{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T05:41:47Z","timestamp":1791092507868,"version":"4.1.0"},"reference-count":23,"publisher":"National Academy of Sciences","issue":"26","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1998,12,22]]},"abstract":"<jats:p>\n                    The\n                    <jats:italic>GNAS1<\/jats:italic>\n                    gene encodes the \u03b1 subunit of the guanine nucleotide-binding protein G\n                    <jats:sub>s<\/jats:sub>\n                    , which couples signaling through peptide hormone receptors to cAMP generation.\n                    <jats:italic>GNAS1<\/jats:italic>\n                    mutations underlie the hormone resistance syndrome pseudohypoparathyroidism type Ia (PHP-Ia), so the maternal inheritance displayed by PHP-Ia has raised suspicions that\n                    <jats:italic>GNAS1<\/jats:italic>\n                    is imprinted. Despite this suggestion, in most tissues G\n                    <jats:sub>s<\/jats:sub>\n                    \u03b1 is biallelically encoded. In contrast, the large G protein XL\u03b1s, also encoded by\n                    <jats:italic>GNAS1<\/jats:italic>\n                    , is paternally derived. Because the inheritance of PHP-Ia predicts the existence of maternally, rather than paternally, expressed transcripts, we have investigated the allelic origin of other mRNAs derived from\n                    <jats:italic>GNAS1<\/jats:italic>\n                    . We find this gene to be remarkable in the complexity of its allele-specific regulation. Two upstream promoters, each associated with a large coding exon, lie only 11 kb apart, yet show opposite patterns of allele-specific methylation and monoallelic transcription. The more 5\u2032 of these exons encodes the neuroendocrine secretory protein NESP55, which is expressed exclusively from the maternal allele. The NESP55 exon is 11 kb 5\u2032 to the paternally expressed XL\u03b1s exon. The transcripts from these two promoters both splice onto\n                    <jats:italic>GNAS1<\/jats:italic>\n                    exon 2, yet share no coding sequences. Despite their structural unrelatedness, the encoded proteins, of opposite allelic origin, both have been implicated in regulated secretion in neuroendocrine tissues. Remarkably, maternally (NESP55), paternally (XL\u03b1s), and biallelically (G\n                    <jats:sub>s<\/jats:sub>\n                    \u03b1) derived proteins all are produced by different patterns of promoter use and alternative splicing of\n                    <jats:italic>GNAS1<\/jats:italic>\n                    , a gene showing simultaneous imprinting in both the paternal and maternal directions.\n                  <\/jats:p>","DOI":"10.1073\/pnas.95.26.15475","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:31:44Z","timestamp":1027679504000},"page":"15475-15480","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":237,"title":["Bidirectional imprinting of a single gene:\n                    <i>GNAS1<\/i>\n                    encodes maternally, paternally, and biallelically derived proteins"],"prefix":"10.1073","volume":"95","author":[{"given":"Bruce E.","family":"Hayward","sequence":"first","affiliation":[{"name":"Human Genetics Unit, University of Edinburgh, Western General Hospital, Edinburgh EH4 2XU, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronica","family":"Moran","sequence":"additional","affiliation":[{"name":"Human Genetics Unit, University of Edinburgh, Western General Hospital, Edinburgh EH4 2XU, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Strain","sequence":"additional","affiliation":[{"name":"Human Genetics Unit, University of Edinburgh, Western General Hospital, Edinburgh EH4 2XU, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David T.","family":"Bonthron","sequence":"additional","affiliation":[{"name":"Human Genetics Unit, University of Edinburgh, Western General Hospital, Edinburgh EH4 2XU, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[1998,12,22]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.85.7.2081"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/0888-7543(91)90377-Q"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.85.2.617"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199005173222002"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.87.21.8287"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1210\/jcem-62-3-497"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.30.2.101"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1159\/000185501"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF01956140"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.31.11.835"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-8628(19980526)77:4<261::AID-AJMG2>3.0.CO;2-Q"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.31.8.607"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1006\/geno.1996.0463"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.15.8715"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.17.10038"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/372804a0"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.17.11657"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1006\/geno.1997.5195"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.2337\/diab.43.12.1413"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1095-164"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)38910-0"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/39631"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.20.11798"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.95.26.15475","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T16:05:06Z","timestamp":1649865906000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.95.26.15475"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1998,12,22]]},"references-count":23,"journal-issue":{"issue":"26","published-print":{"date-parts":[[1998,12,22]]}},"alternative-id":["10.1073\/pnas.95.26.15475"],"URL":"https:\/\/doi.org\/10.1073\/pnas.95.26.15475","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[1998,12,22]]},"assertion":[{"value":"1998-08-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication 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