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    KCNE1 potassium voltage-gated channel subfamily E regulatory subunit 1 [ Homo sapiens (human) ]

    Gene ID: 3753, updated on 27-Nov-2024

    Summary

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    Official Symbol
    KCNE1provided by HGNC
    Official Full Name
    potassium voltage-gated channel subfamily E regulatory subunit 1provided by HGNC
    Primary source
    HGNC:HGNC:6240
    See related
    Ensembl:ENSG00000180509 MIM:176261; AllianceGenome:HGNC:6240
    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
    ISK; JLNS; LQT5; MinK; JLNS2; LQT2/5
    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]
    Expression
    Biased expression in heart (RPKM 1.7), kidney (RPKM 1.5) and 7 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See KCNE1 in Genome Data Viewer
    Location:
    21q22.12
    Exon count:
    7
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 21 NC_000021.9 (34446688..34512210, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 21 NC_060945.1 (32829243..32898958, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 21 NC_000021.8 (35818986..35884508, complement)

    Chromosome 21 - NC_000021.9Genomic Context describing neighboring genes Neighboring gene salivary glue protein Sgs-3 Neighboring gene chromosome 21 open reading frame 140 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr21:35788990-35790189 Neighboring gene NANOG hESC enhancer GRCh37_chr21:35802003-35802504 Neighboring gene small integral membrane protein 34 Neighboring gene NANOG hESC enhancer GRCh37_chr21:35825641-35826142 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr21:35827602-35828102 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr21:35828103-35828603 Neighboring gene small nucleolar RNA SNORA11 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr21:35831243-35832104 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr21:35832105-35832965 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 18395 Neighboring gene VISTA enhancer hs2084 Neighboring gene regulator of calcineurin 1 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr21:35954416-35954916 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr21:35954917-35955417 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 13269 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 13270 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 18396 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 18397 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 18398 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 18399 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 18400 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 13271 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 13272 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 13273 Neighboring gene chloride intracellular channel 6

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • 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

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    Related articles in PubMed

    1. Immunolocalization of P2Y4 and P2Y2 purinergic receptors in strial marginal cells and vestibular dark cells. Sage CL, et al. J Membr Biol, 2002 Jan 15. PMID 11891569
    2. Expression of multiple KCNE genes in human heart may enable variable modulation of I(Ks). Lundquist AL, et al. J Mol Cell Cardiol, 2005 Feb. PMID 15698834
    3. Glycine/Serine polymorphism at position 38 influences KCNE1 subunit's modulatory actions on rapid and slow delayed rectifier K+ currents. Yamaguchi Y, et al. Circ J, 2014. PMID 24419801
    4. Genetic diversity of the KCNE1 gene and susceptibility to postoperative atrial fibrillation. Voudris KV, et al. Am Heart J, 2014 Feb. PMID 24439990
    5. Charybdotoxin binding in the I(Ks) pore demonstrates two MinK subunits in each channel complex. Chen H, et al. Neuron, 2003 Sep 25. PMID 14527430

    See all (236) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. High-throughput functional mapping of variants in an arrhythmia gene, KCNE1, reveals novel biology.
      Title: High-throughput functional mapping of variants in an arrhythmia gene, KCNE1, reveals novel biology.
    2. PKC-isoform specific regulation of receptor desensitization and KCNQ1/KCNE1 K(+) channel activity by mutant alpha1B-adrenergic receptors.
      Title: PKC-isoform specific regulation of receptor desensitization and KCNQ1/KCNE1 K(+) channel activity by mutant α(1B)-adrenergic receptors.
    3. Common Variants in KCNE1, KCNH2, and SCN5A May Impact Cardiac Arrhythmia Risk.
      Title: Common Variants in KCNE1, KCNH2, and SCN5A May Impact Cardiac Arrhythmia Risk.
    4. Development of a Patient-Specific p.D85N-Potassium Voltage-Gated Channel Subfamily E Member 1-Induced Pluripotent Stem Cell-Derived Cardiomyocyte Model for Drug-Induced Long QT Syndrome.
      Title: Development of a Patient-Specific p.D85N-Potassium Voltage-Gated Channel Subfamily E Member 1-Induced Pluripotent Stem Cell-Derived Cardiomyocyte Model for Drug-Induced Long QT Syndrome.
    5. Genetic predictors of sick sinus syndrome.
      Title: Genetic predictors of sick sinus syndrome.
    6. A general mechanism of KCNE1 modulation of KCNQ1 channels involving non-canonical VSD-PD coupling.
      Title: A general mechanism of KCNE1 modulation of KCNQ1 channels involving non-canonical VSD-PD coupling.
    7. Association Analysis of Candidate Gene Polymorphisms and Tinnitus in Young Musicians.
      Title: Association Analysis of Candidate Gene Polymorphisms and Tinnitus in Young Musicians.
    8. KCNE1 is an auxiliary subunit of two distinct ion channel superfamilies.
      Title: KCNE1 is an auxiliary subunit of two distinct ion channel superfamilies.
    9. Elevation of propofol sensitivity of cardiac IKs channel by KCNE1 polymorphism D85N.
      Title: Elevation of propofol sensitivity of cardiac I(Ks) channel by KCNE1 polymorphism D85N.
    10. Clinical and functional reappraisal of alleged type 5 long QT syndrome: Causative genetic variants in the KCNE1-encoded minK beta-subunit.
      Title: Clinical and functional reappraisal of alleged type 5 long QT syndrome: Causative genetic variants in the KCNE1-encoded minK β-subunit.
    Submit: New GeneRIF Correction See all GeneRIFs (160)

    Phenotypes

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

    Review eQTL and phenotype association data in this region using PheGenI

    EBI GWAS Catalog

    Description
    Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization.
    EBI GWAS Catalog
    Several common variants modulate heart rate, PR interval and QRS duration.
    EBI GWAS Catalog

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • FLJ18426, FLJ38123, FLJ94103, MGC33114

    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 delayed 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 protein-containing complex binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables telethonin binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables transmembrane transporter binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    NOT enables voltage-gated potassium channel activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    contributes_to voltage-gated potassium channel activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    contributes_to voltage-gated potassium channel activity involved in cardiac muscle cell action potential repolarization IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    contributes_to voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarization IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    contributes_to 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 cardiac muscle cell contraction NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    involved_in cellular response to acidic pH IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in cellular response to cAMP IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in cellular response to light stimulus IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in epithelial cell maturation IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in male gonad development IEA
    Inferred from Electronic Annotation
    more info
    		  
    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 IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in membrane repolarization during cardiac muscle cell action potential IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in membrane repolarization during cardiac muscle cell action potential IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in membrane repolarization during cardiac muscle cell action potential NAS
    Non-traceable Author Statement
    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 negative regulation of protein targeting to membrane ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in positive regulation of potassium ion transmembrane transport 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 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 potassium ion transmembrane transport IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in regulation of potassium ion 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 secretory granule organization IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in sensory perception of sound TAS
    Traceable Author Statement
    more info
    		 PubMed 
    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 
    involved_in vestibular nucleus development IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    located_in Z disc ISS
    Inferred from Sequence or Structural Similarity
    more info
    		 PubMed 
    located_in apical plasma membrane ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    located_in cell surface IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in lysosome HDA PubMed 
    located_in membrane raft IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in plasma membrane HDA 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 IC
    Inferred by Curator
    more info
    		 PubMed 
    part_of voltage-gated potassium channel complex IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    part_of voltage-gated potassium channel complex IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    potassium voltage-gated channel subfamily E member 1
    Names
    IKs producing slow voltage-gated potassium channel subunit beta Mink
    Long QT syndrome 5
    cardiac delayed rectifier potassium channel protein
    delayed rectifier potassium channel subunit IsK
    minimal potassium channel
    potassium channel, voltage gated subfamily E regulatory beta subunit 1
    potassium voltage-gated channel, Isk-related family, member 1
    potassium voltage-gated channel, Isk-related subfamily, member 1
    voltage gated potassiun channel accessory subunit

    NCBI Reference Sequences (RefSeq)

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    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

    1. NG_009091.1 RefSeqGene

      Range
      4041..69628
      Download
      GenBank, FASTA, Sequence Viewer (Graphics), LRG_290

    mRNA and Protein(s)

    1. NM_000219.6 → NP_000210.2  potassium voltage-gated channel subfamily E member 1

      See identical proteins and their annotated locations for NP_000210.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) is the longest transcript. All variants encode the same protein.
      Source sequence(s)
      AI720140, AP000324, BC046224, KC877871
      Consensus CDS
      CCDS13636.1
      UniProtKB/Swiss-Prot
      A5H1P2, P15382, Q8N709, Q91Z94
      UniProtKB/TrEMBL
      C7S316, Q6FHJ6
      Related
      ENSP00000382226.2, ENST00000399286.3
      Conserved Domains (1) summary
      pfam02060
      Location:2 → 126
      ISK_Channel; Slow voltage-gated potassium channel

    2. NM_001127668.4 → NP_001121140.1  potassium voltage-gated channel subfamily E member 1

      See identical proteins and their annotated locations for NP_001121140.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) differs in the 5' UTR, compared to variant 2. All variants encode the same protein.
      Source sequence(s)
      AI720140, AP000324, BC036452, EU008568, KC877871
      Consensus CDS
      CCDS13636.1
      UniProtKB/Swiss-Prot
      A5H1P2, P15382, Q8N709, Q91Z94
      UniProtKB/TrEMBL
      C7S316, Q6FHJ6
      Related
      ENSP00000412498.1, ENST00000432085.5
      Conserved Domains (1) summary
      pfam02060
      Location:2 → 126
      ISK_Channel; Slow voltage-gated potassium channel

    3. NM_001127669.4 → NP_001121141.1  potassium voltage-gated channel subfamily E member 1

      See identical proteins and their annotated locations for NP_001121141.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) differs in the 5' UTR, compared to variant 2. All variants encode the same protein.
      Source sequence(s)
      AI720140, AP000324, BC036452, EU008569, KC877871
      Consensus CDS
      CCDS13636.1
      UniProtKB/Swiss-Prot
      A5H1P2, P15382, Q8N709, Q91Z94
      UniProtKB/TrEMBL
      C7S316, Q6FHJ6
      Related
      ENSP00000382228.3, ENST00000399289.7
      Conserved Domains (1) summary
      pfam02060
      Location:2 → 126
      ISK_Channel; Slow voltage-gated potassium channel

    4. NM_001127670.4 → NP_001121142.1  potassium voltage-gated channel subfamily E member 1

      See identical proteins and their annotated locations for NP_001121142.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) differs in the 5' UTR, compared to variant 2. All variants encode the same protein.
      Source sequence(s)
      AI720140, AP000324, EU008570, KC877871
      Consensus CDS
      CCDS13636.1
      UniProtKB/Swiss-Prot
      A5H1P2, P15382, Q8N709, Q91Z94
      UniProtKB/TrEMBL
      C7S316, Q6FHJ6
      Related
      ENSP00000416258.2, ENST00000416357.6
      Conserved Domains (1) summary
      pfam02060
      Location:2 → 126
      ISK_Channel; Slow voltage-gated potassium channel

    5. NM_001270402.3 → NP_001257331.1  potassium voltage-gated channel subfamily E member 1

      See identical proteins and their annotated locations for NP_001257331.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (5) differs in the 5' UTR, compared to variant 2. All variants encode the same protein.
      Source sequence(s)
      AI720140, AP000324, DA418828, DB233067, KC877871
      Consensus CDS
      CCDS13636.1
      UniProtKB/Swiss-Prot
      A5H1P2, P15382, Q8N709, Q91Z94
      UniProtKB/TrEMBL
      C7S316, Q6FHJ6
      Related
      ENSP00000337255.3, ENST00000337385.7
      Conserved Domains (1) summary
      pfam02060
      Location:2 → 126
      ISK_Channel; Slow voltage-gated potassium channel

    6. NM_001270403.2 → NP_001257332.1  potassium voltage-gated channel subfamily E member 1

      See identical proteins and their annotated locations for NP_001257332.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (6) differs in the 5' UTR, compared to variant 2. All variants encode the same protein.
      Source sequence(s)
      AI720140, AP000324, DB223354, DB230009, KC877871
      Consensus CDS
      CCDS13636.1
      UniProtKB/Swiss-Prot
      A5H1P2, P15382, Q8N709, Q91Z94
      UniProtKB/TrEMBL
      C7S316, Q6FHJ6
      Related
      ENSP00000382225.1, ENST00000399284.1
      Conserved Domains (1) summary
      pfam02060
      Location:2 → 126
      ISK_Channel; Slow voltage-gated potassium channel

    7. NM_001270404.3 → NP_001257333.1  potassium voltage-gated channel subfamily E member 1

      See identical proteins and their annotated locations for NP_001257333.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (7) differs in the 5' UTR, compared to variant 2. All variants encode the same protein.
      Source sequence(s)
      AI720140, AP000324, DB214219, DB223354, KC877871
      Consensus CDS
      CCDS13636.1
      UniProtKB/Swiss-Prot
      A5H1P2, P15382, Q8N709, Q91Z94
      UniProtKB/TrEMBL
      C7S316, Q6FHJ6
      Related
      ENSP00000478215.1, ENST00000611936.1
      Conserved Domains (1) summary
      pfam02060
      Location:2 → 126
      ISK_Channel; Slow voltage-gated potassium channel

    8. NM_001270405.3 → NP_001257334.1  potassium voltage-gated channel subfamily E member 1

      See identical proteins and their annotated locations for NP_001257334.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (8) differs in the 5' UTR, compared to variant 2. All variants encode the same protein.
      Source sequence(s)
      AI720140, AP000324, DA806205, KC877871
      Consensus CDS
      CCDS13636.1
      UniProtKB/Swiss-Prot
      A5H1P2, P15382, Q8N709, Q91Z94
      UniProtKB/TrEMBL
      C7S316, Q6FHJ6
      Related
      ENSP00000483895.1, ENST00000621601.4
      Conserved Domains (1) summary
      pfam02060
      Location:2 → 126
      ISK_Channel; Slow voltage-gated potassium channel

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

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

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000021.9 Reference GRCh38.p14 Primary Assembly

      Range
      34446688..34512210 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_047440764.1 → XP_047296720.1  potassium voltage-gated channel subfamily E member 1 isoform X1

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060945.1 Alternate T2T-CHM13v2.0

      Range
      32829243..32898958 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054324469.1 → XP_054180444.1  potassium voltage-gated channel subfamily E member 1 isoform X1

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    P15382.1 GenPept UniProtKB/Swiss-Prot:P15382

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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