Details of Disease

General Information of Disease (ID: DISYJI6J)

• Disease Name: Sinoatrial node disorder
• Synonyms: sinuatrial node; SA node; sinoatrial node disease or disorder; sinoatrial node disease; disorder of sinoatrial node; disease or disorder of sinoatrial node; disease of sinoatrial node
• Definition: A disease involving the sinoatrial node.
• Disease Hierarchy:
  DISWD40R: Disease
  DISLKUNL: Heart arrhythmia
  DISED5HG: Conduction system disorder
  DISYJI6J: Sinoatrial node disorder
• Disease Identifiers:
  MONDO ID: MONDO_0000469
  MESH ID: D012804
  UMLS CUI: C0428908
  MedGen ID: 98448
  SNOMED CT ID: 60423000

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 9 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
CACNA2D1	TTFK1JQ	Disputed	Biomarker	[1]
HCN4	TTQP04A	Disputed	Biomarker	[2]
KCND3	TTPLQO0	Disputed	Biomarker	[3]
SCN10A	TT90XZ8	Disputed	Biomarker	[4]
CACNA1D	TT7RGTM	Strong	Biomarker	[5]
GJA5	TTFQKZ7	Strong	Biomarker	[6]
GJC1	TTEP7OC	Strong	Biomarker	[7]
SCN5A	TTZOVE0	Strong	Genetic Variation	[8]
KCNJ1	TTJ13ST	Definitive	Genetic Variation	[9]

This Disease Is Related to 1 DTP Molecule(s)

Gene Name	DTP ID	Evidence Level	Mode of Inheritance	REF
CACNB2	DTBZWL4	Disputed	Biomarker	[10]

This Disease Is Related to 12 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
GPD1L	OTVLWW9T	Disputed	Biomarker	[11]
KCNJ8	OTZ8G8FE	Disputed	Biomarker	[12]
PKP2	OTJOVF68	Disputed	Biomarker	[13]
SCN1B	OTGD78J3	Disputed	Biomarker	[14]
SCN2B	OTFAHJ38	Disputed	Biomarker	[15]
SCN3B	OTNTQT9O	Disputed	Biomarker	[16]
ANK2	OTWB4R1Y	Strong	Genetic Variation	[17]
GNB2	OT3JPRCQ	Strong	Genetic Variation	[18]
MYH6	OT3YNCH1	Strong	Biomarker	[19]
KCNE2	OTUO214Y	Definitive	Genetic Variation	[20]
NAA50	OTFJ8S47	Definitive	Biomarker	[21]
TLX2	OTPFAUM8	Definitive	Biomarker	[22]

References

• [1] Functional characterization of CaV2 mutations associated with sudden cardiac death.J Biol Chem. 2015 Jan 30;290(5):2854-69. doi: 10.1074/jbc.M114.597930. Epub 2014 Dec 19.
• [2] Targeting miR-423-5p Reverses Exercise Training-Induced HCN4 Channel Remodeling and Sinus Bradycardia.Circ Res. 2017 Oct 13;121(9):1058-1068. doi: 10.1161/CIRCRESAHA.117.311607. Epub 2017 Aug 17.
• [3] Two novel Brugada syndrome-associated mutations increase KV4.3 membrane expression and function.Int J Mol Med. 2015 Jul;36(1):309-15. doi: 10.3892/ijmm.2015.2223. Epub 2015 May 26.
• [4] Association of common and rare variants of SCN10A gene with sudden unexplained nocturnal death syndrome in Chinese Han population.Int J Legal Med. 2017 Jan;131(1):53-60. doi: 10.1007/s00414-016-1397-1. Epub 2016 Jun 7.
• [5] G protein-gated IKACh channels as therapeutic targets for treatment of sick sinus syndrome and heart block.Proc Natl Acad Sci U S A. 2016 Feb 16;113(7):E932-41. doi: 10.1073/pnas.1517181113. Epub 2016 Feb 1.
• [6] Relationship between two arrhythmias: sinus node dysfunction and atrial fibrillation.Arch Med Res. 2014 May;45(4):351-5. doi: 10.1016/j.arcmed.2014.04.005. Epub 2014 May 11.
• [7] Progressive Atrial Conduction Defects Associated With Bone Malformation Caused by a Connexin-45 Mutation.J Am Coll Cardiol. 2017 Jul 18;70(3):358-370. doi: 10.1016/j.jacc.2017.05.039.
• [8] Enhanced closed-state inactivation of mutant cardiac sodium channels (SCN5A N1541D and R1632C) through different mechanisms.J Mol Cell Cardiol. 2019 May;130:88-95. doi: 10.1016/j.yjmcc.2019.03.023. Epub 2019 Mar 30.
• [9] Genetic variation in the inwardly rectifying K channel subunits KCNJ3 (GIRK1) and KCNJ5 (GIRK4) in patients with sinus node dysfunction.Cardiology. 2010;115(3):176-81. doi: 10.1159/000279319. Epub 2010 Jan 29.
• [10] Brugada-like syndrome in infancy presenting with rapid ventricular tachycardia and intraventricular conduction delay.Circulation. 2012 Jan 3;125(1):14-22. doi: 10.1161/CIRCULATIONAHA.111.054007. Epub 2011 Nov 16.
• [11] GPD1L links redox state to cardiac excitability by PKC-dependent phosphorylation of the sodium channel SCN5A.Am J Physiol Heart Circ Physiol. 2009 Oct;297(4):H1446-52. doi: 10.1152/ajpheart.00513.2009. Epub 2009 Aug 7.
• [12] Role of ATP-sensitive K+ channels in cardiac arrhythmias.J Cardiovasc Pharmacol Ther. 2014 May;19(3):237-43. doi: 10.1177/1074248413515078. Epub 2013 Dec 23.
• [13] Epicardial Ventricular Tachycardia Ablation in a Patient With Brugada ECG Pattern and Mutation of PKP2 and DSP Genes.Circ Arrhythm Electrophysiol. 2015 Apr;8(2):505-7. doi: 10.1161/CIRCEP.114.002342.
• [14] Cardiac conduction defects and Brugada syndrome: A family with overlap syndrome carrying a nonsense SCN5A mutation.J Arrhythm. 2017 Feb;33(1):35-39. doi: 10.1016/j.joa.2016.05.007. Epub 2016 Jul 2.
• [15] Scn2b Deletion in Mice Results in Ventricular and Atrial Arrhythmias.Circ Arrhythm Electrophysiol. 2016 Dec;9(12):e003923. doi: 10.1161/CIRCEP.116.003923.
• [16] Embryonic type Na(+) channel -subunit, SCN3B masks the disease phenotype of Brugada syndrome.Sci Rep. 2016 Sep 28;6:34198. doi: 10.1038/srep34198.
• [17] A Novel Mechanism for Human Cardiac Ankyrin-B Syndrome due to Reciprocal Chromosomal Translocation.Heart Lung Circ. 2017 Jun;26(6):612-618. doi: 10.1016/j.hlc.2016.09.013. Epub 2016 Nov 16.
• [18] Exome reports A de novo GNB2 variant associated with global developmental delay, intellectual disability, and dysmorphic features. Eur J Med Genet. 2020 Apr;63(4):103804. doi: 10.1016/j.ejmg.2019.103804. Epub 2019 Nov 4.
• [19] A rare variant in MYH6 is associated with high risk of sick sinus syndrome.Nat Genet. 2011 Mar 6;43(4):316-20. doi: 10.1038/ng.781.
• [20] Pacemaker activity of the human sinoatrial node: effects of HCN4 mutations on the hyperpolarization-activated current.Europace. 2014 Mar;16(3):384-95. doi: 10.1093/europace/eut348.
• [21] Oxidized CaMKII causes cardiac sinus node dysfunction in mice.J Clin Invest. 2011 Aug;121(8):3277-88. doi: 10.1172/JCI57833. Epub 2011 Jul 25.
• [22] Heterogeneity of transverse-axial tubule system in mouse atria: Remodeling in atrial-specific Na(+)-Ca(2+) exchanger knockout mice.J Mol Cell Cardiol. 2017 Jul;108:50-60. doi: 10.1016/j.yjmcc.2017.05.008. Epub 2017 May 19.