LOCUS       NM_000238               4292 bp    mRNA    linear   PRI 29-OCT-2024
DEFINITION  Homo sapiens potassium voltage-gated channel subfamily H member 2
            (KCNH2), transcript variant 1, mRNA.
ACCESSION   NM_000238
VERSION     NM_000238.4
KEYWORDS    RefSeq; MANE Select.
SOURCE      Homo sapiens (human)
  ORGANISM  Homo sapiens
            Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
            Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
            Catarrhini; Hominidae; Homo.
REFERENCE   1  (bases 1 to 4292)
  AUTHORS   Davis,J., Cornwell,J.D., Campagna,N., Guo,J., Li,W., Yang,T.,
            Wang,T. and Zhang,S.
  TITLE     Rescue of expression and function of long QT syndrome-causing
            mutant hERG channels by enhancing channel stability in the plasma
            membrane
  JOURNAL   J Biol Chem 300 (8), 107526 (2024)
   PUBMED   38960041
  REMARK    GeneRIF: Rescue of expression and function of long QT
            syndrome-causing mutant hERG channels by enhancing channel
            stability in the plasma membrane.
REFERENCE   2  (bases 1 to 4292)
  AUTHORS   Zavarzina,I.I., Kuzmenkov,A.I., Dobrokhotov,N.A., Maleeva,E.E.,
            Korolkova,Y.V., Peigneur,S., Tytgat,J., Krylov,N.A.,
            Vassilevski,A.A. and Chugunov,A.O.
  TITLE     The scorpion toxin BeKm-1 blocks hERG cardiac potassium channels
            using an indispensable arginine residue
  JOURNAL   FEBS Lett 598 (8), 889-901 (2024)
   PUBMED   38563123
REFERENCE   3  (bases 1 to 4292)
  AUTHORS   Liu,Z., Wang,F., Yuan,H., Tian,F., Yang,C., Hu,F., Liu,Y., Tang,M.,
            Ping,M., Kang,C., Luo,T., Yang,G., Hu,M., Gao,Z. and Li,P.
  TITLE     An LQT2-related mutation in the voltage-sensing domain is involved
            in switching the gating polarity of hERG
  JOURNAL   BMC Biol 22 (1), 29 (2024)
   PUBMED   38317233
  REMARK    GeneRIF: An LQT2-related mutation in the voltage-sensing domain is
            involved in switching the gating polarity of hERG.
            Publication Status: Online-Only
REFERENCE   4  (bases 1 to 4292)
  AUTHORS   Gong,Q., Stump,M.R., Dunn,A.R., Deng,V. and Zhou,Z.
  TITLE     Alternative splicing and polyadenylation contribute to the
            generation of hERG1 C-terminal isoforms
  JOURNAL   J Biol Chem 285 (42), 32233-32241 (2010)
   PUBMED   20693282
  REMARK    GeneRIF: Data suggest that post-transcriptional regulation of hERG1
            pre-mRNA may represent a novel mechanism to modulate the expression
            and function of hERG1 channels.
REFERENCE   5  (bases 1 to 4292)
  AUTHORS   Kupershmidt,S., Snyders,D.J., Raes,A. and Roden,D.M.
  TITLE     A K+ channel splice variant common in human heart lacks a
            C-terminal domain required for expression of rapidly activating
            delayed rectifier current
  JOURNAL   J Biol Chem 273 (42), 27231-27235 (1998)
   PUBMED   9765245
REFERENCE   6  (bases 1 to 4292)
  AUTHORS   Trudeau,M.C., Warmke,J.W., Ganetzky,B. and Robertson,G.A.
  TITLE     HERG, a human inward rectifier in the voltage-gated potassium
            channel family
  JOURNAL   Science 269 (5220), 92-95 (1995)
   PUBMED   7604285
  REMARK    Erratum:[Science. 1996 May 24;272(5265):1087.. PMID: 8638148]
REFERENCE   7  (bases 1 to 4292)
  AUTHORS   Sanguinetti,M.C., Jiang,C., Curran,M.E. and Keating,M.T.
  TITLE     A mechanistic link between an inherited and an acquired cardiac
            arrhythmia: HERG encodes the IKr potassium channel
  JOURNAL   Cell 81 (2), 299-307 (1995)
   PUBMED   7736582
REFERENCE   8  (bases 1 to 4292)
  AUTHORS   Curran,M.E., Splawski,I., Timothy,K.W., Vincent,G.M., Green,E.D.
            and Keating,M.T.
  TITLE     A molecular basis for cardiac arrhythmia: HERG mutations cause long
            QT syndrome
  JOURNAL   Cell 80 (5), 795-803 (1995)
   PUBMED   7889573
REFERENCE   9  (bases 1 to 4292)
  AUTHORS   Brugada,R., Campuzano,O., Sarquella-Brugada,G., Brugada,P.,
            Brugada,J. and Hong,K.
  TITLE     Brugada Syndrome
  JOURNAL   (in) Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE and
            Amemiya A (Eds.);
            GENEREVIEWS(R);
            (1993)
   PUBMED   20301690
REFERENCE   10 (bases 1 to 4292)
  AUTHORS   Groffen,A.J., Bikker,H. and Christiaans,I.
  TITLE     Long QT Syndrome Overview
  JOURNAL   (in) Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE and
            Amemiya A (Eds.);
            GENEREVIEWS(R);
            (1993)
   PUBMED   20301308
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AC011234.2, DQ525913.1,
            AF363636.1 and U04270.1.
            
            On Aug 31, 2019 this sequence version replaced NM_000238.3.
            
            Summary: This gene encodes a component of a voltage-activated
            potassium channel found in cardiac muscle, nerve cells, and
            microglia. Four copies of this protein interact with one copy of
            the KCNE2 protein to form a functional potassium channel. Mutations
            in this gene can cause long QT syndrome type 2 (LQT2). Transcript
            variants encoding distinct isoforms have been identified. [provided
            by RefSeq, May 2022].
            
            Transcript Variant: This variant (1) encodes the longest isoform
            (a).
            
            Publication Note:  This RefSeq record includes a subset of the
            publications that are available for this gene. Please see the Gene
            record to access additional publications.
            
            ##Evidence-Data-START##
            Transcript exon combination :: DQ525913.1, U04270.1 [ECO:0000332]
            RNAseq introns              :: mixed sample support SAMEA1965299,
                                           SAMEA1966682 [ECO:0006172]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000262186.10/ ENSP00000262186.5
            RefSeq Select criteria :: based on conservation, expression
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-7                 AC011234.2         4968-4974
            8-408               DQ525913.1         1-401
            409-1874            AF363636.1         1-1466
            1875-4292           U04270.1           1650-4067
FEATURES             Location/Qualifiers
     source          1..4292
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="7"
                     /map="7q36.1"
     gene            1..4292
                     /gene="KCNH2"
                     /gene_synonym="ERG-1; ERG1; H-ERG; HERG; HERG1; Kv11.1;
                     LQT2; SQT1"
                     /note="potassium voltage-gated channel subfamily H member
                     2"
                     /db_xref="GeneID:3757"
                     /db_xref="HGNC:HGNC:6251"
                     /db_xref="MIM:152427"
     exon            1..484
                     /gene="KCNH2"
                     /gene_synonym="ERG-1; ERG1; H-ERG; HERG; HERG1; Kv11.1;
                     LQT2; SQT1"
                     /inference="alignment:Splign:2.1.0"
     CDS             409..3888
                     /gene="KCNH2"
                     /gene_synonym="ERG-1; ERG1; H-ERG; HERG; HERG1; Kv11.1;
                     LQT2; SQT1"
                     /note="isoform a is encoded by transcript variant 1;
                     ether-a-go-go-related potassium channel protein; human
                     ether-a-go-go-related; potassium channel, voltage gated
                     eag related subfamily H, member 2; potassium voltage-gated
                     channel, subfamily H (eag-related), member 2; eag homolog;
                     eag-related protein 1; ether-a-go-go-related protein 1;
                     ether-a-go-go-related gene potassium channel 1;
                     voltage-gated potassium channel subunit Kv11.1; long QT
                     syndrome type 2; voltage-gated inwardly rectifying
                     potassium channel KCNH2"
                     /codon_start=1
                     /product="voltage-gated inwardly rectifying potassium
                     channel KCNH2 isoform a"
                     /protein_id="NP_000229.1"
                     /db_xref="CCDS:CCDS5910.1"
                     /db_xref="GeneID:3757"
                     /db_xref="HGNC:HGNC:6251"
                     /db_xref="MIM:152427"
                     /translation="MPVRRGHVAPQNTFLDTIIRKFEGQSRKFIIANARVENCAVIYC
                     NDGFCELCGYSRAEVMQRPCTCDFLHGPRTQRRAAAQIAQALLGAEERKVEIAFYRKD
                     GSCFLCLVDVVPVKNEDGAVIMFILNFEVVMEKDMVGSPAHDTNHRGPPTSWLAPGRA
                     KTFRLKLPALLALTARESSVRSGGAGGAGAPGAVVVDVDLTPAAPSSESLALDEVTAM
                     DNHVAGLGPAEERRALVGPGSPPRSAPGQLPSPRAHSLNPDASGSSCSLARTRSRESC
                     ASVRRASSADDIEAMRAGVLPPPPRHASTGAMHPLRSGLLNSTSDSDLVRYRTISKIP
                     QITLNFVDLKGDPFLASPTSDREIIAPKIKERTHNVTEKVTQVLSLGADVLPEYKLQA
                     PRIHRWTILHYSPFKAVWDWLILLLVIYTAVFTPYSAAFLLKETEEGPPATECGYACQ
                     PLAVVDLIVDIMFIVDILINFRTTYVNANEEVVSHPGRIAVHYFKGWFLIDMVAAIPF
                     DLLIFGSGSEELIGLLKTARLLRLVRVARKLDRYSEYGAAVLFLLMCTFALIAHWLAC
                     IWYAIGNMEQPHMDSRIGWLHNLGDQIGKPYNSSGLGGPSIKDKYVTALYFTFSSLTS
                     VGFGNVSPNTNSEKIFSICVMLIGSLMYASIFGNVSAIIQRLYSGTARYHTQMLRVRE
                     FIRFHQIPNPLRQRLEEYFQHAWSYTNGIDMNAVLKGFPECLQADICLHLNRSLLQHC
                     KPFRGATKGCLRALAMKFKTTHAPPGDTLVHAGDLLTALYFISRGSIEILRGDVVVAI
                     LGKNDIFGEPLNLYARPGKSNGDVRALTYCDLHKIHRDDLLEVLDMYPEFSDHFWSSL
                     EITFNLRDTNMIPGSPGSTELEGGFSRQRKRKLSFRRRTDKDTEQPGEVSALGPGRAG
                     AGPSSRGRPGGPWGESPSSGPSSPESSEDEGPGRSSSPLRLVPFSSPRPPGEPPGGEP
                     LMEDCEKSSDTCNPLSGAFSGVSNIFSFWGDSRGRQYQELPRCPAPTPSLLNIPLSSP
                     GRRPRGDVESRLDALQRQLNRLETRLSADMATVLQLLQRQMTLVPPAYSAVTTPGPGP
                     TSTSPLLPVSPLPTLTLDSLSQVSQFMACEELPPGAPELPQEGPTRRLSLPGQLGALT
                     SQPLHRHGSDPGS"
     exon            485..715
                     /gene="KCNH2"
                     /gene_synonym="ERG-1; ERG1; H-ERG; HERG; HERG1; Kv11.1;
                     LQT2; SQT1"
                     /inference="alignment:Splign:2.1.0"
     exon            716..880
                     /gene="KCNH2"
                     /gene_synonym="ERG-1; ERG1; H-ERG; HERG; HERG1; Kv11.1;
                     LQT2; SQT1"
                     /inference="alignment:Splign:2.1.0"
     exon            881..1324
                     /gene="KCNH2"
                     /gene_synonym="ERG-1; ERG1; H-ERG; HERG; HERG1; Kv11.1;
                     LQT2; SQT1"
                     /inference="alignment:Splign:2.1.0"
     exon            1325..1536
                     /gene="KCNH2"
                     /gene_synonym="ERG-1; ERG1; H-ERG; HERG; HERG1; Kv11.1;
                     LQT2; SQT1"
                     /inference="alignment:Splign:2.1.0"
     exon            1537..1965
                     /gene="KCNH2"
                     /gene_synonym="ERG-1; ERG1; H-ERG; HERG; HERG1; Kv11.1;
                     LQT2; SQT1"
                     /inference="alignment:Splign:2.1.0"
     exon            1966..2353
                     /gene="KCNH2"
                     /gene_synonym="ERG-1; ERG1; H-ERG; HERG; HERG1; Kv11.1;
                     LQT2; SQT1"
                     /inference="alignment:Splign:2.1.0"
     exon            2354..2553
                     /gene="KCNH2"
                     /gene_synonym="ERG-1; ERG1; H-ERG; HERG; HERG1; Kv11.1;
                     LQT2; SQT1"
                     /inference="alignment:Splign:2.1.0"
     exon            2554..2806
                     /gene="KCNH2"
                     /gene_synonym="ERG-1; ERG1; H-ERG; HERG; HERG1; Kv11.1;
                     LQT2; SQT1"
                     /inference="alignment:Splign:2.1.0"
     exon            2807..3000
                     /gene="KCNH2"
                     /gene_synonym="ERG-1; ERG1; H-ERG; HERG; HERG1; Kv11.1;
                     LQT2; SQT1"
                     /inference="alignment:Splign:2.1.0"
     exon            3001..3100
                     /gene="KCNH2"
                     /gene_synonym="ERG-1; ERG1; H-ERG; HERG; HERG1; Kv11.1;
                     LQT2; SQT1"
                     /inference="alignment:Splign:2.1.0"
     exon            3101..3373
                     /gene="KCNH2"
                     /gene_synonym="ERG-1; ERG1; H-ERG; HERG; HERG1; Kv11.1;
                     LQT2; SQT1"
                     /inference="alignment:Splign:2.1.0"
     exon            3374..3560
                     /gene="KCNH2"
                     /gene_synonym="ERG-1; ERG1; H-ERG; HERG; HERG1; Kv11.1;
                     LQT2; SQT1"
                     /inference="alignment:Splign:2.1.0"
     exon            3561..3738
                     /gene="KCNH2"
                     /gene_synonym="ERG-1; ERG1; H-ERG; HERG; HERG1; Kv11.1;
                     LQT2; SQT1"
                     /inference="alignment:Splign:2.1.0"
     exon            3739..4292
                     /gene="KCNH2"
                     /gene_synonym="ERG-1; ERG1; H-ERG; HERG; HERG1; Kv11.1;
                     LQT2; SQT1"
                     /inference="alignment:Splign:2.1.0"
     regulatory      4270..4275
                     /regulatory_class="polyA_signal_sequence"
                     /gene="KCNH2"
                     /gene_synonym="ERG-1; ERG1; H-ERG; HERG; HERG1; Kv11.1;
                     LQT2; SQT1"
                     /note="hexamer: AATAAA"
     polyA_site      4292
                     /gene="KCNH2"
                     /gene_synonym="ERG-1; ERG1; H-ERG; HERG; HERG1; Kv11.1;
                     LQT2; SQT1"
                     /note="major polyA site"
ORIGIN      
        1 aacccttccg cggccgggcc gagccgcagg cgctgcccga gccgcgggcg ctggagcggc
       61 tgtcggcgcg gtggcaggcg ggagccagga gtccggggct cgggcgggcg gagcgcagcg
      121 cggggacgcg gcggagcggg ccccgcggct cggcgggggc cggcagacag gtgtgccggc
      181 ggcgggcggc tcgcgctcag gcggctccag gccgggcccg gggtccggag cggggagccg
      241 ggagccgagc gaggacccgg cgcccgcagt ccagtcttgg ccgcgcccgt gctcggcttg
      301 gccgcggggt gcggggacca cggcccggcc gggccacccg aagcctagtg ctgggccggg
      361 ccgggccggg gtgggtgggg gcccgcccgg cccgcccatg ggctcaggat gccggtgcgg
      421 aggggccacg tcgcgccgca gaacaccttc ctggacacca tcatccgcaa gtttgagggc
      481 cagagccgta agttcatcat cgccaacgct cgggtggaga actgcgccgt catctactgc
      541 aacgacggct tctgcgagct gtgcggctac tcgcgggccg aggtgatgca gcgaccctgc
      601 acctgcgact tcctgcacgg gccgcgcacg cagcgccgcg ctgccgcgca gatcgcgcag
      661 gcactgctgg gcgccgagga gcgcaaagtg gaaatcgcct tctaccggaa agatgggagc
      721 tgcttcctat gtctggtgga tgtggtgccc gtgaagaacg aggatggggc tgtcatcatg
      781 ttcatcctca atttcgaggt ggtgatggag aaggacatgg tggggtcccc ggctcatgac
      841 accaaccacc ggggcccccc caccagctgg ctggccccag gccgcgccaa gaccttccgc
      901 ctgaagctgc ccgcgctgct ggcgctgacg gcccgggagt cgtcggtgcg gtcgggcggc
      961 gcgggcggcg cgggcgcccc gggggccgtg gtggtggacg tggacctgac gcccgcggca
     1021 cccagcagcg agtcgctggc cctggacgaa gtgacagcca tggacaacca cgtggcaggg
     1081 ctcgggcccg cggaggagcg gcgtgcgctg gtgggtcccg gctctccgcc ccgcagcgcg
     1141 cccggccagc tcccatcgcc ccgggcgcac agcctcaacc ccgacgcctc gggctccagc
     1201 tgcagcctgg cccggacgcg ctcccgagaa agctgcgcca gcgtgcgccg cgcctcgtcg
     1261 gccgacgaca tcgaggccat gcgcgccggg gtgctgcccc cgccaccgcg ccacgccagc
     1321 accggggcca tgcacccact gcgcagcggc ttgctcaact ccacctcgga ctccgacctc
     1381 gtgcgctacc gcaccattag caagattccc caaatcaccc tcaactttgt ggacctcaag
     1441 ggcgacccct tcttggcttc gcccaccagt gaccgtgaga tcatagcacc taagataaag
     1501 gagcgaaccc acaatgtcac tgagaaggtc acccaggtcc tgtccctggg cgccgacgtg
     1561 ctgcctgagt acaagctgca ggcaccgcgc atccaccgct ggaccatcct gcattacagc
     1621 cccttcaagg ccgtgtggga ctggctcatc ctgctgctgg tcatctacac ggctgtcttc
     1681 acaccctact cggctgcctt cctgctgaag gagacggaag aaggcccgcc tgctaccgag
     1741 tgtggctacg cctgccagcc gctggctgtg gtggacctca tcgtggacat catgttcatt
     1801 gtggacatcc tcatcaactt ccgcaccacc tacgtcaatg ccaacgagga ggtggtcagc
     1861 caccccggcc gcatcgccgt ccactacttc aagggctggt tcctcatcga catggtggcc
     1921 gccatcccct tcgacctgct catcttcggc tctggctctg aggagctgat cgggctgctg
     1981 aagactgcgc ggctgctgcg gctggtgcgc gtggcgcgga agctggatcg ctactcagag
     2041 tacggcgcgg ccgtgctgtt cttgctcatg tgcacctttg cgctcatcgc gcactggcta
     2101 gcctgcatct ggtacgccat cggcaacatg gagcagccac acatggactc acgcatcggc
     2161 tggctgcaca acctgggcga ccagataggc aaaccctaca acagcagcgg cctgggcggc
     2221 ccctccatca aggacaagta tgtgacggcg ctctacttca ccttcagcag cctcaccagt
     2281 gtgggcttcg gcaacgtctc tcccaacacc aactcagaga agatcttctc catctgcgtc
     2341 atgctcattg gctccctcat gtatgctagc atcttcggca acgtgtcggc catcatccag
     2401 cggctgtact cgggcacagc ccgctaccac acacagatgc tgcgggtgcg ggagttcatc
     2461 cgcttccacc agatccccaa tcccctgcgc cagcgcctcg aggagtactt ccagcacgcc
     2521 tggtcctaca ccaacggcat cgacatgaac gcggtgctga agggcttccc tgagtgcctg
     2581 caggctgaca tctgcctgca cctgaaccgc tcactgctgc agcactgcaa acccttccga
     2641 ggggccacca agggctgcct tcgggccctg gccatgaagt tcaagaccac acatgcaccg
     2701 ccaggggaca cactggtgca tgctggggac ctgctcaccg ccctgtactt catctcccgg
     2761 ggctccatcg agatcctgcg gggcgacgtc gtcgtggcca tcctggggaa gaatgacatc
     2821 tttggggagc ctctgaacct gtatgcaagg cctggcaagt cgaacgggga tgtgcgggcc
     2881 ctcacctact gtgacctaca caagatccat cgggacgacc tgctggaggt gctggacatg
     2941 taccctgagt tctccgacca cttctggtcc agcctggaga tcaccttcaa cctgcgagat
     3001 accaacatga tcccgggctc ccccggcagt acggagttag agggtggctt cagtcggcaa
     3061 cgcaagcgca agttgtcctt ccgcaggcgc acggacaagg acacggagca gccaggggag
     3121 gtgtcggcct tggggccggg ccgggcgggg gcagggccga gtagccgggg ccggccgggg
     3181 gggccgtggg gggagagccc gtccagtggc ccctccagcc ctgagagcag tgaggatgag
     3241 ggcccaggcc gcagctccag ccccctccgc ctggtgccct tctccagccc caggcccccc
     3301 ggagagccgc cgggtgggga gcccctgatg gaggactgcg agaagagcag cgacacttgc
     3361 aaccccctgt caggcgcctt ctcaggagtg tccaacattt tcagcttctg gggggacagt
     3421 cggggccgcc agtaccagga gctccctcga tgccccgccc ccacccccag cctcctcaac
     3481 atccccctct ccagcccggg tcggcggccc cggggcgacg tggagagcag gctggatgcc
     3541 ctccagcgcc agctcaacag gctggagacc cggctgagtg cagacatggc cactgtcctg
     3601 cagctgctac agaggcagat gacgctggtc ccgcccgcct acagtgctgt gaccaccccg
     3661 gggcctggcc ccacttccac atccccgctg ttgcccgtca gccccctccc caccctcacc
     3721 ttggactcgc tttctcaggt ttcccagttc atggcgtgtg aggagctgcc cccgggggcc
     3781 ccagagcttc cccaagaagg ccccacacga cgcctctccc taccgggcca gctgggggcc
     3841 ctcacctccc agcccctgca cagacacggc tcggacccgg gcagttagtg gggctgccca
     3901 gtgtggacac gtggctcacc cagggatcaa ggcgctgctg ggccgctccc cttggaggcc
     3961 ctgctcagga ggccctgacc gtggaagggg agaggaactc gaaagcacag ctcctccccc
     4021 agcccttggg accatcttct cctgcagtcc cctgggcccc agtgagaggg gcaggggcag
     4081 ggccggcagt aggtggggcc tgtggtcccc ccactgccct gagggcatta gctggtctaa
     4141 ctgcccggag gcacccggcc ctgggcctta ggcacctcaa ggacttttct gctatttact
     4201 gctcttattg ttaaggataa taattaagga tcatatgaat aattaatgaa gatgctgatg
     4261 actatgaata ataaataatt atcctgagga ga
//
