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Q14524

- SCN5A_HUMAN

UniProt

Q14524 - SCN5A_HUMAN

Protein

Sodium channel protein type 5 subunit alpha

Gene

SCN5A

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 162 (01 Oct 2014)
      Sequence version 2 (25 Nov 2008)
      Previous versions | rss
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    Functioni

    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.1 Publication

    GO - Molecular functioni

    1. ankyrin binding Source: BHF-UCL
    2. calmodulin binding Source: BHF-UCL
    3. enzyme binding Source: BHF-UCL
    4. fibroblast growth factor binding Source: BHF-UCL
    5. ion channel binding Source: BHF-UCL
    6. nitric-oxide synthase binding Source: BHF-UCL
    7. protein binding Source: IntAct
    8. protein kinase binding Source: BHF-UCL
    9. scaffold protein binding Source: BHF-UCL
    10. ubiquitin protein ligase binding Source: BHF-UCL
    11. voltage-gated sodium channel activity Source: UniProtKB
    12. voltage-gated sodium channel activity involved in cardiac muscle cell action potential Source: BHF-UCL

    GO - Biological processi

    1. AV node cell to bundle of His cell communication Source: BHF-UCL
    2. brainstem development Source: BHF-UCL
    3. bundle of His cell to Purkinje myocyte communication Source: BHF-UCL
    4. cardiac muscle cell action potential involved in contraction Source: BHF-UCL
    5. cardiac muscle contraction Source: BHF-UCL
    6. cardiac ventricle development Source: BHF-UCL
    7. cellular response to calcium ion Source: UniProtKB
    8. cerebellum development Source: BHF-UCL
    9. membrane depolarization Source: BHF-UCL
    10. membrane depolarization during action potential Source: BHF-UCL
    11. membrane depolarization during cardiac muscle cell action potential Source: BHF-UCL
    12. membrane depolarization during SA node cell action potential Source: BHF-UCL
    13. neuronal action potential Source: RefGenome
    14. odontogenesis of dentin-containing tooth Source: BHF-UCL
    15. positive regulation of action potential Source: BHF-UCL
    16. positive regulation of epithelial cell proliferation Source: BHF-UCL
    17. positive regulation of sodium ion transport Source: BHF-UCL
    18. regulation of atrial cardiac muscle cell membrane depolarization Source: BHF-UCL
    19. regulation of atrial cardiac muscle cell membrane repolarization Source: BHF-UCL
    20. regulation of cardiac muscle cell contraction Source: BHF-UCL
    21. regulation of heart rate Source: BHF-UCL
    22. regulation of heart rate by cardiac conduction Source: BHF-UCL
    23. regulation of sodium ion transmembrane transport Source: BHF-UCL
    24. regulation of ventricular cardiac muscle cell membrane depolarization Source: BHF-UCL
    25. regulation of ventricular cardiac muscle cell membrane repolarization Source: BHF-UCL
    26. response to denervation involved in regulation of muscle adaptation Source: BHF-UCL
    27. SA node cell to atrial cardiac muscle cell communication Source: BHF-UCL
    28. sodium ion transmembrane transport Source: BHF-UCL
    29. sodium ion transport Source: UniProtKB
    30. telencephalon development Source: BHF-UCL
    31. ventricular cardiac muscle cell action potential Source: BHF-UCL

    Keywords - Molecular functioni

    Ion channel, Sodium channel, Voltage-gated channel

    Keywords - Biological processi

    Ion transport, Sodium transport, Transport

    Keywords - Ligandi

    Calmodulin-binding, Sodium

    Enzyme and pathway databases

    ReactomeiREACT_22266. Interaction between L1 and Ankyrins.

    Protein family/group databases

    TCDBi1.A.1.10.3. the voltage-gated ion channel (vic) superfamily.

    Names & Taxonomyi

    Protein namesi
    Recommended 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 namesi
    Name:SCN5A
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 3

    Organism-specific databases

    HGNCiHGNC:10593. SCN5A.

    Subcellular locationi

    Membrane 1 Publication; Multi-pass membrane protein 1 Publication

    GO - Cellular componenti

    1. caveola Source: BHF-UCL
    2. cell surface Source: BHF-UCL
    3. endoplasmic reticulum Source: BHF-UCL
    4. integral component of membrane Source: UniProtKB
    5. intercalated disc Source: BHF-UCL
    6. lateral plasma membrane Source: BHF-UCL
    7. plasma membrane Source: BHF-UCL
    8. sarcolemma Source: BHF-UCL
    9. T-tubule Source: BHF-UCL
    10. voltage-gated sodium channel complex Source: BHF-UCL

    Keywords - Cellular componenti

    Membrane

    Pathology & Biotechi

    Involvement in diseasei

    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.3 Publications
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti161 – 1611E → K in BRGDA1 and PFHB1A. 2 Publications
    VAR_026344
    Natural varianti212 – 2121L → P in PFHB1A.
    VAR_055162
    Natural varianti225 – 2251R → W in PFHB1A. 1 Publication
    VAR_055164
    Natural varianti298 – 2981G → 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. 1 Publication
    VAR_017671
    Natural varianti512 – 5121T → 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. 1 Publication
    VAR_036662
    Natural varianti514 – 5141G → C in BRGDA1 and PFHB1A. 1 Publication
    VAR_017673
    Natural varianti752 – 7521G → R in BRGDA1 and PFHB1A. 2 Publications
    VAR_026361
    Natural varianti1232 – 12321R → W in BRGDA1 and PFHB1A. 2 Publications
    VAR_017679
    Natural varianti1275 – 12751D → N in CMD1E, BRGDA1, PFHB1A and ATRST1; in familial atrial standstill is found in association with polymorphisms in the regulatory region of GJA5. 3 Publications
    VAR_026373
    Natural varianti1595 – 15951D → N in PFHB1A; significant defect in the kinetics of fast-channel inactivation distinct from mutations reported in LQT3.
    VAR_017683
    Natural varianti1620 – 16201T → K in LQT3 and PFHB1A.
    VAR_055201
    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.21 Publications
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti9 – 91G → V in LQT3. 1 Publication
    VAR_036660
    Natural varianti18 – 181R → W in LQT3. 1 Publication
    VAR_068325
    Natural varianti43 – 431R → Q in LQT3; does not affect baseline kinetics of sodium currents; causes an unusual hyperpolarizing shift of the activation kinetics after lidocaine treatment. 1 Publication
    VAR_055159
    Natural varianti125 – 1251V → L in LQT3. 1 Publication
    VAR_068326
    Natural varianti225 – 2251R → Q in LQT3. 1 Publication
    VAR_036661
    Natural varianti245 – 2451Q → K in LQT3. 1 Publication
    VAR_068327
    Natural varianti404 – 4041L → Q in LQT3. 1 Publication
    VAR_068328
    Natural varianti406 – 4061N → K in LQT3. 1 Publication
    VAR_055170
    Natural varianti411 – 4111V → M in LQT3. 1 Publication
    VAR_068329
    Natural varianti462 – 4621E → K in LQT3. 1 Publication
    VAR_068330
    Natural varianti572 – 5721A → D in LQT3 and ATFB10. 2 Publications
    Corresponds to variant rs36210423 [ dbSNP | Ensembl ].
    VAR_055178
    Natural varianti586 – 5872Missing in LQT3.
    VAR_055179
    Natural varianti615 – 6151G → E in LQT3; drug-induced LQT syndrome. 2 Publications
    Corresponds to variant rs12720452 [ dbSNP | Ensembl ].
    VAR_026358
    Natural varianti619 – 6191L → F in LQT3. 2 Publications
    VAR_015682
    Natural varianti637 – 6371P → L in LQT3. 1 Publication
    VAR_068331
    Natural varianti639 – 6391G → R in LQT3. 1 Publication
    VAR_036664
    Natural varianti648 – 6481P → L in LQT3. 1 Publication
    VAR_068332
    Natural varianti680 – 6801R → H in LQT3.
    VAR_055181
    Natural varianti941 – 9411S → N in LQT3; also in SIDS. 1 Publication
    VAR_017675
    Natural varianti971 – 9711R → C in LQT3. 1 Publication
    VAR_068333
    Natural varianti997 – 9971A → 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. 1 Publication
    VAR_017676
    Natural varianti1069 – 10691T → M in LQT3. 1 Publication
    VAR_068334
    Natural varianti1114 – 11141D → N in LQT3. 1 Publication
    VAR_009935
    Natural varianti1193 – 11931R → 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. 1 Publication
    Corresponds to variant rs41261344 [ dbSNP | Ensembl ].
    VAR_017678
    Natural varianti1225 – 12251E → K in BRGDA1 and LQT3. 2 Publications
    VAR_026369
    Natural varianti1231 – 12311E → K in LQT3. 1 Publication
    VAR_068335
    Natural varianti1250 – 12501F → L in LQT3; drug-induced LQT syndrome. 1 Publication
    Corresponds to variant rs45589741 [ dbSNP | Ensembl ].
    VAR_026372
    Natural varianti1295 – 12951E → K in LQT3; causes significant positive shifts in the half-maximal voltage of steady-state inactivation and activation. 1 Publication
    VAR_055187
    Natural varianti1304 – 13041T → M in LQT3. 1 Publication
    VAR_008956
    Natural varianti1325 – 13251N → S in LQT3. 1 Publication
    Corresponds to variant rs28937317 [ dbSNP | Ensembl ].
    VAR_001577
    Natural varianti1330 – 13301A → P in LQT3.
    VAR_055189
    Natural varianti1330 – 13301A → T in LQT3.
    VAR_055190
    Natural varianti1332 – 13321P → L in LQT3.
    VAR_055191
    Natural varianti1333 – 13331S → Y in LQT3 and SIDS. 2 Publications
    VAR_036666
    Natural varianti1458 – 14581S → Y in LQT3. 1 Publication
    VAR_068336
    Natural varianti1473 – 14731F → C in LQT3. 1 Publication
    VAR_055194
    Natural varianti1481 – 14811G → E in LQT3. 1 Publication
    VAR_068337
    Natural varianti1486 – 14861F → L in LQT3.
    VAR_055195
    Natural varianti1501 – 15011L → V in LQT3. 1 Publication
    VAR_009936
    Natural varianti1505 – 15073Missing in LQT3. 1 Publication
    VAR_001576
    Natural varianti1507 – 15093Missing in LQT3.
    VAR_055197
    Natural varianti1595 – 15951D → N in PFHB1A; significant defect in the kinetics of fast-channel inactivation distinct from mutations reported in LQT3.
    VAR_017683
    Natural varianti1609 – 16091S → W in LQT3. 1 Publication
    VAR_036667
    Natural varianti1617 – 16171Missing in LQT3 and BRGDA1. 1 Publication
    VAR_055200
    Natural varianti1620 – 16201T → K in LQT3 and PFHB1A.
    VAR_055201
    Natural varianti1623 – 16231R → L in LQT3. 2 Publications
    VAR_009937
    Natural varianti1623 – 16231R → Q in LQT3. 2 Publications
    VAR_001578
    Natural varianti1626 – 16261R → P in LQT3.
    VAR_055202
    Natural varianti1644 – 16441R → C in LQT3 and BRGDA1.
    VAR_055203
    Natural varianti1644 – 16441R → H in LQT3. 2 Publications
    Corresponds to variant rs28937316 [ dbSNP | Ensembl ].
    VAR_001579
    Natural varianti1645 – 16451T → M in LQT3. 1 Publication
    VAR_008958
    Natural varianti1652 – 16521M → R in LQT3.
    VAR_055205
    Natural varianti1667 – 16671V → I in LQT3. 1 Publication
    VAR_068338
    Natural varianti1763 – 17631V → M in LQT3. 1 Publication
    VAR_055209
    Natural varianti1766 – 17661M → L in LQT3; affects protein trafficking. 1 Publication
    VAR_055210
    Natural varianti1768 – 17681I → 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. 1 Publication
    VAR_055211
    Natural varianti1777 – 17771V → M in LQT3. 1 Publication
    VAR_055212
    Natural varianti1779 – 17791T → M in LQT3. 1 Publication
    VAR_068339
    Natural varianti1784 – 17841E → K in LQT3 and BRGDA1. 4 Publications
    VAR_008959
    Natural varianti1787 – 17871S → N in LQT3. 1 Publication
    VAR_009938
    Natural varianti1790 – 17901D → G in LQT3. 1 Publication
    VAR_001580
    Natural varianti1795 – 17951Y → 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. 2 Publications
    VAR_019123
    Natural varianti1795 – 17951Y → 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.
    VAR_017686
    Natural varianti1819 – 18191D → N in LQT3; digenic; associated with Gly-100 mutation on the KCNH2 gene. 1 Publication
    VAR_036668
    Natural varianti1825 – 18251L → P in LQT3; drug-induced LQT syndrome.
    VAR_055213
    Natural varianti1826 – 18261R → H in LQT3; sodium current characterized by slower decay and a 2- to 3-fold increase in late sodium current.
    VAR_017687
    Natural varianti1839 – 18391D → G in LQT3. 1 Publication
    VAR_001581
    Natural varianti1904 – 19041S → L in LQT3; promotes late sodium currents by increasing the propensity of the channel to reopen during prolonged depolarization. 1 Publication
    VAR_055217
    Natural varianti1909 – 19091Q → R in LQT3. 1 Publication
    VAR_068340
    Natural varianti1949 – 19491A → S in LQT3. 1 Publication
    VAR_068341
    Natural varianti1951 – 19511V → L in BRGDA1 and LQT3; also found in patients with atrial fibrillation. 2 Publications
    Corresponds to variant rs41315493 [ dbSNP | Ensembl ].
    VAR_026386
    Natural varianti1958 – 19581R → Q in LQT3. 1 Publication
    VAR_068342
    Natural varianti2004 – 20041F → 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. 2 Publications
    Corresponds to variant rs41311117 [ dbSNP | Ensembl ].
    VAR_055221
    Natural varianti2006 – 20061P → A in LQT3; causes an increase of persistent sodium current and produces a depolarizing shift in voltage dependence of inactivation.
    VAR_055222
    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.22 Publications
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti27 – 271R → H in BRGDA1. 1 Publication
    VAR_026341
    Natural varianti95 – 951V → I in BRGDA1. 1 Publication
    VAR_055160
    Natural varianti126 – 1261K → E in BRGDA1. 1 Publication
    VAR_026343
    Natural varianti161 – 1611E → K in BRGDA1 and PFHB1A. 2 Publications
    VAR_026344
    Natural varianti187 – 1871T → I in BRGDA1; loss of function. 1 Publication
    VAR_026345
    Natural varianti226 – 2261A → V in BRGDA1. 1 Publication
    VAR_026346
    Natural varianti230 – 2301I → V in BRGDA1. 1 Publication
    VAR_026347
    Natural varianti282 – 2821R → H in BRGDA1. 1 Publication
    VAR_026348
    Natural varianti294 – 2941V → M in BRGDA1. 1 Publication
    VAR_026349
    Natural varianti319 – 3191G → S in BRGDA1. 1 Publication
    VAR_026350
    Natural varianti325 – 3251L → R in BRGDA1.
    VAR_055166
    Natural varianti336 – 3361P → 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. 2 Publications
    VAR_055167
    Natural varianti351 – 3511G → V in BRGDA1; 7-fold current reduction. 1 Publication
    VAR_026351
    Natural varianti353 – 3531T → I in BRGDA1. 1 Publication
    VAR_055168
    Natural varianti356 – 3561D → N in BRGDA1; loss of function. 1 Publication
    VAR_026352
    Natural varianti367 – 3671R → C in BRGDA1; express no current. 2 Publications
    Corresponds to variant rs28937318 [ dbSNP | Ensembl ].
    VAR_026353
    Natural varianti367 – 3671R → H in BRGDA1; express no current. 1 Publication
    Corresponds to variant rs28937318 [ dbSNP | Ensembl ].
    VAR_017672
    Natural varianti369 – 3691M → K in BRGDA1. 1 Publication
    VAR_026354
    Natural varianti393 – 3931Missing in BRGDA1. 1 Publication
    VAR_026355
    Natural varianti406 – 4061N → S in BRGDA1.
    VAR_055171
    Natural varianti514 – 5141G → C in BRGDA1 and PFHB1A. 1 Publication
    VAR_017673
    Natural varianti567 – 5671L → Q in BRGDA1. 1 Publication
    VAR_026357
    Natural varianti681 – 6811H → P in BRGDA1. 1 Publication
    VAR_026359
    Natural varianti735 – 7351A → E in BRGDA1. 1 Publication
    VAR_026360
    Natural varianti735 – 7351A → 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. 1 Publication
    VAR_017674
    Natural varianti752 – 7521G → R in BRGDA1 and PFHB1A. 2 Publications
    VAR_026361
    Natural varianti814 – 8141R → Q in BRGDA1.
    VAR_055182
    Natural varianti851 – 8511F → L in BRGDA1. 1 Publication
    VAR_026362
    Natural varianti878 – 8781R → C in BRGDA1. 1 Publication
    VAR_055183
    Natural varianti892 – 8921F → I in BRGDA1. 1 Publication
    VAR_026363
    Natural varianti896 – 8961C → S in BRGDA1. 1 Publication
    VAR_026364
    Natural varianti910 – 9101S → L in BRGDA1. 1 Publication
    VAR_026365
    Natural varianti965 – 9651R → C in BRGDA1; steady state inactivation shifted to a more negative potential; slower recovery from inactivation. 2 Publications
    VAR_026366
    Natural varianti1023 – 10231R → H in BRGDA1.
    VAR_055184
    Natural varianti1053 – 10531E → K in BRGDA1 and ATFB10; abolishes binding to ANK3 and also prevents accumulation of SCN5A at cell surface sites in ventricular cardiomyocytes. 3 Publications
    VAR_026368
    Natural varianti1193 – 11931R → 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. 1 Publication
    Corresponds to variant rs41261344 [ dbSNP | Ensembl ].
    VAR_017678
    Natural varianti1225 – 12251E → K in BRGDA1 and LQT3. 2 Publications
    VAR_026369
    Natural varianti1232 – 12321R → W in BRGDA1 and PFHB1A. 2 Publications
    VAR_017679
    Natural varianti1236 – 12361K → N in BRGDA1. 1 Publication
    VAR_026370
    Natural varianti1240 – 12401E → Q in BRGDA1. 1 Publication
    VAR_026371
    Natural varianti1262 – 12621G → S in BRGDA1. 1 Publication
    VAR_036665
    Natural varianti1275 – 12751D → N in CMD1E, BRGDA1, PFHB1A and ATRST1; in familial atrial standstill is found in association with polymorphisms in the regulatory region of GJA5. 3 Publications
    VAR_026373
    Natural varianti1293 – 12931F → S in BRGDA1. 1 Publication
    Corresponds to variant rs41311127 [ dbSNP | Ensembl ].
    VAR_026374
    Natural varianti1319 – 13191G → V in BRGDA1. 2 Publications
    VAR_026375
    Natural varianti1344 – 13441F → S in BRGDA1. 1 Publication
    VAR_026376
    Natural varianti1382 – 13821S → I in BRGDA1. 1 Publication
    VAR_026377
    Natural varianti1405 – 14051V → L in BRGDA1. 1 Publication
    VAR_026378
    Natural varianti1406 – 14061G → R in BRGDA1. 1 Publication
    VAR_026379
    Natural varianti1408 – 14081G → R in SSS1 and BRGDA1; also in cardiac conduction defect. 3 Publications
    Corresponds to variant rs28936971 [ dbSNP | Ensembl ].
    VAR_017681
    Natural varianti1432 – 14321R → G in BRGDA1.
    VAR_055192
    Natural varianti1438 – 14381P → L in BRGDA1.
    VAR_055193
    Natural varianti1479 – 14791Missing in BRGDA1. 1 Publication
    VAR_026380
    Natural varianti1494 – 14941Y → N in BRGDA1. 1 Publication
    VAR_055196
    Natural varianti1500 – 15001Missing in BRGDA1. 1 Publication
    VAR_026381
    Natural varianti1502 – 15021G → S in BRGDA1. 1 Publication
    VAR_026382
    Natural varianti1512 – 15121R → W in BRGDA1; significantly affects cardiac sodium channel characteristics; associated with an increase in inward sodium current during the action potential upstroke. 2 Publications
    VAR_017682
    Natural varianti1527 – 15271K → R in BRGDA1; asymptomatic patient; associated with P-1569. 1 Publication
    VAR_055198
    Natural varianti1569 – 15691A → P in BRGDA1; asymptomatic patient; associated with R-1527. 1 Publication
    VAR_055199
    Natural varianti1617 – 16171Missing in LQT3 and BRGDA1. 1 Publication
    VAR_055200
    Natural varianti1620 – 16201T → M in BRGDA1; arrhythmogenicity revealed only at temperatures approaching the physiologic range. 1 Publication
    VAR_017684
    Natural varianti1644 – 16441R → C in LQT3 and BRGDA1.
    VAR_055203
    Natural varianti1649 – 16491A → V in BRGDA1. 1 Publication
    VAR_055204
    Natural varianti1660 – 16601I → 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. 1 Publication
    VAR_055206
    Natural varianti1714 – 17141D → G in BRGDA1; strong decrease of current density; does not affect ion selectivity properties. 2 Publications
    VAR_026383
    Natural varianti1740 – 17401G → R in BRGDA1. 2 Publications
    VAR_026384
    Natural varianti1743 – 17431G → E in BRGDA1. 2 Publications
    VAR_026385
    Natural varianti1743 – 17431G → R in BRGDA1; yields nearly undetectable currents in transfected cells. 1 Publication
    VAR_055208
    Natural varianti1784 – 17841E → K in LQT3 and BRGDA1. 4 Publications
    VAR_008959
    Natural varianti1795 – 17951Y → 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. 1 Publication
    VAR_019124
    Natural varianti1795 – 17951Y → 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.
    VAR_017686
    Natural varianti1850 – 18501C → S in BRGDA1; decreased I(Na) density; shift of the steady-state inactivation towards negative potentials. 1 Publication
    VAR_055215
    Natural varianti1924 – 19241A → T in BRGDA1; significantly affect cardiac sodium channel characteristics; associated with an increase in inward sodium current during the action potential upstroke. 2 Publications
    VAR_017688
    Natural varianti1935 – 19351G → S in BRGDA1.
    VAR_055218
    Natural varianti1951 – 19511V → L in BRGDA1 and LQT3; also found in patients with atrial fibrillation. 2 Publications
    Corresponds to variant rs41315493 [ dbSNP | Ensembl ].
    VAR_026386
    Natural varianti1968 – 19681I → S in BRGDA1.
    VAR_055220
    Natural varianti2004 – 20041F → 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. 2 Publications
    Corresponds to variant rs41311117 [ dbSNP | Ensembl ].
    VAR_055221
    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.2 Publications
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti220 – 2201T → I in SSS1. 1 Publication
    Corresponds to variant rs45620037 [ dbSNP | Ensembl ].
    VAR_017670
    Natural varianti735 – 7351A → 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. 1 Publication
    VAR_017674
    Natural varianti1298 – 12981P → L in SSS1. 1 Publication
    Corresponds to variant rs28937319 [ dbSNP | Ensembl ].
    VAR_017680
    Natural varianti1408 – 14081G → R in SSS1 and BRGDA1; also in cardiac conduction defect. 3 Publications
    Corresponds to variant rs28936971 [ dbSNP | Ensembl ].
    VAR_017681
    Natural varianti1792 – 17921D → N in SSS1. 1 Publication
    VAR_068475
    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.1 Publication
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti1710 – 17101S → L in VF1. 1 Publication
    VAR_017685
    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.2 Publications
    Note: Disease susceptibility is associated with variations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti532 – 5321F → C in SIDS. 1 Publication
    VAR_055177
    Natural varianti941 – 9411S → N in LQT3; also in SIDS. 1 Publication
    VAR_017675
    Natural varianti1084 – 10841G → S in SIDS; may be a rare polymorphism. 1 Publication
    VAR_055185
    Natural varianti1333 – 13331S → Y in LQT3 and SIDS. 2 Publications
    VAR_036666
    Natural varianti1705 – 17051F → S in SIDS; causes a hyperpolarizing shift of steady-state inactivation and delayed recovery from inactivation. 1 Publication
    VAR_055207
    Atrial standstill 1 (ATRST1) [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.1 Publication
    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.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti1275 – 12751D → N in CMD1E, BRGDA1, PFHB1A and ATRST1; in familial atrial standstill is found in association with polymorphisms in the regulatory region of GJA5. 3 Publications
    VAR_026373
    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.1 Publication
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti1275 – 12751D → N in CMD1E, BRGDA1, PFHB1A and ATRST1; in familial atrial standstill is found in association with polymorphisms in the regulatory region of GJA5. 3 Publications
    VAR_026373
    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.2 Publications
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti138 – 1381M → I in ATFB10. 1 Publication
    VAR_055161
    Natural varianti428 – 4281E → K in ATFB10. 1 Publication
    VAR_055172
    Natural varianti445 – 4451H → D in ATFB10. 1 Publication
    VAR_055173
    Natural varianti470 – 4701N → K in ATFB10. 1 Publication
    VAR_055175
    Natural varianti572 – 5721A → D in LQT3 and ATFB10. 2 Publications
    Corresponds to variant rs36210423 [ dbSNP | Ensembl ].
    VAR_055178
    Natural varianti655 – 6551E → K in ATFB10. 1 Publication
    VAR_055180
    Natural varianti1053 – 10531E → K in BRGDA1 and ATFB10; abolishes binding to ANK3 and also prevents accumulation of SCN5A at cell surface sites in ventricular cardiomyocytes. 3 Publications
    VAR_026368
    Natural varianti1131 – 11311T → I in ATFB10. 1 Publication
    VAR_055186
    Natural varianti1826 – 18261R → C in ATFB10. 1 Publication
    VAR_055214
    Natural varianti1951 – 19511V → M in ATFB10. 1 Publication
    Corresponds to variant rs41315493 [ dbSNP | Ensembl ].
    VAR_055219
    Natural varianti1987 – 19871N → K in ATFB10. 1 Publication
    VAR_065865

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi1476 – 14761Q → K: Induces accelerated recovery from channel fast inactivation. 2 Publications
    Mutagenesisi1802 – 18043DPE → APA: Abolishes calcium response on channel inactivation. 1 Publication
    Mutagenesisi1974 – 19741P → A: Strongly reduces interaction with NEDD4, NEDD4L or WWP2. 2 Publications
    Mutagenesisi1975 – 19751P → A: Strongly reduces interaction with NEDD4, NEDD4L or WWP2. 2 Publications
    Mutagenesisi1976 – 19761S → A: Strongly reduces interaction with NEDD4, NEDD4L or WWP2. 2 Publications
    Mutagenesisi1977 – 19771Y → A: Strongly reduces interaction with NEDD4, NEDD4L or WWP2. 3 Publications
    Mutagenesisi1978 – 19781D → A: No effect on interaction with NEDD4, NEDD4L or WWP2. 2 Publications
    Mutagenesisi1979 – 19791S → A: No effect on interaction with NEDD4, NEDD4L or WWP2. 2 Publications
    Mutagenesisi1980 – 19801V → A: No effect on interaction with NEDD4, NEDD4L or WWP2. 3 Publications
    Mutagenesisi1980 – 19801V → D or R: Strongly reduces interaction with NEDD4L. 3 Publications

    Keywords - Diseasei

    Atrial fibrillation, Brugada syndrome, Cardiomyopathy, Disease mutation, Long QT syndrome

    Organism-specific databases

    MIMi108770. phenotype.
    113900. phenotype.
    272120. phenotype.
    601144. phenotype.
    601154. phenotype.
    603829. phenotype.
    603830. phenotype.
    608567. phenotype.
    614022. phenotype.
    Orphaneti1344. 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.
    PharmGKBiPA304.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 20162016Sodium channel protein type 5 subunit alphaPRO_0000048497Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei36 – 361Phosphoserine1 Publication
    Modified residuei38 – 381Phosphothreonine1 Publication
    Glycosylationi214 – 2141N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi283 – 2831N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi288 – 2881N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi291 – 2911N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi318 – 3181N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi328 – 3281N-linked (GlcNAc...)Sequence Analysis
    Modified residuei457 – 4571Phosphoserine1 Publication
    Modified residuei460 – 4601Phosphoserine1 Publication
    Modified residuei483 – 4831Phosphoserine1 Publication
    Modified residuei484 – 4841Phosphoserine1 Publication
    Modified residuei497 – 4971Phosphoserine1 Publication
    Modified residuei510 – 5101Phosphoserine1 Publication
    Modified residuei513 – 5131Dimethylated arginine; alternate1 Publication
    Modified residuei513 – 5131Omega-N-methylarginine; alternate1 Publication
    Modified residuei526 – 5261Dimethylated arginine; alternate1 Publication
    Modified residuei526 – 5261Omega-N-methylarginine; alternate1 Publication
    Modified residuei571 – 5711Phosphoserine1 Publication
    Modified residuei664 – 6641Phosphoserine1 Publication
    Modified residuei667 – 6671Phosphoserine1 Publication
    Modified residuei680 – 6801Dimethylated arginine; alternate1 Publication
    Modified residuei680 – 6801Omega-N-methylarginine; alternate1 Publication
    Glycosylationi740 – 7401N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi803 – 8031N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi864 – 8641N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi1365 – 13651N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi1374 – 13741N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi1380 – 13801N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi1388 – 13881N-linked (GlcNAc...)Sequence Analysis
    Modified residuei1503 – 15031Phosphoserine; by PKCBy similarity
    Glycosylationi1736 – 17361N-linked (GlcNAc...)Sequence Analysis

    Post-translational modificationi

    Regulated through phosphorylation by CaMK2D.By similarity
    Ubiquitinated by NEDD4L; which promotes its endocytosis. Does not seem to be ubiquitinated by NEDD4 or WWP2.2 Publications
    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

    Keywords - PTMi

    Glycoprotein, Methylation, Phosphoprotein, Ubl conjugation

    Proteomic databases

    PaxDbiQ14524.
    PRIDEiQ14524.

    PTM databases

    PhosphoSiteiQ14524.

    Expressioni

    Tissue specificityi

    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.1 Publication

    Gene expression databases

    ArrayExpressiQ14524.
    BgeeiQ14524.
    CleanExiHS_SCN5A.
    GenevestigatoriQ14524.

    Interactioni

    Subunit structurei

    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.By similarity6 Publications