LOCUS       NM_000742               4037 bp    mRNA    linear   PRI 07-SEP-2020
DEFINITION  Homo sapiens cholinergic receptor nicotinic alpha 2 subunit
            (CHRNA2), transcript variant 1, mRNA.
ACCESSION   NM_000742
VERSION     NM_000742.4
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 4037)
  AUTHORS   Demontis D, Rajagopal VM, Thorgeirsson TE, Als TD, Grove J, Leppala
            K, Gudbjartsson DF, Pallesen J, Hjorthoj C, Reginsson GW,
            Tyrfingsson T, Runarsdottir V, Qvist P, Christensen JH,
            Bybjerg-Grauholm J, Baekvad-Hansen M, Huckins LM, Stahl EA,
            Timmermann A, Agerbo E, Hougaard DM, Werge T, Mors O, Mortensen PB,
            Nordentoft M, Daly MJ, Stefansson H, Stefansson K, Nyegaard M and
            Borglum AD.
  TITLE     Genome-wide association study implicates CHRNA2 in cannabis use
            disorder
  JOURNAL   Nat. Neurosci. 22 (7), 1066-1074 (2019)
   PUBMED   31209380
  REMARK    GeneRIF: The index variant (rs56372821) is a strong expression
            quantitative trait locus for CHRNA2; analyses of the genetically
            regulated gene expression identified a significant association of
            CHRNA2 expression with cannabis use disorder (CUD) in brain tissue.
            At the polygenic level, analyses revealed a significant decrease in
            the risk of CUD with increased load of variants associated with
            cognitive performance.
REFERENCE   2  (bases 1 to 4037)
  AUTHORS   Wang M, Liu D, Schwender H, Wang H, Wang P, Zhou Z, Li J, Wu T, Zhu
            H and Beaty TH.
  TITLE     Evaluating the effect of nicotinic cholinergic receptor genes on
            the risk of nonsyndromic cleft lip with or without cleft palate
  JOURNAL   Oral Dis 24 (6), 1068-1072 (2018)
   PUBMED   29688589
  REMARK    GeneRIF: In our analysis, we found one pair of SNPs in CHRNA1 and
            CHRNA7, plus one pair of SNPs in CHRNA2 and CHRNA3 reached
            corrected significance in tests for GxG interaction. Our study
            suggested evidence of interactions between CHRNs in controlling the
            risk of NSCL/P.
REFERENCE   3  (bases 1 to 4037)
  AUTHORS   Jun H, Yu H, Gong J, Jiang J, Qiao X, Perkey E, Kim DI, Emont MP,
            Zestos AG, Cho JS, Liu J, Kennedy RT, Maillard I, Xu XZS and Wu J.
  TITLE     An immune-beige adipocyte communication via nicotinic acetylcholine
            receptor signaling
  JOURNAL   Nat. Med. 24 (6), 814-822 (2018)
   PUBMED   29785025
  REMARK    GeneRIF: These results reveal a beige-selective immune-adipose
            interaction mediated through CHRNA2 and identify a novel function
            of nicotinic acetylcholine receptors in energy metabolism.
REFERENCE   4  (bases 1 to 4037)
  AUTHORS   Kouvatsos N, Giastas P, Chroni-Tzartou D, Poulopoulou C and Tzartos
            SJ.
  TITLE     Crystal structure of a human neuronal nAChR extracellular domain in
            pentameric assembly: Ligand-bound alpha2 homopentamer
  JOURNAL   Proc. Natl. Acad. Sci. U.S.A. 113 (34), 9635-9640 (2016)
   PUBMED   27493220
  REMARK    GeneRIF: A crystal structure of a human neuronal CHRNA2
            extracellular domain in pentameric assembly has been reported.
REFERENCE   5  (bases 1 to 4037)
  AUTHORS   Trivisano M, Terracciano A, Milano T, Cappelletti S, Pietrafusa N,
            Bertini ES, Vigevano F and Specchio N.
  TITLE     Mutation of CHRNA2 in a family with benign familial infantile
            seizures: Potential role of nicotinic acetylcholine receptor in
            various phenotypes of epilepsy
  JOURNAL   Epilepsia 56 (5), e53-e57 (2015)
   PUBMED   25847220
  REMARK    GeneRIF: a heterozygous single-nucleotide substitution in CHRNA2
            gene (c.1126 C>T; p. Arg376Trp) in subjects with benign familial
            infantile seizures
REFERENCE   6  (bases 1 to 4037)
  AUTHORS   Elliott KJ, Ellis SB, Berckhan KJ, Urrutia A, Chavez-Noriega LE,
            Johnson EC, Velicelebi G and Harpold MM.
  TITLE     Comparative structure of human neuronal alpha 2-alpha 7 and beta
            2-beta 4 nicotinic acetylcholine receptor subunits and functional
            expression of the alpha 2, alpha 3, alpha 4, alpha 7, beta 2, and
            beta 4 subunits
  JOURNAL   J. Mol. Neurosci. 7 (3), 217-228 (1996)
   PUBMED   8906617
REFERENCE   7  (bases 1 to 4037)
  AUTHORS   Garcia-Colunga J and Miledi R.
  TITLE     Effects of serotonergic agents on neuronal nicotinic acetylcholine
            receptors
  JOURNAL   Proc. Natl. Acad. Sci. U.S.A. 92 (7), 2919-2923 (1995)
   PUBMED   7708749
REFERENCE   8  (bases 1 to 4037)
  AUTHORS   Wood S, Schertzer M and Yaremko ML.
  TITLE     Identification of the human neuronal nicotinic cholinergic alpha 2
            receptor locus, (CHRNA2), within an 8p21 mapped locus, by sequence
            homology with rat DNA
  JOURNAL   Somat. Cell Mol. Genet. 21 (2), 147-150 (1995)
   PUBMED   7570187
REFERENCE   9  (bases 1 to 4037)
  AUTHORS   Kurahashi,H. and Hirose,S.
  TITLE     Autosomal Dominant Nocturnal Frontal Lobe Epilepsy
  JOURNAL   (in) Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens
            K and Amemiya A (Eds.);
            GENEREVIEWS((R));
            (1993)
   PUBMED   20301348
REFERENCE   10 (bases 1 to 4037)
  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
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from DA407151.1, U62431.1,
            DA096824.1, CD013901.1, AF311103.5 and AW292180.1.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Nov 23, 2018 this sequence version replaced NM_000742.3.
            
            Summary: Nicotinic acetylcholine receptors (nAChRs) are
            ligand-gated ion channels formed by a pentameric arrangement of
            alpha and beta subunits to create distinct muscle and neuronal
            receptors. Neuronal receptors are found throughout the peripheral
            and central nervous system where they are involved in fast synaptic
            transmission. This gene encodes an alpha subunit that is widely
            expressed in the brain. The proposed structure for nAChR subunits
            is a conserved N-terminal extracellular domain followed by three
            conserved transmembrane domains, a variable cytoplasmic loop, a
            fourth conserved transmembrane domain, and a short C-terminal
            extracellular region. Mutations in this gene cause autosomal
            dominant nocturnal frontal lobe epilepsy type 4. Single nucleotide
            polymorphisms (SNPs) in this gene have been associated with
            nicotine dependence. [provided by RefSeq, Nov 2009].
            
            Transcript Variant: This variant (1) represents the longest
            transcript and encodes the longest isoform (1).
            
            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 :: SRR1803613.124252.1,
                                           SRR1660809.23572.1 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA2145743, SAMEA2153427
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000407991.3/ ENSP00000385026.1
            RefSeq Select criteria :: based on conservation, expression,
                                      longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-500               DA407151.1         36-535
            501-946             U62431.1           481-926
            947-1059            DA096824.1         374-486
            1060-2190           U62431.1           1040-2170
            2191-2674           CD013901.1         1792-2275
            2675-3973           AF311103.5         69703-71001         c
            3974-4032           AW292180.1         17-75               c
            4033-4037           AF311103.5         69639-69643         c
FEATURES             Location/Qualifiers
     source          1..4037
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="8"
                     /map="8p21.2"
     gene            1..4037
                     /gene="CHRNA2"
                     /note="cholinergic receptor nicotinic alpha 2 subunit"
                     /db_xref="GeneID:1135"
                     /db_xref="HGNC:HGNC:1956"
                     /db_xref="MIM:118502"
     exon            1..438
                     /gene="CHRNA2"
                     /inference="alignment:Splign:2.1.0"
     exon            439..647
                     /gene="CHRNA2"
                     /inference="alignment:Splign:2.1.0"
     CDS             575..2164
                     /gene="CHRNA2"
                     /note="isoform 1 precursor is encoded by transcript
                     variant 1; cholinergic receptor, nicotinic, alpha
                     polypeptide 2 (neuronal); cholinergic receptor, nicotinic,
                     alpha 2 (neuronal); neuronal acetylcholine receptor
                     subunit alpha-2; acetylcholine receptor, nicotinic, alpha
                     2 (neuronal); cholinergic receptor, nicotinic alpha 2"
                     /codon_start=1
                     /product="neuronal acetylcholine receptor subunit alpha-2
                     isoform 1 precursor"
                     /protein_id="NP_000733.2"
                     /db_xref="CCDS:CCDS6059.1"
                     /db_xref="GeneID:1135"
                     /db_xref="HGNC:HGNC:1956"
                     /db_xref="MIM:118502"
                     /translation="MGPSCPVFLSFTKLSLWWLLLTPAGGEEAKRPPPRAPGDPLSSP
                     SPTALPQGGSHTETEDRLFKHLFRGYNRWARPVPNTSDVVIVRFGLSIAQLIDVDEKN
                     QMMTTNVWLKQEWSDYKLRWNPTDFGNITSLRVPSEMIWIPDIVLYNNADGEFAVTHM
                     TKAHLFSTGTVHWVPPAIYKSSCSIDVTFFPFDQQNCKMKFGSWTYDKAKIDLEQMEQ
                     TVDLKDYWESGEWAIVNATGTYNSKKYDCCAEIYPDVTYAFVIRRLPLFYTINLIIPC
                     LLISCLTVLVFYLPSDCGEKITLCISVLLSLTVFLLLITEIIPSTSLVIPLIGEYLLF
                     TMIFVTLSIVITVFVLNVHHRSPSTHTMPHWVRGALLGCVPRWLLMNRPPPPVELCHP
                     LRLKLSPSYHWLESNVDAEEREVVVEEEDRWACAGHVAPSVGTLCSHGHLHSGASGPK
                     AEALLQEGELLLSPHMQKALEGVHYIADHLRSEDADSSVKEDWKYVAMVIDRIFLWLF
                     IIVCFLGTIGLFLPPFLAGMI"
     exon            648..868
                     /gene="CHRNA2"
                     /inference="alignment:Splign:2.1.0"
     exon            869..913
                     /gene="CHRNA2"
                     /inference="alignment:Splign:2.1.0"
     exon            914..1023
                     /gene="CHRNA2"
                     /inference="alignment:Splign:2.1.0"
     exon            1024..2038
                     /gene="CHRNA2"
                     /inference="alignment:Splign:2.1.0"
     exon            2039..4037
                     /gene="CHRNA2"
                     /inference="alignment:Splign:2.1.0"
     regulatory      3997..4002
                     /regulatory_class="polyA_signal_sequence"
                     /gene="CHRNA2"
                     /note="hexamer: AATAAA"
     regulatory      4010..4015
                     /regulatory_class="polyA_signal_sequence"
                     /gene="CHRNA2"
                     /note="hexamer: AATAAA"
     polyA_site      4015
                     /gene="CHRNA2"
                     /note="major polyA site"
     polyA_site      4037
                     /gene="CHRNA2"
ORIGIN      
        1 gtgtgtgtgt gtgagagaga gagagaacag cgtgagcctg tgtgcttgtg tgctgagccc
       61 tcatcccctc ctggggccag gcttgggttt cacctgcaga atcgcttgtg ctgggctgcc
      121 tgggctgtcc tcagtggcac ctgcatgaag ccgttctggc tgccagagct ggacagcccc
      181 aggaaaaccc acctctctgc agagcttgcc cagctgtccc cgggaagcca aatgcctctc
      241 atgtaagtct tctgctcgac ggggtgtctc ctaaaccctc actcttcagc ctctgtttga
      301 ccatgaaatg aagtgactga gctctattct gtacctgcca ctctatttct ggggtgactt
      361 ttgtcagctg cccagaatct ccaagccagg ctggttctct gcatcctttc aatgacctgt
      421 tttcttctgt aaccacaggt tcggtggtga gaggaagcct cgcagaatcc agcagaatcc
      481 tcacagaatc cagcagcagc tctgctgggg acatggtcca tggtgcaacc cacagcaaag
      541 ccctgacctg acctcctgat gctcaggaga agccatgggc ccctcctgtc ctgtgttcct
      601 gtccttcaca aagctcagcc tgtggtggct ccttctgacc ccagcaggtg gagaggaagc
      661 taagcgccca cctcccaggg ctcctggaga cccactctcc tctcccagtc ccacggcatt
      721 gccgcaggga ggctcgcata ccgagactga ggaccggctc ttcaaacacc tcttccgggg
      781 ctacaaccgc tgggcgcgcc cggtgcccaa cacttcagac gtggtgattg tgcgctttgg
      841 actgtccatc gctcagctca tcgatgtgga tgagaagaac caaatgatga ccaccaacgt
      901 ctggctaaaa caggagtgga gcgactacaa actgcgctgg aaccccactg attttggcaa
      961 catcacatct ctcagggtcc cttctgagat gatctggatc cccgacattg ttctctacaa
     1021 caatgcagat ggggagtttg cagtgaccca catgaccaag gcccacctct tctccacggg
     1081 cactgtgcac tgggtgcccc cggccatcta caagagctcc tgcagcatcg acgtcacctt
     1141 cttccccttc gaccagcaga actgcaagat gaagtttggc tcctggactt atgacaaggc
     1201 caagatcgac ctggagcaga tggagcagac tgtggacctg aaggactact gggagagcgg
     1261 cgagtgggcc atcgtcaatg ccacgggcac ctacaacagc aagaagtacg actgctgcgc
     1321 cgagatctac cccgacgtca cctacgcctt cgtcatccgg cggctgccgc tcttctacac
     1381 catcaacctc atcatcccct gcctgctcat ctcctgcctc actgtgctgg tcttctacct
     1441 gccctccgac tgcggcgaga agatcacgct gtgcatttcg gtgctgctgt cactcaccgt
     1501 cttcctgctg ctcatcactg agatcatccc gtccacctcg ctggtcatcc cgctcatcgg
     1561 cgagtacctg ctgttcacca tgatcttcgt caccctgtcc atcgtcatca ccgtcttcgt
     1621 gctcaatgtg caccaccgct cccccagcac ccacaccatg ccccactggg tgcggggggc
     1681 ccttctgggc tgtgtgcccc ggtggcttct gatgaaccgg cccccaccac ccgtggagct
     1741 ctgccacccc ctacgcctga agctcagccc ctcttatcac tggctggaga gcaacgtgga
     1801 tgccgaggag agggaggtgg tggtggagga ggaggacaga tgggcatgtg caggtcatgt
     1861 ggccccctct gtgggcaccc tctgcagcca cggccacctg cactctgggg cctcaggtcc
     1921 caaggctgag gctctgctgc aggagggtga gctgctgcta tcaccccaca tgcagaaggc
     1981 actggaaggt gtgcactaca ttgccgacca cctgcggtct gaggatgctg actcttcggt
     2041 gaaggaggac tggaagtatg ttgccatggt catcgacagg atcttcctct ggctgtttat
     2101 catcgtctgc ttcctgggga ccatcggcct ctttctgcct ccgttcctag ctggaatgat
     2161 ctgactgcac ctccctcgag ctggctccca gggcaccccc gctgaccatc ttttgaccgt
     2221 ctctgctaca gctgcctctg gtgtcccctt tgggatgagc aggtgcctct ccgcggagtc
     2281 tggacactga cccagggatt gcaggcttcc atccagctta acgttattgt accagggctg
     2341 acagcctgct gggtgcaaag ccctgttttg gatacggagg agctggggaa gctctgcaga
     2401 aggtcgcaat agtgtggtga ccaagtgggg cagagtaaga ttctcctgga ggagcagtgc
     2461 agaccctaag tgacagaagg gtcaaccagg gggacagtgg ggccagggtg acgaggaagg
     2521 gaatgcagac ctcaaaggag gggccgtggg ggcaaagggg agggttcttg gatgtggaag
     2581 ggctttgaac aatgtttaga tttggagatg agcccaaagt gccagggaga acagccaggt
     2641 gaggtgggag gttggagagc caggtgaggt ctctgtaagt caggctgggg ttgaagtttg
     2701 gagtctgtcc gagtttgcag ggtgctgagc tgtatggtcc agcaggggag taataagggc
     2761 tcttctggaa ggggaggaag cgggaggcag ggcctgcacc tgatgtggag gtacagggca
     2821 gatcttccct accggggagg gatggatggt tggatacagg tggctgggct attccatcca
     2881 tctggaagca catttgagcc tccaggcttc tccttgacgt cattcctctc cttccttgct
     2941 gcaaaatggc tctgcaccag ccggccccca ggaggtctgg cagagctgag agccatggcc
     3001 tgcaggggct ccatatgtcc ctacgcgtgc agcaggcaaa caagaaagac catcctgagc
     3061 tgctcctgac ccacctcaaa ctcatctcat ttggcctgtc ctccctccct tcacccctcc
     3121 ttccctcccc aggaaccctg ttccctgtgc ctggctccat caggaggagg cctcacttgg
     3181 gagttgaaga tctttgcctt tagttccttt gattctgaac ttctcaaagg caggtactct
     3241 gcctgttatt tttcccaccc ccagcaccta gcacagcgcc gggtgagtgg ggtcagcact
     3301 tagggcgttt gttctgagtg gttgagggga gcaagctgga ttgtttgggc cccaggactg
     3361 ttgtgtagat ggcaaagctg tggtcccgtc ccttatcagc ctgcctcgtc tctcccagag
     3421 ccccgaggtg tgttgacctg ctctgaaccc ttcagagcag cctgtgtgtg caccttggaa
     3481 tgcaatgcac caccccacag tctgaggctg cacccaggat cccaggccga gctgctgctc
     3541 ctgggatcgg gcaacagacc tccccccaac tctgtccaga ctggagggtg ggacattggc
     3601 agctaacaga tgtgggcatc gggttctcgg gacagcatgg aggctccagg caggaagccg
     3661 agcagggcga gcttccagtt tccttttggt cctaggggtc ccctccttcc aaaccccaaa
     3721 atgtctctcc ctgacactct caggggaaac cagcctggct gtgacgccct ggcccaggcc
     3781 ctgccatgcc tcacttctct cccacaaccc ccctgctcat ggcacatctg gtctctggct
     3841 cctgtctact cgtgtgcatg cagcccccag cgccccctct cctcccactt gctctccgga
     3901 ggcctcagag ctctcgggtc caggctccca gacccactct cctgagacag tgatgttcac
     3961 ttctgttatc catgtctccc atccatcttg catgtgaata aagagattaa ataaagctgc
     4021 acctactgct gactcaa
//
