LOCUS       NM_020897               3838 bp    mRNA    linear   PRI 01-AUG-2024
DEFINITION  Homo sapiens hyperpolarization activated cyclic nucleotide gated
            potassium channel 3 (HCN3), transcript variant 1, mRNA.
ACCESSION   NM_020897 XM_086565
VERSION     NM_020897.3
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 3838)
  AUTHORS   Yu,B., Lu,Q., Li,J., Cheng,X., Hu,H., Li,Y., Che,T., Hua,Y.,
            Jiang,H., Zhang,Y., Xian,C., Yang,T., Fu,Y., Chen,Y., Nan,W.,
            McCormick,P.J., Xiong,B., Duan,J., Zeng,B., Li,Y., Fu,Y. and
            Zhang,J.
  TITLE     Cryo-EM structure of human HCN3 channel and its regulation by cAMP
  JOURNAL   J Biol Chem 300 (6), 107288 (2024)
   PUBMED   38636662
  REMARK    GeneRIF: Cryo-EM structure of human HCN3 channel and its regulation
            by cAMP.
REFERENCE   2  (bases 1 to 3838)
  AUTHORS   Zhang,Y., Liu,X., Sun,K., Luo,Y., Yang,J., Li,A., Kiupel,M.,
            Fenske,S., Biel,M., Mi,Q.S., Wang,H. and Xiao,H.
  TITLE     Hyperpolarization-activated cyclic nucleotide-gated cation channel
            3 promotes HCC development in a female-biased manner
  JOURNAL   Cell Rep 42 (10), 113157 (2023)
   PUBMED   37733590
  REMARK    GeneRIF: Hyperpolarization-activated cyclic nucleotide-gated cation
            channel 3 promotes HCC development in a female-biased manner.
REFERENCE   3  (bases 1 to 3838)
  AUTHORS   Yi,F., Danko,T., Botelho,S.C., Patzke,C., Pak,C., Wernig,M. and
            Sudhof,T.C.
  TITLE     Autism-associated SHANK3 haploinsufficiency causes Ih channelopathy
            in human neurons
  JOURNAL   Science 352 (6286), aaf2669 (2016)
   PUBMED   26966193
REFERENCE   4  (bases 1 to 3838)
  AUTHORS   O'Donnell,A.M., Coyle,D. and Puri,P.
  TITLE     Decreased expression of hyperpolarisation-activated cyclic
            nucleotide-gated channel 3 in Hirschsprung's disease
  JOURNAL   World J Gastroenterol 21 (18), 5635-5640 (2015)
   PUBMED   25987789
  REMARK    GeneRIF: Reduced HCN3 expression in aganglionic bowel suggests its
            potential role in Hirschsprung's disease pathophysiology.
REFERENCE   5  (bases 1 to 3838)
  AUTHORS   Xue,L., Li,Y., Han,X., Yao,L., Yuan,J., Qin,W., Liu,F. and Wang,H.
  TITLE     Investigation of hyperpolarization-activated cyclic
            nucleotide-gated channels in interstitial cells of Cajal of human
            bladder
  JOURNAL   Urology 80 (1), 224 (2012)
   PUBMED   22748890
REFERENCE   6  (bases 1 to 3838)
  AUTHORS   Tu,E., Waterhouse,L., Duflou,J., Bagnall,R.D. and Semsarian,C.
  TITLE     Genetic analysis of hyperpolarization-activated cyclic
            nucleotide-gated cation channels in sudden unexpected death in
            epilepsy cases
  JOURNAL   Brain Pathol 21 (6), 692-698 (2011)
   PUBMED   21615589
  REMARK    GeneRIF: Genetic analysis in 48 Sudden unexpected death in epilepsy
            cases identified six novel and three previously reported
            nonsynonymous (amino acid changing) variants in HCN1 , HCN2, HCN3
            and HCN4.
REFERENCE   7  (bases 1 to 3838)
  AUTHORS   Varghese,A., Tenbroek,E.M., Coles,J. Jr. and Sigg,D.C.
  TITLE     Endogenous channels in HEK cells and potential roles in HCN ionic
            current measurements
  JOURNAL   Prog Biophys Mol Biol 90 (1-3), 26-37 (2006)
   PUBMED   15979128
  REMARK    Review article
REFERENCE   8  (bases 1 to 3838)
  AUTHORS   Hofmann,F., Biel,M. and Kaupp,U.B.
  TITLE     International Union of Pharmacology. LI. Nomenclature and
            structure-function relationships of cyclic nucleotide-regulated
            channels
  JOURNAL   Pharmacol Rev 57 (4), 455-462 (2005)
   PUBMED   16382102
  REMARK    Review article
REFERENCE   9  (bases 1 to 3838)
  AUTHORS   Stieber,J., Stockl,G., Herrmann,S., Hassfurth,B. and Hofmann,F.
  TITLE     Functional expression of the human HCN3 channel
  JOURNAL   J Biol Chem 280 (41), 34635-34643 (2005)
   PUBMED   16043489
  REMARK    GeneRIF: human HCN3 is not modulated by intracellular cAMP, in
            contrast to other HCN subtypes
REFERENCE   10 (bases 1 to 3838)
  AUTHORS   Liu,Y., Wang,Y., Folander,K., Xie,G. and Blevins,R.
  TITLE     An interactive tool for extracting exons and SNP from genomic
            sequence: isolation of HCN1 and HCN3 ion channel genes
  JOURNAL   J Bioinform Comput Biol 1 (3), 433-446 (2003)
   PUBMED   15290763
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from DA127524.1, AB040968.2,
            AL713999.28 and BC028024.1.
            
            On Nov 23, 2018 this sequence version replaced NM_020897.2.
            
            Summary: This gene encodes a multi-pass membrane protein that
            functions as a voltage gated cation channel. The encoded protein is
            a member of a family of closely related cyclic adenosine
            monophosphate-binding channel proteins. Alternative splicing
            results in multiple transcript variants. [provided by RefSeq, Aug
            2012].
            
            Transcript Variant: This variant (1) represents the longer
            transcript and encodes the protein.
            
            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 :: SRR1803615.115093.1, AB040968.2
                                           [ECO:0000332]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000368358.4/ ENSP00000357342.3
            RefSeq Select criteria :: based on conservation, expression,
                                      longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-315               DA127524.1         37-351
            316-2218            AB040968.2         1-1903
            2219-2328           AL713999.28        116509-116618
            2329-3837           AB040968.2         2014-3522
            3838-3838           BC028024.1         2739-2739
FEATURES             Location/Qualifiers
     source          1..3838
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="1"
                     /map="1q22"
     gene            1..3838
                     /gene="HCN3"
                     /note="hyperpolarization activated cyclic nucleotide gated
                     potassium channel 3"
                     /db_xref="GeneID:57657"
                     /db_xref="HGNC:HGNC:19183"
                     /db_xref="MIM:609973"
     exon            1..406
                     /gene="HCN3"
                     /inference="alignment:Splign:2.1.0"
     CDS             129..2453
                     /gene="HCN3"
                     /codon_start=1
                     /product="potassium/sodium hyperpolarization-activated
                     cyclic nucleotide-gated channel 3"
                     /protein_id="NP_065948.1"
                     /db_xref="CCDS:CCDS1108.1"
                     /db_xref="GeneID:57657"
                     /db_xref="HGNC:HGNC:19183"
                     /db_xref="MIM:609973"
                     /translation="MEAEQRPAAGASEGATPGLEAVPPVAPPPATAASGPIPKSGPEP
                     KRRHLGTLLQPTVNKFSLRVFGSHKAVEIEQERVKSAGAWIIHPYSDFRFYWDLIMLL
                     LMVGNLIVLPVGITFFKEENSPPWIVFNVLSDTFFLLDLVLNFRTGIVVEEGAEILLA
                     PRAIRTRYLRTWFLVDLISSIPVDYIFLVVELEPRLDAEVYKTARALRIVRFTKILSL
                     LRLLRLSRLIRYIHQWEEIFHMTYDLASAVVRIFNLIGMMLLLCHWDGCLQFLVPMLQ
                     DFPPDCWVSINHMVNHSWGRQYSHALFKAMSHMLCIGYGQQAPVGMPDVWLTMLSMIV
                     GATCYAMFIGHATALIQSLDSSRRQYQEKYKQVEQYMSFHKLPADTRQRIHEYYEHRY
                     QGKMFDEESILGELSEPLREEIINFTCRGLVAHMPLFAHADPSFVTAVLTKLRFEVFQ
                     PGDLVVREGSVGRKMYFIQHGLLSVLARGARDTRLTDGSYFGEICLLTRGRRTASVRA
                     DTYCRLYSLSVDHFNAVLEEFPMMRRAFETVAMDRLLRIGKKNSILQRKRSEPSPGSS
                     GGIMEQHLVQHDRDMARGVRGRAPSTGAQLSGKPVLWEPLVHAPLQAAAVTSNVAIAL
                     THQRGPLPLSPDSPATLLARSAWRSAGSPASPLVPVRAGPWASTSRLPAPPARTLHAS
                     LSRAGRSQVSLLGPPPGGGGRRLGPRGRPLSASQPSLPQRATGDGSPGRKGSGSERLP
                     PSGLLAKPPRTAQPPRPPVPEPATPRGLQLSANM"
     exon            407..836
                     /gene="HCN3"
                     /inference="alignment:Splign:2.1.0"
     exon            837..998
                     /gene="HCN3"
                     /inference="alignment:Splign:2.1.0"
     exon            999..1217
                     /gene="HCN3"
                     /inference="alignment:Splign:2.1.0"
     exon            1218..1364
                     /gene="HCN3"
                     /inference="alignment:Splign:2.1.0"
     exon            1365..1605
                     /gene="HCN3"
                     /inference="alignment:Splign:2.1.0"
     exon            1606..1770
                     /gene="HCN3"
                     /inference="alignment:Splign:2.1.0"
     exon            1771..3838
                     /gene="HCN3"
                     /inference="alignment:Splign:2.1.0"
     regulatory      3706..3711
                     /regulatory_class="polyA_signal_sequence"
                     /gene="HCN3"
                     /note="hexamer: ATTAAA"
     polyA_site      3727
                     /gene="HCN3"
     regulatory      3820..3825
                     /regulatory_class="polyA_signal_sequence"
                     /gene="HCN3"
                     /note="hexamer: TATAAA"
     polyA_site      3838
                     /gene="HCN3"
                     /note="major polyA site"
ORIGIN      
        1 gattccgagc ctacgacgcc tccgctagag cccgcggggc tgcgccgact cctgctctgg
       61 aggggttgcg ggtacctgat ggccacagag ggctctagga ggccgagcgt gtaagcgggg
      121 tgggcgccat ggaggcagag cagcggccgg cggcgggggc cagcgaaggg gcgacccctg
      181 gactggaggc ggtgcctccc gttgctcccc cgcctgcgac cgcggcctca ggtccgatcc
      241 ccaaatctgg gcctgagcct aagaggaggc accttgggac gctgctccag cctacggtca
      301 acaagttctc ccttcgggtg ttcggcagcc acaaagcagt ggaaatcgag caggagcggg
      361 tgaagtcagc gggggcctgg atcatccacc cctacagcga cttccggttt tactgggacc
      421 tgatcatgct gctgctgatg gtggggaacc tcatcgtcct gcctgtgggc atcaccttct
      481 tcaaggagga gaactccccg ccttggatcg tcttcaacgt attgtctgat actttcttcc
      541 tactggatct ggtgctcaac ttccgaacgg gcatcgtggt ggaggagggt gctgagatcc
      601 tgctggcacc gcgggccatc cgcacgcgct acctgcgcac ctggttcctg gttgacctca
      661 tctcttctat ccctgtggat tacatcttcc tagtggtgga gctggagcca cggttggacg
      721 ctgaggtcta caaaacggca cgggccctac gcatcgttcg cttcaccaag atcctaagcc
      781 tgctgaggct gctccgcctc tcccgcctca tccgctacat acaccagtgg gaggagatct
      841 ttcacatgac ctatgacctg gccagtgctg tggttcgcat cttcaacctc attgggatga
      901 tgctgctgct atgtcactgg gatggctgtc tgcagttcct ggtgcccatg ctgcaggact
      961 tccctcccga ctgctgggtc tccatcaacc acatggtgaa ccactcgtgg ggccgccagt
     1021 attcccatgc cctgttcaag gccatgagcc acatgctgtg cattggctat gggcagcagg
     1081 cacctgtagg catgcccgac gtctggctca ccatgctcag catgatcgta ggtgccacat
     1141 gctacgccat gttcatcggc catgccacgg cactcatcca gtccctggac tcttcccggc
     1201 gtcagtacca ggagaagtac aagcaggtgg agcagtacat gtccttccac aagctgccag
     1261 cagacacgcg gcagcgcatc cacgagtact atgagcaccg ctaccagggc aagatgttcg
     1321 atgaggaaag catcctgggc gagctgagcg agccgcttcg cgaggagatc attaacttca
     1381 cctgtcgggg cctggtggcc cacatgccgc tgtttgccca tgccgacccc agcttcgtca
     1441 ctgcagttct caccaagctg cgctttgagg tcttccagcc gggggatctc gtggtgcgtg
     1501 agggctccgt ggggaggaag atgtacttca tccagcatgg gctgctcagt gtgctggccc
     1561 gcggcgcccg ggacacacgc ctcaccgatg gatcctactt tggggagatc tgcctgctaa
     1621 ctaggggccg gcgcacagcc agtgttcggg ctgacaccta ctgccgcctt tactcactca
     1681 gcgtggacca tttcaatgct gtgcttgagg agttccccat gatgcgccgg gcctttgaga
     1741 ctgtggccat ggatcggctg ctccgcatcg gcaagaagaa ttccatactg cagcggaagc
     1801 gctccgagcc aagtccaggc agcagtggtg gcatcatgga gcagcacttg gtgcaacatg
     1861 acagagacat ggctcggggt gttcggggtc gggccccgag cacaggagct cagcttagtg
     1921 gaaagccagt actgtgggag ccactggtac atgcgcccct tcaggcagct gctgtgacct
     1981 ccaatgtggc cattgccctg actcatcagc ggggccctct gcccctctcc cctgactctc
     2041 cagccaccct ccttgctcgc tctgcttggc gctcagcagg ctctccagct tccccgctgg
     2101 tgcccgtccg agctggccca tgggcatcca cctcccgcct gcccgcccca cctgcccgaa
     2161 ccctgcacgc cagcctatcc cgggcagggc gctcccaggt ctccctgctg ggtccccctc
     2221 caggaggagg tggacggcgg ctaggacctc ggggccgccc actctcagcc tcccaaccct
     2281 ctctgcctca gcgggcaaca ggcgatggct ctcctgggcg taagggatca ggaagtgagc
     2341 ggctgcctcc ctcagggctc ctggccaaac ctccaaggac agcccagccc cccaggccac
     2401 cagtgcctga gccagccaca ccccggggtc tccagctttc tgccaacatg taaaaccttt
     2461 gagtacatcc agccttagtt cttggggtgc agtagtatgt acccaagggc agatgcctct
     2521 tggggaaggc catggggacc tgaaacattg ccccatggaa atgtcgaccc tgtgcggaca
     2581 ttccgcatac tgccatgaag acggtctctg tgtcctcagc tcaagaatcc tgtagcttgt
     2641 cccatcataa tccattcacc cgttcatcat gtgtactgag cagctaccat gttcaaggta
     2701 atatgccagg cgctgtatgt ctccactgcc aagtagaagt gactcaaaac cctctgacaa
     2761 ggatattccc ttggctatgg tcctgccagg tgcaggccca ggcccatgac cccaccttta
     2821 ctaagcacaa gtacttgcca ctgccatcac tgccaagtaa ctagatgtct ctgtttccct
     2881 gccaatgatc ctgcaggttc tgcccggtct ggttatcttc ctgttcctgt agcatagcca
     2941 ggcactgcca gtcacctgtg cccccattgc tgtcagcaga tgtcttgggt cctgagtgtg
     3001 ggtatccact tttacccgct cactgccacc tgtggacact ctgtgtctac cctctgagtg
     3061 ggaacatact tctaagttcc ctgcagtctc tgtcctgtgg tagaccatct ttttgtaaac
     3121 tgcgagcttc ctcttccctg taccctctgc cccagtcgtg accccctaaa agttaagggg
     3181 tagttggcac ctccttatta atatgccagc ctagatcccc cccggtggag gggcaaatgg
     3241 ctgaatcctt gtgtgatatt tttttcttcg cttgtttatt tattcattta tttaattgta
     3301 tttattcatt tactaacttt atgtgttacc aattaatttt gtttacccat tcctttatcc
     3361 atccctcccc tccttttcag gtaaggagac aggaggagta ggaggaggca gggcctctcc
     3421 atgccagcct ctgtggtcct tgcccaaacc catcagcgca atacttgaac cttctcccag
     3481 gtaggggcag gaggagccac atgagagagg gagaaggacc gcgtttacct ttagagtttt
     3541 gttttgtttt ttccttctga gtttgctgtt ggtgcaggaa taagggaaag gcccaaggta
     3601 tccaagcctg gggaagggca ggccagccag cacctctgcc ttctcaggga caagagtagt
     3661 cctttaccac cctcactctg cctgtcccct ctcctactct acagcattaa agactgtggg
     3721 accaggaccc taagtctcct ttccttctgg gtggggagtt ctggggttct tggtgtgtgg
     3781 gagaagtttt ataattgctt ccaaacagct gggtttaaat ataaaataga cacactca
//
