LOCUS       NM_000516               1854 bp    mRNA    linear   PRI 18-OCT-2024
DEFINITION  Homo sapiens GNAS complex locus (GNAS), transcript variant 1, mRNA.
ACCESSION   NM_000516
VERSION     NM_000516.7
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 1854)
  AUTHORS   Qi,J., Huang,Y. and Bian,Y.
  TITLE     GNAS, not a Highly Mutated Gene, Has Prognostic Significance and
            Carcinogenic Effects in Osteosarcoma
  JOURNAL   Cell Physiol Biochem 58 (5), 510-526 (2024)
   PUBMED   39305132
  REMARK    GeneRIF: GNAS, not a Highly Mutated Gene, Has Prognostic
            Significance and Carcinogenic Effects in Osteosarcoma.
REFERENCE   2  (bases 1 to 1854)
  AUTHORS   Crane,J.L., Shamblott,M.J., Axelman,J., Hsu,S., Levine,M.A. and
            Germain-Lee,E.L.
  TITLE     Imprinting status of Galpha(s), NESP55, and XLalphas in cell
            cultures derived from human embryonic germ cells: GNAS imprinting
            in human embryonic germ cells
  JOURNAL   Clin Transl Sci 2 (5), 355-360 (2009)
   PUBMED   20443919
  REMARK    GeneRIF: analysis of the imprinting Status of Galpha(s), NESP55,
            and XLalphas in cell cultures derived from human embryonic germ
            cells
REFERENCE   3  (bases 1 to 1854)
  AUTHORS   Bastepe,M.
  TITLE     The GNAS Locus: Quintessential Complex Gene Encoding Gsalpha,
            XLalphas, and other Imprinted Transcripts
  JOURNAL   Curr Genomics 8 (6), 398-414 (2007)
   PUBMED   19412439
  REMARK    GeneRIF: GNAS locus has a highly complex imprinted expression
            pattern, giving rise to transcripts (including non-coding) that are
            maternally, paternally, or biallelically expressed.
REFERENCE   4  (bases 1 to 1854)
  AUTHORS   Jakobsen,A.M., Ahlman,H., Kolby,L., Abrahamsson,J.,
            Fischer-Colbrie,R. and Nilsson,O.
  TITLE     NESP55, a novel chromogranin-like peptide, is expressed in
            endocrine tumours of the pancreas and adrenal medulla but not in
            ileal carcinoids
  JOURNAL   Br J Cancer 88 (11), 1746-1754 (2003)
   PUBMED   12771991
  REMARK    GeneRIF: Neuroendocrine secretory protein 55 is found in a subset
            of neuroendocrine tumours showing differentiation towards adrenal
            chromaffin cells and pancreatic islets cells and not in ileal
            carcinoids
REFERENCE   5  (bases 1 to 1854)
  AUTHORS   Freson,K., Jaeken,J., Van Helvoirt,M., de Zegher,F.,
            Wittevrongel,C., Thys,C., Hoylaerts,M.F., Vermylen,J. and Van
            Geet,C.
  TITLE     Functional polymorphisms in the paternally expressed XLalphas and
            its cofactor ALEX decrease their mutual interaction and enhance
            receptor-mediated cAMP formation
  JOURNAL   Hum Mol Genet 12 (10), 1121-1130 (2003)
   PUBMED   12719376
REFERENCE   6  (bases 1 to 1854)
  AUTHORS   Weiss,U., Ischia,R., Eder,S., Lovisetti-Scamihorn,P., Bauer,R. and
            Fischer-Colbrie,R.
  TITLE     Neuroendocrine secretory protein 55 (NESP55): alternative splicing
            onto transcripts of the GNAS gene and posttranslational processing
            of a maternally expressed protein
  JOURNAL   Neuroendocrinology 71 (3), 177-186 (2000)
   PUBMED   10729789
REFERENCE   7  (bases 1 to 1854)
  AUTHORS   Ischia,R., Lovisetti-Scamihorn,P., Hogue-Angeletti,R.,
            Wolkersdorfer,M., Winkler,H. and Fischer-Colbrie,R.
  TITLE     Molecular cloning and characterization of NESP55, a novel
            chromogranin-like precursor of a peptide with 5-HT1B receptor
            antagonist activity
  JOURNAL   J Biol Chem 272 (17), 11657-11662 (1997)
   PUBMED   9111083
REFERENCE   8  (bases 1 to 1854)
  AUTHORS   Haldeman-Englert,C.R., Hurst,A.C.E. and Levine,M.A.
  TITLE     Disorders of GNAS Inactivation
  JOURNAL   (in) Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE and
            Amemiya A (Eds.);
            GENEREVIEWS(R);
            (1993)
   PUBMED   29072892
REFERENCE   9  (bases 1 to 1854)
  AUTHORS   Szymczuk,V., Florenzano,P., de Castro,L.F., Collins,M.T. and
            Boyce,A.M.
  TITLE     Fibrous Dysplasia / McCune-Albright Syndrome
  JOURNAL   (in) Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE and
            Amemiya A (Eds.);
            GENEREVIEWS(R);
            (1993)
   PUBMED   25719192
REFERENCE   10 (bases 1 to 1854)
  AUTHORS   Weinstein,L.S., Gejman,P.V., de Mazancourt,P., American,N. and
            Spiegel,A.M.
  TITLE     A heterozygous 4-bp deletion mutation in the Gs alpha gene (GNAS1)
            in a patient with Albright hereditary osteodystrophy
  JOURNAL   Genomics 13 (4), 1319-1321 (1992)
   PUBMED   1505964
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from BU857975.1, AF493897.1,
            AF105253.1 and BC008855.2.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Jun 19, 2020 this sequence version replaced NM_000516.6.
            
            Summary: This locus has a highly complex imprinted expression
            pattern. It gives rise to maternally, paternally, and biallelically
            expressed transcripts that are derived from four alternative
            promoters and 5' exons. Some transcripts contain a differentially
            methylated region (DMR) at their 5' exons, and this DMR is commonly
            found in imprinted genes and correlates with transcript expression.
            An antisense transcript is produced from an overlapping locus on
            the opposite strand. One of the transcripts produced from this
            locus, and the antisense transcript, are paternally expressed
            noncoding RNAs, and may regulate imprinting in this region. In
            addition, one of the transcripts contains a second overlapping ORF,
            which encodes a structurally unrelated protein - Alex. Alternative
            splicing of downstream exons is also observed, which results in
            different forms of the stimulatory G-protein alpha subunit, a key
            element of the classical signal transduction pathway linking
            receptor-ligand interactions with the activation of adenylyl
            cyclase and a variety of cellular reponses. Multiple transcript
            variants encoding different isoforms have been found for this gene.
            Mutations in this gene result in pseudohypoparathyroidism type 1a,
            pseudohypoparathyroidism type 1b, Albright hereditary
            osteodystrophy, pseudopseudohypoparathyroidism, McCune-Albright
            syndrome, progressive osseus heteroplasia, polyostotic fibrous
            dysplasia of bone, and some pituitary tumors. [provided by RefSeq,
            Aug 2012].
            
            Transcript Variant: This variant (1) is biallelically expressed and
            encodes guanine nucleotide binding protein alpha s long (GNASL),
            also known as alpha-S2, a form of the G-protein alpha subunit.
            
            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 :: X04408.1, X07036.1 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1965299, SAMEA1966682
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            imprinted gene         :: PMID: 19412439
            MANE Ensembl match     :: ENST00000371085.8/ ENSP00000360126.3
            RefSeq Select criteria :: based on manual assertion, expression
            ##RefSeq-Attributes-END##
            COMPLETENESS: complete on the 3' end.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-306               BU857975.1         9-314
            307-1491            AF493897.1         1-1185
            1492-1851           AF105253.1         2197-2556
            1852-1854           BC008855.2         1691-1693
FEATURES             Location/Qualifiers
     source          1..1854
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="20"
                     /map="20q13.32"
     gene            1..1854
                     /gene="GNAS"
                     /gene_synonym="AHO; AIMAH1; C20orf45; GNAS1; GPSA; GSA;
                     GSP; NESP; PITA3; POH; SCG6; SgVI"
                     /note="GNAS complex locus"
                     /db_xref="GeneID:2778"
                     /db_xref="HGNC:HGNC:4392"
                     /db_xref="MIM:139320"
     exon            1..445
                     /gene="GNAS"
                     /gene_synonym="AHO; AIMAH1; C20orf45; GNAS1; GPSA; GSA;
                     GSP; NESP; PITA3; POH; SCG6; SgVI"
                     /inference="alignment:Splign:2.1.0"
     CDS             307..1491
                     /gene="GNAS"
                     /gene_synonym="AHO; AIMAH1; C20orf45; GNAS1; GPSA; GSA;
                     GSP; NESP; PITA3; POH; SCG6; SgVI"
                     /note="isoform GNASL is encoded by transcript variant 1;
                     secretogranin VI; G protein subunit alpha S; guanine
                     nucleotide binding protein (G protein), alpha stimulating
                     activity polypeptide 1; guanine nucleotide regulatory
                     protein; adenylate cyclase-stimulating G alpha protein;
                     protein ALEX; extra large alphas protein; alternative gene
                     product encoded by XL-exon"
                     /codon_start=1
                     /product="protein GNAS isoform GNASL"
                     /protein_id="NP_000507.1"
                     /db_xref="CCDS:CCDS13472.1"
                     /db_xref="GeneID:2778"
                     /db_xref="HGNC:HGNC:4392"
                     /db_xref="MIM:139320"
                     /translation="MGCLGNSKTEDQRNEEKAQREANKKIEKQLQKDKQVYRATHRLL
                     LLGAGESGKSTIVKQMRILHVNGFNGEGGEEDPQAARSNSDGEKATKVQDIKNNLKEA
                     IETIVAAMSNLVPPVELANPENQFRVDYILSVMNVPDFDFPPEFYEHAKALWEDEGVR
                     ACYERSNEYQLIDCAQYFLDKIDVIKQADYVPSDQDLLRCRVLTSGIFETKFQVDKVN
                     FHMFDVGGQRDERRKWIQCFNDVTAIIFVVASSSYNMVIREDNQTNRLQEALNLFKSI
                     WNNRWLRTISVILFLNKQDLLAEKVLAGKSKIEDYFPEFARYTTPEDATPEPGEDPRV
                     TRAKYFIRDEFLRISTASGDGRHYCYPHFTCAVDTENIRRVFNDCRDIIQRMHLRQYE
                     LL"
     exon            446..518
                     /gene="GNAS"
                     /gene_synonym="AHO; AIMAH1; C20orf45; GNAS1; GPSA; GSA;
                     GSP; NESP; PITA3; POH; SCG6; SgVI"
                     /inference="alignment:Splign:2.1.0"
     exon            519..563
                     /gene="GNAS"
                     /gene_synonym="AHO; AIMAH1; C20orf45; GNAS1; GPSA; GSA;
                     GSP; NESP; PITA3; POH; SCG6; SgVI"
                     /inference="alignment:Splign:2.1.0"
     exon            564..618
                     /gene="GNAS"
                     /gene_synonym="AHO; AIMAH1; C20orf45; GNAS1; GPSA; GSA;
                     GSP; NESP; PITA3; POH; SCG6; SgVI"
                     /inference="alignment:Splign:2.1.0"
     exon            619..738
                     /gene="GNAS"
                     /gene_synonym="AHO; AIMAH1; C20orf45; GNAS1; GPSA; GSA;
                     GSP; NESP; PITA3; POH; SCG6; SgVI"
                     /inference="alignment:Splign:2.1.0"
     exon            739..836
                     /gene="GNAS"
                     /gene_synonym="AHO; AIMAH1; C20orf45; GNAS1; GPSA; GSA;
                     GSP; NESP; PITA3; POH; SCG6; SgVI"
                     /inference="alignment:Splign:2.1.0"
     exon            837..891
                     /gene="GNAS"
                     /gene_synonym="AHO; AIMAH1; C20orf45; GNAS1; GPSA; GSA;
                     GSP; NESP; PITA3; POH; SCG6; SgVI"
                     /inference="alignment:Splign:2.1.0"
     exon            892..965
                     /gene="GNAS"
                     /gene_synonym="AHO; AIMAH1; C20orf45; GNAS1; GPSA; GSA;
                     GSP; NESP; PITA3; POH; SCG6; SgVI"
                     /inference="alignment:Splign:2.1.0"
     exon            966..1024
                     /gene="GNAS"
                     /gene_synonym="AHO; AIMAH1; C20orf45; GNAS1; GPSA; GSA;
                     GSP; NESP; PITA3; POH; SCG6; SgVI"
                     /inference="alignment:Splign:2.1.0"
     exon            1025..1145
                     /gene="GNAS"
                     /gene_synonym="AHO; AIMAH1; C20orf45; GNAS1; GPSA; GSA;
                     GSP; NESP; PITA3; POH; SCG6; SgVI"
                     /inference="alignment:Splign:2.1.0"
     exon            1146..1276
                     /gene="GNAS"
                     /gene_synonym="AHO; AIMAH1; C20orf45; GNAS1; GPSA; GSA;
                     GSP; NESP; PITA3; POH; SCG6; SgVI"
                     /inference="alignment:Splign:2.1.0"
     exon            1277..1344
                     /gene="GNAS"
                     /gene_synonym="AHO; AIMAH1; C20orf45; GNAS1; GPSA; GSA;
                     GSP; NESP; PITA3; POH; SCG6; SgVI"
                     /inference="alignment:Splign:2.1.0"
     exon            1345..1854
                     /gene="GNAS"
                     /gene_synonym="AHO; AIMAH1; C20orf45; GNAS1; GPSA; GSA;
                     GSP; NESP; PITA3; POH; SCG6; SgVI"
                     /inference="alignment:Splign:2.1.0"
     regulatory      1829..1834
                     /regulatory_class="polyA_signal_sequence"
                     /gene="GNAS"
                     /gene_synonym="AHO; AIMAH1; C20orf45; GNAS1; GPSA; GSA;
                     GSP; NESP; PITA3; POH; SCG6; SgVI"
                     /note="hexamer: AATAAA"
     regulatory      1836..1841
                     /regulatory_class="polyA_signal_sequence"
                     /gene="GNAS"
                     /gene_synonym="AHO; AIMAH1; C20orf45; GNAS1; GPSA; GSA;
                     GSP; NESP; PITA3; POH; SCG6; SgVI"
                     /note="hexamer: ATTAAA"
     polyA_site      1851
                     /gene="GNAS"
                     /gene_synonym="AHO; AIMAH1; C20orf45; GNAS1; GPSA; GSA;
                     GSP; NESP; PITA3; POH; SCG6; SgVI"
                     /note="major polyA site"
     polyA_site      1854
                     /gene="GNAS"
                     /gene_synonym="AHO; AIMAH1; C20orf45; GNAS1; GPSA; GSA;
                     GSP; NESP; PITA3; POH; SCG6; SgVI"
                     /note="major polyA site"
ORIGIN      
        1 agcagctccc gcagctcctg ctctggtccg cctcggcccg gcggcggcca tcagccccct
       61 cggcctcggc tcgaggggcg gggagctgcg cgcgcccctc ggtccgaccg acaccctccc
      121 cttcccgccc gtccgcgcgc cccgcggccc gcggcccgca gtccgccccg cgcgctcctt
      181 gccgaggagc cgagcccgcg cccggcccgc ccgcccggcg ctgccccggc cctcccggcc
      241 cgcgtgaggc cgcccgcgcc cgccgccgcc gcagcccggc cgcgccccgc cgccgccgcc
      301 gccgccatgg gctgcctcgg gaacagtaag accgaggacc agcgcaacga ggagaaggcg
      361 cagcgtgagg ccaacaaaaa gatcgagaag cagctgcaga aggacaagca ggtctaccgg
      421 gccacgcacc gcctgctgct gctgggtgct ggagaatctg gtaaaagcac cattgtgaag
      481 cagatgagga tcctgcatgt taatgggttt aatggagagg gcggcgaaga ggacccgcag
      541 gctgcaagga gcaacagcga tggtgagaag gcaaccaaag tgcaggacat caaaaacaac
      601 ctgaaagagg cgattgaaac cattgtggcc gccatgagca acctggtgcc ccccgtggag
      661 ctggccaacc ccgagaacca gttcagagtg gactacatcc tgagtgtgat gaacgtgcct
      721 gactttgact tccctcccga attctatgag catgccaagg ctctgtggga ggatgaagga
      781 gtgcgtgcct gctacgaacg ctccaacgag taccagctga ttgactgtgc ccagtacttc
      841 ctggacaaga tcgacgtgat caagcaggct gactatgtgc cgagcgatca ggacctgctt
      901 cgctgccgtg tcctgacttc tggaatcttt gagaccaagt tccaggtgga caaagtcaac
      961 ttccacatgt ttgacgtggg tggccagcgc gatgaacgcc gcaagtggat ccagtgcttc
     1021 aacgatgtga ctgccatcat cttcgtggtg gccagcagca gctacaacat ggtcatccgg
     1081 gaggacaacc agaccaaccg cctgcaggag gctctgaacc tcttcaagag catctggaac
     1141 aacagatggc tgcgcaccat ctctgtgatc ctgttcctca acaagcaaga tctgctcgct
     1201 gagaaagtcc ttgctgggaa atcgaagatt gaggactact ttccagaatt tgctcgctac
     1261 actactcctg aggatgctac tcccgagccc ggagaggacc cacgcgtgac ccgggccaag
     1321 tacttcattc gagatgagtt tctgaggatc agcactgcca gtggagatgg gcgtcactac
     1381 tgctaccctc atttcacctg cgctgtggac actgagaaca tccgccgtgt gttcaacgac
     1441 tgccgtgaca tcattcagcg catgcacctt cgtcagtacg agctgctcta agaagggaac
     1501 ccccaaattt aattaaagcc ttaagcacaa ttaattaaaa gtgaaacgta attgtacaag
     1561 cagttaatca cccaccatag ggcatgatta acaaagcaac ctttcccttc ccccgagtga
     1621 ttttgcgaaa cccccttttc ccttcagctt gcttagatgt tccaaattta gaaagcttaa
     1681 ggcggcctac agaaaaagga aaaaaggcca caaaagttcc ctctcacttt cagtaaaaat
     1741 aaataaaaca gcagcagcaa acaaataaaa tgaaataaaa gaaacaaatg aaataaatat
     1801 tgtgttgtgc agcattaaaa aaaatcaaaa taaaaattaa atgtgagcaa agaa
//
