{"entity":{"id":"smad2","kind":"target","name":"SMAD2","aka":["SMAD family member 2","MADR2","JV18-1","MADH2"],"tldr":"SMAD2 (SMAD family member 2) is a protein that switches other genes on and off. The public catalogues list it as a drug target, an oncogene driver, a tumour suppressor and a biomarker, and an approved or late-stage drug is recorded against it. Tied to Colorectal cancer, Skin cancer, Gastric & gastro-oesophageal junction cancer and 1 more.","summary":"Receptor-regulated SMAD (R-SMAD) that is an intracellular signal transducer and transcriptional modulator activated by TGF-beta (transforming growth factor) and activin type 1 receptor kinases. Binds the TRE element in the promoter region of many genes that are regulated by TGF-beta and, on formation of the SMAD2/SMAD4 complex, activates transcription. Promotes TGFB1-mediated transcription of odontoblastic differentiation genes in dental papilla cells.\n\nCIViC holds 1 clinical evidence item and 0 assertions across 1 variant. Open Targets scores its association with cancer at 0.80 (direct and indirect evidence; datatypes literature 0.98, affected pathway 0.76, genetic association 0.59, somatic mutation 0.94). IntOGen calls it a driver in 5 cohorts (2 activating, 3 loss-of-function), covering Colon Adenocarcinoma, Colorectal Adenocarcinoma. In OnCo, 1 product record names it (Luspatercept).","asOf":"2026-09-23","links":[{"label":"HGNC HGNC:6768","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:6768"},{"label":"UniProt Q15796","url":"https://www.uniprot.org/uniprotkb/Q15796/entry"},{"label":"NCBI Gene 4087","url":"https://www.ncbi.nlm.nih.gov/gene/4087"},{"label":"Ensembl ENSG00000175387","url":"https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000175387"}],"tags":["cancer-genes-wave"],"related":["civic","open-targets","intogen"],"cancers":["colorectal","skin-cancer","gastric","melanoma"],"sections":[],"technologies":[],"targets":[],"drugs":["luspatercept"],"companies":[],"institutions":[],"pathways":["tgf-beta"],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"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: 1 OnCo product record names it; IntOGen calls it an activating (Act) driver in 2 cohorts; IntOGen calls it a loss-of-function (LoF) driver in 3 cohorts; CIViC holds 1 clinical evidence items on its variants. Evidence tier \"approved-drug\" is the strongest of those signals.","Prevalence not recorded: none of the sources gives a positivity rate."],"provenance":{"editedBy":"scripts/fetch-cancer-genes.ts (CIViC, Open Targets, IntOGen, HGNC, UniProt)","editedOn":"2026-09-23"},"symbol":"SMAD2","role":["drug-target","oncogene-driver","tumour-suppressor","biomarker"],"evidenceTier":"approved-drug","sources":[{"label":"HGNC HGNC:6768","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:6768","note":"approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)"},{"label":"UniProt Q15796","url":"https://www.uniprot.org/uniprotkb/Q15796/entry","note":"protein name, function text, keywords and locations (REST API)"},{"label":"CIViC gene SMAD2","url":"https://civicdb.org/features/3375","note":"1 evidence items, 0 assertions, 1 variants; diseases:  (GraphQL API, CC0)"},{"label":"Open Targets ENSG00000175387","url":"https://platform.opentargets.org/target/ENSG00000175387/associations","note":"association with cancer (MONDO_0004992) 0.80; per-cancer scores at or above 0.5: colorectal cancer 0.67, gastric cancer 0.52, melanoma 0.55, skin cancer 0.54 (GraphQL API, CC0)"},{"label":"IntOGen SMAD2","url":"https://www.intogen.org/search?gene=SMAD2","note":"driver in 5 cohorts (Act 2, LoF 3); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0"}],"hgnc":"HGNC:6768","ensembl":"ENSG00000175387","uniprot":"Q15796","entrez":"4087","biology":"Receptor-regulated SMAD (R-SMAD) that is an intracellular signal transducer and transcriptional modulator activated by TGF-beta (transforming growth factor) and activin type 1 receptor kinases. Binds the TRE element in the promoter region of many genes that are regulated by TGF-beta and, on formation of the SMAD2/SMAD4 complex, activates transcription. Promotes TGFB1-mediated transcription of odontoblastic differentiation genes in dental papilla cells. Positively regulates PDPK1 kinase activity by stimulating its dissociation from the 14-3-3 protein YWHAQ which acts as a negative regulator. May act as a tumour suppressor in colorectal carcinoma. Location: Cytoplasm; Nucleus (UniProt). Locus 18q21.1 (HGNC).","whereFound":["Colorectal cancer: Open Targets association 0.67 with colorectal cancer (MONDO_0005575); IntOGen driver in 5 cohorts (COAD, COADREAD)","Skin cancer: Open Targets association 0.54 with skin cancer (MONDO_0002898)","Gastric & gastro-oesophageal junction cancer: Open Targets association 0.52 with gastric cancer (MONDO_0001056)","Melanoma: Open Targets association 0.55 with melanoma (MONDO_0005105)"],"targetClass":"transcription","prevalence":[]},"route":"/targets/smad2/","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":"colorectal","kind":"cancer","name":"Colorectal cancer","route":"/cancers/colorectal/"},{"id":"gastric","kind":"cancer","name":"Gastric & gastro-oesophageal junction cancer","route":"/cancers/gastric/"},{"id":"melanoma","kind":"cancer","name":"Melanoma","route":"/cancers/melanoma/"},{"id":"skin-cancer","kind":"cancer","name":"Skin cancer (all types)","route":"/cancers/skin-cancer/"}],"drug":[{"id":"luspatercept","kind":"drug","name":"Luspatercept","route":"/drugs/luspatercept/"}],"pathway":[{"id":"tgf-beta","kind":"pathway","name":"TGF-β signalling","route":"/pathways/tgf-beta/"}]}}