in BRGDA1. Ref.47
VAR_026380
Natural variant14811G → E in LQT3. Ref.68
VAR_068337
Natural variant14861F → L in LQT3.
VAR_055195
Natural variant14941Y → N in BRGDA1. Ref.77
VAR_055196
Natural variant15001K → N. Ref.32
VAR_008957
Natural variant15001Missing in BRGDA1. Ref.50
VAR_026381
Natural variant15011L → V in LQT3. Ref.39
VAR_009936
Natural variant15021G → S in BRGDA1. Ref.47
VAR_026382
Natural variant1505 – 15073Missing in LQT3.
VAR_001576
Natural variant1507 – 15093Missing in LQT3.
VAR_055197
Natural variant15121R → W in BRGDA1; significantly affects cardiac sodium channel characteristics; associated with an increase in inward sodium current during the action potential upstroke. Ref.33 Ref.47 Ref.92
VAR_017682
Natural variant15271K → R in BRGDA1; asymptomatic patient; associated with P-1569. Ref.67
VAR_055198
Natural variant15691A → P in BRGDA1; asymptomatic patient; associated with R-1527. Ref.67
VAR_055199
Natural variant15951D → N in PFHB1A; significant defect in the kinetics of fast-channel inactivation distinct from mutations reported in LQT3. Ref.48
VAR_017683
Natural variant16091S → W in LQT3. Ref.72
VAR_036667
Natural variant16171Missing in LQT3 and BRGDA1. Ref.73
VAR_055200
Natural variant16201T → K in LQT3 and PFHB1A.
VAR_055201
Natural variant16201T → M in BRGDA1; arrhythmogenicity revealed only at temperatures approaching the physiologic range. Ref.31 Ref.35 Ref.38
VAR_017684
Natural variant16231R → L in LQT3. Ref.39 Ref.68
VAR_009937
Natural variant16231R → Q in LQT3. Ref.28 Ref.30
VAR_001578
Natural variant16261R → P in LQT3.
VAR_055202
Natural variant16441R → C in LQT3 and BRGDA1.
VAR_055203
Natural variant16441R → H in LQT3. Ref.39 Ref.68
Corresponds to variant rs28937316 [ dbSNP | Ensembl ].
VAR_001579
Natural variant16451T → M in LQT3. Ref.32
VAR_008958
Natural variant16491A → V in BRGDA1. Ref.73
VAR_055204
Natural variant16521M → R in LQT3.
VAR_055205
Natural variant16601I → V in BRGDA1; detected in a compound heterozygote also carrying L-336; the presence of both mutations is necessary for the phenotypic expression of the disease; complete loss of sodium currents due to defective channel trafficking to the plasma membrane. Ref.71
VAR_055206
Natural variant16671V → I in LQT3. Ref.68
VAR_068338
Natural variant17051F → S in SIDS; causes a hyperpolarizing shift of steady-state inactivation and delayed recovery from inactivation. Ref.89
VAR_055207
Natural variant17101S → L in VF1. Ref.40
VAR_017685
Natural variant17141D → G in BRGDA1; strong decrease of current density; does not affect ion selectivity properties. Ref.66 Ref.92
VAR_026383
Natural variant17401G → R in BRGDA1. Ref.50 Ref.92
VAR_026384
Natural variant17431G → E in BRGDA1. Ref.47 Ref.92
VAR_026385
Natural variant17431G → R in BRGDA1; yields nearly undetectable currents in transfected cells. Ref.62
VAR_055208
Natural variant17631V → M in LQT3. Ref.68
VAR_055209
Natural variant17661M → L in LQT3; affects protein trafficking. Ref.4 Ref.68
VAR_055210
Natural variant17681I → V in LQT3; increases the rate of recovery from inactivation and the channel availability, observed as a positive shift of the steady-state inactivation curve. Ref.55
VAR_055211
Natural variant17771V → M in LQT3. Ref.68
VAR_055212
Natural variant17791T → M in LQT3. Ref.68
VAR_068339
Natural variant17841E → K in LQT3 and BRGDA1. Ref.34 Ref.50 Ref.68 Ref.87
VAR_008959
Natural variant17871S → N in LQT3. Ref.39
VAR_009938
Natural variant17901D → G in LQT3. Ref.27
VAR_001580
Natural variant17921D → N in SSS1. Ref.95
VAR_068475
Natural variant17951Y → C in LQT3; also in a family associating LQT syndrome and atrial fibrillation; slows the onset of activation, but does not cause a marked negative shift in the voltage dependence of inactivation or affect the kinetics of the recovery from inactivation; increases the expression of sustained Na(+) channel activity and promotes entrance into an intermediate or slowly developing inactivated state. Ref.43 Ref.68 Ref.84
VAR_019123
Natural variant17951Y → H in BRGDA1; accelerates the onset of activation and causes a marked negative shift in the voltage dependence of inactivation; does not affect the kinetics of the recovery from inactivation; increases the expression of sustained Na(+) channel activity and promotes entrance into an intermediate or slowly developing inactivated state. Ref.43 Ref.50
VAR_019124
Natural variant17951Y → YD in LQT3 and BRGDA1; 7.3-mV negative shift of the steady-state inactivation curve and 8.1-mV positive shift of the steady-state activation curve; may reduced sodium current during the upstroke of the action potential. Ref.36 Ref.49
VAR_017686
Natural variant18191D → N in LQT3; digenic; associated with Gly-100 mutation on the KCNH2 gene. Ref.72
VAR_036668
Natural variant18251L → P in LQT3; drug-induced LQT syndrome.
VAR_055213
Natural variant18261R → C in ATFB10. Ref.82
VAR_055214
Natural variant18261R → H in LQT3; sodium current characterized by slower decay and a 2- to 3-fold increase in late sodium current. Ref.45
VAR_017687
Natural variant18391D → G in LQT3. Ref.29
VAR_001581
Natural variant18501C → S in BRGDA1; decreased I(Na) density; shift of the steady-state inactivation towards negative potentials. Ref.80
VAR_055215
Natural variant18751M → T in atrial fibrillation; pronounced depolarized shift of the voltage dependence of steady-state inactivation; no persistent sodium current. Ref.86
VAR_055216
Natural variant19041S → L in LQT3; promotes late sodium currents by increasing the propensity of the channel to reopen during prolonged depolarization. Ref.74
VAR_055217
Natural variant19091Q → R in LQT3. Ref.68
VAR_068340
Natural variant19241A → T in BRGDA1; significantly affect cardiac sodium channel characteristics; associated with an increase in inward sodium current during the action potential upstroke. Ref.33 Ref.47 Ref.92
VAR_017688
Natural variant19351G → S in BRGDA1.
VAR_055218
Natural variant19491A → S in LQT3. Ref.68
VAR_068341
Natural variant19511V → L in BRGDA1 and LQT3; also found in patients with atrial fibrillation. Ref.50 Ref.82
Corresponds to variant rs41315493 [ dbSNP | Ensembl ].
VAR_026386
Natural variant19511V → M in ATFB10. Ref.82
Corresponds to variant rs41315493 [ dbSNP | Ensembl ].
VAR_055219
Natural variant19581R → Q in LQT3. Ref.68
VAR_068342
Natural variant19681I → S in BRGDA1.
VAR_055220
Natural variant19871N → K in ATFB10. Ref.83
VAR_065865
Natural variant20041F → L in LQT3 and BRGDA1; also found in patients with atrial fibrillation; results in channels with decreased peak and persistent current amplitudes; increased closed-state and slow inactivation; decelerated recovery from inactivation. Ref.79 Ref.82
Corresponds to variant rs41311117 [ dbSNP | Ensembl ].
VAR_055221
Natural variant20061P → A in LQT3; causes an increase of persistent sodium current and produces a depolarizing shift in voltage dependence of inactivation. Ref.94
VAR_055222

Experimental info

Mutagenesis14761Q → K: Induces accelerated recovery from channel fast inactivation. Ref.13
Mutagenesis1802 – 18043DPE → APA: Abolishes calcium response on channel inactivation. Ref.21
Mutagenesis19741P → A: Strongly reduces interaction with NEDD4, NEDD4L or WWP2. Ref.12
Mutagenesis19751P → A: Strongly reduces interaction with NEDD4, NEDD4L or WWP2. Ref.12
Mutagenesis19761S → A: Strongly reduces interaction with NEDD4, NEDD4L or WWP2. Ref.12
Mutagenesis19771Y → A: Strongly reduces interaction with NEDD4, NEDD4L or WWP2. Ref.11 Ref.12
Mutagenesis19781D → A: No effect on interaction with NEDD4, NEDD4L or WWP2. Ref.12
Mutagenesis19791S → A: No effect on interaction with NEDD4, NEDD4L or WWP2. Ref.12
Mutagenesis19801V → A: No effect on interaction with NEDD4, NEDD4L or WWP2. Ref.11 Ref.12
Mutagenesis19801V → D or R: Strongly reduces interaction with NEDD4L. Ref.11 Ref.12
Sequence conflict911K → R in ABR15763. Ref.6
Sequence conflict911K → R in ABR15764. Ref.6
Sequence conflict961L → P in ABR15763. Ref.6
Sequence conflict961L → P in ABR15764. Ref.6
Sequence conflict1201I → V in AAA58644. Ref.1
Sequence conflict1621Y → H in ABR15763. Ref.6
Sequence conflict1621Y → H in ABR15764. Ref.6
Sequence conflict1801G → A in AAA58644. Ref.1
Sequence conflict1811F → S in ABR15763. Ref.6
Sequence conflict1811F → S in ABR15764. Ref.6
Sequence conflict1911D → G in BAD12084. Ref.5
Sequence conflict1911D → G in BAD12085. Ref.5
Sequence conflict1911D → G in ABR15763. Ref.6
Sequence conflict1911D → G in ABR15764. Ref.6
Sequence conflict1961L → P in ABR15763. Ref.6
Sequence conflict1961L → P in ABR15764. Ref.6
Sequence conflict2151V → L in BAD12084. Ref.5
Sequence conflict2151V → L in BAD12085. Ref.5
Sequence conflict2151V → L in ABR15763. Ref.6
Sequence conflict2151V → L in ABR15764. Ref.6
Sequence conflict2151V → L in AAI44622. Ref.9
Sequence conflict2151V → L in AAI40814. Ref.9
Sequence conflict2341S → P in BAD12084. Ref.5
Sequence conflict2341S → P in BAD12085. Ref.5
Sequence conflict2341S → P in ABR15763. Ref.6
Sequence conflict2341S → P in ABR15764. Ref.6
Sequence conflict2341S → P in AAI44622. Ref.9
Sequence conflict2341S → P in AAI40814. Ref.9
Sequence conflict2801C → R in ABR15763. Ref.6
Sequence conflict2801C → R in ABR15764. Ref.6
Sequence conflict2901T → I in ABR15763. Ref.6
Sequence conflict2901T → I in ABR15764. Ref.6
Sequence conflict5161S → N in ABR15763. Ref.6
Sequence conflict5161S → N in ABR15764. Ref.6
Sequence conflict6081D → N in ABR15763. Ref.6
Sequence conflict6081D → N in ABR15764. Ref.6
Sequence conflict6181L → I in AAO91669. Ref.4
Sequence conflict6531F → V in BAD12084. Ref.5
Sequence conflict6531F → V in BAD12085. Ref.5
Sequence conflict9181V → G in ABR15763. Ref.6
Sequence conflict9181V → G in ABR15764. Ref.6
Sequence conflict9871Q → H in AAA58644. Ref.1
Sequence conflict9871Q → H in BAD12084. Ref.5
Sequence conflict9871Q → H in BAD12085. Ref.5
Sequence conflict9871Q → H in ABR15763. Ref.6
Sequence conflict9871Q → H in ABR15764. Ref.6
Sequence conflict10851G → W in AAA58644. Ref.1
Sequence conflict10851G → W in BAD12084. Ref.5
Sequence conflict10871E → R in AAA58644. Ref.1
Sequence conflict10871E → R in BAD12084. Ref.5
Sequence conflict10881A → G in AAA58644. Ref.1
Sequence conflict10881A → G in BAD12084. Ref.5
Sequence conflict13421L → H in ABR15763. Ref.6
Sequence conflict13421L → H in ABR15764. Ref.6
Sequence conflict14791K → T in BAD12084. Ref.5
Sequence conflict14791K → T in BAD12085. Ref.5
Sequence conflict1480 – 14812LG → IR in ABQ01244. Ref.7
Sequence conflict14981M → T in BAD12084. Ref.5
Sequence conflict14981M → T in BAD12085. Ref.5
Sequence conflict16161F → S in BAD92103. Ref.10
Sequence conflict16571L → P in ABR15763. Ref.6
Sequence conflict16571L → P in ABR15764. Ref.6
Sequence conflict18501C → R in ABR15763. Ref.6
Sequence conflict18501C → R in ABR15764. Ref.6

Secondary structure

........................ 2016
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (CAG-inclusive variant) (Nav1.5c) [UniParc].

Last modified November 25, 2008. Version 2.
Checksum: 841E3A365931190B

FASTA2,016226,940
        10         20         30         40         50         60 
MANFLLPRGT SSFRRFTRES LAAIEKRMAE KQARGSTTLQ ESREGLPEEE APRPQLDLQA 

        70         80         90        100        110        120 
SKKLPDLYGN PPQELIGEPL EDLDPFYSTQ KTFIVLNKGK TIFRFSATNA LYVLSPFHPI 

       130        140        150        160        170        180 
RRAAVKILVH SLFNMLIMCT ILTNCVFMAQ HDPPPWTKYV EYTFTAIYTF ESLVKILARG 

       190        200        210        220        230        240 
FCLHAFTFLR DPWNWLDFSV IIMAYTTEFV DLGNVSALRT FRVLRALKTI SVISGLKTIV 

       250        260        270        280        290        300 
GALIQSVKKL ADVMVLTVFC LSVFALIGLQ LFMGNLRHKC VRNFTALNGT NGSVEADGLV 

       310        320        330        340        350        360 
WESLDLYLSD PENYLLKNGT SDVLLCGNSS DAGTCPEGYR CLKAGENPDH GYTSFDSFAW 

       370        380        390        400        410        420 
AFLALFRLMT QDCWERLYQQ TLRSAGKIYM IFFMLVIFLG SFYLVNLILA VVAMAYEEQN 

       430        440        450        460        470        480 
QATIAETEEK EKRFQEAMEM LKKEHEALTI RGVDTVSRSS LEMSPLAPVN SHERRSKRRK 

       490        500        510        520        530        540 
RMSSGTEECG EDRLPKSDSE DGPRAMNHLS LTRGLSRTSM KPRSSRGSIF TFRRRDLGSE 

       550        560        570        580        590        600 
ADFADDENST AGESESHHTS LLVPWPLRRT SAQGQPSPGT SAPGHALHGK KNSTVDCNGV 

       610        620        630        640        650        660 
VSLLGAGDPE ATSPGSHLLR PVMLEHPPDT TTPSEEPGGP QMLTSQAPCV DGFEEPGARQ 

       670        680        690        700        710        720 
RALSAVSVLT SALEELEESR HKCPPCWNRL AQRYLIWECC PLWMSIKQGV KLVVMDPFTD 

       730        740        750        760        770        780 
LTITMCIVLN TLFMALEHYN MTSEFEEMLQ VGNLVFTGIF TAEMTFKIIA LDPYYYFQQG 

       790        800        810        820        830        840 
WNIFDSIIVI LSLMELGLSR MSNLSVLRSF RLLRVFKLAK SWPTLNTLIK IIGNSVGALG 

       850        860        870        880        890        900 
NLTLVLAIIV FIFAVVGMQL FGKNYSELRD SDSGLLPRWH MMDFFHAFLI IFRILCGEWI 

       910        920        930        940        950        960 
ETMWDCMEVS GQSLCLLVFL LVMVIGNLVV LNLFLALLLS SFSADNLTAP DEDREMNNLQ 

       970        980        990       1000       1010       1020 
LALARIQRGL RFVKRTTWDF CCGLLRQRPQ KPAALAAQGQ LPSCIATPYS PPPPETEKVP 

      1030       1040       1050       1060       1070       1080 
PTRKETRFEE GEQPGQGTPG DPEPVCVPIA VAESDTDDQE EDEENSLGTE EESSKQQESQ 

      1090       1100       1110       1120       1130       1140 
PVSGGPEAPP DSRTWSQVSA TASSEAEASA SQADWRQQWK AEPQAPGCGE TPEDSCSEGS 

      1150       1160       1170       1180       1190       1200 
TADMTNTAEL LEQIPDLGQD VKDPEDCFTE GCVRRCPCCA VDTTQAPGKV WWRLRKTCYH 

      1210       1220       1230       1240       1250       1260 
IVEHSWFETF IIFMILLSSG ALAFEDIYLE ERKTIKVLLE YADKMFTYVF VLEMLLKWVA 

      1270       1280       1290       1300       1310       1320 
YGFKKYFTNA WCWLDFLIVD VSLVSLVANT LGFAEMGPIK SLRTLRALRP LRALSRFEGM 

      1330       1340       1350       1360       1370       1380 
RVVVNALVGA IPSIMNVLLV CLIFWLIFSI MGVNLFAGKF GRCINQTEGD LPLNYTIVNN 

      1390       1400       1410       1420       1430       1440 
KSQCESLNLT GELYWTKVKV NFDNVGAGYL ALLQVATFKG WMDIMYAAVD SRGYEEQPQW 

      1450       1460       1470       1480       1490       1500 
EYNLYMYIYF VIFIIFGSFF TLNLFIGVII DNFNQQKKKL GGQDIFMTEE QKKYYNAMKK 

      1510       1520       1530       1540       1550       1560 
LGSKKPQKPI PRPLNKYQGF IFDIVTKQAF DVTIMFLICL NMVTMMVETD DQSPEKINIL 

      1570       1580       1590       1600       1610       1620 
AKINLLFVAI FTGECIVKLA ALRHYYFTNS WNIFDFVVVI LSIVGTVLSD IIQKYFFSPT 

      1630       1640       1650       1660       1670       1680 
LFRVIRLARI GRILRLIRGA KGIRTLLFAL MMSLPALFNI GLLLFLVMFI YSIFGMANFA 

      1690       1700       1710       1720       1730       1740 
YVKWEAGIDD MFNFQTFANS MLCLFQITTS AGWDGLLSPI LNTGPPYCDP TLPNSNGSRG 

      1750       1760       1770       1780       1790       1800 
DCGSPAVGIL FFTTYIIISF LIVVNMYIAI ILENFSVATE ESTEPLSEDD FDMFYEIWEK 

      1810       1820       1830       1840       1850       1860 
FDPEATQFIE YSVLSDFADA LSEPLRIAKP NQISLINMDL PMVSGDRIHC MDILFAFTKR 

      1870       1880       1890       1900       1910       1920 
VLGESGEMDA LKIQMEEKFM AANPSKISYE PITTTLRRKH EEVSAMVIQR AFRRHLLQRS 

      1930       1940       1950       1960       1970       1980 
LKHASFLFRQ QAGSGLSEED APEREGLIAY VMSENFSRPL GPPSSSSISS TSFPPSYDSV 

      1990       2000       2010 
TRATSDNLQV RGSDYSHSED LADFPPSPDR DRESIV 

« Hide

Isoform 2 (Nav1.5b) [UniParc].

Checksum: D760403C3F90EFD8
Show »

FASTA2,015226,812
Isoform 3 [UniParc].

Checksum: 03F558B8E4E69834
Show »

FASTA1,983223,076
Isoform 4 (Nav1.5e) (neonatal) [UniParc].

Checksum: 488DEFD1D9F93256
Show »

FASTA2,016226,918
Isoform 5 (Ex18del) (Nav1.5a) [UniParc].

Checksum: F8F9E267F9927F80
Show »

FASTA1,962221,279
Isoform 6 (Ex24del) (Nav1.5f) [UniParc].

Checksum: C301F1A8375CD3AB
Show »

FASTA1,998224,917

References

« Hide 'large scale' references
[1]"Primary structure and functional expression of the human cardiac tetrodotoxin-insensitive voltage-dependent sodium channel."
Gellens M.E., George A.L. Jr., Chen L.Q., Chahine M., Horn R., Barchi R.L., Kallen R.G.
Proc. Natl. Acad. Sci. U.S.A. 89:554-558(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANTS ARG-552 AND GLN-1027.
Tissue: Heart.
[2]"SCN5A is expressed in human jejunal circular smooth muscle cells."
Ou Y., Gibbons S.J., Miller S.M., Strege P.R., Rich A., Distad M.A., Ackerman M.J., Rae J.L., Szurszewski J.H., Farrugia G.
Neurogastroenterol. Motil. 14:477-486(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), TISSUE SPECIFICITY, VARIANT ARG-552.
Tissue: Jejunal smooth muscle.
[3]"A ubiquitous splice variant and a common polymorphism affect heterologous expression of recombinant human SCN5A heart sodium channels."
Makielski J.C., Ye B., Valdivia C.R., Pagel M.D., Pu J., Tester D.J., Ackerman M.J.
Circ. Res. 93:821-828(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), VARIANTS ARG-558 AND TYR-1103.
[4]"A common human SCN5A polymorphism modifies expression of an arrhythmia causing mutation."
Ye B., Valdivia C.R., Ackerman M.J., Makielski J.C.
Physiol. Genomics 12:187-193(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), VARIANT ARG-558, CHARACTERIZATION OF VARIANT LQT3 LEU-1766.
[5]"Tetrodotoxin-resistant Na+ channels in human neuroblastoma cells are encoded by new variants of Nav1.5/SCN5A."
Ou S.-W., Kameyama A., Hao L.-Y., Horiuchi M., Minobe E., Wang W.-Y., Makita N., Kameyama M.
Eur. J. Neurosci. 22:793-801(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 4 AND 5).
[6]"Cloning, distribution and analysis of the new exon encoding Nav1.5 channel in brain tissues."
Wang J., Ou S.-W., Wang Y.-J., Zong Z.-H.
Sheng Wu Hua Xue Yu Sheng Wu Wu Li Jin Zhan 34:255-259(2007)
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 4 AND 6), VARIANTS LEU-336 AND GLN-1027.
[7]NHLBI resequencing and genotyping service (RS&G)
Submitted (JUN-2006) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[8]"The DNA sequence, annotation and analysis of human chromosome 3."
Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J. expand/collapse author list , Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B., Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H., Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J., Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.
Nature 440:1194-1198(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[9]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3), VARIANT ARG-558.
[10]Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S., Ohara O., Nagase T., Kikuno R.F.
Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 422-2016 (ISOFORMS 3/6).
Tissue: Brain.
[11]"Cardiac voltage-gated sodium channel Nav1.5 is regulated by Nedd4-2 mediated ubiquitination."
van Bemmelen M.X., Rougier J.-S., Gavillet B., Apotheloz F., Daidie D., Tateyama M., Rivolta I., Thomas M.A., Kass R.S., Staub O., Abriel H.
Circ. Res. 95:284-291(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH NEDD4L, UBIQUITINATION, MUTAGENESIS OF TYR-1977 AND VAL-1980.
[12]"Molecular determinants of voltage-gated sodium channel regulation by the Nedd4/Nedd4-like proteins."
Rougier J.-S., van Bemmelen M.X., Bruce M.C., Jespersen T., Gavillet B., Apotheloz F., Cordonier S., Staub O., Rotin D., Abriel H.
Am. J. Physiol. 288:C692-C701(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH NEDD4; NEDD4L AND WWP2, UBIQUITINATION, MUTAGENESIS OF PRO-1974; PRO-1975; SER-1976; TYR-1977; ASP-1978; SER-1979 AND VAL-1980.
[13]"Mutation in the neuronal voltage-gated sodium channel SCN1A in familial hemiplegic migraine."
Dichgans M., Freilinger T., Eckstein G., Babini E., Lorenz-Depiereux B., Biskup S., Ferrari M.D., Herzog J., van den Maagdenberg A.M.J.M., Pusch M., Strom T.M.
Lancet 366:371-377(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS OF GLN-1476.
[14]"GPD1L links redox state to cardiac excitability by PKC-dependent phosphorylation of the sodium channel SCN5A."
Valdivia C.R., Ueda K., Ackerman M.J., Makielski J.C.
Am. J. Physiol. 297:H1446-H1452(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH GPD1L.
[15]"Analysis of four novel variants of Nav1.5/SCN5A cloned from the brain."
Wang J., Ou S.-W., Wang Y.-J., Kameyama M., Kameyama A., Zong Z.-H.
Neurosci. Res. 64:339-347(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: ALTERNATIVE SPLICING, TISSUE SPECIFICITY (ISOFORM 4).
[16]"SCN5A channelopathies - An update on mutations and mechanisms."
Zimmer T., Surber R.
Prog. Biophys. Mol. Biol. 98:120-136(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON VARIANTS.
[17]"Structure and function of splice variants of the cardiac voltage-gated sodium channel Na(v)1.5."
Schroeter A., Walzik S., Blechschmidt S., Haufe V., Benndorf K., Zimmer T.
J. Mol. Cell. Cardiol. 49:16-24(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: ALTERNATIVE SPLICING.
[18]"Fibroblast growth factor homologous factor 13 regulates Na+ channels and conduction velocity in murine hearts."
Wang C., Hennessey J.A., Kirkton R.D., Wang C., Graham V., Puranam R.S., Rosenberg P.B., Bursac N., Pitt G.S.
Circ. Res. 109:775-782(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH FGF13.
[19]"The cardiac sodium channel is post-translationally modified by arginine methylation."
Beltran-Alvarez P., Pagans S., Brugada R.
J. Proteome Res. 10:3712-3719(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: METHYLATION AT ARG-513; ARG-526 AND ARG-680.
[20]"Mass spectrometry-based identification of native cardiac Nav1.5 channel alpha subunit phosphorylation sites."
Marionneau C., Lichti C.F., Lindenbaum P., Charpentier F., Nerbonne J.M., Townsend R.R., Merot J.
J. Proteome Res. 11:5994-6007(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-36; THR-38; SER-457; SER-460; SER-483; SER-497; SER-510; SER-571; SER-664 AND SER-667.
[21]"Solution NMR structure of the C-terminal EF-hand domain of human cardiac sodium channel NaV1.5."
Chagot B., Potet F., Balser J.R., Chazin W.J.
J. Biol. Chem. 284:6436-6445(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 1773-1865, FUNCTION, SUBCELLULAR LOCATION, RESPONSE TO CALCIUM, MUTAGENESIS OF 1802-ASP--GLU-1804.
[22]"Solution NMR structure of Apo-calmodulin in complex with the IQ motif of human cardiac sodium channel NaV1.5."
Chagot B., Chazin W.J.
J. Mol. Biol. 406:106-119(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 1901-1927 IN COMPLEX WITH CALM, INTERACTION WITH CALM.
[23]"Crystal structure of the ternary complex of a NaV C-terminal domain, a fibroblast growth factor homologous factor, and calmodulin."
Wang C., Chung B.C., Yan H., Lee S.Y., Pitt G.S.
Structure 20:1167-1176(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 1773-1940 IN COMPLEX WITH FGF13 AND CALMODULIN.
[24]"SCN5A mutations associated with an inherited cardiac arrhythmia, long QT syndrome."
Wang Q., Shen J., Splawski I., Atkinson D., Li Z., Robinson J.L., Moss A.J., Towbin J.A., Keating M.T.
Cell 80:805-811(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS LQT3.
[25]"Cardiac sodium channel mutations in patients with long QT syndrome, an inherited cardiac arrhythmia."
Wang Q., Shen J., Li Z., Timothy K.W., Vincent G.M., Priori S.G., Schwartz P.J., Keating M.T.
Hum. Mol. Genet. 4:1603-1607(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS LQT3.
[26]"Molecular mechanism for an inherited cardiac arrhythmia."
Bennett P.B., Yazawa K., Makita N., George A.L. Jr.
Nature 376:683-685(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT LQT3 1505-LYS--GLN-1507 DEL.
[27]"Novel LQT-3 mutation affects Na+ channel activity through interactions between alpha- and beta1-subunits."
An R.H., Wang X.L., Kerem B., Benhorin J., Medina A., Goldmit M., Kass R.S.
Circ. Res. 83:141-146(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT LQT3 GLY-1790.
[28]"A de novo missense mutation of human cardiac Na(+) channel exhibiting novel molecular mechanisms of long QT syndrome."
Makita N., Shirai N., Nagashima M., Matsuoka R., Yamada Y., Tohse N., Kitabatake A.
FEBS Lett. 423:5-9(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT LQT3 GLN-1623.
[29]"Identification of a new SCN5A mutation, D1840G, associated with the long QT syndrome."
Benhorin J., Goldmit M., Maccluer J.W., Blangero J., Goffen R., Leibovitch A., Rahat A., Wang Q., Medina A., Towbin J.A., Kerem B.
Hum. Mutat. 12:72-72(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT LQT3 GLY-1839.
[30]"A De Novo missense mutation (R1623Q) of the SCN5A gene in a Japanese girl with sporadic long QT syndrome."
Yamagishi H., Furutani M., Kamisago M., Morikawa Y., Kojima Y., Hino Y., Furutani Y., Kimura M., Imamura S., Takao A., Momma K., Matsuoka R.
Hum. Mutat. 12:481-481(1998)
Cited for: VARIANT LQT3 GLN-1623.
[31]"Genetic basis and molecular mechanism for idiopathic ventricular fibrillation."
Chen Q., Kirsch G.E., Zhang D., Brugada R., Brugada J., Brugada P., Potenza D., Moya A., Borggrefe M., Breithardt G., Ortiz-Lopez R., Wang Z., Antzelevitch C., O'Brien R.E., Schulze-Bahr E., Keating M.T., Towbin J.A., Wang Q.
Nature 392:293-296(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS BRGDA1 TRP-1232 AND MET-1620.
[32]"Sodium channel abnormalities are infrequent in patients with long QT syndrome: identification of two novel SCN5A mutations."
Wattanasirichaigoon D., Vesely M.R., Duggal P., Levine J.C., Blume E.D., Wolff G.S., Edwards S.B., Beggs A.H.
Am. J. Med. Genet. 86:470-476(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS LQT3 MET-1304 AND MET-1645, VARIANT ASN-1500.
[33]"Human SCN5A gene mutations alter cardiac sodium channel kinetics and are associated with the Brugada syndrome."
Rook M.B., Bezzina Alshinawi C., Groenewegen W.A., van Gelder I.C., van Ginneken A.C.G., Jongsma H.J., Mannens M.M.A.M., Wilde A.A.M.
Cardiovasc. Res. 44:507-517(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION OF VARIANTS BRGDA1 TRP-1512 AND THR-1924.
[34]"Congenital long-QT syndrome caused by a novel mutation in a conserved acidic domain of the cardiac Na+ channel."
Wei J., Wang D.W., Alings M., Fish F., Wathen M., Roden D.M., George A.L. Jr.
Circulation 99:3165-3171(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT LQT3 LYS-1784.
[35]"Ionic mechanisms responsible for the electrocardiographic phenotype of the Brugada syndrome are temperature dependent."
Dumaine R., Towbin J.A., Brugada P., Vatta M., Nesterenko D.V., Nesterenko V.V., Brugada J., Brugada R., Antzelevitch C.
Circ. Res. 85:803-809(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION OF VARIANT BRGDA1 MET-1620.
[36]"A single Na(+) channel mutation causing both long-QT and Brugada syndromes."
Bezzina C.R., Veldkamp M.W., van Den Berg M.P., Postma A.V., Rook M.B., Viersma J.-W., van Langen I.M., Tan-Sindhunata G., Bink-Boelkens M.T.E., van Der Hout A.H., Mannens M.M.A.M., Wilde A.A.M.
Circ. Res. 85:1206-1213(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION OF VARIANT LQT3/BRGDA1 ASP-1795 INS.
[37]"Cardiac conduction defects associate with mutations in SCN5A."
Schott J.-J., Alshinawi C., Kyndt F., Probst V., Hoorntje T.M., Hulsbeek M., Wilde A.A.M., Escande D., Mannens M.M.A.M., Le Marec H.
Nat. Genet. 23:20-21(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: DISEASE.
[38]"Cardiac Na(+) channel dysfunction in Brugada syndrome is aggravated by beta(1)-subunit."
Makita N., Shirai N., Wang D.W., Sasaki K., George A.L. Jr., Kanno M., Kitabatake A.
Circulation 101:54-60(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION OF VARIANT BRGDA1 MET-1620.
[39]"Spectrum of mutations in long-QT syndrome genes. KVLQT1, HERG, SCN5A, KCNE1, and KCNE2."
Splawski I., Shen J., Timothy K.W., Lehmann M.H., Priori S.G., Robinson J.L., Moss A.J., Schwartz P.J., Towbin J.A., Vincent G.M., Keating M.T.
Circulation 102:1178-1185(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS LQT3 ASN-1114; VAL-1501; LEU-1623; HIS-1644 AND ASN-1787.
[40]"A novel SCN5A mutation associated with idiopathic ventricular fibrillation without typical ECG findings of Brugada syndrome."
Akai J., Makita N., Sakurada H., Shirai N., Ueda K., Kitabatake A., Nakazawa K., Kimura A., Hiraoka M.
FEBS Lett. 479:29-34(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT VF1 LEU-1710.
[41]"A molecular link between the sudden infant death syndrome and the long-QT syndrome."
Schwartz P.J., Priori S.G., Dumaine R., Napolitano C., Antzelevitch C., Stramba-Badiale M., Richard T.A., Berti M.R., Bloise R.
N. Engl. J. Med. 343:262-267(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT LQT3 ASN-941.
[42]"Novel arrhythmogenic mechanism revealed by a long-QT syndrome mutation in the cardiac Na(+) channel."
Abriel H., Cabo C., Wehrens X.H., Rivolta I., Motoike H.K., Memmi M., Napolitano C., Priori S.G., Kass R.S.
Circ. Res. 88:740-745(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT LQT3 LYS-1295, CHARACTERIZATION OF VARIANT LQT3 LYS-1295.
[43]"Inherited Brugada and long QT-3 syndrome mutations of a single residue of the cardiac sodium channel confer distinct channel and clinical phenotypes."
Rivolta I., Abriel H., Tateyama M., Liu H., Memmi M., Vardas P., Napolitano C., Priori S.G., Kass R.S.
J. Biol. Chem. 276:30623-30630(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION OF VARIANT LQT3 CYS-1795, CHARACTERIZATION OF VARIANT BRGDA1 HIS-1795.
[44]"Novel SCN5A mutation leading either to isolated cardiac conduction defect or Brugada syndrome in a large French family."
Kyndt F., Probst V., Potet F., Demolombe S., Chevallier J.-C., Baro I., Moisan J.-P., Boisseau P., Schott J.-J., Escande D., Le Marec H.
Circulation 104:3081-3086(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT SSS1/BRGDA1 ARG-1408.
[45]"Postmortem molecular analysis of SCN5A defects in sudden infant death syndrome."
Ackerman M.J., Siu B.L., Sturner W.Q., Tester D.J., Valdivia C.R., Makielski J.C., Towbin J.A.
JAMA 286:2264-2269(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION OF VARIANTS LQT3 SER-997 AND HIS-1826.
[46]"A sodium-channel mutation causes isolated cardiac conduction disease."
Tan H.L., Bink-Boelkens M.T.E., Bezzina C.R., Viswanathan P.C., Beaufort-Krol G.C.M., van Tintelen P.J., van den Berg M.P., Wilde A.A.M., Balser J.R.
Nature 409:1043-1047(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION OF VARIANT PFHB1A CYS-514.
[47]"Genotype-phenotype relationship in Brugada syndrome: electrocardiographic features differentiate SCN5A-related patients from non-SCN5A-related patients."
Smits J.P.P., Eckardt L., Probst V., Bezzina C.R., Schott J.-J., Remme C.A., Haverkamp W., Breithardt G., Escande D., Schulze-Bahr E., LeMarec H., Wilde A.A.M.
J. Am. Coll. Cardiol. 40:350-356(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS BRGDA1 LYS-161; CYS-367; LYS-369; ARG-752; LYS-1225; VAL-1319; ILE-1382; LEU-1405; ARG-1406; LYS-1479 DEL; SER-1502; TRP-1512; GLU-1743 AND THR-1924.
[48]"Clinical, genetic and biophysical characterisation of SCN5A mutations associated with atrioventricular conduction block."
Wang D.W., Viswanathan P.C., Balser J.R., George A.L. Jr., Benson D.W.
Circulation 105:341-346(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION OF VARIANTS PFHB1A SER-298 AND ASN-1595.
[49]"Na(+) channel mutation that causes both Brugada and long-QT syndrome phenotypes: a simulation study of mechanism."
Clancy C.E., Rudy Y.
Circulation 105:1208-1213(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: MODELING OF VARIANT LQT3/BRGDA1 ASP-1795 INS.
[50]"Natural history of Brugada syndrome: insights for risk stratification and management."
Priori S.G., Napolitano C., Gasparini M., Pappone C., Della Bella P., Giordano U., Bloise R., Giustetto C., De Nardis R., Grillo M., Ronchetti E., Faggiano G., Nastoli J.
Circulation 105:1342-1347(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS BRGDA1 HIS-27; VAL-226; VAL-230; HIS-282; MET-294; SER-319; PHE-393 DEL; GLN-567; PRO-681; GLU-735; LEU-851; ILE-892; SER-896; LEU-910; CYS-965; LYS-1053; ASN-1236; GLN-1240; SER-1293; LYS-1500 DEL; ARG-1740; LYS-1784; HIS-1795 AND LEU-1951.
[51]"Allelic variants in long-QT disease genes in patients with drug-associated torsades de pointes."
Yang P., Kanki H., Drolet B., Yang T., Wei J., Viswanathan P.C., Hohnloser S.H., Shimizu W., Schwartz P.J., Stanton M., Murray K.T., Norris K., George A.L. Jr., Roden D.M.
Circulation 105:1943-1948(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS LQT3 GLU-615; PHE-619 AND LEU-1250, VARIANTS CYS-34 AND ARG-558.
[52]"Genetic and biophysical basis of sudden unexplained nocturnal death syndrome (SUNDS), a disease allelic to Brugada syndrome."
Vatta M., Dumaine R., Varghese G., Richard T.A., Shimizu W., Aihara N., Nademanee K., Brugada R., Brugada J., Veerakul G., Li H., Bowles N.E., Brugada P., Antzelevitch C., Towbin J.A.
Hum. Mol. Genet. 11:337-345(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION OF VARIANTS BRGDA1 HIS-367; VAL-735 AND GLN-1193.
[53]"SNP S1103Y in the cardiac sodium channel gene SCN5A is associated with cardiac arrhythmias and sudden death in a white family."
Chen S., Chung M.K., Martin D., Rozich R., Tchou P.J., Wang Q.
J. Med. Genet. 39:913-915(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT TYR-1103.
[54]"Novel mutations in domain I of SCN5A cause Brugada syndrome."
Vatta M., Dumaine R., Antzelevitch C., Brugada R., Li H., Bowles N.E., Nademanee K., Brugada J., Brugada P., Towbin J.A.
Mol. Genet. Metab. 75:317-324(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS BRGDA1 GLU-126 AND VAL-351, CHARACTERIZATION OF VARIANT BRGDA1 VAL-351, VARIANT ARG-558.
[55]"A novel SCN5A mutation associated with long QT-3: altered inactivation kinetics and channel dysfunction."
Rivolta I., Clancy C.E., Tateyama M., Liu H., Priori S.G., Kass R.S.
Physiol. Genomics 10:191-197(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT LQT3 VAL-1768, CHARACTERIZATION OF VARIANT LQT3 VAL-1768.
[56]"Variant of SCN5A sodium channel implicated in risk of cardiac arrhythmia."
Splawski I., Timothy K.W., Tateyama M., Clancy C.E., Malhotra A., Beggs A.H., Cappuccio F.P., Sagnella G.A., Kass R.S., Keating M.T.
Science 297:1333-1336(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT TYR-1103.
[57]"A cardiac sodium channel mutation cosegregates with a rare connexin40 genotype in familial atrial standstill."
Groenewegen W.A., Firouzi M., Bezzina C.R., Vliex S., van Langen I.M., Sandkuijl L., Smits J.P., Hulsbeek M., Rook M.B., Jongsma H.J., Wilde A.A.M.
Circ. Res. 92:14-22(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT ATST ASN-1275.
[58]"Compound heterozygosity for mutations (W156X and R225W) in SCN5A associated with severe cardiac conduction disturbances and degenerative changes in the conduction system."
Bezzina C.R., Rook M.B., Groenewegen W.A., Herfst L.J., van der Wal A.C., Lam J., Jongsma H.J., Wilde A.A.M., Mannens M.M.
Circ. Res. 92:159-168(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PFHB1A TRP-225.
[59]"A novel mutation L619F in the cardiac Na+ channel SCN5A associated with long-QT syndrome (LQT3): a role for the I-II linker in inactivation gating."
Wehrens X.H., Rossenbacker T., Jongbloed R.J., Gewillig M., Heidbuchel H., Doevendans P.A., Vos M.A., Wellens H.J., Kass R.S.
Hum. Mutat. 21:552-552(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT LQT3 PHE-619.
[60]"A common SCN5A polymorphism modulates the biophysical effects of an SCN5A mutation."
Viswanathan P.C., Benson D.W., Balser J.R.
J. Clin. Invest. 111:341-346(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PFHB1A ILE-512, CHARACTERIZATION OF VARIANT PFHB1A ILE-512, VARIANT ARG-558, CHARACTERIZATION OF VARIANT ARG-558.
[61]"Congenital sick sinus syndrome caused by recessive mutations in the cardiac sodium channel gene (SCN5A)."
Benson D.W., Wang D.W., Dyment M., Knilans T.K., Fish F.A., Strieper M.J., Rhodes T.H., George A.L. Jr.
J. Clin. Invest. 112:1019-1028(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS SSS1 ILE-220; LEU-1298 AND ARG-1408.
[62]"A trafficking defective, Brugada syndrome-causing SCN5A mutation rescued by drugs."
Valdivia C.R., Tester D.J., Rok B.A., Porter C.B., Munger T.M., Jahangir A., Makielski J.C., Ackerman M.J.
Cardiovasc. Res. 62:53-62(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT BRGDA1 ARG-1743, CHARACTERIZATION OF VARIANT BRGDA1 ARG-1743.
[63]"SCN5A mutation associated with dilated cardiomyopathy, conduction disorder, and arrhythmia."
The familial cardiomyopathy registry research group
McNair W.P., Ku L., Taylor M.R.G., Fain P.R., Dao D., Wolfel E., Mestroni L.
Circulation 110:2163-2167(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT CMD1E ASN-1275.
[64]"Genetic analysis of the cardiac sodium channel gene SCN5A in Koreans with Brugada syndrome."
Shin D.-J., Jang Y., Park H.-Y., Lee J.E., Yang K., Kim E., Bae Y., Kim J., Kim J., Kim S.S., Lee M.H., Chahine M., Yoon S.K.
J. Hum. Genet. 49:573-578(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT BRGDA1 SER-1262.
[65]"Nav1.5 E1053K mutation causing Brugada syndrome blocks binding to ankyrin-G and expression of Nav1.5 on the surface of cardiomyocytes."
Mohler P.J., Rivolta I., Napolitano C., LeMaillet G., Lambert S., Priori S.G., Bennett V.
Proc. Natl. Acad. Sci. U.S.A. 101:17533-17538(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT BRGDA1 LYS-1053, CHARACTERIZATION OF VARIANT BRGDA1 LYS-1053.
[66]"Novel Brugada syndrome-causing mutation in ion-conducting pore of cardiac Na+ channel does not affect ion selectivity properties."
Amin A.S., Verkerk A.O., Bhuiyan Z.A., Wilde A.A.M., Tan H.L.
Acta Physiol. Scand. 185:291-301(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT BRGDA1 GLY-1714, CHARACTERIZATION OF VARIANT BRGDA1 GLY-1714.
[67]"Double SCN5A mutation underlying asymptomatic Brugada syndrome."
Yokoi H., Makita N., Sasaki K., Takagi Y., Okumura Y., Nishino T., Makiyama T., Kitabatake A., Horie M., Watanabe I., Tsutsui H.
Heart Rhythm 2:285-292(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS BRGDA1 ARG-1527 AND PRO-1569.
[68]"Compendium of cardiac channel mutations in 541 consecutive unrelated patients referred for long QT syndrome genetic testing."
Tester D.J., Will M.L., Haglund C.M., Ackerman M.J.
Heart Rhythm 2:507-517(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS LQT3 TRP-18; LEU-125; LYS-245; GLN-404; LYS-406; MET-411; LYS-462; ASP-572; GLU-615; PHE-618; LEU-637; LEU-648; CYS-971; MET-1069; LYS-1225; LYS-1231; SER-1325; TYR-1458; GLU-1481; 1505-LYS--GLN-1507 DEL; LEU-1623; HIS-1644; ILE-1667; MET-1763; LEU-1766; MET-1777; MET-1779; LYS-1784; CYS-1795; ARG-1909; SER-1949 AND GLN-1958.
[69]"High risk for bradyarrhythmic complications in patients with Brugada syndrome caused by SCN5A gene mutations."
Makiyama T., Akao M., Tsuji K., Doi T., Ohno S., Takenaka K., Kobori A., Ninomiya T., Yoshida H., Takano M., Makita N., Yanagisawa F., Higashi Y., Takeyama Y., Kita T., Horie M.
J. Am. Coll. Cardiol. 46:2100-2106(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS BRGDA1 ILE-187 AND ASN-356, CHARACTERIZATION OF VARIANTS BRGDA1 ILE-187 AND ASN-356.
[70]"A novel SCN5A mutation, F1344S, identified in a patient with Brugada syndrome and fever-induced ventricular fibrillation."
Keller D.I., Huang H., Zhao J., Frank R., Suarez V., Delacretaz E., Brink M., Osswald S., Schwick N., Chahine M.
Cardiovasc. Res. 70:521-529(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT BRGDA1 SER-1344, VARIANTS ARG-552 AND GLN-1027.
[71]"Compound heterozygous mutations P336L and I1660V in the human cardiac sodium channel associated with the Brugada syndrome."
Cordeiro J.M., Barajas-Martinez H., Hong K., Burashnikov E., Pfeiffer R., Orsino A.M., Wu Y.S., Hu D., Brugada J., Brugada P., Antzelevitch C., Dumaine R., Brugada R.
Circulation 114:2026-2033(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS BRGDA1 LEU-336 AND VAL-1660, CHARACTERIZATION OF VARIANTS BRGDA1 LEU-336 AND VAL-1660.
[72]"Spectrum of pathogenic mutations and associated polymorphisms in a cohort of 44 unrelated patients with long QT syndrome."
Millat G., Chevalier P., Restier-Miron L., Da Costa A., Bouvagnet P., Kugener B., Fayol L., Gonzalez Armengod C., Oddou B., Chanavat V., Froidefond E., Perraudin R., Rousson R., Rodriguez-Lafrasse C.
Clin. Genet. 70:214-227(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS LQT3 VAL-9; GLN-225; ARG-639; TYR-1333; TRP-1609 AND ASN-1819.
[73]"Novel SCN5A gene mutations associated with Brugada syndrome: V95I, A1649V and delF1617."
Liang P., Liu W.L., Hu D.Y., Li C.L., Tao W.H., Li L.
Zhonghua Xin Xue Guan Bing Za Zhi 34:616-619(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS BRGDA1 ILE-95; PHE-1617 DEL AND VAL-1649.
[74]"A novel LQT-3 mutation disrupts an inactivation gate complex with distinct rate-dependent phenotypic consequences."
Bankston J.R., Sampson K.J., Kateriya S., Glaaser I.W., Malito D.L., Chung W.K., Kass R.S.
Channels 1:273-280(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT LQT3 LEU-1904, CHARACTERIZATION OF VARIANT LQT3 LEU-1904.
[75]"A sodium channel pore mutation causing Brugada syndrome."
Pfahnl A.E., Viswanathan P.C., Weiss R., Shang L.L., Sanyal S., Shusterman V., Kornblit C., London B., Dudley S.C. Jr.
Heart Rhythm 4:46-53(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT BRGDA1 ILE-353.
[76]"A novel and lethal de novo LQT-3 mutation in a newborn with distinct molecular pharmacology and therapeutic response."
Bankston J.R., Yue M., Chung W., Spyres M., Pass R.H., Silver E., Sampson K.J., Kass R.S.
PLoS ONE 2:E1258-E1258(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT LQT3 CYS-1473.
[77]"Gene (SCN5A) mutation analysis of a Chinese family with Brugada syndrome."
Tian L., Zhu J.F., Yang J.G.
Zhonghua Xin Xue Guan Bing Za Zhi 35:1122-1125(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT BRGDA1 ASN-1494.
[78]"Correlations between clinical and physiological consequences of the novel mutation R878C in a highly conserved pore residue in the cardiac Na+ channel."
Zhang Y., Wang T., Ma A., Zhou X., Gui J., Wan H., Shi R., Huang C., Grace A.A., Huang C.L., Trump D., Zhang H., Zimmer T., Lei M.
Acta Physiol. 194:311-323(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT BRGDA1 CYS-878.
[79]"Subepicardial phase 0 block and discontinuous transmural conduction underlie right precordial ST-segment elevation by a SCN5A loss-of-function mutation."
Bebarova M., O'Hara T., Geelen J.L.M.C., Jongbloed R.J., Timmermans C., Arens Y.H., Rodriguez L.-M., Rudy Y., Volders P.G.A.
Am. J. Physiol. 295:H48-H58(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT BRGDA1 LEU-2004, CHARACTERIZATION OF VARIANT BRGDA1 LEU-2004.
[80]"Analyses of a novel SCN5A mutation (C1850S): conduction vs. repolarization disorder hypotheses in the Brugada syndrome."
Petitprez S., Jespersen T., Pruvot E., Keller D.I., Corbaz C., Schlapfer J., Abriel H., Kucera J.P.
Cardiovasc. Res. 78:494-504(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT BRGDA1 SER-1850, CHARACTERIZATION OF VARIANT BRGDA1 SER-1850.
[81]"Lidocaine-induced Brugada syndrome phenotype linked to a novel double mutation in the cardiac sodium channel."
Barajas-Martinez H.M., Hu D., Cordeiro J.M., Wu Y., Kovacs R.J., Meltser H., Kui H., Elena B., Brugada R., Antzelevitch C., Dumaine R.
Circ. Res. 103:396-404(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS ILE-232 AND PHE-1308.
[82]"Cardiac sodium channel (SCN5A) variants associated with atrial fibrillation."
Darbar D., Kannankeril P.J., Donahue B.S., Kucera G., Stubblefield T., Haines J.L., George A.L. Jr., Roden D.M.
Circulation 117:1927-1935(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS ATFB10 ILE-138; LYS-428; ASP-445; LYS-470; ASP-572; LYS-655; LYS-1053; ILE-1131; CYS-1826 AND MET-1951, VARIANTS CYS-34; LEU-216; HIS-376; VAL-461; TRP-481; TYR-524; ARG-558; PHE-618; SER-997; TYR-1103; GLN-1193; LEU-1951 AND LEU-2004.
[83]"Cardiac sodium channel mutation in atrial fibrillation."
Ellinor P.T., Nam E.G., Shea M.A., Milan D.J., Ruskin J.N., MacRae C.A.
Heart Rhythm 5:99-105(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT ATFB10 LYS-1987.
[84]"A mutation in the sodium channel is responsible for the association of long QT syndrome and familial atrial fibrillation."
Benito B., Brugada R., Perich R.M., Lizotte E., Cinca J., Mont L., Berruezo A., Tolosana J.M., Freixa X., Brugada P., Brugada J.
Heart Rhythm 5:1434-1440(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT LQT3 CYS-1795.
[85]"In utero onset of long QT syndrome with atrioventricular block and spontaneous or lidocaine-induced ventricular tachycardia: compound effects of hERG pore region mutation and SCN5A N-terminus variant."
Lin M.-T., Wu M.-H., Chang C.-C., Chiu S.-N., Theriault O., Huang H., Christe G., Ficker E., Chahine M.
Heart Rhythm 5:1567-1574(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT LQT3 GLN-43, CHARACTERIZATION OF VARIANT LQT3 GLN-43.
[86]"A novel SCN5A gain-of-function mutation M1875T associated with familial atrial fibrillation."
Makiyama T., Akao M., Shizuta S., Doi T., Nishiyama K., Oka Y., Ohno S., Nishio Y., Tsuji K., Itoh H., Kimura T., Kita T., Horie M.
J. Am. Coll. Cardiol. 52:1326-1334(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT ATRIAL FIBRILLATION THR-1875, CHARACTERIZATION OF VARIANT ATRIAL FIBRILLATION THR-1875.
[87]"The E1784K mutation in SCN5A is associated with mixed clinical phenotype of type 3 long QT syndrome."
Makita N., Behr E., Shimizu W., Horie M., Sunami A., Crotti L., Schulze-Bahr E., Fukuhara S., Mochizuki N., Makiyama T., Itoh H., Christiansen M., McKeown P., Miyamoto K., Kamakura S., Tsutsui H., Schwartz P.J., George A.L. Jr., Roden D.M.
J. Clin. Invest. 118:2219-2229(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT LQT3/BRGDA1/SSS1 LYS-1784.
[88]"SCN5A variants in Japanese patients with left ventricular noncompaction and arrhythmia."
Shan L., Makita N., Xing Y., Watanabe S., Futatani T., Ye F., Saito K., Ibuki K., Watanabe K., Hirono K., Uese K., Ichida F., Miyawaki T., Origasa H., Bowles N.E., Towbin J.A.
Mol. Genet. Metab. 93:468-474(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS ARG-558 AND LEU-1090.
[89]"Cardiac ion channel gene mutations in sudden infant death syndrome."
Otagiri T., Kijima K., Osawa M., Ishii K., Makita N., Matoba R., Umetsu K., Hayasaka K.
Pediatr. Res. 64:482-487(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS SIDS CYS-532; SER-1084 AND SER-1705, CHARACTERIZATION OF VARIANT SIDS SER-1705.
[90]"Sodium channel mutation in irritable bowel syndrome: evidence for an ion channelopathy."
Saito Y.A., Strege P.R., Tester D.J., Locke G.R. III, Talley N.J., Bernard C.E., Rae J.L., Makielski J.C., Ackerman M.J., Farrugia G.
Am. J. Physiol. 296:G211-G218(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT IRRITABLE BOWEL SYNDROME SER-298, CHARACTERIZATION OF VARIANT IRRITABLE BOWEL SYNDROME SER-298.
[91]"Biophysical characterization of a new SCN5A mutation S1333Y in a SIDS infant linked to long QT syndrome."
Huang H., Millat G., Rodriguez-Lafrasse C., Rousson R., Kugener B., Chevalier P., Chahine M.
FEBS Lett. 583:890-896(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT SIDS TYR-1333.
[92]"Type of SCN5A mutation determines clinical severity and degree of conduction slowing in loss-of-function sodium channelopathies."
Meregalli P.G., Tan H.L., Probst V., Koopmann T.T., Tanck M.W., Bhuiyan Z.A., Sacher F., Kyndt F., Schott J.-J., Albuisson J., Mabo P., Bezzina C.R., Le Marec H., Wilde A.A.M.
Heart Rhythm 6:341-348(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS BRGDA1 LYS-161; CYS-367; HIS-367; CYS-514; ARG-752; TRP-1232; ASN-1275; VAL-1319; ARG-1408; TRP-1512; GLY-1714; ARG-1740; GLU-1743 AND THR-1924, VARIANTS PFHB1A LYS-161; CYS-367; HIS-367; CYS-514; ARG-752; TRP-1232; ASN-1275; VAL-1319; ARG-1408; TRP-1512; GLY-1714; ARG-1740; GLU-1743 AND THR-1924.
[93]"Distinct functional defect of three novel Brugada syndrome related cardiac sodium channel mutations."
Hsueh C.H., Chen W.P., Lin J.L., Tsai C.T., Liu Y.B., Juang J.M., Tsao H.M., Su M.J., Lai L.P.
J. Biomed. Sci. 16:23-23(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT BRGDA1 CYS-965, CHARACTERIZATION OF VARIANT BRGDA1 CYS-965.
[94]"A common SCN5A polymorphism modulates the biophysical defects of SCN5A mutations."
Shinlapawittayatorn K., Du X.X., Liu H., Ficker E., Kaufman E.S., Deschenes I.
Heart Rhythm 8:455-462(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION OF VARIANT LQT3 ALA-2006, CHARACTERIZATION OF VARIANT ARG-558.
[95]"Cardiac sinus node dysfunction due to a new mutation of the SCN5A gene."
Selly J.B., Boumahni B., Edmar A., Jamal Bey K., Randrianaivo H., Clerici G., Millat G., Caillet D.
Arch. Pediatr. 19:837-841(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS SSS1 VAL-735 AND ASN-1792.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M77235 mRNA. Translation: AAA58644.1.
AY038064 mRNA. Translation: AAK74065.1.
AY148488 mRNA. Translation: AAN61120.1.
AF482988 mRNA. Translation: AAO91669.1.
AB158469 mRNA. Translation: BAD12084.1.
AB158470 mRNA. Translation: BAD12085.1.
EF629346 mRNA. Translation: ABR15763.1.
EF629347 mRNA. Translation: ABR15764.1.
DQ784809 Genomic DNA. Translation: ABQ01244.1.
EF179185 Genomic DNA. Translation: ABN05288.1.
AP006241 Genomic DNA. No translation available.
BC140813 mRNA. Translation: AAI40814.1.
BC144621 mRNA. Translation: AAI44622.1.
AB208866 mRNA. Translation: BAD92103.1.
PIRA38195.
RefSeqNP_000326.2. NM_000335.4.
NP_001092874.1. NM_001099404.1.
NP_001092875.1. NM_001099405.1.
NP_001153632.1. NM_001160160.1.
NP_001153633.1. NM_001160161.1.
NP_932173.1. NM_198056.2.
UniGeneHs.517898.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2KBINMR-A1773-1865[»]
2L53NMR-B1901-1927[»]
4DCKX-ray2.20A1773-1940[»]
4DJCX-ray1.35B1491-1522[»]
ProteinModelPortalQ14524.
SMRQ14524. Positions 127-272, 354-417, 721-939, 1195-1480, 1521-1773, 1776-1928.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid112236. 10 interactions.
DIPDIP-38416N.
DIP-46144N.
IntActQ14524. 7 interactions.
MINTMINT-249922.

Chemistry

BindingDBQ14524.
ChEMBLCHEMBL2331043.
DrugBankDB00868. Benzonatate.
DB01244. Bepridil.
DB00564. Carbamazepine.
DB00907. Cocaine.
DB00527. Dibucaine.
DB00280. Disopyramide.
DB01228. Encainide.
DB00754. Ethotoin.
DB01195. Flecainide.
DB01320. Fosphenytoin.
DB00473. Hexylcaine.
DB00192. Indecainide.
DB00555. Lamotrigine.
DB00281. Lidocaine.
DB00532. Mephenytoin.
DB00379. Mexiletine.
DB01388. Mibefradil.
DB00680. Moricizine.
DB00776. Oxcarbazepine.
DB00252. Phenytoin.
DB00750. Prilocaine.
DB01035. Procainamide.
DB01182. Propafenone.
DB00908. Quinidine.
DB00740. Riluzole.
DB01056. Tocainide.
DB00661. Verapamil.
GuidetoPHARMACOLOGY582.

Protein family/group databases

TCDB1.A.1.10.3. the voltage-gated ion channel (vic) superfamily.

PTM databases

PhosphoSiteQ14524.

Polymorphism databases

DMDM215273881.

Proteomic databases

PaxDbQ14524.
PRIDEQ14524.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000333535; ENSP00000328968; ENSG00000183873. [Q14524-1]
ENST00000423572; ENSP00000398266; ENSG00000183873. [Q14524-2]
ENST00000443581; ENSP00000397915; ENSG00000183873. [Q14524-2]
GeneID6331.
KEGGhsa:6331.
UCSCuc021wvn.1. human. [Q14524-2]
uc021wvo.1. human. [Q14524-1]

Organism-specific databases

CTD6331.
GeneCardsGC03M038589.
HGNCHGNC:10593. SCN5A.
MIM108770. phenotype.
113900. phenotype.
272120. phenotype.
600163. gene.
601144. phenotype.
601154. phenotype.
603829. phenotype.
603830. phenotype.
608567. phenotype.
614022. phenotype.
neXtProtNX_Q14524.
Orphanet1344. Atrial stand still.
130. Brugada syndrome.
334. Familial atrial fibrillation.
154. Familial isolated dilated cardiomyopathy.
871. Familial progressive cardiac conduction defect.
166282. Familial sick sinus syndrome.
228140. Idiopathic ventricular fibrillation, not Brugada type.
101016. Romano-Ward syndrome.
PharmGKBPA304.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG1226.
HOVERGENHBG053100.
InParanoidQ14524.
KOK04838.
OrthoDBEOG7DJSK9.
PhylomeDBQ14524.

Enzyme and pathway databases

ReactomeREACT_111045. Developmental Biology.

Gene expression databases

ArrayExpressQ14524.
BgeeQ14524.
CleanExHS_SCN5A.
GenevestigatorQ14524.

Family and domain databases

Gene3D1.20.120.350. 4 hits.
InterProIPR027359. Channel_four-helix_dom.
IPR024583. DUF3451.
IPR005821. Ion_trans_dom.
IPR000048. IQ_motif_EF-hand-BS.
IPR008053. Na_channel_a5su.
IPR001696. Na_channel_asu.
IPR010526. Na_trans_assoc.
[Graphical view]
PfamPF11933. DUF3451. 1 hit.
PF00520. Ion_trans. 4 hits.
PF06512. Na_trans_assoc. 1 hit.
[Graphical view]
PRINTSPR00170. NACHANNEL.
PR01666. NACHANNEL5.
SMARTSM00015. IQ. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceQ14524.
GeneWikiNav1.5.
GenomeRNAi6331.
NextBio24578.
PROQ14524.
SOURCESearch...

Entry information

Entry nameSCN5A_HUMAN
AccessionPrimary (citable) accession number: Q14524
Secondary accession number(s): A5H1P8 expand/collapse secondary AC list , A6N922, A6N923, B2RTU0, E7ET19, E9PEF3, E9PEK2, E9PFW7, Q59H93, Q75RX9, Q75RY0, Q86UR3, Q8IZC9, Q96J69
Entry history
Integrated into UniProtKB/Swiss-Prot: December 15, 1998
Last sequence update: November 25, 2008
Last modified: April 16, 2014
This is version 157 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 3

Human chromosome 3: entries, gene names and cross-references to MIM