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FLASH GENE
Symbol KCNQ1 contributors: mct - updated : 26-04-2017
HGNC name potassium voltage-gated channel, KQT-like subfamily, member 1
HGNC id 6294
Corresponding disease
ATFB3 atrial fibrillation, familial, 3
JLNS1 Jervell and Lange-Nielsen syndrome 1
LQT1 long QT syndrome with ventricular tachyarrhythmia, type 1
SQT2 short QT syndrome-2
Location 11p15.5      Physical location : 2.466.220 - 2.870.339
Synonym name
  • IKs producing slow voltage-gated potassium channel subunit
  • alpha KvLQT1
  • Jervell and Lange-Nielsen syndrome 1
  • KQT-like 1
  • kidney and cardiac voltage dependend K+ channel
  • long (electrocardiographic) QT syndrome, Ward-Romano
  • syndrome 1
  • slow delayed rectifier channel subunit
  • Synonym symbol(s) KCNA8, KCNA9, KVLQT1, ATFB1, RWS, WRS, Kv1.9, Kv7.1, LQT, JLNS1
    DNA
    TYPE functioning gene
    STRUCTURE 404.12 kb     16 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    text structure 14 exons plus alternative exons 1a1, 1a2, 1d, 1b, 1c, 2a, including an antisense overlapping methylated CpG island associated with an antisense paternal transcript (KCNQ1OT1 in the differentially methylated region, DMR) see symbol
    MAPPING cloned Y linked N status confirmed
    Physical map
    LOC387742 11 hypothetical gene supported by AK124823 CTSD 11p15.5 cathepsin D (lysosomal aspartyl protease) LOC255701 11p15.5 similar to large subunit ribosomal protein L36a LOC390029 11 similar to A-X actin SYT8 11p15.5 synaptotagmin VIII TNNI2 11p15.5 troponin I, skeletal, fast LSP1 11p15.5 lymphocyte-specific protein 1 TNNT3 11p15.5 troponin T3, skeletal, fast MRPL23 11p15.5 mitochondrial ribosomal protein L23 LOC387743 11 LOC387743 H19 11p15.5 H19, imprinted maternally expressed untranslated mRNA IGF2 11p15.5 insulin-like growth factor 2 (somatomedin A) IGF2AS 11p15.5 insulin-like growth factor 2, antisense INS 11p15.5 insulin TH 11p15.5 tyrosine hydroxylase ASCL2 11p15.5 achaete-scute complex-like 2 (Drosophila) C11orf21 11p15.5 chromosome 11 open reading frame 21 PHEMX 11p15.5 pan-hematopoietic expression CD81 11p15.5 CD81 antigen (target of antiproliferative antibody 1) TSSC4 11p15.5 tumor suppressing subtransferable candidate 4 TRPM5 11p15.5 transient receptor potential cation channel, subfamily M, member 5 KCNQ1 11p15.5 potassium voltage-gated channel, KQT-like subfamily, member 1 CDKN1C 11p15.5 cyclin-dependent kinase inhibitor 1C (p57, Kip2) HSA404617 11p15.5 BWRT protein SLC22A1LS 11p15.5 solute carrier family 22 (organic cation transporter), member 1-like antisense SLC22A1L 11p15.5 solute carrier family 22 (organic cation transporter), member 1-like PHLDA2 11p15.5 pleckstrin homology-like domain, family A, member 2 NAP1L4 11p15.5 nucleosome assembly protein 1-like 4 PRO0943 11p15.5 hypothetical protein PRO0943 CARS 11p15.5 cysteinyl-tRNA synthetase OSBPL5 11p15.4 oxysterol binding protein-like 5
    regionally located encompassing all the BWS breakpoints within the BWSCR cluster
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    16 splicing 3262 74.7 676 - 2009 19056345
  • also called variant 1/isoform 1
  • including exons 1a1, 1a2
  • - - - - - - 1997 9108097
    including exons 1b, 1c
    - - - - - - 1997 9108097
    including exons 1b, 1c, 2a
    - - - - - - 1997 9302275
    including exon 1c
    - - - - - - 1997 930227
    including exons 1d, 1a2
    16 splicing 3029 61 549 - 2009 19056345
  • also called variant 2/isoform 2
  • differing in the 5' UTR and CDS compared to variant 1
  • maybe identical to another isoform
  • EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    blood / hematopoieticspleen   lowly
    Cardiovascularheart   predominantly Homo sapiens
    Endocrinethyroid   highly
    Hearing/Equilibriumearinner   
    Reproductivefemale systemovary  lowly
     male systemtestis  lowly
    Respiratorylung   lowly
    Urinarykidney    
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Epithelialsecretoryglandularendocrine 
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Blood/Hematopoieticleukocyte
    Endocrinethyroid cell
    Muscularmyocyte
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period embryo, pregnancy
    Text apical surface of the vestibular dark cells, placenta
    IMPRINTING paternally
    text
  • paternally imprinted (centromeric imprinting domain at 11p15, containing TSSC3, TSSC5 and KCNQ1)
  • is imprinted in early cardiac development but becomes biallelic after midgestation
  • PROTEIN
    PHYSICAL PROPERTIES Hydrophobic
    STRUCTURE
    motifs/domains
  • N-terminal juxtamembranous domain critical for channel surface expression, an trafficking
  • six putative membrane-spanning domains (S1 to S6)
  • an hydrophobic pore including the P domain with the K+ channel signature
  • TM domains five and six, sensitive to changes in membrane potential, invoved in channel function but this depends on the electrical charge or the size of amino acid residue
  • a C terminal assembly domain for KVLQT1 subunits, that may be important for the subunit dominant-negative actions
  • mono polymer heteromer , polymer
    HOMOLOGY
    interspecies homolog to Drosophila shaker-related subfamily
    ortholog to rattus Kcnq1
    ortholog to murine Kcnq1
    homolog to C. elegans kqt-31
    Homologene
    FAMILY
  • KCNE protein family
  • KQT subfamily
  • CATEGORY transport channel
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,endosome
    intracellular,cytoplasm,organelle,lysosome
    intracellular,cytoplasm,cytosolic,vesicle
    text
  • located in or toward the apical membrane of the cells
  • basic FUNCTION
  • required for the repolarization phase of the cardiac action potential
  • playing a role in muscle contraction
  • role of a number of KCNQ channel members in controlling basal anion secretion in the airway epithelium
  • potassium channel subunits KCNQ1 and KCNE2 form a thyroid-stimulating hormone–stimulated, constitutively active, thyrocyte K+ channel required for normal thyroid hormone biosynthesis
  • KCNQ1 voltage-gated potassium channel and its auxiliary subunit KCNE1 play a crucial role in the regulation of the heartbeat
  • is endocytosed upon initiation of the polarization process and sent for degradation by the lysosomal pathway
  • KCNQ1 voltage sensors move relatively independently, but the channel can conduct before all voltage sensors have activated
  • crucial for heart development and function (PUID: 23028363)
  • KCNQ1 ion channels require a lipid to couple voltage sensing to pore opening
  • plays a critical role in the cardiac action potential
  • plays important roles in the cardiac action potential
  • is a voltage-gated potassium channel and its channel activity is regulated by membrane potentials
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    text cation transport
    PATHWAY
    metabolism
    signaling sensory transduction/hearing
    a component
  • associating with KCNE1 to form the slow delayed-rectifier IKS channel (KCNQ1 and KCNE1 subunits coassemble to form the I(Ks) channel)
  • forming multimer with KCNE1, KCNE3
  • directly associates with KCNE4, and can co-associate together with KCNE1 in the same KCNQ1 complex to form a 'triple subunit' complex (KCNE1-KCNQ1-KCNE4)
  • KCNQ1, KCNQ5 form heterotetrameric channels increasing the diversity of structures which fine-tune blood vessel reactivity
  • INTERACTION
    DNA
    RNA
    small molecule metal binding,
  • K+
  • protein
  • KCNE2 resulting in a drastic change of current amplitude and gating properties
  • interacting with NEDD4, NEDD4L (KCNQ1 internalization and stability is physiologically regulated by its NEDD4/NEDD4-like-dependent ubiquitylation)
  • interaction with KCNE1 (distal C-terminus interacts with the coiled-coil helix C of KCNQ1 tetramerization domain)
  • protein-protein interaction between the KCNE1 C-terminal domain and the KCNQ1 S6 activation gate and S4-S5 linker
  • KCNE2 influences blood-cerebrospinal fluid anion flux by regulating KCNQ1 and KCNA3 in the choroid plexus epithelium
  • in later developmental stages, KCNQ1OT1 has a role in modulating KCNQ1 levels, since its absence leads to overexpression of KCNQ1
  • direct interactions between KCNQ1 and KCNH2 occuring in both intact heterologous cells and primary cardiomyocytes and are mediated by their COOH termini
  • KCNE1 (mutation affecting KCNE1 activation through interaction with KCNQ1), association of KCNE1 subunit is necessary for maintaining the normal conductance and kinetics of KCNQ1 channel
  • Klotho upregulates KCNQ1/KCNE1 channel activity by “mainly” enhancing channel protein abundance in the plasma cell membrane
  • conductance and dynamics of KCNQ1 could be modulated by different single transmembrane helical auxiliary proteins (such as KCNE1, KCNE2)
  • when co-expressed in oocytes, CALML3 rendered KCNQ1 channels resistant to the voltage-dependent depletion of phosphatidylinositol 4,5-bisphosphate by voltage-sensitive phosphatase
  • cell & other
    REGULATION
    inhibited by KCNE4 (has a dramatic inhibitory effect on KCNQ1 that differs substantially from the activating effects of KCNE1 and KCNE3)
    Other by PKA-dependent phosphorylation requiring a macromolecular complex including PRKARZA, PPP1CA and yotiao (AKAP9)
    ASSOCIATED DISORDERS
    corresponding disease(s) JLNS1 , LQT1 , ATFB3 , SQT2
    related resource Long QT Syndrome Database
    Gene Connection for the Heart
    Congenital Long QT Syndrome
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional   deletion    
    maybe disrupted in (some) Beckwith-Wiedemann syndromes, see KCNQ1OT1
    constitutional germinal mutation      
    massive truncation of the C-terminal domain of KCNQ1 subunit (Y461X) severely impairs channel assembly, trafficking, and function and homozygous inheritance might cause arrhythmic disorders due to the total loss of the cardiac slow delayed rectifier K+ current
    Susceptibility
  • to arrhythmia or sudden death
  • to type 2 diabetes mellitus
  • to atrial fibrillation
  • to sudden infant death syndrome (with short or long QT)
  • Variant & Polymorphism SNP , other
  • 2031+932 A>G increasing the risk of risk of arrhythmia or sudden death
  • polymorphisms increasing the risk of to type 2 diabetes mellitus
  • variants associated to sudden infant death syndrome (with short or long QT)
  • K1493R associated to atrial fibrillation (leads to a significant positive shift in voltage-dependence of inactivation and a large ramp current near resting membrane potential, indicating a gain-of-function)
  • Candidate gene
  • physical interaction between KCNQ1 and KCNE1 is potentially affected in some LQTS mutations
  • Marker
    Therapy target
    SystemTypeDisorderPubmed
    cardiovascularrythm 
    modulation of KCNQ1 splicing may help prevent arrhythmia
    ANIMAL & CELL MODELS
  • targeted disruption of mouse Kcnq1
  • Kcne2-deficient mice had hypothyroidism, dwarfism, alopecia, goiter and cardiac abnormalities including hypertrophy, fibrosis, and reduced fractional shortening
  • potential therapeutic target for thyroid disorders