{"entity":{"id":"smad3","kind":"target","name":"SMAD3","aka":["SMAD family member 3","JV15-2","HsT17436","MADH3"],"tldr":"SMAD3 (SMAD family member 3) is a gene whose normal job is to hold cell growth in check. The public catalogues list it as 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, Skin cancer and 4 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 SMAD3/SMAD4 complex, activates transcription. Also can form a SMAD3/SMAD4/JUN/FOS complex at the AP-1/SMAD site to regulate TGF-beta-mediated transcription.\n\nCIViC holds 1 clinical evidence item and 0 assertions across 1 variant. Open Targets scores its association with cancer at 0.82 (direct and indirect evidence; datatypes genetic literature 0.30, affected pathway 0.76, literature 0.99, genetic association 0.80, somatic mutation 0.89, animal model 0.47). IntOGen calls it a driver in 4 cohorts (0 activating, 4 loss-of-function), covering Colorectal Adenocarcinoma, Pancreatic Adenocarcinoma.","asOf":"2026-09-23","links":[{"label":"HGNC HGNC:6769","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:6769"},{"label":"UniProt P84022","url":"https://www.uniprot.org/uniprotkb/P84022/entry"},{"label":"NCBI Gene 4088","url":"https://www.ncbi.nlm.nih.gov/gene/4088"},{"label":"Ensembl ENSG00000166949","url":"https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000166949"}],"tags":["cancer-genes-wave"],"related":["civic","open-targets","intogen"],"cancers":["colorectal","pancreatic","skin-cancer","breast-cancer","thyroid","lung-cancer","melanoma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"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: IntOGen calls it a loss-of-function (LoF) driver in 4 cohorts; CIViC holds 1 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."],"provenance":{"editedBy":"scripts/fetch-cancer-genes.ts (CIViC, Open Targets, IntOGen, HGNC, UniProt)","editedOn":"2026-09-23"},"symbol":"SMAD3","role":["tumour-suppressor","biomarker"],"evidenceTier":"clinical-evidence","sources":[{"label":"HGNC HGNC:6769","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:6769","note":"approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)"},{"label":"UniProt P84022","url":"https://www.uniprot.org/uniprotkb/P84022/entry","note":"protein name, function text, keywords and locations (REST API)"},{"label":"CIViC gene SMAD3","url":"https://civicdb.org/features/3376","note":"1 evidence items, 0 assertions, 1 variants; diseases:  (GraphQL API, CC0)"},{"label":"Open Targets ENSG00000166949","url":"https://platform.opentargets.org/target/ENSG00000166949/associations","note":"association with cancer (MONDO_0004992) 0.82; per-cancer scores at or above 0.5: colorectal cancer 0.68, melanoma 0.53, thyroid cancer 0.53, skin cancer 0.55, breast cancer 0.54, lung cancer 0.51 (GraphQL API, CC0)"},{"label":"IntOGen SMAD3","url":"https://www.intogen.org/search?gene=SMAD3","note":"driver in 4 cohorts (Act 0, LoF 4); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0"}],"hgnc":"HGNC:6769","ensembl":"ENSG00000166949","uniprot":"P84022","entrez":"4088","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 SMAD3/SMAD4 complex, activates transcription. Also can form a SMAD3/SMAD4/JUN/FOS complex at the AP-1/SMAD site to regulate TGF-beta-mediated transcription. Has an inhibitory effect on wound healing probably by modulating both growth and migration of primary keratinocytes and by altering the TGF-mediated chemotaxis of monocytes. This effect on wound healing appears to be hormone-sensitive. Regulator of chondrogenesis and osteogenesis and inhibits early healing of bone fractures. Location: Cytoplasm; Nucleus (UniProt). Locus 15q22.33 (HGNC).","whereFound":["Colorectal cancer: Open Targets association 0.68 with colorectal cancer (MONDO_0005575); IntOGen driver in 3 cohorts (COADREAD)","Pancreatic ductal adenocarcinoma: IntOGen driver in 1 cohort (PAAD)","Skin cancer: Open Targets association 0.55 with skin cancer (MONDO_0002898)","Breast cancer: Open Targets association 0.54 with breast cancer (MONDO_0007254)","Thyroid cancer: Open Targets association 0.53 with thyroid cancer (MONDO_0002108)","Lung cancer: Open Targets association 0.51 with lung cancer (MONDO_0008903)"],"targetClass":"tumor-suppressor","prevalence":[]},"route":"/targets/smad3/","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":"breast-cancer","kind":"cancer","name":"Breast cancer (all types)","route":"/cancers/breast-cancer/"},{"id":"colorectal","kind":"cancer","name":"Colorectal cancer","route":"/cancers/colorectal/"},{"id":"lung-cancer","kind":"cancer","name":"Lung cancer (all types)","route":"/cancers/lung-cancer/"},{"id":"melanoma","kind":"cancer","name":"Melanoma","route":"/cancers/melanoma/"},{"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/"},{"id":"thyroid","kind":"cancer","name":"Thyroid cancer","route":"/cancers/thyroid/"}]}}