{"entity":{"id":"gnas","kind":"target","name":"GNAS","aka":["GNAS complex locus","Neuroendocrine secretory protein 55","NESP55","GNASXL","SCG6","SgVI","GNAS1"],"tldr":"GNAS (Neuroendocrine secretory protein 55) is a gene that drives cell growth when it is altered. The public catalogues list it as a drug target, an oncogene driver, a tumour suppressor and a biomarker, and clinical evidence ties its variants to diagnosis, prognosis or drug response. Tied to Colorectal cancer, Pancreatic ductal adenocarcinoma, Breast cancer and 5 more.","summary":"UniProt has no function text for O95467; HGNC names it \"GNAS complex locus\".\n\nCIViC holds 17 clinical evidence items and 0 assertions across 5 variants, naming Trametinib, Palbociclib, Vemurafenib and Gefitinib and others. Open Targets scores its association with cancer at 0.77 (direct and indirect evidence; datatypes genetic literature 0.30, affected pathway 0.61, literature 0.98, genetic association 0.03, somatic mutation 0.97, animal model 0.25). IntOGen calls it a driver in 12 cohorts (11 activating, 1 loss-of-function), covering Invasive Breast Carcinoma, Colorectal Adenocarcinoma, Oesophageal Adenocarcinoma, Hepatocellular Carcinoma, Lung Adenocarcinoma, Medulloblastoma and others.","asOf":"2026-09-23","links":[{"label":"HGNC HGNC:4392","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:4392"},{"label":"UniProt O95467","url":"https://www.uniprot.org/uniprotkb/O95467/entry"},{"label":"NCBI Gene 2778","url":"https://www.ncbi.nlm.nih.gov/gene/2778"},{"label":"Ensembl ENSG00000087460","url":"https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000087460"}],"tags":["cancer-genes-wave"],"related":["civic","open-targets","intogen"],"cancers":["colorectal","pancreatic","breast-cancer","urothelial","esophageal","skin-cancer","hcc","gastric"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-tcga-pancreatic-integrated-characterisation-cancer-cell-2017","paper-wu-gnas-ipmn-sci-transl-med-2011"],"journals":[],"dependsOn":[],"notes":["Written by scripts/fetch-cancer-genes.ts from CIViC, Open Targets, IntOGen, HGNC and UniProt; the function text is UniProt's, condensed and in UK spelling. Roles: CIViC lists 11 therapies; IntOGen calls it an activating (Act) driver in 11 cohorts; IntOGen calls it a loss-of-function (LoF) driver in 1 cohort; CIViC holds 17 clinical evidence items on its variants. Evidence tier \"clinical-evidence\" is the strongest of those signals.","Prevalence not recorded: none of the sources gives a positivity rate.","Diseases the sources name that have no OnCo cancer page yet, so they are not linked: Pseudomyxoma Peritonei; Appendix Cancer; Follicular Thyroid Carcinoma; Histiocytosis-Lymphadenopathy Plus Syndrome.","Pancreatic ductal adenocarcinoma: GNAS R201 hotspot mutations in 2 to 4% of invasive cancers (cBioPortal) and 66% of intraductal papillary mucinous neoplasms, with KRAS or GNAS in 96% of them; the same mutation is carried into the invasive cancer in 7 of 8 IPMN-associated carcinomas and is absent from other cyst types (Wu 2011). A GNAS mutation therefore marks IPMN origin, and it defines 'incipient IPMN' in the Baltimore consensus (Basturk 2015)."],"provenance":{"editedBy":"scripts/fetch-cancer-genes.ts (CIViC, Open Targets, IntOGen, HGNC, UniProt)","editedOn":"2026-09-23"},"symbol":"GNAS","role":["drug-target","oncogene-driver","tumour-suppressor","biomarker"],"evidenceTier":"clinical-evidence","sources":[{"label":"HGNC HGNC:4392","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:4392","note":"approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)"},{"label":"UniProt O95467","url":"https://www.uniprot.org/uniprotkb/O95467/entry","note":"protein name, function text, keywords and locations (REST API)"},{"label":"CIViC gene GNAS","url":"https://civicdb.org/features/2319","note":"17 evidence items, 0 assertions, 5 variants; diseases: Colorectal Cancer, Pseudomyxoma Peritonei, Appendix Cancer, Melanoma, Lung Non-small Cell Carcinoma and 9 more (GraphQL API, CC0)"},{"label":"Open Targets ENSG00000087460","url":"https://platform.opentargets.org/target/ENSG00000087460/associations","note":"association with cancer (MONDO_0004992) 0.77; per-cancer scores at or above 0.5: colorectal cancer 0.67, gastric cancer 0.51, ovarian cancer 0.51, melanoma 0.57, skin cancer 0.57 (GraphQL API, CC0)"},{"label":"IntOGen GNAS","url":"https://www.intogen.org/search?gene=GNAS","note":"driver in 12 cohorts (Act 11, LoF 1); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0"}],"specificity":"tumour-specific","distribution":"many-types","specificityNote":"Tumour-specific alteration: the catalogues call it an oncogene driver (IntOGen cohort analysis finds it activated more often than chance) and a tumour suppressor (IntOGen finds it knocked out more often than chance), so the direction differs between cohorts but the alteration is somatic either way; what a medicine would aim at or exploit is the altered form or its loss, absent from normal cells; no corpus medicine is aimed at it yet. HPA GNAS: RNA low tissue specificity; no normal tissue stained high; highest cancer staining colorectal cancer (5 of 12 high). Distribution: 8 cancer families in the corpus carry a prevalence row, label threshold or catalogue link for it (Colorectal cancer, Pancreatic ductal adenocarcinoma, Breast cancer (all types), Bladder & urothelial cancer, Oesophageal cancer, Skin cancer (all types), Hepatocellular carcinoma and more); Open Targets associates it with 1 specific cancer type at or above 0.5 (pituitary adenoma 3, multiple types). (Rule 6 of scripts/fetch-target-specificity.ts.)","specificitySources":[{"label":"UniProt O95467","url":"https://www.uniprot.org/uniprotkb/O95467/entry","note":"protein name, function text, keywords and locations (REST API)"},{"label":"CIViC gene GNAS","url":"https://civicdb.org/features/2319","note":"17 evidence items, 0 assertions, 5 variants; diseases: Colorectal Cancer, Pseudomyxoma Peritonei, Appendix Cancer, Melanoma, Lung Non-small Cell Carcinoma and 9 more (GraphQL API, CC0)"},{"label":"IntOGen GNAS","url":"https://www.intogen.org/search?gene=GNAS","note":"driver in 12 cohorts (Act 11, LoF 1); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0"},{"label":"Human Protein Atlas GNAS tissue","url":"https://www.proteinatlas.org/ENSG00000087460-GNAS/tissue","note":"RNA tissue and blood lineage specificity, normal tissue antibody staining (version 25.1, CC BY-SA 3.0)"},{"label":"Open Targets ENSG00000087460 associations","url":"https://platform.opentargets.org/target/ENSG00000087460/associations","note":"cancer associations at or above 0.5 (CC0)"}],"hgnc":"HGNC:4392","ensembl":"ENSG00000087460","uniprot":"O95467","entrez":"2778","firstDescribed":1998,"firstDescribedBasis":"sequence","firstDescribedNote":"Earliest sequence paper UniProt cites for the protein: Hayward B.E. et al, Proc. Natl. Acad. Sci. U.S.A, 1998, \"Bidirectional imprinting of a single gene: human GNAS1 encodes distinct maternally, paternally and biallelically derived proteins\".","firstDescribedSource":"https://pubmed.ncbi.nlm.nih.gov/9860993/","biology":"UniProt has no function text for O95467; HGNC names it \"GNAS complex locus\". Location: Cytoplasmic vesicle, secretory vesicle; Secreted (UniProt). Locus 20q13.32 (HGNC).","whereFound":["Colorectal cancer: Open Targets association 0.67 with colorectal cancer (MONDO_0005575); CIViC evidence names this disease","Pancreatic ductal adenocarcinoma: CIViC evidence names this disease; IntOGen driver in 5 cohorts (PAAD, PANCREAS)","Breast cancer: CIViC evidence names this disease; IntOGen driver in 2 cohorts (BRCA)","Bladder & urothelial cancer: CIViC evidence names this disease","Oesophageal cancer: CIViC evidence names this disease; IntOGen driver in 1 cohort (ESCA)","Skin cancer: Open Targets association 0.57 with skin cancer (MONDO_0002898)","Pancreatic ductal adenocarcinoma: r201 hotspot mutation (ipmn-derived tumours) 2-4%"],"targetClass":"oncogene","prevalence":[{"cancerId":"pancreatic","pct":"2-4","measure":"R201 hotspot mutation (IPMN-derived tumours)","source":"https://www.cbioportal.org/study/summary?id=pdac_msk_2024","note":"cBioPortal: 76 of 2,336, 3.3% (R201H 39, R201C 21, R201S 3), in pdac_msk_2024; 7 of 179, 3.9% (R201C 4, R201H 2), in paad_tcga_pan_can_atlas_2018; 10 of 383, 2.6%, in paad_qcmg_uq_2016; 9 of 395, 2.3%, in pancreas_msk_2024; 5 of 109 in paad_utsw_2015; GNAS was a recurrent gene in the TCGA analysis and KRAS wild-type tumours carried GNAS among their drivers (Cancer Genome Atlas 2017). GNAS mutations in 66% of 132 IPMNs, KRAS or GNAS in 96%, carried into the invasive cancer in 7 of 8 IPMN-associated carcinomas and absent from other cysts and from non-IPMN cancers (Wu 2011); 27 of 456 QCMG tumours were IPMN with invasion (cBioPortal histology)."}]},"route":"/targets/gnas/","neighbours":{"collection":[{"id":"civic","kind":"collection","name":"CIViC","route":"/collections/civic/"},{"id":"intogen","kind":"collection","name":"IntOGen","route":"/collections/intogen/"},{"id":"open-targets","kind":"collection","name":"Open Targets Platform","route":"/collections/open-targets/"}],"cancer":[{"id":"urothelial","kind":"cancer","name":"Bladder & urothelial cancer","route":"/cancers/urothelial/"},{"id":"breast-cancer","kind":"cancer","name":"Breast cancer (all types)","route":"/cancers/breast-cancer/"},{"id":"colorectal","kind":"cancer","name":"Colorectal cancer","route":"/cancers/colorectal/"},{"id":"gastric","kind":"cancer","name":"Gastric & gastro-oesophageal junction cancer","route":"/cancers/gastric/"},{"id":"hcc","kind":"cancer","name":"Hepatocellular carcinoma","route":"/cancers/hcc/"},{"id":"esophageal","kind":"cancer","name":"Oesophageal cancer","route":"/cancers/esophageal/"},{"id":"pancreatic","kind":"cancer","name":"Pancreatic ductal adenocarcinoma","route":"/cancers/pancreatic/"},{"id":"skin-cancer","kind":"cancer","name":"Skin cancer (all types)","route":"/cancers/skin-cancer/"}],"paper":[{"id":"paper-springer-pancreatic-cyst-molecular-classification-gastroenterology-2015","kind":"paper","name":"A combination of molecular markers and clinical features improve the classification of pancreatic cysts","route":"/key-papers/paper-springer-pancreatic-cyst-molecular-classification-gastroenterology-2015/"},{"id":"paper-basturk-baltimore-consensus-precursor-lesions-ajsp-2015","kind":"paper","name":"A revised classification system and recommendations from the Baltimore consensus meeting for neoplastic precursor lesions in the pancreas","route":"/key-papers/paper-basturk-baltimore-consensus-precursor-lesions-ajsp-2015/"},{"id":"paper-loree-tumour-location-continuum-colorectal-ccr-2018","kind":"paper","name":"Classifying colorectal cancer by tumor location rather than sidedness highlights a continuum in mutation profiles and consensus molecular subtypes","route":"/key-papers/paper-loree-tumour-location-continuum-colorectal-ccr-2018/"},{"id":"paper-tcga-pancreatic-integrated-characterisation-cancer-cell-2017","kind":"paper","name":"Integrated genomic characterization of pancreatic ductal adenocarcinoma","route":"/key-papers/paper-tcga-pancreatic-integrated-characterisation-cancer-cell-2017/"},{"id":"paper-felsenstein-ipmn-cooccurring-cancer-relatedness-gut-2018","kind":"paper","name":"IPMNs with co-occurring invasive cancers: neighbours but not always relatives","route":"/key-papers/paper-felsenstein-ipmn-cooccurring-cancer-relatedness-gut-2018/"},{"id":"paper-omori-ipmn-progression-pathways-gastroenterology-2019","kind":"paper","name":"Pathways of progression from intraductal papillary mucinous neoplasm to pancreatic ductal adenocarcinoma based on molecular features","route":"/key-papers/paper-omori-ipmn-progression-pathways-gastroenterology-2019/"},{"id":"paper-kanda-panin-1-somatic-mutations-gastroenterology-2012","kind":"paper","name":"Presence of somatic mutations in most early-stage pancreatic intraepithelial neoplasia","route":"/key-papers/paper-kanda-panin-1-somatic-mutations-gastroenterology-2012/"},{"id":"paper-wu-gnas-ipmn-sci-transl-med-2011","kind":"paper","name":"Recurrent GNAS mutations define an unexpected pathway for pancreatic cyst development","route":"/key-papers/paper-wu-gnas-ipmn-sci-transl-med-2011/"}]}}