GeneBe

KCNE1

protein-coding

potassium voltage-gated channel subfamily E regulatory subunit 1, the group of Potassium voltage-gated channel regulatory subunits

Gene summary

The product of this gene belongs to the potassium channel KCNE family. Potassium ion channels are essential to many cellular functions and show a high degree of diversity, varying in their electrophysiologic and pharmacologic properties. This gene encodes a transmembrane protein known to associate with the product of the KVLQT1 gene to form the delayed rectifier potassium channel. Mutation in this gene are associated with both Jervell and Lange-Nielsen and Romano-Ward forms of long-QT syndrome. Alternatively spliced transcript variants encoding the same protein have been identified. [provided by RefSeq, Jul 2008]

MANE transcript

NM_000219.6

Inheritance

AR, AD, Digenic

ClinVar variants

P:32U:1023B:80

Top phenotype

Long QT syndrome 5; Jervell and Lange-Nielsen syndrome 2

gnomAD constraint

pLI —, LoF o/e 1.48

Max pathogenic AF

—

Genomic locus

chr21:34,446,688-34,512,214

External References & Databases

Ensembl (ENSG00000180509)NCBI Gene (3753)OMIM (176261)HGNC:6240GenCCUniProt (P15382)AlphaFoldClinVar (KCNE1)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~65.5 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

Jervell and Lange-Nielsen syndrome 2STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0012871

Submitter: G2P

long QT syndrome 5DEFINITIVE

Inheritance Pattern: AD

Disease ID:MONDO:0013372

Submitter: Ambry Genetics

Jervell and Lange-Nielsen syndrome 2STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0012871

Submitter: Labcorp Genetics (formerly Invitae)

Jervell and Lange-Nielsen syndromeSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0009078

Submitter: Orphanet

atrial fibrillationLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0004981

Submitter: Ambry Genetics

long QT syndrome 5LIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0013372

Submitter: ClinGen

KCNE1 encodes the beta-subunit of voltage-gated potassium channels and is thought to assemble with KCNQ1/KVLQT1 to form Iks (the slowly activating delayed rectifier cardiac potassium channel). There is strong evidence associating KCNE1 with acquired LQTS, however, only limited evidence for its association with unprovoked LQTS. Furthermore, several case reports have identified homozygous or compound heterozygous rare variants in KCNE1 in patients with Jervell-Lange-Nielsen Syndrome, however parents or siblings carrying only one allele have reported normal phenotypes suggesting an association of this gene with an autosomal-recessive form of LQTS (PMIDs 9354783, 9328483, 9445165). Note: All LQTS genes were curated by 3 separate blinded teams. The evidence and scores reached by these 3 teams were reviewed by the LQTS Clinical Domain Expert Panel. For a detailed discussion of this group's work and the separate scores of the 3 teams please see "Adler et al. An International, Multicentered, Evidence-Based Reappraisal of Genes Reported to Cause Congenital Long QT Syndrome. Circulation 2020;141(6):418-428. doi: 10.1161/CIRCULATIONAHA.119.043132”

long QT syndrome 5LIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0013372

Submitter: G2P

long QT syndrome 5STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0013372

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Long QT syndrome 5; Jervell and Lange-Nielsen syndrome 2AD/AR/Digenic

Manifestation: Audiologic/Otolaryngologic; Cardiovascular

Intervention: Audiologic/Otolaryngologic; Cardiovascular

Rationale: Preventive measures and medical management may be helpful to help decrease morbidity related to long-QT syndrome; In JLNS, treatment of deafness may also be beneficial for language and related development

Comments: Heterozygous variants cause long QT-syndrome 1 (Ward Romano syndrome); Biallelic variants cause Jervell and Lang-Nielsen syndrome, which includes congenital deafness; Digenic/complex inheritance has been reported

Refs: 13435203; 6991948; 9354802; 9328483; 10973849; 15051636; 14760488; 15840476; 16922724; 20301308; 20301579; 20809527; 21070882Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to KCNE1 variants in ClinVar

22 Conditions Cataloged
Long QT syndromeTotal: 180
Cardiovascular phenotypeTotal: 121
not providedTotal: 113
Jervell and Lange-Nielsen syndrome 2Total: 52
Long QT syndrome 5Total: 51
not specifiedTotal: 44
Congenital long QT syndromeTotal: 26
KCNE1-related disorderTotal: 6

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_000219.6. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
187
clinvar
60
clinvar
 247
missense
3
clinvar
14
clinvar
784
clinvar
16
clinvar
4
clinvar
 821
nonsense
3
clinvar
2
clinvar
38
clinvar
 43
start loss
1
clinvar
8
clinvar
 9
frameshift
6
clinvar
3
clinvar
5
clinvar
 14
splice donor/acceptor (+/-2bp)
1
clinvar
 1
Total131910237641135

Highest pathogenic variant AF is 0.00012196663

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 34 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_000219.6RefSeqNP_000210.21MANE Select
ENST00000399286.3EnsemblENSP00000382226.21MANE Select
NM_001127668.4RefSeqNP_001121140.11Standard
NM_001127669.4RefSeqNP_001121141.11Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • Adrenergic signaling in cardiomyocytes - Homo sapiens (human)
  • Antiarrhythmic Pathway, Pharmacodynamics
  • Disopyramide Action Pathway
  • Procainamide (Antiarrhythmic) Action Pathway
  • Phenytoin (Antiarrhythmic) Action Pathway

Biological Process

  • sensory perception of sound
  • regulation of ventricular cardiac muscle cell membrane repolarization
  • cellular response to cAMP
  • potassium ion transmembrane transport
  • cardiac muscle cell action potential involved in contraction

Molecular Function

  • voltage-gated potassium channel activity
  • delayed rectifier potassium channel activity
  • protein binding
  • potassium channel regulator activity
  • telethonin binding

Cellular Component

  • lysosome
  • plasma membrane
  • voltage-gated potassium channel complex
  • cell surface
  • apical plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000337385
Coding exons
1
Length
65586
Individuals with no LoFs
125730
Homozygous LoFs
0
Heterozygous LoFs
6
Defined
125736
p
0.0000239
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense-0.6169781.41.190.00000536837
Missense (PolyPhen)2425.3670.9461291
Synonymous-1.394837.21.290.00000279267
Loss of Function-0.63432.031.488.72e-822

Population LoF Frequency

PopulationCAFp-valueStatus
African00.0absent
Latino/Admixed American00.0absent
Ashkenazi Jewish0.0000990.000099rare
East Asian00.0absent
Finnish00.0absent
European (Non-Finnish)0.0000260.000026rare
South Asian0.0000650.000065rare
Other00.0absent

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: Ancillary protein that assembles as a beta subunit with a voltage-gated potassium channel complex of pore-forming alpha subunits. Modulates the gating kinetics and enhances stability of the channel complex. Assembled with KCNB1 modulates the gating characteristics of the delayed rectifier voltage-dependent potassium channel KCNB1 (PubMed:19219384). Assembled with KCNQ1/KVLQT1 is proposed to form the slowly activating delayed rectifier cardiac potassium (IKs) channel. The outward current reaches its steady state only after 50 seconds. Assembled with KCNH2/HERG may modulate the rapidly activating component of the delayed rectifying potassium current in heart (IKr). {ECO:0000269|PubMed:19219384}.;
Disease
DISEASE: Jervell and Lange-Nielsen syndrome 2 (JLNS2) [MIM:612347]: An autosomal recessive disorder characterized by congenital deafness, prolongation of the QT interval, syncopal attacks due to ventricular arrhythmias, and a high risk of sudden death. {ECO:0000269|PubMed:10400998, ECO:0000269|PubMed:21676880, ECO:0000269|PubMed:9328483, ECO:0000269|PubMed:9354783}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Long QT syndrome 5 (LQT5) [MIM:613695]: 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. {ECO:0000269|PubMed:10400998, ECO:0000269|PubMed:10973849, ECO:0000269|PubMed:11692163, ECO:0000269|PubMed:16414944, ECO:0000269|PubMed:19716085, ECO:0000269|PubMed:25037568, ECO:0000269|PubMed:9354802, ECO:0000269|PubMed:9445165}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec
0.333

Intolerance Scores

LoFtool
0.0168
RVIS EVS
0.06
RVIS percentile EVS
58.53

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
E
Indispensability score
0.814

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
Feedback | API | Annotate VCF | Sitemap | About | Privacy & Terms
For research and educational, non-commercial use only. Not for clinical or diagnostic use. GeneBe does not provide medical advice. Data use for AI modeling is prohibited: if used, the cost is $0.001 per byte of downloaded uncompressed data.