SubmitCancel

Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.

Q14524

- SCN5A_HUMAN

UniProt

Q14524 - SCN5A_HUMAN

(max 400 entries)x

Your basket is currently empty.

Select item(s) and click on "Add to basket" to create your own collection here
(400 entries max)

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

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. scaffold protein binding Source: BHF-UCL
  9. ubiquitin protein ligase binding Source: BHF-UCL
  10. voltage-gated sodium channel activity Source: UniProtKB
  11. 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
Complete GO annotation...

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; Multi-pass membrane protein 1 Publication

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 126126Cytoplasmic Reviewed predictionAdd
BLAST
Transmembranei127 – 15024Helical; Name=S1 of repeat I; Reviewed predictionAdd
BLAST
Topological domaini151 – 1588Extracellular Reviewed prediction
Transmembranei159 – 17820Helical; Name=S2 of repeat I; Reviewed predictionAdd
BLAST
Topological domaini179 – 19113Cytoplasmic Reviewed predictionAdd
BLAST
Transmembranei192 – 21019Helical; Name=S3 of repeat I; Reviewed predictionAdd
BLAST
Topological domaini211 – 2166Extracellular Reviewed prediction
Transmembranei217 – 23620Helical; Voltage-sensor; Name=S4 of repeat I; Reviewed predictionAdd
BLAST
Topological domaini237 – 25216Cytoplasmic Reviewed predictionAdd
BLAST
Transmembranei253 – 27624Helical; Name=S5 of repeat I; Reviewed predictionAdd
BLAST
Topological domaini277 – 389113Extracellular Reviewed predictionAdd
BLAST
Transmembranei390 – 41526Helical; Name=S6 of repeat I; Reviewed predictionAdd
BLAST
Topological domaini416 – 711296Cytoplasmic Reviewed predictionAdd
BLAST
Transmembranei712 – 73625Helical; Name=S1 of repeat II; Reviewed predictionAdd
BLAST
Topological domaini737 – 74711Extracellular Reviewed predictionAdd
BLAST
Transmembranei748 – 77124Helical; Name=S2 of repeat II; Reviewed predictionAdd
BLAST
Topological domaini772 – 7798Cytoplasmic Reviewed prediction
Transmembranei780 – 79920Helical; Name=S3 of repeat II; Reviewed predictionAdd
BLAST
Topological domaini800 – 8056Extracellular Reviewed prediction
Transmembranei806 – 82520Helical; Voltage-sensor; Name=S4 of repeat II; Reviewed predictionAdd
BLAST
Topological domaini826 – 84116Cytoplasmic Reviewed predictionAdd
BLAST
Transmembranei842 – 86221Helical; Name=S5 of repeat II; Reviewed predictionAdd
BLAST
Topological domaini863 – 91351Extracellular Reviewed predictionAdd
BLAST
Transmembranei914 – 93926Helical; Name=S6 of repeat II; Reviewed predictionAdd
BLAST
Topological domaini940 – 1200261Cytoplasmic Reviewed predictionAdd
BLAST
Transmembranei1201 – 122424Helical; Name=S1 of repeat III; Reviewed predictionAdd
BLAST
Topological domaini1225 – 123713Extracellular Reviewed predictionAdd
BLAST
Transmembranei1238 – 126326Helical; Name=S2 of repeat III; Reviewed predictionAdd
BLAST
Topological domaini1264 – 12696Cytoplasmic Reviewed prediction
Transmembranei1270 – 129122Helical; Name=S3 of repeat III; Reviewed predictionAdd
BLAST
Topological domaini1292 – 12954Extracellular Reviewed prediction
Transmembranei1296 – 131722Helical; Voltage-sensor; Name=S4 of repeat III; Reviewed predictionAdd
BLAST
Topological domaini1318 – 133619Cytoplasmic Reviewed predictionAdd
BLAST
Transmembranei1337 – 135923Helical; Name=S5 of repeat III; Reviewed predictionAdd
BLAST
Topological domaini1360 – 144384Extracellular Reviewed predictionAdd
BLAST
Transmembranei1444 – 147027Helical; Name=S6 of repeat III; Reviewed predictionAdd
BLAST
Topological domaini1471 – 152353Cytoplasmic Reviewed predictionAdd
BLAST
Transmembranei1524 – 154724Helical; Name=S1 of repeat IV; Reviewed predictionAdd
BLAST
Topological domaini1548 – 155811Extracellular Reviewed predictionAdd
BLAST
Transmembranei1559 – 158224Helical; Name=S2 of repeat IV; Reviewed predictionAdd
BLAST
Topological domaini1583 – 15886Cytoplasmic Reviewed prediction
Transmembranei1589 – 161224Helical; Name=S3 of repeat IV; Reviewed predictionAdd
BLAST
Topological domaini1613 – 162210Extracellular Reviewed prediction
Transmembranei1623 – 164422Helical; Voltage-sensor; Name=S4 of repeat IV; Reviewed predictionAdd
BLAST
Topological domaini1645 – 165915Cytoplasmic Reviewed predictionAdd
BLAST
Transmembranei1660 – 168223Helical; Name=S5 of repeat IV; Reviewed predictionAdd
BLAST
Topological domaini1683 – 174765Extracellular Reviewed predictionAdd
BLAST
Transmembranei1748 – 177225Helical; Name=S6 of repeat IV; Reviewed predictionAdd
BLAST
Topological domaini1773 – 2016244Cytoplasmic Reviewed predictionAdd
BLAST

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
Complete GO annotation...

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.
Note: The disease is caused by mutations affecting the gene represented in this entry.6 Publications
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. 2 Publications
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. 2 Publications
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. 1 Publication
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.
Note: The disease is caused by mutations affecting the gene represented in this entry.29 Publications
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. 2 Publications
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. 2 Publications
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.
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. 1 Publication
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. 2 Publications
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. 3 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. 2 Publications
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. 1 Publication
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. 1 Publication
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.
Note: The disease is caused by mutations affecting the gene represented in this entry.26 Publications
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. 2 Publications
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. 2 Publications
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. 2 Publications
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. 2 Publications
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. 3 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. 3 Publications
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. 2 Publications
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. 2 Publications
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. 3 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.
Note: The disease is caused by mutations affecting the gene represented in this entry.4 Publications
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. 2 Publications
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.
Note: The disease is caused by mutations affecting the gene represented in this entry.2 Publications
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.
Note: Disease susceptibility is associated with variations affecting the gene represented in this entry.3 Publications
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.
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.
Note: The disease is caused by mutations affecting the gene represented in this entry.2 Publications
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.
Note: The disease is caused by mutations affecting the gene represented in this entry.3 Publications
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. 1 Publication
Mutagenesisi1802 – 18043DPE → APA: Abolishes calcium response on channel inactivation. 1 Publication
Mutagenesisi1974 – 19741P → A: Strongly reduces interaction with NEDD4, NEDD4L or WWP2. 1 Publication
Mutagenesisi1975 – 19751P → A: Strongly reduces interaction with NEDD4, NEDD4L or WWP2. 1 Publication
Mutagenesisi1976 – 19761S → A: Strongly reduces interaction with NEDD4, NEDD4L or WWP2. 1 Publication
Mutagenesisi1977 – 19771Y → A: Strongly reduces interaction with NEDD4, NEDD4L or WWP2. 2 Publications
Mutagenesisi1978 – 19781D → A: No effect on interaction with NEDD4, NEDD4L or WWP2. 1 Publication
Mutagenesisi1979 – 19791S → A: No effect on interaction with NEDD4, NEDD4L or WWP2. 1 Publication
Mutagenesisi1980 – 19801V → A: No effect on interaction with NEDD4, NEDD4L or WWP2. 2 Publications
Mutagenesisi1980 – 19801V → D or R: Strongly reduces interaction with NEDD4L. 2 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...) Reviewed prediction
Glycosylationi283 – 2831N-linked (GlcNAc...) Reviewed prediction
Glycosylationi288 – 2881N-linked (GlcNAc...) Reviewed prediction
Glycosylationi291 – 2911N-linked (GlcNAc...) Reviewed prediction
Glycosylationi318 – 3181N-linked (GlcNAc...) Reviewed prediction
Glycosylation