LOCUS       NM_001194               3420 bp    mRNA    linear   PRI 27-APR-2025
DEFINITION  Homo sapiens hyperpolarization activated cyclic nucleotide gated
            potassium and sodium channel 2 (HCN2), mRNA.
ACCESSION   NM_001194
VERSION     NM_001194.4
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 3420)
  AUTHORS   Pai,V.P. and Levin,M.
  TITLE     HCN2 channel-induced rescue of brain, eye, heart and gut
            teratogenesis caused by nicotine, ethanol and aberrant notch
            signalling
  JOURNAL   Wound Repair Regen 30 (6), 681-706 (2022)
   PUBMED   35662339
  REMARK    GeneRIF: HCN2 channel-induced rescue of brain, eye, heart and gut
            teratogenesis caused by nicotine, ethanol and aberrant notch
            signalling.
REFERENCE   2  (bases 1 to 3420)
  AUTHORS   Lin,W., Qin,J., Ni,G., Li,Y., Xie,H., Yu,J., Li,H., Sui,L., Guo,Q.,
            Fang,Z. and Zhou,L.
  TITLE     Downregulation of hyperpolarization-activated cyclic
            nucleotide-gated channels (HCN) in the hippocampus of patients with
            medial temporal lobe epilepsy and hippocampal sclerosis (MTLE-HS)
  JOURNAL   Hippocampus 30 (10), 1112-1126 (2020)
   PUBMED   32543742
  REMARK    GeneRIF: Downregulation of hyperpolarization-activated cyclic
            nucleotide-gated channels (HCN) in the hippocampus of patients with
            medial temporal lobe epilepsy and hippocampal sclerosis (MTLE-HS).
REFERENCE   3  (bases 1 to 3420)
  AUTHORS   Zhao,H., Wang,F., Tang,Y., Wang,X., Wang,T., Zhao,Q. and Huang,C.
  TITLE     HCN2 and TBX3 Reprogram Human-Induced Pluripotent Stem
            Cells-Derived Cardiomyocytes into Pacemaker-Like Cells
  JOURNAL   DNA Cell Biol 39 (2), 289-298 (2020)
   PUBMED   31916853
  REMARK    GeneRIF: overexpression of TBX3 and HCN2 could reprogram
            human-induced pluripotent stem cells-derived cardiomyocytes into
            pacemaker-like cells
REFERENCE   4  (bases 1 to 3420)
  AUTHORS   Thomas,M., Ranjith,G., Radhakrishnan,A. and Arun Anirudhan,V.
  TITLE     Effects of HCN2 Mutations on Dendritic Excitability and Synaptic
            Plasticity: A Computational Study
  JOURNAL   Neuroscience 423, 148-161 (2019)
   PUBMED   31682955
  REMARK    GeneRIF: Effects of HCN2 Mutations on Dendritic Excitability and
            Synaptic Plasticity: A Computational Study.
REFERENCE   5  (bases 1 to 3420)
  AUTHORS   Li,M., Maljevic,S., Phillips,A.M., Petrovski,S., Hildebrand,M.S.,
            Burgess,R., Mount,T., Zara,F., Striano,P., Schubert,J., Thiele,H.,
            Nurnberg,P., Wong,M., Weisenberg,J.L., Thio,L.L., Lerche,H.,
            Scheffer,I.E., Berkovic,S.F., Petrou,S. and Reid,C.A.
  TITLE     Gain-of-function HCN2 variants in genetic epilepsy
  JOURNAL   Hum Mutat 39 (2), 202-209 (2018)
   PUBMED   29064616
  REMARK    GeneRIF: Data suggest that HCN2 variants can confer susceptibility
            to Genetic generalized epilepsy via a gain-of-function mechanism.
REFERENCE   6  (bases 1 to 3420)
  AUTHORS   Vaccari,T., Moroni,A., Rocchi,M., Gorza,L., Bianchi,M.E.,
            Beltrame,M. and DiFrancesco,D.
  TITLE     The human gene coding for HCN2, a pacemaker channel of the heart
  JOURNAL   Biochim Biophys Acta 1446 (3), 419-425 (1999)
   PUBMED   10524219
REFERENCE   7  (bases 1 to 3420)
  AUTHORS   Ludwig,A., Zong,X., Stieber,J., Hullin,R., Hofmann,F. and Biel,M.
  TITLE     Two pacemaker channels from human heart with profoundly different
            activation kinetics
  JOURNAL   EMBO J 18 (9), 2323-2329 (1999)
   PUBMED   10228147
REFERENCE   8  (bases 1 to 3420)
  AUTHORS   Kleiderlein,J.J., Nisson,P.E., Jessee,J., Li,W.B., Becker,K.G.,
            Derby,M.L., Ross,C.A. and Margolis,R.L.
  TITLE     CCG repeats in cDNAs from human brain
  JOURNAL   Hum Genet 103 (6), 666-673 (1998)
   PUBMED   9921901
  REMARK    Erratum:[Hum Genet 1999 Jan;104(1):113]
REFERENCE   9  (bases 1 to 3420)
  AUTHORS   Santoro,B., Liu,D.T., Yao,H., Bartsch,D., Kandel,E.R.,
            Siegelbaum,S.A. and Tibbs,G.R.
  TITLE     Identification of a gene encoding a hyperpolarization-activated
            pacemaker channel of brain
  JOURNAL   Cell 93 (5), 717-729 (1998)
   PUBMED   9630217
REFERENCE   10 (bases 1 to 3420)
  AUTHORS   Santoro,B., Grant,S.G., Bartsch,D. and Kandel,E.R.
  TITLE     Interactive cloning with the SH3 domain of N-src identifies a new
            brain specific ion channel protein, with homology to eag and cyclic
            nucleotide-gated channels
  JOURNAL   Proc Natl Acad Sci U S A 94 (26), 14815-14820 (1997)
   PUBMED   9405696
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AC005559.2, AJ012582.1,
            BC039619.1 and AF065164.2.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Nov 23, 2018 this sequence version replaced NM_001194.3.
            
            Summary: The protein encoded by this gene is a
            hyperpolarization-activated cation channel involved in the
            generation of native pacemaker activity in the heart and in the
            brain. The encoded protein is activated by cAMP and can produce a
            fast, large current. Defects in this gene were noted as a possible
            cause of some forms of epilepsy. [provided by RefSeq, Jan 2017].
            
            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 :: AJ012582.1, AF065164.2 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1965299, SAMEA1968968
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000251287.3/ ENSP00000251287.1
            RefSeq Select criteria :: based on single protein-coding transcript
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-12                AC005559.2         17705-17716
            13-985              AJ012582.1         1-973
            986-1231            BC039619.1         487-732
            1232-1936           AJ012582.1         1220-1924
            1937-3402           AF065164.2         1907-3372
            3403-3420           AJ012582.1         3391-3408
FEATURES             Location/Qualifiers
     source          1..3420
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="19"
                     /map="19p13.3"
     gene            1..3420
                     /gene="HCN2"
                     /gene_synonym="BCNG-2; BCNG2; EIG17; FEB2; GEFSP11; HAC-1"
                     /note="hyperpolarization activated cyclic nucleotide gated
                     potassium and sodium channel 2"
                     /db_xref="GeneID:610"
                     /db_xref="HGNC:HGNC:4846"
                     /db_xref="MIM:602781"
     exon            1..697
                     /gene="HCN2"
                     /gene_synonym="BCNG-2; BCNG2; EIG17; FEB2; GEFSP11; HAC-1"
                     /inference="alignment:Splign:2.1.0"
     CDS             66..2735
                     /gene="HCN2"
                     /gene_synonym="BCNG-2; BCNG2; EIG17; FEB2; GEFSP11; HAC-1"
                     /note="brain cyclic nucleotide-gated channel 2;
                     hyperpolarization activated cyclic nucleotide gated
                     potassium channel 2"
                     /codon_start=1
                     /product="potassium/sodium hyperpolarization-activated
                     cyclic nucleotide-gated channel 2"
                     /protein_id="NP_001185.3"
                     /db_xref="CCDS:CCDS12035.1"
                     /db_xref="GeneID:610"
                     /db_xref="HGNC:HGNC:4846"
                     /db_xref="MIM:602781"
                     /translation="MDARGGGGRPGESPGATPAPGPPPPPPPAPPQQQPPPPPPPAPP
                     PGPGPAPPQHPPRAEALPPEAADEGGPRGRLRSRDSSCGRPGTPGAASTAKGSPNGEC
                     GRGEPQCSPAGPEGPARGPKVSFSCRGAASGPAPGPGPAEEAGSEEAGPAGEPRGSQA
                     SFMQRQFGALLQPGVNKFSLRMFGSQKAVEREQERVKSAGAWIIHPYSDFRFYWDFTM
                     LLFMVGNLIIIPVGITFFKDETTAPWIVFNVVSDTFFLMDLVLNFRTGIVIEDNTEII
                     LDPEKIKKKYLRTWFVVDFVSSIPVDYIFLIVEKGIDSEVYKTARALRIVRFTKILSL
                     LRLLRLSRLIRYIHQWEEIFHMTYDLASAVMRICNLISMMLLLCHWDGCLQFLVPMLQ
                     DFPRNCWVSINGMVNHSWSELYSFALFKAMSHMLCIGYGRQAPESMTDIWLTMLSMIV
                     GATCYAMFIGHATALIQSLDSSRRQYQEKYKQVEQYMSFHKLPADFRQKIHDYYEHRY
                     QGKMFDEDSILGELNGPLREEIVNFNCRKLVASMPLFANADPNFVTAMLTKLKFEVFQ
                     PGDYIIREGTIGKKMYFIQHGVVSVLTKGNKEMKLSDGSYFGEICLLTRGRRTASVRA
                     DTYCRLYSLSVDNFNEVLEEYPMMRRAFETVAIDRLDRIGKKNSILLHKVQHDLNSGV
                     FNNQENAIIQEIVKYDREMVQQAELGQRVGLFPPPPPPPQVTSAIATLQQAAAMSFCP
                     QVARPLVGPLALGSPRLVRRPPPGPAPAAASPGPPPPASPPGAPASPRAPRTSPYGGL
                     PAAPLAGPALPARRLSRASRPLSASQPSLPHGAPGPAASTRPASSSTPRLGPTPAARA
                     AAPSPDRRDSASPGAAGGLDPQDSARSRLSSNL"
     exon            698..1121
                     /gene="HCN2"
                     /gene_synonym="BCNG-2; BCNG2; EIG17; FEB2; GEFSP11; HAC-1"
                     /inference="alignment:Splign:2.1.0"
     exon            1122..1283
                     /gene="HCN2"
                     /gene_synonym="BCNG-2; BCNG2; EIG17; FEB2; GEFSP11; HAC-1"
                     /inference="alignment:Splign:2.1.0"
     exon            1284..1502
                     /gene="HCN2"
                     /gene_synonym="BCNG-2; BCNG2; EIG17; FEB2; GEFSP11; HAC-1"
                     /inference="alignment:Splign:2.1.0"
     exon            1503..1649
                     /gene="HCN2"
                     /gene_synonym="BCNG-2; BCNG2; EIG17; FEB2; GEFSP11; HAC-1"
                     /inference="alignment:Splign:2.1.0"
     exon            1650..1890
                     /gene="HCN2"
                     /gene_synonym="BCNG-2; BCNG2; EIG17; FEB2; GEFSP11; HAC-1"
                     /inference="alignment:Splign:2.1.0"
     exon            1891..2055
                     /gene="HCN2"
                     /gene_synonym="BCNG-2; BCNG2; EIG17; FEB2; GEFSP11; HAC-1"
                     /inference="alignment:Splign:2.1.0"
     exon            2056..3420
                     /gene="HCN2"
                     /gene_synonym="BCNG-2; BCNG2; EIG17; FEB2; GEFSP11; HAC-1"
                     /inference="alignment:Splign:2.1.0"
     regulatory      3397..3402
                     /regulatory_class="polyA_signal_sequence"
                     /gene="HCN2"
                     /gene_synonym="BCNG-2; BCNG2; EIG17; FEB2; GEFSP11; HAC-1"
                     /note="hexamer: AATAAA"
     polyA_site      3420
                     /gene="HCN2"
                     /gene_synonym="BCNG-2; BCNG2; EIG17; FEB2; GEFSP11; HAC-1"
                     /note="major polyA site"
ORIGIN      
        1 ccctcgggct ccggccggcg gcggcggcgg cggctccgct ccgcactgcc cggcgccgcc
       61 tcgccatgga cgcgcgcggg ggcggcgggc ggcccgggga gagcccgggc gcgacccccg
      121 cgccggggcc gccgccgccg ccgccgcccg cgccccccca acagcagccg ccgccgccgc
      181 cgccgcccgc gccccccccg ggccccgggc ccgcgccccc ccagcacccg ccccgggccg
      241 aggcgttgcc cccggaggcg gcggatgagg gcggcccgcg gggccggctc cgcagccgcg
      301 acagctcgtg cggccgcccc ggcaccccgg gcgcggcgag cacggccaag ggcagcccga
      361 acggcgagtg cgggcgcggc gagccgcagt gcagccccgc ggggcccgag ggcccggcgc
      421 gggggcccaa ggtgtcgttc tcgtgccgcg gggcggcctc ggggcccgcg ccggggccgg
      481 ggccggcgga ggaggcgggc agcgaggagg cgggcccggc gggggagccg cgcggcagcc
      541 aggccagctt catgcagcgc cagttcggcg cgctcctgca gccgggcgtc aacaagttct
      601 cgctgcggat gttcggcagc cagaaggccg tggagcgcga gcaggagcgc gtcaagtcgg
      661 cgggggcctg gatcatccac ccgtacagcg acttcaggtt ctactgggac ttcaccatgc
      721 tgctgttcat ggtgggaaac ctcatcatca tcccagtggg catcaccttc ttcaaggatg
      781 agaccactgc cccgtggatc gtgttcaacg tggtctcgga caccttcttc ctcatggacc
      841 tggtgttgaa cttccgcacc ggcattgtga tcgaggacaa cacggagatc atcctggacc
      901 ccgagaagat caagaagaag tatctgcgca cgtggttcgt ggtggacttc gtgtcctcca
      961 tccccgtgga ctacatcttc cttatcgtgg agaagggcat tgactccgag gtctacaaga
     1021 cggcacgcgc cctgcgcatc gtgcgcttca ccaagatcct cagcctcctg cggctgctgc
     1081 gcctctcacg cctgatccgc tacatccatc agtgggagga gatcttccac atgacctatg
     1141 acctggccag cgcggtgatg aggatctgca atctcatcag catgatgctg ctgctctgcc
     1201 actgggacgg ctgcctgcag ttcctggtgc ctatgctgca ggacttcccg cgcaactgct
     1261 gggtgtccat caatggcatg gtgaaccact cgtggagtga actgtactcc ttcgcactct
     1321 tcaaggccat gagccacatg ctgtgcatcg ggtacggccg gcaggcgccc gagagcatga
     1381 cggacatctg gctgaccatg ctcagcatga ttgtgggtgc cacctgctac gccatgttca
     1441 tcggccacgc cactgccctc atccagtcgc tggactcctc gcggcgccag taccaggaga
     1501 agtacaagca ggtggagcag tacatgtcct tccacaagct gccagctgac ttccgccaga
     1561 agatccacga ctactatgag caccgttacc agggcaagat gtttgacgag gacagcatcc
     1621 tgggcgagct caacgggccc ctgcgggagg agatcgtcaa cttcaactgc cggaagctgg
     1681 tggcctccat gccgctgttc gccaacgccg accccaactt cgtcacggcc atgctgacca
     1741 agctcaagtt cgaggtcttc cagccgggtg actacatcat ccgcgaaggc accatcggga
     1801 agaagatgta cttcatccag cacggcgtgg tcagcgtgct cactaagggc aacaaggaga
     1861 tgaagctgtc cgatggctcc tacttcgggg agatctgcct gctcacccgg ggccgccgca
     1921 cggcgagcgt gcgggctgac acctactgcc gcctctattc gctgagcgtg gacaacttca
     1981 acgaggtgct ggaggagtac cccatgatgc ggcgcgcctt cgagacggtg gccatcgacc
     2041 gcctggaccg catcggcaag aagaattcca tcctcctgca caaggtgcag catgacctca
     2101 actcgggcgt attcaacaac caggagaacg ccatcatcca ggagatcgtc aagtacgacc
     2161 gcgagatggt gcagcaggcc gagctgggtc agcgcgtggg cctcttcccg ccgccgccgc
     2221 cgccgccgca ggtcacctcg gccatcgcca cgctgcagca ggcggcggcc atgagcttct
     2281 gcccgcaggt ggcgcggccg ctcgtggggc cgctggcgct cggctcgccg cgcctcgtgc
     2341 gccgcccgcc cccggggccc gcacctgccg ccgcctcacc cgggcccccg ccccccgcca
     2401 gccccccggg cgcgcccgcc agcccccggg caccgcggac ctcgccctac ggcggcctgc
     2461 ccgccgcccc ccttgctggg cccgccctgc ccgcgcgccg cctgagccgc gcgtcgcgcc
     2521 cactgtccgc ctcgcagccc tcgctgcctc acggcgcccc cggccccgcg gcctccacac
     2581 gcccggccag cagctccaca ccgcgcttgg ggcccacgcc cgctgcccgg gccgccgcgc
     2641 ccagcccgga ccgcagggac tcggcctcac ccggcgccgc cggcggcctg gacccccagg
     2701 actccgcgcg ctcgcgcctc tcgtccaact tgtgaccctc gccgaccgcc ccgcgggccc
     2761 aggcgggccg ggggcggggc cgtcatccag accaaagcca tgccattgcg ctgccccggc
     2821 cgccagtccg cccagaagcc atagacgaga cgtaggtagc cgtagttgga cggacgggca
     2881 gggccggcgg ggcagccccc tccgcgcccc cggccgtccc ccctcatcgc cccgcgccca
     2941 cccccatcgc ccctgccccc ggcggcggcc tcgcgtgcga gggggctccc ttcacctcgg
     3001 tgcctcagtt cccccagctg taagacaggg acggggcggc ccagtggctg agaggagccg
     3061 gctgtggagc cccgcccgcc ccccaccctc taggtggccc ccgtccgagg aggatcgttt
     3121 tctaagtgca atacttggcc cgccggcttc ccgctgcccc catcgcgctc acgcaataac
     3181 cggcccggcc cccgtccgcg cgcgtccccc ggtgacctcg gggagcagca ccccgcctcc
     3241 ctccagcact ggcaccgaga ggcaggcctg gctgcgcagg gcgcgggggg gaggctgggg
     3301 tcccgccgcc gtgatgaatg tactgacgag ccgaggcagc agtgccccca ccgtggcccc
     3361 ccacgcccca ttaaccccca cacccccatt ccgcgcaata aacgacagca ttggcgccaa
//
