KCNE2 potassium voltage-gated channel subfamily E regulatory subunit 2 [Homo sapiens (human)] - Gene

Summary

Official Symbol: KCNE2provided by HGNC
Official Full Name: potassium voltage-gated channel subfamily E regulatory subunit 2provided by HGNC
Primary source: HGNC:HGNC:6242
See related: Ensembl:ENSG00000159197 MIM:603796; AllianceGenome:HGNC:6242
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: LQT5; LQT6; ATFB4; MIRP1
Summary: Voltage-gated potassium (Kv) channels represent the most complex class of voltage-gated ion channels from both functional and structural standpoints. Their diverse functions include regulating neurotransmitter release, heart rate, insulin secretion, neuronal excitability, epithelial electrolyte transport, smooth muscle contraction, and cell volume. This gene encodes a member of the potassium channel, voltage-gated, isk-related subfamily. This member is a small integral membrane subunit that assembles with the KCNH2 gene product, a pore-forming protein, to alter its function. This gene is expressed in heart and muscle and the gene mutations are associated with cardiac arrhythmia. [provided by RefSeq, Jul 2008]
Expression: Biased expression in stomach (RPKM 72.9) and duodenum (RPKM 4.0) See more
Orthologs: mouse all
NEW: Try the new Gene table
Try the new Transcript table

Genomic context

Location:: 21q22.11

Exon count:: 2

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	21	NC_000021.9 (34364006..34371381)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	21	NC_060945.1 (32746055..32753431)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	21	NC_000021.8 (35736305..35743680)

Chromosome 21 - NC_000021.9 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

Go to the top of the page Help

Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

Go to the top of the page Help

See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

Go to the top of the page Help

GeneRIFs: Gene References Into Functions

What's a GeneRIF?

An arginine/lysine-based motif ([R/K](S)[R/K][R/K]) in the proximal C-terminus regulating the endoplasmic reticulum (ER) export of KCNE1 and KCNE2.
Title: A conserved arginine/lysine-based motif promotes ER export of KCNE1 and KCNE2 to regulate KCNQ1 channel activity.
KCNE2 rs8134775 was associated with a decreased atrial fibrillation (AF) risk in the Chinese Han population in the allele model. Minor allele T of GJA5 rs35594137 was associated with a decreased AF risk, and the minor allele G of KCNJ2 rs8079702 was associated with an increased AF risk in the recessive models. Results suggest that KCNE2, KCNJ2, and GJA5 influence the development of AF in the Chinese Han population.
Title: The research of ion channel-related gene polymorphisms with atrial fibrillation in the Chinese Han population.
In vitro functional assays showed miR-584-5p depletion decreased HCC cell proliferation, cell migration, and cell invasion. Moreover, miR-584-5p functions by directly targeting KCNE2, and it in turn, mediates the effects of miR-584-5p on HCC cell behaviors.
Title: miR-584-5p regulates hepatocellular carcinoma cell migration and invasion through targeting KCNE2.
On the basis of clinical phenotype, the high allelic frequencies of LQT6 mutations in the Exome Aggregation Consortium database, and absence of previous documentation of genotype-phenotype segregation, our findings suggest that many KCNE2 variants, and perhaps all, have been erroneously designated as LQTS-causative mutations. Instead, KCNE2 variants may confer proarrhythmic susceptibility when provoked by additional envir
Title: Loss-of-Function KCNE2 Variants: True Monogenic Culprits of Long-QT Syndrome or Proarrhythmic Variants Requiring Secondary Provocation?
These results demonstrate that KCNE2 is required for normal beta-cell electrical activity and insulin secretion, and that Kcne2 deletion causes T2DM.
Title: Kcne2 deletion impairs insulin secretion and causes type 2 diabetes mellitus.
The identification of Filamin C as a novel KCNE2 ligand not only enhances current understanding of ion channel function and regulation, but also provides valuable information about possible pathways likely to be involved in long-QT syndrome pathogenesis
Title: Filamin C: a novel component of the KCNE2 interactome during hypoxia.
KCNE2 has been widely studied since its role in the heart was discovered; it is association with inherited and acquired human Long QT syndrome; physiological analyses together with genetics studies have uncovered a startling array of functions for KCNE2, in the heart, stomach, thyroid and choroid plexus. [Review]
Title: The KCNE2 K⁺ channel regulatory subunit: Ubiquitous influence, complex pathobiology.
Women with elevated BMI have enhanced hERG activity as a result of low beta-inhibitory protein expression, which likely contributes to weak contractions and poor labour outcomes.
Title: Diminished hERG K+ channel activity facilitates strong human labour contractions but is dysregulated in obese women.
M54T MiRP1 mutation axecerbate drug-induced long QT syndrome and arrhythmia.
Title: In silico screening of the impact of hERG channel kinetic abnormalities on channel block and susceptibility to acquired long QT syndrome.
The effect of KCNE2 mutations on KV7.1 was abolished in the presence of the major IKs beta-subunit KCNE1, when coexpressed in a 1:1:1 molar ratio.
Title: Gain-of-function mutations in potassium channel subunit KCNE2 associated with early-onset lone atrial fibrillation.

Submit: New GeneRIF Correction See all GeneRIFs (44)

Phenotypes

Go to the top of the page Help

Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Atrial fibrillation, familial, 4 MedGen: C1862394 OMIM: 611493 GeneReviews: Not available	Compare labs
Long QT syndrome MedGen: C0023976 GeneReviews: Long QT Syndrome Overview	Compare labs
Long QT syndrome 6 MedGen: C3150953 OMIM: 613693 GeneReviews: Long QT Syndrome Overview	Compare labs

EBI GWAS Catalog

Description
Gene-environment interactions and obesity traits among postmenopausal African-American and Hispanic women in the Women's Health Initiative SHARe Study. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association and large-scale follow up identifies 16 new loci influencing lung function. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association of early-onset myocardial infarction with single nucleotide polymorphisms and copy number variants. EBI GWAS Catalog EBI GWAS CatalogPubMed
Hundreds of variants clustered in genomic loci and biological pathways affect human height. EBI GWAS Catalog EBI GWAS CatalogPubMed
Shared genetic susceptibility to ischemic stroke and coronary artery disease: a genome-wide analysis of common variants. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

Go to the top of the page Help

See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

Go to the top of the page Help

Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

Go to the top of the page Help

Markers

D8S2279 (e-PCR)
- UniSTS:473907

sY3084 (e-PCR)
- UniSTS:515126

KCNE2_1321 (e-PCR)
- UniSTS:277415

KCNE2_v409 (e-PCR)
- UniSTS:277415

NoName (e-PCR)
- UniSTS:483515

SHGC-87567 (e-PCR)
- UniSTS:54483

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
contributes_to delayed rectifier potassium channel activity	IBA Inferred from Biological aspect of Ancestor more info
contributes_to delayed rectifier potassium channel activity	IDA Inferred from Direct Assay more info	PubMed
enables identical protein binding	IEA Inferred from Electronic Annotation more info
contributes_to inward rectifier potassium channel activity	IDA Inferred from Direct Assay more info	PubMed
enables potassium channel regulator activity	IBA Inferred from Biological aspect of Ancestor more info
enables potassium channel regulator activity	IDA Inferred from Direct Assay more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables transmembrane transporter binding	IBA Inferred from Biological aspect of Ancestor more info
enables transmembrane transporter binding	IDA Inferred from Direct Assay more info	PubMed
enables voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarization	IMP Inferred from Mutant Phenotype more info	PubMed

Process	Evidence Code	Pubs
involved_in cardiac muscle cell action potential involved in contraction	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cellular response to xenobiotic stimulus	IDA Inferred from Direct Assay more info	PubMed
involved_in membrane repolarization	IDA Inferred from Direct Assay more info	PubMed
involved_in membrane repolarization during action potential	IBA Inferred from Biological aspect of Ancestor more info
involved_in membrane repolarization during action potential	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in membrane repolarization during ventricular cardiac muscle cell action potential	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of delayed rectifier potassium channel activity	IBA Inferred from Biological aspect of Ancestor more info
involved_in negative regulation of delayed rectifier potassium channel activity	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of proteasomal protein catabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in potassium ion export across plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
involved_in potassium ion export across plasma membrane	IDA Inferred from Direct Assay more info	PubMed
involved_in potassium ion import across plasma membrane	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in potassium ion transmembrane transport	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of delayed rectifier potassium channel activity	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of heart rate by cardiac conduction	IBA Inferred from Biological aspect of Ancestor more info
involved_in regulation of heart rate by cardiac conduction	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of inward rectifier potassium channel activity	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of membrane repolarization	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of potassium ion transmembrane transport	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of ventricular cardiac muscle cell membrane repolarization	IBA Inferred from Biological aspect of Ancestor more info
involved_in regulation of ventricular cardiac muscle cell membrane repolarization	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in tongue development	IEA Inferred from Electronic Annotation more info
involved_in ventricular cardiac muscle cell action potential	IBA Inferred from Biological aspect of Ancestor more info
involved_in ventricular cardiac muscle cell action potential	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
located_in apical plasma membrane	IEA Inferred from Electronic Annotation more info
located_in cell surface	IDA Inferred from Direct Assay more info	PubMed
located_in lysosome	HDA more info	PubMed
located_in plasma membrane	HDA more info	PubMed
located_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	TAS Traceable Author Statement more info
part_of voltage-gated potassium channel complex	IBA Inferred from Biological aspect of Ancestor more info
part_of voltage-gated potassium channel complex	IDA Inferred from Direct Assay more info	PubMed

General protein information

Go to the top of the page Help

Preferred Names: potassium voltage-gated channel subfamily E member 2

Names: cardiac voltage-gated potassium channel accessory subunit 2; minK-related peptide-1; minimum potassium ion channel-related peptide 1; potassium channel subunit beta MiRP1; potassium channel subunit, MiRP1; potassium channel, voltage gated subfamily E regulatory beta subunit 2; potassium voltage-gated channel, Isk-related family, member 2; voltage-gated K+ channel subunit MIRP1

NCBI Reference Sequences (RefSeq)

Go to the top of the page Help

NEW Try the new Transcript table

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_008804.1 RefSeqGene

Range

5001..12118

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_291

mRNA and Protein(s)

NM_172201.2 → NP_751951.1 potassium voltage-gated channel subfamily E member 2

See identical proteins and their annotated locations for NP_751951.1

Status: REVIEWED

Source sequence(s)

AP000320

Consensus CDS

CCDS13635.1

UniProtKB/Swiss-Prot

A5H1P3, D3DSF8, Q52LJ5, Q9Y6J6

UniProtKB/TrEMBL

Q2N1I3

Related

ENSP00000290310.2, ENST00000290310.4

Conserved Domains (1) summary

pfam02060
Location:50 → 113

ISK_Channel; Slow voltage-gated potassium channel

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000021.9 Reference GRCh38.p14 Primary Assembly

Range

34364006..34371381

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

NC_060945.1 Alternate T2T-CHM13v2.0

Range

32746055..32753431

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

NM_005136.2: Suppressed sequence

Description

NM_005136.2: This RefSeq record was removed by NCBI staff. Contact info@ncbi.nlm.nih.gov for further information.