LOCUS       NM_000744               5583 bp    mRNA    linear   PRI 20-FEB-2025
DEFINITION  Homo sapiens cholinergic receptor nicotinic alpha 4 subunit
            (CHRNA4), transcript variant 1, mRNA.
ACCESSION   NM_000744
VERSION     NM_000744.7
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 5583)
  AUTHORS   Mazzaferro,S., Kang,G., Natarajan,K., Hibbs,R.E. and Sine,S.M.
  TITLE     Structural bases for stoichiometry-selective calcium potentiation
            of a neuronal nicotinic receptor
  JOURNAL   Br J Pharmacol 181 (13), 1973-1992 (2024)
   PUBMED   38454578
REFERENCE   2  (bases 1 to 5583)
  AUTHORS   Guo,L., Zhang,Y., Lu,J., Li,X., Zhang,C., Song,W., Dong,Y., Zhou,X.
            and Li,R.
  TITLE     Nicotine promotes renal interstitial fibrosis via upregulation of
            XIAP in an alpha7-nAChR-dependent manner
  JOURNAL   Mol Cell Endocrinol 576, 111989 (2023)
   PUBMED   37451424
  REMARK    GeneRIF: Nicotine promotes renal interstitial fibrosis via
            upregulation of XIAP in an alpha7-nAChR-dependent manner.
REFERENCE   3  (bases 1 to 5583)
  AUTHORS   Nielsen,T.O., Herlin,M.K., Linnet,K.M., Beniczky,S., Sommerlund,M.,
            Granild-Jensen,J.B. and Gregersen,P.A.
  TITLE     Autosomal dominant sleep-related hypermotor epilepsy caused by a
            previously unreported CHRNA4 variant
  JOURNAL   Eur J Med Genet 65 (3), 104444 (2022)
   PUBMED   35093606
  REMARK    GeneRIF: Autosomal dominant sleep-related hypermotor epilepsy
            caused by a previously unreported CHRNA4 variant.
REFERENCE   4  (bases 1 to 5583)
  AUTHORS   Weltzin,M.M., George,A.A., Lukas,R.J. and Whiteaker,P.
  TITLE     Sleep-related hypermotor epilepsy associated mutations uncover
            important kinetic roles of alpha4beta2- nicotinic acetylcholine
            receptor intracellular structures
  JOURNAL   PLoS One 16 (3), e0247825 (2021)
   PUBMED   33657187
  REMARK    GeneRIF: Sleep-related hypermotor epilepsy associated mutations
            uncover important kinetic roles of alpha4beta2- nicotinic
            acetylcholine receptor intracellular structures.
            Publication Status: Online-Only
REFERENCE   5  (bases 1 to 5583)
  AUTHORS   Eggert,M., Aichinger,E., Pfaffl,M.W., Steinlein,O.K. and Pfob,M.
  TITLE     Nicotinic acetylcholine receptor subunits alpha4 and alpha5
            associated with smoking behaviour and lung cancer are regulated by
            upstream open reading frames
  JOURNAL   PLoS One 8 (7), e66157 (2013)
   PUBMED   23843950
  REMARK    GeneRIF: Nicotinic acetylcholine receptor subunits alpha4 and
            alpha5 associated with smoking behavior and lung cancer are
            regulated by upstream open reading frames.
            Publication Status: Online-Only
REFERENCE   6  (bases 1 to 5583)
  AUTHORS   Phillips,H.A., Scheffer,I.E., Berkovic,S.F., Hollway,G.E.,
            Sutherland,G.R. and Mulley,J.C.
  TITLE     Localization of a gene for autosomal dominant nocturnal frontal
            lobe epilepsy to chromosome 20q 13.2
  JOURNAL   Nat Genet 10 (1), 117-118 (1995)
   PUBMED   7647781
REFERENCE   7  (bases 1 to 5583)
  AUTHORS   Kurahashi,H. and Hirose,S.
  TITLE     Autosomal Dominant Sleep-Related Hypermotor (Hyperkinetic) Epilepsy
  JOURNAL   (in) Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE and
            Amemiya A (Eds.);
            GENEREVIEWS(R);
            (1993)
   PUBMED   20301348
REFERENCE   8  (bases 1 to 5583)
  AUTHORS   Pilz,A.J., Willer,E., Povey,S. and Abbott,C.M.
  TITLE     The genes coding for phosphoenolpyruvate carboxykinase-1 (PCK1) and
            neuronal nicotinic acetylcholine receptor alpha 4 subunit (CHRNA4)
            map to human chromosome 20, extending the known region of homology
            with mouse chromosome 2
  JOURNAL   Ann Hum Genet 56 (4), 289-293 (1992)
   PUBMED   1492743
REFERENCE   9  (bases 1 to 5583)
  AUTHORS   Anand,R. and Lindstrom,J.
  TITLE     Chromosomal localization of seven neuronal nicotinic acetylcholine
            receptor subunit genes in humans
  JOURNAL   Genomics 13 (4), 962-967 (1992)
   PUBMED   1505988
REFERENCE   10 (bases 1 to 5583)
  AUTHORS   McLane,K.E., Wu,X.D. and Conti-Tronconi,B.M.
  TITLE     Identification of a brain acetylcholine receptor alpha subunit able
            to bind alpha-bungarotoxin
  JOURNAL   J Biol Chem 265 (17), 9816-9824 (1990)
   PUBMED   2351675
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from U62433.1, AL121827.34,
            L35901.1, BC096291.1, AK296430.1 and AB209359.1.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Feb 27, 2020 this sequence version replaced NM_000744.6.
            
            Summary: This gene encodes a nicotinic acetylcholine receptor,
            which belongs to a superfamily of ligand-gated ion channels that
            play a role in fast signal transmission at synapses. These
            pentameric receptors can bind acetylcholine, which causes an
            extensive change in conformation that leads to the opening of an
            ion-conducting channel across the plasma membrane. This protein is
            an integral membrane receptor subunit that can interact with either
            nAChR beta-2 or nAChR beta-4 to form a functional receptor.
            Mutations in this gene cause nocturnal frontal lobe epilepsy type
            1. Polymorphisms in this gene that provide protection against
            nicotine addiction have been described. Alternative splicing
            results in multiple transcript variants. [provided by RefSeq, Feb
            2012].
            
            Transcript Variant: This variant (1) encodes the longer isoform
            (1).
            
            Sequence Note: This RefSeq record was created from transcript and
            genomic sequence data to make the sequence consistent with the
            reference genome assembly. The genomic coordinates used for the
            transcript record were based on transcript alignments.
            
            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 :: BC096290.1, L35901.1 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1968968, SAMEA2145743
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000370263.9/ ENSP00000359285.4
            RefSeq Select criteria :: based on manual assertion, conservation,
                                      expression, longest protein
            regulatory uORF        :: PMID: 23843950
            ##RefSeq-Attributes-END##
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-1                 U62433.1           48-48
            2-6                 AL121827.34        130846-130850       c
            7-1812              L35901.1           1-1806
            1813-2212           BC096291.1         1676-2075
            2213-2601           AK296430.1         531-919
            2602-2602           AL121827.34        115706-115706       c
            2603-4737           AB209359.1         3067-5201
            4738-5583           AL121827.34        112725-113570       c
FEATURES             Location/Qualifiers
     source          1..5583
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="20"
                     /map="20q13.33"
     gene            1..5583
                     /gene="CHRNA4"
                     /gene_synonym="BFNC; EBN; EBN1; NACHR; NACHRA4; NACRA4"
                     /note="cholinergic receptor nicotinic alpha 4 subunit"
                     /db_xref="GeneID:1137"
                     /db_xref="HGNC:HGNC:1958"
                     /db_xref="MIM:118504"
     exon            1..260
                     /gene="CHRNA4"
                     /gene_synonym="BFNC; EBN; EBN1; NACHR; NACHRA4; NACRA4"
                     /inference="alignment:Splign:2.1.0"
     regulatory      104..163
                     /regulatory_class="uORF"
                     /gene="CHRNA4"
                     /gene_synonym="BFNC; EBN; EBN1; NACHR; NACHRA4; NACRA4"
                     /experiment="DESCRIPTION:regulatory uORF[PMID:23843950]"
                     /note="this uORF is predicted to encode a 19 aa peptide
                     (PMID:23843950)"
     CDS             185..2068
                     /gene="CHRNA4"
                     /gene_synonym="BFNC; EBN; EBN1; NACHR; NACHRA4; NACRA4"
                     /note="isoform 1 precursor is encoded by transcript
                     variant 1; cholinergic receptor, nicotinic, alpha
                     polypeptide 4; neuronal acetylcholine receptor subunit
                     alpha-4; neuronal nicotinic acetylcholine receptor alpha-4
                     subunit; cholinergic receptor, nicotinic, alpha 4
                     (neuronal); cholinergic receptor, nicotinic alpha 4"
                     /codon_start=1
                     /product="neuronal acetylcholine receptor subunit alpha-4
                     isoform 1 precursor"
                     /protein_id="NP_000735.1"
                     /db_xref="CCDS:CCDS13517.1"
                     /db_xref="GeneID:1137"
                     /db_xref="HGNC:HGNC:1958"
                     /db_xref="MIM:118504"
                     /translation="MELGGPGAPRLLPPLLLLLGTGLLRASSHVETRAHAEERLLKKL
                     FSGYNKWSRPVANISDVVLVRFGLSIAQLIDVDEKNQMMTTNVWVKQEWHDYKLRWDP
                     ADYENVTSIRIPSELIWRPDIVLYNNADGDFAVTHLTKAHLFHDGRVQWTPPAIYKSS
                     CSIDVTFFPFDQQNCTMKFGSWTYDKAKIDLVNMHSRVDQLDFWESGEWVIVDAVGTY
                     NTRKYECCAEIYPDITYAFVIRRLPLFYTINLIIPCLLISCLTVLVFYLPSECGEKIT
                     LCISVLLSLTVFLLLITEIIPSTSLVIPLIGEYLLFTMIFVTLSIVITVFVLNVHHRS
                     PRTHTMPTWVRRVFLDIVPRLLLMKRPSVVKDNCRRLIESMHKMASAPRFWPEPEGEP
                     PATSGTQSLHPPSPSFCVPLDVPAEPGPSCKSPSDQLPPQQPLEAEKASPHPSPGPCR
                     PPHGTQAPGLAKARSLSVQHMSSPGEAVEGGVRCRSRSIQYCVPRDDAAPEADGQAAG
                     ALASRNTHSAELPPPDQPSPCKCTCKKEPSSVSPSATVKTRSTKAPPPHLPLSPALTR
                     AVEGVQYIADHLKAEDTDFSVKEDWKYVAMVIDRIFLWMFIIVCLLGTVGLFLPPWLA
                     GMI"
     exon            261..412
                     /gene="CHRNA4"
                     /gene_synonym="BFNC; EBN; EBN1; NACHR; NACHRA4; NACRA4"
                     /inference="alignment:Splign:2.1.0"
     exon            413..457
                     /gene="CHRNA4"
                     /gene_synonym="BFNC; EBN; EBN1; NACHR; NACHRA4; NACRA4"
                     /inference="alignment:Splign:2.1.0"
     exon            458..567
                     /gene="CHRNA4"
                     /gene_synonym="BFNC; EBN; EBN1; NACHR; NACHRA4; NACRA4"
                     /inference="alignment:Splign:2.1.0"
     exon            568..1942
                     /gene="CHRNA4"
                     /gene_synonym="BFNC; EBN; EBN1; NACHR; NACHRA4; NACRA4"
                     /inference="alignment:Splign:2.1.0"
     exon            1943..5583
                     /gene="CHRNA4"
                     /gene_synonym="BFNC; EBN; EBN1; NACHR; NACHRA4; NACRA4"
                     /inference="alignment:Splign:2.1.0"
     regulatory      4711..4716
                     /regulatory_class="polyA_signal_sequence"
                     /gene="CHRNA4"
                     /gene_synonym="BFNC; EBN; EBN1; NACHR; NACHRA4; NACRA4"
                     /note="hexamer: AATAAA"
     polyA_site      4738
                     /gene="CHRNA4"
                     /gene_synonym="BFNC; EBN; EBN1; NACHR; NACHRA4; NACRA4"
                     /note="major polyA site"
     regulatory      5564..5569
                     /regulatory_class="polyA_signal_sequence"
                     /gene="CHRNA4"
                     /gene_synonym="BFNC; EBN; EBN1; NACHR; NACHRA4; NACRA4"
                     /note="hexamer: AATAAA"
     polyA_site      5583
                     /gene="CHRNA4"
                     /gene_synonym="BFNC; EBN; EBN1; NACHR; NACHRA4; NACRA4"
ORIGIN      
        1 gcccacagcc cggcgctccc tgccgcgccg ccgccgcacc gcgccccaca ggagaagacg
       61 aaccgggccc ggcggccgaa gcggcccgcg aggcgcggga ggcatgaagt tgggcgcgca
      121 cgggcctcga agcggcgggg agccgggagc cgcccgcatc tagagcccgc gaggtgcgtg
      181 cgccatggag ctagggggcc ccggagcgcc gcggctgctg ccgccgctgc tgctgcttct
      241 ggggaccggc ctcctgcgcg ccagcagcca tgtggagacc cgggcccacg ccgaggagcg
      301 gctcctgaag aaactcttct ccggttacaa caagtggtcc cgacccgtgg ccaacatctc
      361 ggacgtggtc ctcgtccgct tcggcctgtc catcgctcag ctcattgacg tggatgagaa
      421 gaaccagatg atgaccacga acgtatgggt gaagcaggag tggcacgact acaagctgcg
      481 ctgggaccca gctgactatg agaatgtcac ctccatccgc atcccctccg agctcatctg
      541 gcggccggac atcgtcctct acaacaatgc tgacggggac ttcgcggtca cccacctgac
      601 caaggcccac ctgttccatg acgggcgggt gcagtggact cccccggcca tttacaagag
      661 ctcctgcagc atcgacgtca ccttcttccc cttcgaccag cagaactgca ccatgaaatt
      721 cggctcctgg acctacgaca aggccaagat cgacctggtg aacatgcaca gccgcgtgga
      781 ccagctggac ttctgggaga gtggcgagtg ggtcatcgtg gatgccgtgg gcacctacaa
      841 caccaggaag tacgagtgct gtgccgagat ctacccggac atcacctatg ccttcgtcat
      901 ccggcggctg ccgctcttct acaccatcaa cctcatcatc ccctgcctgc tcatctcctg
      961 cctcaccgtg ctggtcttct acctgccctc cgagtgtggc gagaagatca cgctgtgcat
     1021 ctccgtgctg ctgtcgctca ccgtcttcct gctgctcatc accgagatca tcccgtccac
     1081 ctcactggtc atcccactca tcggcgagta cctgctgttc accatgatct tcgtcaccct
     1141 gtccatcgtc atcacggtct tcgtgctcaa cgtgcaccac cgctcgccac gcacgcacac
     1201 catgcccacc tgggtacgca gggtcttcct ggacatcgtg ccacgcctgc tcctcatgaa
     1261 gcggccgtcc gtggtcaagg acaattgccg gcggctcatc gagtccatgc ataagatggc
     1321 cagtgccccg cgcttctggc ccgagccaga aggggagccc cctgccacga gcggcaccca
     1381 gagcctgcac ccgccctcac cgtccttctg tgtccccctg gatgtgccgg ctgagcctgg
     1441 gccttcctgc aagtcaccct ccgaccagct ccctcctcag cagcccctgg aagctgagaa
     1501 agccagcccc cacccctcgc ctggaccctg ccgcccgccc cacggcaccc aggcaccagg
     1561 gctggccaaa gccaggtccc tcagcgtcca gcacatgtcc agccctggcg aagcggtgga
     1621 aggcggcgtc cggtgccggt ctcggagcat ccagtactgt gttccccgag acgatgccgc
     1681 ccccgaggca gatggccagg ctgccggcgc cctggcctct cgcaacaccc actcggctga
     1741 gctcccaccc ccagaccagc cctctccgtg caaatgcaca tgcaagaagg agccctcttc
     1801 ggtgtccccg agcgccacgg tcaagacccg cagcaccaaa gcgccgcccc cgcacctgcc
     1861 cctgtcgccg gccctgaccc gggcggtgga gggcgtccag tacattgcag accacctgaa
     1921 ggccgaagac acagacttct cggtgaagga ggactggaag tacgtggcca tggtcatcga
     1981 ccgcatcttc ctctggatgt tcatcatcgt ctgcctgctg gggacggtgg gcctcttcct
     2041 gccgccctgg ctggctggca tgatctagga agggaccggg agcctgcgtg gcctggggct
     2101 gccgtgcacg gggccagcat ccatgcggcc ggcctggggc cgggctggct tctccctgga
     2161 ctctgtgggg ccacacgttt gccaaatttt ccttcctgtt ctgtgtctgc tgtaagacgg
     2221 ccttggacgg ggacacggcc tctggggaga ccgagtgtgg agctgcttcc agttggactg
     2281 tggcctcagg aggcagtggc ttggagcaga ggtgggggtc ggcgccttct acctgcagga
     2341 ctcgggctaa gtccagttca agagtctcct gagctcccct gcagatggaa ctcactcctc
     2401 ccagtctctc agcagatctg gtgatggtcc cgaccgcccc aaggggccct tgaagggagt
     2461 tcacgcccct tcagccccaa gcgccccgtc ttctggaggc ccggccgcct ctcccaccca
     2521 ccgtgtcctg cgcctgtgtg ggcttcaact tctcccccag ggtccttgag cctctcgggc
     2581 cccatgaggg tgagccagca gcgctccaat ctgcttcgct aggagagggt ccaggcaggg
     2641 attgtgtttg gttgtgtttt gggtaagtta gtgagaactc aagtcttgtg cctaaggagc
     2701 cttggagaac agagttttgt ggagctggtt ccgcgtgggg agaatcggga ggcccacgcg
     2761 ggaccagctc tcccctgcgc aggccctccg cgggggacag gaacacccag ccccagcgag
     2821 tctggagacc aggactctgc cttccaggcg tagggccagg gctctggcag gtggccaggg
     2881 ctccacgggg gcctagtggc ttcagcccct ggggtacttc tgtgttgtga ttccccggag
     2941 ctgggaaggt cccgaatgga gtccagacct gggccctggt tcccccagga ccctgagggt
     3001 ttccaccttg gcgcgcagcc cgggagatcc gccctgggct ctgggttcgg gaagaaggac
     3061 ttcctgctac agtagctgtg gggagctggt gggggcatcc ttgaggacct ccacctggga
     3121 gatgctggga ccctcggggc aggaagtccc tgagaagcct catgggagtc agggagccct
     3181 ggggtttcca cacaggccca tgccctccgt cctggcaggg caggcagagc tcagcacagc
     3241 ctcacccctg caggcggtat ccagaggtga gggaggcctg aaatgtttcc aggcatgacc
     3301 ctggagcccg gcagtgcacc ccctaaagat ggcgcacccg gcagcccccc agtgtcccca
     3361 ggggcacact tccccttggg atgggcacag gctgccccac ccctccatga ttccaagggc
     3421 ccagaggggc ggggccagga tggcgtgtcc cctgcctgtg agtgacatcg gttcaggagg
     3481 agacagtcag gaagcctcct gctgagtggt ccacattctg ctgcccccag accccatcca
     3541 gccaggggtg gggatggggt tgggctctgc gtcccactga gtctcattcc tctgtccccg
     3601 agccgagctc tcctgggcca gggtctcgtc aggaggtgcc tgagagcaga atgaataatt
     3661 gaggttagga acccggcatg ccgagtgccc cagaaatgcc gctgtgtccc cgcgggcagt
     3721 gacgtgagtg gggaggagac tcaggcccac attgcccaca cctgcctctg aactgctgct
     3781 ggtcaccccc acccccgggt gcctgtgacc ggggtcctga ggctggggct tttgtgccag
     3841 gagtgggtgg gacacagaga cccccgtgcc aaatcctggg catccccagc cccctggccc
     3901 ctcccacatc ccccgtgtat tcaggacccc atctgctgag ctctgacctg cccccgctct
     3961 gccatcagcc cctgctgctc ctcggccaga gctcccagga cgcagggaga ccctgggaga
     4021 gtgaggtcat cccggggcca tggaagctgg caggagacac tggtctcaga ggagggatag
     4081 agacgcagat ttcagatgta agaagcccga tccacattgc ataagtggac ccagctgcca
     4141 gatgtgtggg cagctgcagg gagtggcccg gggtgctggg cccagctgtg gttgttcttt
     4201 tctgggtcag gagtgactgc ggagtggctg ggacgctcct gccgggggac cctcctgccg
     4261 ggggtggccg cttgcctggg ggaagacccc tttccctttc tttttttttt tgaggctcaa
     4321 aaaaaaaatc caaataaagc accatattcc caccacgcca aattaacctt gacaacaatg
     4381 ttggcgtatt tgcgtccagt gctgttttta ttaattaagg taaaatttac atatggtgag
     4441 atgcatgctc ttcagtggag acccagcccc tagaaggtcc ctccagccct tcctgtcggc
     4501 gtccctcccc atctgtggct ctgacttaag caccgtggat tgacctctcc ggctcacgac
     4561 cttcgaggag tcagaatcct gcagttggag cctttgatgt ctggcttctt catcctatga
     4621 cttagagctt catccgtgct gttgtgtgtg tccgtagctc cttgctgtct gttccttcgt
     4681 ttttaattgt gagcagtgtt cttctgtctg aataaactaa gacgcagttt gtccatcacc
     4741 tgttagtgga ctttgcttgc agctgtcggt gattaggaat ggaggtgccg gtgtgtgcat
     4801 ggcactctat ccgttatgca tgtttatttt ctgcatctgt taatgtttta acatctttca
     4861 gacccaggac tgctcctcct agggccagtt agttcccggg ggtggacagc ttgcctagaa
     4921 cccaccttgc cagggctgtg acccccgacc ccctatcaaa gtctcacact aagccaacgt
     4981 ttccccgccc tgtgccaggc accaggcagc gggagacact gctgcagctc gaagcctgcc
     5041 ggggcgccgg cccctctgcg gctgcttgcg ccatcctgcc ccctccttcc caggggaggc
     5101 cccagtgaag gccctggcca gggcttccca gccccttctg cctccggacc ggcctgggtg
     5161 cttcccgtgt ggcccggcct ggggcgacgt ggccctcctc tcaggaagcg tggtaatctc
     5221 tcaatggctg gcctccggag ttgtcactca ggctcccttg taagttaagg ccgggcccag
     5281 gacactctag ggcacgcagc tgctgtggga ctgctgggtt aggtgtcccc tggagcagag
     5341 gcggcttcgg atttctaaag tggctgagtc ctttcacctt gcaccagaaa tgctggatca
     5401 ggcgcagcac acacagcacc tggggatgca agcccggcca gccccatgga ccaagccccg
     5461 ccgaccgtgt ggcccgccga gcccaggtgc ggccgcccgg cttctgcagg caatgtctgc
     5521 caagccctgg aatgtgctcc cagtgtgtgc acagacttca atgaataaaa cgcaccgtca
     5581 cca
//
