LOCUS       NM_139137               5596 bp    mRNA    linear   PRI 05-AUG-2024
DEFINITION  Homo sapiens potassium voltage-gated channel subfamily C member 2
            (KCNC2), transcript variant 2, mRNA.
ACCESSION   NM_139137
VERSION     NM_139137.4
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 5596)
  AUTHORS   Li,L., Liu,Z., Yang,H., Li,Y., Zeng,Q., Chen,L., Liu,Y., Chen,Y.,
            Zhu,F., Cao,D., Hu,J. and Shen,X.
  TITLE     Investigation of novel de novo KCNC2 variants causing severe
            developmental and early-onset epileptic encephalopathy
  JOURNAL   Seizure 101, 218-224 (2022)
   PUBMED   36087422
  REMARK    GeneRIF: Investigation of novel de novo KCNC2 variants causing
            severe developmental and early-onset epileptic encephalopathy.
REFERENCE   2  (bases 1 to 5596)
  AUTHORS   Wang,S., Yu,Y., Wang,X., Deng,X., Ma,J., Liu,Z., Gu,W. and Sun,D.
  TITLE     Emerging evidence of genotype-phenotype associations of
            developmental and epileptic encephalopathy due to KCNC2 mutation:
            Identification of novel R405G
  JOURNAL   Front Mol Neurosci 15, 950255 (2022)
   PUBMED   36090251
  REMARK    Publication Status: Online-Only
REFERENCE   3  (bases 1 to 5596)
  AUTHORS   Schwarz,N., Seiffert,S., Pendziwiat,M., Rademacher,A.V.,
            Brunger,T., Hedrich,U.B.S., Augustijn,P.B., Baier,H., Bayat,A.,
            Bisulli,F., Buono,R.J., Bruria,B.Z., Doyle,M.G., Guerrini,R.,
            Heimer,G., Iacomino,M., Kearney,H., Klein,K.M., Kousiappa,I.,
            Kunz,W.S., Lerche,H., Licchetta,L., Lohmann,E., Minardi,R.,
            McDonald,M., Montgomery,S., Mulahasanovic,L., Oegema,R., Ortal,B.,
            Papacostas,S.S., Ragona,F., Granata,T., Reif,P.S., Rosenow,F.,
            Rothschild,A., Scudieri,P., Striano,P., Tinuper,P., Tanteles,G.A.,
            Vetro,A., Zahnert,F., Goldberg,E.M., Zara,F., Lal,D., May,P.,
            Muhle,H., Helbig,I. and Weber,Y.
  TITLE     Spectrum of Phenotypic, Genetic, and Functional Characteristics in
            Patients With Epilepsy With KCNC2 Pathogenic Variants
  JOURNAL   Neurology 98 (20), e2046-e2059 (2022)
   PUBMED   35314505
  REMARK    GeneRIF: Spectrum of Phenotypic, Genetic, and Functional
            Characteristics in Patients With Epilepsy With KCNC2 Pathogenic
            Variants.
REFERENCE   4  (bases 1 to 5596)
  AUTHORS   Rydzanicz,M., Zwolinski,P., Gasperowicz,P., Pollak,A.,
            Kostrzewa,G., Walczak,A., Konarzewska,M. and Ploski,R.
  TITLE     A recurrent de novo variant supports KCNC2 involvement in the
            pathogenesis of developmental and epileptic encephalopathy
  JOURNAL   Am J Med Genet A 185 (11), 3384-3389 (2021)
   PUBMED   34448338
  REMARK    GeneRIF: A recurrent de novo variant supports KCNC2 involvement in
            the pathogenesis of developmental and epileptic encephalopathy.
REFERENCE   5  (bases 1 to 5596)
  AUTHORS   Rademacher,A., Schwarz,N., Seiffert,S., Pendziwiat,M., Rohr,A., van
            Baalen,A., Helbig,I., Weber,Y. and Muhle,H.
  TITLE     Whole-Exome Sequencing in NF1-Related West Syndrome Leads to the
            Identification of KCNC2 as a Novel Candidate Gene for Epilepsy
  JOURNAL   Neuropediatrics 51 (5), 368-372 (2020)
   PUBMED   32392612
REFERENCE   6  (bases 1 to 5596)
  AUTHORS   Boda,E., Hoxha,E., Pini,A., Montarolo,F. and Tempia,F.
  TITLE     Brain expression of Kv3 subunits during development, adulthood and
            aging and in a murine model of Alzheimer's disease
  JOURNAL   J Mol Neurosci 46 (3), 606-615 (2012)
   PUBMED   21912965
  REMARK    GeneRIF: Although all KV3 subunit transcripts are significantly
            expressed at embryonic age in whole brain extracts, only KV3.1,
            KV3.2 and KV3.4 subunit transgenic proteins are present.
REFERENCE   7  (bases 1 to 5596)
  AUTHORS   Wang,Z., Wong,N.C., Cheng,Y., Kehl,S.J. and Fedida,D.
  TITLE     Control of voltage-gated K+ channel permeability to NMDG+ by a
            residue at the outer pore
  JOURNAL   J Gen Physiol 133 (4), 361-374 (2009)
   PUBMED   19332619
  REMARK    GeneRIF: In the absence of potassium ion, significant
            N-methyl-D-glucamine (NMDG)-positive currents could be recorded
            from human embryonic kidney cells expressing Kv3.1 or Kv3.2b
            channels and Kv1.5 Arg487Tyr/Val, but not wild-type channels.
REFERENCE   8  (bases 1 to 5596)
  AUTHORS   Gutman,G.A., Chandy,K.G., Grissmer,S., Lazdunski,M., McKinnon,D.,
            Pardo,L.A., Robertson,G.A., Rudy,B., Sanguinetti,M.C., Stuhmer,W.
            and Wang,X.
  TITLE     International Union of Pharmacology. LIII. Nomenclature and
            molecular relationships of voltage-gated potassium channels
  JOURNAL   Pharmacol Rev 57 (4), 473-508 (2005)
   PUBMED   16382104
  REMARK    Review article
REFERENCE   9  (bases 1 to 5596)
  AUTHORS   Yan,L., Herrington,J., Goldberg,E., Dulski,P.M., Bugianesi,R.M.,
            Slaughter,R.S., Banerjee,P., Brochu,R.M., Priest,B.T.,
            Kaczorowski,G.J., Rudy,B. and Garcia,M.L.
  TITLE     Stichodactyla helianthus peptide, a pharmacological tool for
            studying Kv3.2 channels
  JOURNAL   Mol Pharmacol 67 (5), 1513-1521 (2005)
   PUBMED   15709110
REFERENCE   10 (bases 1 to 5596)
  AUTHORS   Haas,M., Ward,D.C., Lee,J., Roses,A.D., Clarke,V., D'Eustachio,P.,
            Lau,D., Vega-Saenz de Miera,E. and Rudy,B.
  TITLE     Localization of Shaw-related K+ channel genes on mouse and human
            chromosomes
  JOURNAL   Mamm Genome 4 (12), 711-715 (1993)
   PUBMED   8111118
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AC091534.7, DC323864.1,
            AY118169.1, AC073525.25 and DA218546.1.
            
            On Jun 2, 2019 this sequence version replaced NM_139137.3.
            
            Summary: The Shaker gene family of Drosophila encodes components of
            voltage-gated potassium channels and is comprised of four
            subfamilies. Based on sequence similarity, this gene is similar to
            one of these subfamilies, namely the Shaw subfamily. The protein
            encoded by this gene belongs to the delayed rectifier class of
            channel proteins and is an integral membrane protein that mediates
            the voltage-dependent potassium ion permeability of excitable
            membranes. Several transcript variants encoding different isoforms
            have been found for this gene. [provided by RefSeq, May 2012].
            
            Transcript Variant: This variant (2) encodes the longest isoform
            (KV3.2b). Variants 2 and 7 both encode the same isoform (KV3.2b).
            
            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 :: AB209994.1, SRR1803616.450.1
                                           [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA2145743, SAMEA2154665
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000549446.6/ ENSP00000449253.2
            RefSeq Select criteria :: based on manual assertion, conservation,
                                      expression, longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-91                AC091534.7         110306-110396       c
            92-652              DC323864.1         1-561
            653-2569            AY118169.1         1-1917
            2570-5055           AC073525.25        18320-20805
            5056-5596           DA218546.1         7-547
FEATURES             Location/Qualifiers
     source          1..5596
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="12"
                     /map="12q21.1"
     gene            1..5596
                     /gene="KCNC2"
                     /gene_synonym="DEE103; KV3.2"
                     /note="potassium voltage-gated channel subfamily C member
                     2"
                     /db_xref="GeneID:3747"
                     /db_xref="HGNC:HGNC:6234"
                     /db_xref="MIM:176256"
     exon            1..633
                     /gene="KCNC2"
                     /gene_synonym="DEE103; KV3.2"
                     /inference="alignment:Splign:2.1.0"
     exon            634..1339
                     /gene="KCNC2"
                     /gene_synonym="DEE103; KV3.2"
                     /inference="alignment:Splign:2.1.0"
     CDS             653..2569
                     /gene="KCNC2"
                     /gene_synonym="DEE103; KV3.2"
                     /note="isoform KV3.2b is encoded by transcript variant 2;
                     voltage-gated potassium channel Kv3.2; potassium
                     voltage-gated channel, Shaw-related subfamily, member 2;
                     shaw-like potassium channel; potassium channel, voltage
                     gated Shaw related subfamily C, member 2; voltage-gated
                     potassium channel KCNC2"
                     /codon_start=1
                     /product="voltage-gated potassium channel KCNC2 isoform
                     KV3.2b"
                     /protein_id="NP_631875.1"
                     /db_xref="CCDS:CCDS9007.1"
                     /db_xref="GeneID:3747"
                     /db_xref="HGNC:HGNC:6234"
                     /db_xref="MIM:176256"
                     /translation="MGKIENNERVILNVGGTRHETYRSTLKTLPGTRLALLASSEPPG
                     DCLTTAGDKLQPSPPPLSPPPRAPPLSPGPGGCFEGGAGNCSSRGGRASDHPGGGREF
                     FFDRHPGVFAYVLNYYRTGKLHCPADVCGPLFEEELAFWGIDETDVEPCCWMTYRQHR
                     DAEEALDIFETPDLIGGDPGDDEDLAAKRLGIEDAAGLGGPDGKSGRWRRLQPRMWAL
                     FEDPYSSRAARFIAFASLFFILVSITTFCLETHEAFNIVKNKTEPVINGTSVVLQYEI
                     ETDPALTYVEGVCVVWFTFEFLVRIVFSPNKLEFIKNLLNIIDFVAILPFYLEVGLSG
                     LSSKAAKDVLGFLRVVRFVRILRIFKLTRHFVGLRVLGHTLRASTNEFLLLIIFLALG
                     VLIFATMIYYAERVGAQPNDPSASEHTQFKNIPIGFWWAVVTMTTLGYGDMYPQTWSG
                     MLVGALCALAGVLTIAMPVPVIVNNFGMYYSLAMAKQKLPRKRKKHIPPAPQASSPTF
                     CKTELNMACNSTQSDTCLGKDNRLLEHNRSVLSGDDSTGSEPPLSPPERLPIRRSSTR
                     DKNRRGETCFLLTTGDYTCASDGGIRKGYEKSRSLNNIAGLAGNALRLSPVTSPYNSP
                     CPLRRSRSPIPSIL"
     exon            1340..2267
                     /gene="KCNC2"
                     /gene_synonym="DEE103; KV3.2"
                     /inference="alignment:Splign:2.1.0"
     exon            2268..2432
                     /gene="KCNC2"
                     /gene_synonym="DEE103; KV3.2"
                     /inference="alignment:Splign:2.1.0"
     exon            2433..5596
                     /gene="KCNC2"
                     /gene_synonym="DEE103; KV3.2"
                     /inference="alignment:Splign:2.1.0"
     regulatory      5535..5540
                     /regulatory_class="polyA_signal_sequence"
                     /gene="KCNC2"
                     /gene_synonym="DEE103; KV3.2"
                     /note="hexamer: AATAAA"
     polyA_site      5568
                     /gene="KCNC2"
                     /gene_synonym="DEE103; KV3.2"
     regulatory      5578..5583
                     /regulatory_class="polyA_signal_sequence"
                     /gene="KCNC2"
                     /gene_synonym="DEE103; KV3.2"
                     /note="hexamer: ATTAAA"
     polyA_site      5596
                     /gene="KCNC2"
                     /gene_synonym="DEE103; KV3.2"
                     /note="major polyA site"
ORIGIN      
        1 agaagctcca gagagggtgg agacagagct tcacggaaga aaaatatgtg aacctggttg
       61 gtacacatag cttctccaga cccacccacc cactctttcc tgagccctgt gcttcggatg
      121 gcggcgggag gttgatggcg agtggtgctg aagggacagc tccagcagtg gctgatttgg
      181 gggagaaaca aaatctgcag atggaatccg agcagggcga cttcaccttc aagtggtgag
      241 ctctcctgac ctgcggccag tctccactcc attcacggcc agccgatctg cccgctcccg
      301 gaggggtcgg gcagtgccgg ctggacccgc cccgagctcc atggtttgcc caaccctgcg
      361 cgatggtgac tctgggcgcg gaggttggcg actggcaaat ccgcagatca cagaatgaag
      421 gcggggagcg cggccggcgg ccggcggggg ctttctcccc caccccagcg cccagggaag
      481 cggctcaacc acctgaatcc ggaaaacgcc aacaagtagt ttctcgtcgg agaagggcgg
      541 ctcacctggg cgccaagact cagtcccgct gcccagagaa cctcgtccac tcggaaacca
      601 aagcagaacc acttttctct cggtctcgtt aagtcatgtc tgagtcacag agatgggcaa
      661 gatcgagaac aacgagaggg tgatcctcaa tgtcgggggc acccggcacg aaacctaccg
      721 cagcaccctc aagaccctgc ctggaacacg cctggccctt cttgcctcct ccgagccccc
      781 aggcgactgc ttgaccacgg cgggcgacaa gctgcagccg tcgccgcctc cactgtcgcc
      841 gccgccgaga gcgcccccgc tgtcccccgg gccaggcggc tgcttcgagg gcggcgcggg
      901 caactgcagt tcccgcggcg gcagggccag cgaccatccc ggtggcggcc gcgagttctt
      961 cttcgaccgg cacccgggcg tcttcgccta tgtgctcaat tactaccgca ccggcaagct
     1021 gcactgcccc gcagacgtgt gcgggccgct cttcgaggag gagctggcct tctggggcat
     1081 cgacgagacc gacgtggagc cctgctgctg gatgacctac cggcagcacc gcgacgccga
     1141 ggaggcgctg gacatcttcg agacccccga cctcattggc ggcgaccccg gcgacgacga
     1201 ggacctggcg gccaagaggc tgggcatcga ggacgcggcg gggctcgggg gccccgacgg
     1261 caaatctggc cgctggagga ggctgcagcc ccgcatgtgg gccctcttcg aagaccccta
     1321 ctcgtccaga gccgccaggt ttattgcttt tgcttcttta ttcttcatcc tggtttcaat
     1381 tacaactttt tgcctggaaa cacatgaagc tttcaatatt gttaaaaaca agacagaacc
     1441 agtcatcaat ggcacaagtg ttgttctaca gtatgaaatt gaaacggatc ctgccttgac
     1501 gtatgtagaa ggagtgtgtg tggtgtggtt tacttttgaa tttttagtcc gtattgtttt
     1561 ttcacccaat aaacttgaat tcatcaaaaa tctcttgaat atcattgact ttgtggccat
     1621 cctacctttc tacttagagg tgggactcag tgggctgtca tccaaagctg ctaaagatgt
     1681 gcttggcttc ctcagggtgg taaggtttgt gaggatcctg agaattttca agctcacccg
     1741 ccattttgta ggtctgaggg tgcttggaca tactcttcga gctagtacta atgaattttt
     1801 gctgctgata attttcctgg ctctaggagt tttgatattt gctaccatga tctactatgc
     1861 cgagagagtg ggagctcaac ctaacgaccc ttcagctagt gagcacacac agttcaaaaa
     1921 cattcccatt gggttctggt gggctgtagt gaccatgact accctgggtt atggggatat
     1981 gtacccccaa acatggtcag gcatgctggt gggagccctg tgtgctctgg ctggagtgct
     2041 gacaatagcc atgccagtgc ctgtcattgt caataatttt ggaatgtact actccttggc
     2101 aatggcaaag cagaaacttc caaggaaaag aaagaagcac atccctcctg ctcctcaggc
     2161 aagctcacct actttttgca agacagaatt aaatatggcc tgcaatagta cacagagtga
     2221 cacatgtctg ggcaaagaca atcgacttct ggaacataac agatcagtgt tatcaggtga
     2281 cgacagtaca ggaagtgagc cgccactatc acccccagaa aggctcccca tcagacgctc
     2341 tagtaccaga gacaaaaaca gaagagggga aacatgtttc ctactgacga caggtgatta
     2401 cacgtgtgct tctgatggag ggatcaggaa aggatatgaa aaatcccgaa gcttaaacaa
     2461 catagcgggc ttggcaggca atgctctgag gctctctcca gtaacatcac cctacaactc
     2521 tccttgtcct ctgaggcgct ctcgatctcc catcccatct atcttgtaaa ccaaacaacc
     2581 aaactgcatc agtcggctaa attgtattaa ttcaagtgct gtttacccca taatggaaat
     2641 aattaaatgt agagttactc caggctccat taatacagta taaatcttgc atgatactac
     2701 aatttgaagt cagaaatgcc acttgggtag ctaatgaatc ttacccaggc tttaaagatt
     2761 gtctaaagta gtgctaagat ccctcctatt aattgccctg atatcctttt gcaataaaat
     2821 gacagatagt gtcagatatt gaccagtgca ctaatatata aacatacctt cagggagata
     2881 tatttaaaac agtgtgcttc caaatgccaa ccacttcatt ggaactttat ttcttgtgac
     2941 tgtaaaccat tctgaagatg tctgggatcc tatcttgatt gcacacgaca tgacttgtgt
     3001 cagctcattt gcatggacca tcttgtctct atcacctgaa agcaatgttg cagagttcgg
     3061 ggactgtgga tagctcagga tatgtgtact tgcatcgaac catcctgctg atatgaaagc
     3121 attggtcgac tgttctgcat gttgaattgt ggggcaggga gggcactttt ctccttgaca
     3181 tttttttctt attatttgaa agaaatatat gttttaaata gtttaatttc ttgattgatt
     3241 tacttttctt caaaaatgct gtattggagt tctgaatgtc tctggttgtt tgcacacaga
     3301 taactgcaaa gaggttgtca ttactggtta cacgcaagcc gaggccagat ctcttactta
     3361 atgacttggg gaaggcacaa aacatgagag aaaggtaact gccagccagg cttgcattgt
     3421 ttagccagaa attgctgctt ggttctagac tctttaaaaa aaaaaaatac ccagggtttg
     3481 tcatcatttt cagaggcaga gtgccaaata tcacccaaag ctcttgtgtc ttttttttac
     3541 ccccttattt tatttttatt tattaatttt ttgtgcaaac atcaaatgtc actggtgttc
     3601 acagaaggct tttttgacta gccttaaatt cctgagtcaa aagattaatc agattttcag
     3661 gcagtgttta atcaggtgct ttgtcctgta tgttgttctt gtctgtctta gctccctgtc
     3721 tttcctgtat atgccatctg tctccatgaa gcacagaaat gcctctgtaa gatgtttatg
     3781 attttaatat ttactccctc caaacccgac tccataccat tttttgctat ttggagcagc
     3841 ctctctgctt tgtgtataaa ttaatgatgc tctgtagact acctaagtta atcggcactg
     3901 tgaatctttt tgataagcag ggtttaagca gcaatttcac cattgcactt ggttgcctgc
     3961 tgcagtgtca gtttctacta cctagcaacc agcattcatt actacactcc aacaaaatcc
     4021 ttagggagtc atattcagtc tgagtggaag aaagtctatt tatgcattcc tatgaattca
     4081 acagcaatag cgtgtctcat gtattgagca tgtgagggaa gaaaaagacc gtaatataaa
     4141 tagagggata aataatatca ctaaggcatt tgggagcctt gagactgctg attaattcct
     4201 atttctcatg tttatttttt gttaggaaga caattgtcac ttttattatt ggccacgaaa
     4261 catgtattac tctatatccc caagtcctag agcatgacct gcatgttgga gatgttgtac
     4321 agcaatgtat ttatccagac atacatatat gatatttaga gacacagtga ttcttttgat
     4381 aacaccacac atagaacatt ataattacac acaaatttat ggtaaaagaa ttaatatgct
     4441 gtctggtgct gctgttattg actacagtgt tgtacagaat ttatcatgga ttattgactg
     4501 ctgagaaagg gacagtggaa tttagccata ccaaggacta tactggaaac agacttctgc
     4561 tgctgaatgt gccctgatgt gaccaggttg cacttggaag agatcctcgc gtcttcatga
     4621 ggcacttaaa gcttataaaa gaactgcggc tggaactcat ctggtgctcc ccatgagagt
     4681 gctctgcttg tagactggcc agtgtccatg aaacaactgt aaataccaac atgtgtgcat
     4741 gggtcaacag tcttggccat ttctcatcaa aagaagccaa attcatgatc aacatctctg
     4801 aagtttcaag taaggcccac acttctttga attactcttc atgggcccac attaggttgt
     4861 gctgtgaatt acttaaggca gtgatactga tgtagtatag ttttgtctta atttccctta
     4921 tttctacttc tttggttgaa tctatgaact tgattgtata attttcttat aaattactga
     4981 tgtaatcagc ttgtcaatta tgttgtgaaa ttgttagtat tcatttatca aaaatgacct
     5041 atgtttagtc acatatttgt ttagttctgg gaaattgtta tagcttaaat ggaactcacc
     5101 aacattattc atagtttaag tcttttatca ttattacctc aattataaat attacaaaaa
     5161 cataattctg gcaatgagag tattttttta ttcaatgatc aaggagcaat gtcagtatat
     5221 agtagaatat caattaaatt atatcctaaa atgtatattt tgcataaaag agatattctt
     5281 taatcaatta cttttttgtg agttttgtgg caaatgaagc ttgtacgtgt ctttaaaact
     5341 gttgtagatg aaactgtata agatttttac atcttgctta atcaatattt tcagagtcta
     5401 ttagttcccc tgggattctg aatataacat atagcctatt ataaatccct gtatcgtgga
     5461 ccttttgtga acatttcaag gcgcatgcac aaccttgatg ataaccagtg gaaatgtaac
     5521 taactgaaat gaagaataaa aggcaaatga gctggggata aacttgaatg ttatctgatt
     5581 aaattactca aattat
//
