KCNE5 (potassium voltage-gated channel subfamily E regulatory subunit 5)

Gene

• Entrez ID: 23630
• Gene name: Potassium voltage-gated channel subfamily E regulatory subunit 5
• Gene symbol: KCNE5
• Synonyms (NCBI Gene): KCNE1L
• Chromosome: X
• Chromosome location: Xq23
• Summary: This gene encodes a member of a family of single pass transmembrane domain proteins that function as ancillary subunits to voltage-gated potassium channels. Members of this family affect diverse processes in potassium channel regulation, including ion sel

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0005249	Function	Voltage-gated potassium channel activity	IEA
GO:0005251	Function	Delayed rectifier potassium channel activity	IBA
GO:0005515	Function	Protein binding	IPI	20533308, 32296183
GO:0005886	Component	Plasma membrane	IDA	20533308
GO:0006811	Process	Monoatomic ion transport	IEA
GO:0008016	Process	Regulation of heart contraction	IMP	18313602
GO:0008076	Component	Voltage-gated potassium channel complex	IBA
GO:0008076	Component	Voltage-gated potassium channel complex	IDA	12324418, 21493962
GO:0015459	Function	Potassium channel regulator activity	IBA
GO:0015459	Function	Potassium channel regulator activity	IDA	12324418, 18313602, 21493962
GO:0015459	Function	Potassium channel regulator activity	IEA
GO:0016020	Component	Membrane	IEA
GO:0044325	Function	Transmembrane transporter binding	IBA
GO:0044325	Function	Transmembrane transporter binding	IPI	12324418
GO:0060048	Process	Cardiac muscle contraction	IMP	18313602
GO:0060306	Process	Regulation of membrane repolarization	IDA	21493962
GO:0060307	Process	Regulation of ventricular cardiac muscle cell membrane repolarization	IBA
GO:0060307	Process	Regulation of ventricular cardiac muscle cell membrane repolarization	IMP	21493962
GO:0060372	Process	Regulation of atrial cardiac muscle cell membrane repolarization	IMP	18313602
GO:0086005	Process	Ventricular cardiac muscle cell action potential	IBA
GO:0086005	Process	Ventricular cardiac muscle cell action potential	IMP	21493962
GO:0086011	Process	Membrane repolarization during action potential	IBA
GO:0086014	Process	Atrial cardiac muscle cell action potential	IMP	18313602
GO:0086091	Process	Regulation of heart rate by cardiac conduction	IBA
GO:0086091	Process	Regulation of heart rate by cardiac conduction	IMP	18313602, 21493962
GO:0097623	Process	Potassium ion export across plasma membrane	IBA
GO:0098915	Process	Membrane repolarization during ventricular cardiac muscle cell action potential	IEA
GO:1901379	Process	Regulation of potassium ion transmembrane transport	IDA	12324418, 21493962
GO:1901380	Process	Negative regulation of potassium ion transmembrane transport	IDA	12324418, 18313602
GO:1901381	Process	Positive regulation of potassium ion transmembrane transport	IDA	12324418
GO:1902282	Function	Voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarization	IBA
GO:1903765	Process	Negative regulation of potassium ion export across plasma membrane	IDA	18313602

Other IDs

• MIM: 300328
• HGNC: 6241
• e!Ensembl: ENSG00000176076

Protein

• UniProt ID: Q9UJ90
• Protein name: Potassium voltage-gated channel subfamily E regulatory beta subunit 5 (AMME syndrome candidate gene 2 protein) (Potassium channel subunit beta MiRP4) (Potassium voltage-gated channel subfamily E member 1-like protein)
• Protein function: Potassium channel ancillary subunit that is essential for generation of some native K(+) currents by virtue of formation of heteromeric ion channel complex with voltage-gated potassium (Kv) channel pore-forming alpha subunits. Functions as an in
• Tissue specificity: TISSUE SPECIFICITY: Highly expressed in heart, skeletal muscle, brain, spinal cord and placenta. {ECO:0000269|PubMed:10493825}.
• Sequence:

  MNCSESQRLRTLLSRLLLELHHRGNASGLGAGPRPSMGMGVVPDPFVGREVTSAKGDDAY
  LYILLIMIFYACLAGGLILAYTRSRKLVEAKDEPSQACAEHEWAPGGALTADAEAAAGSQ
  AEGRRQLASEGLPALAQGAERV

• Sequence length: 142

Pathways

Reactome:

Phase 3 - rapid repolarisation
Phase 2 - plateau phase

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
Brugada syndrome	Uncertain significance; Likely benign; Benign; Conflicting classifications of pathogenicity	ClinVar ClinGen, GenCC, Orphanet ClinGen, GenCC, Orphanet	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
KCNE5-related disorder	Benign; Likely benign; Uncertain significance; Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Acute Coronary Syndrome	Coronary Syndrome	BEFREE	21985337		★☆☆☆☆ Found in Text Mining only
Alport Syndrome, Mental Retardation, Midface Hypoplasia, and Elliptocytosis	Amme complex	ORPHANET_DG			★☆☆☆☆ Found in Text Mining only
Alport syndrome-intellectual disability-midface hypoplasia-elliptocytosis syndrome	Alport Syndrome-Intellectual Disability-Midface Hypoplasia-Elliptocytosis Syndrome	Orphanet			★☆☆☆☆ Found in Text Mining only
Arrhythmogenic Right Ventricular Dysplasia	Arrhythmogenic right ventricular cardiomyopathy	Pubtator	30129429	Associate	★☆☆☆☆ Found in Text Mining only
Atrial Fibrillation	Atrial Fibrillation	BEFREE	16054468, 18313602, 30289750		★☆☆☆☆ Found in Text Mining only
Atrial Fibrillation	Atrial Fibrillation	LHGDN	18313602		★☆☆☆☆ Found in Text Mining only
Atrial Fibrillation	Atrial fibrillation	Pubtator	18313602, 21924735, 21967835	Associate	★☆☆☆☆ Found in Text Mining only
Atrial Fibrillation	Atrial Fibrillation	GENOMICS_ENGLAND_DG	29350269, 30289750		★☆☆☆☆ Found in Text Mining only
Brugada syndrome	Brugada Syndrome	Orphanet			★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
Brugada Syndrome	Brugada syndrome	Pubtator	21967835	Associate	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
Brugada Syndrome (disorder)	Brugada Syndrome	CLINGEN_DG	10493825, 21493962, 27484720		★☆☆☆☆ Found in Text Mining only
Brugada Syndrome (disorder)	Brugada Syndrome	BEFREE	21493962, 30289750		★☆☆☆☆ Found in Text Mining only
Brugada Syndrome (disorder)	Brugada Syndrome	ORPHANET_DG	21493962		★☆☆☆☆ Found in Text Mining only
Brugada Syndrome (disorder)	Brugada Syndrome	GENOMICS_ENGLAND_DG	29350269, 30289750		★☆☆☆☆ Found in Text Mining only
Congenital Heart Defects	Congenital heart defects	BEFREE	10493825		★☆☆☆☆ Found in Text Mining only
Contiguous gene syndrome	Contiguous gene syndrome	BEFREE	10493825		★☆☆☆☆ Found in Text Mining only
Elliptocytosis, Hereditary	Elliptocytosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
First degree atrioventricular block	Atrioventricular block	HPO_DG			★☆☆☆☆ Found in Text Mining only
Heart Diseases	Heart disease	Pubtator	21967835	Associate	★☆☆☆☆ Found in Text Mining only
Long QT Syndrome	Long QT Syndrome	BEFREE	15193977		★☆☆☆☆ Found in Text Mining only
Long QT Syndrome	Long qt syndrome	Pubtator	21967835	Associate	★☆☆☆☆ Found in Text Mining only
Myopia	Myopia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Paroxysmal familial ventricular fibrillation	Paroxysmal ventricular fibrillation	BEFREE	21493962		★☆☆☆☆ Found in Text Mining only
Paroxysmal familial ventricular fibrillation	Paroxysmal ventricular fibrillation	GENOMICS_ENGLAND_DG			★☆☆☆☆ Found in Text Mining only
Paroxysmal ventricular tachycardia	Paroxysmal ventricular tachycardia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Patent ductus arteriosus	Patent ductus arteriosus	HPO_DG			★☆☆☆☆ Found in Text Mining only
Renal glomerular disease	Renal Glomerular Disease	HPO_DG			★☆☆☆☆ Found in Text Mining only
Renal Insufficiency	Renal Insufficiency	HPO_DG			★☆☆☆☆ Found in Text Mining only
Right bundle branch block	Bundle Branch Block	HPO_DG			★☆☆☆☆ Found in Text Mining only
Severe intellectual disability	Mental retardation	HPO_DG			★☆☆☆☆ Found in Text Mining only
Sick Sinus Syndrome	Sick Sinus Syndrome	HPO_DG			★☆☆☆☆ Found in Text Mining only
Strabismus	Strabismus	HPO_DG			★☆☆☆☆ Found in Text Mining only
Supraventricular tachycardia	Supraventricular tachycardia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Tachycardia Ventricular	Ventricular tachycardia	Pubtator	30129429	Associate	★☆☆☆☆ Found in Text Mining only
Trifascicular block	Trifascicular block	HPO_DG			★☆☆☆☆ Found in Text Mining only
Ventricular arrhythmia	Ventricular arrhythmia	BEFREE	30289750		★☆☆☆☆ Found in Text Mining only
Ventricular Fibrillation	Ventricular Fibrillation	HPO_DG			★☆☆☆☆ Found in Text Mining only
Ventricular Fibrillation, Paroxysmal Familial, 1	Ventricular Fibrillation	BEFREE	21493962		★☆☆☆☆ Found in Text Mining only
Ventricular tachycardia, polymorphic	Ventricular tachycardia	BEFREE	30289750		★☆☆☆☆ Found in Text Mining only