SMAD3
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.
Overview
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.
CIViC 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.
- Target · the protein and the cell it sits on
- Drug · antibody, small molecule, cell or radioligand
- Effect · signal, damage or kill
In plain words · 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.
- 1 · What it is
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.
- 2 · What goes wrong in cancer
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.
- 3 · How drugs use it
No product in this corpus aims at SMAD3 yet. Because the protein is lost rather than overactive, drugs either restore its function or exploit the weakness its loss leaves (synthetic lethality).
External identifiers
Sources: HGNC HGNC:6769 (approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)); UniProt P84022 (protein name, function text, keywords and locations (REST API)); CIViC gene SMAD3 (1 evidence items, 0 assertions, 1 variants; diseases: (GraphQL API, CC0)); Open Targets ENSG00000166949 (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)); IntOGen SMAD3 (driver in 4 cohorts (Act 0, LoF 4); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0)
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).
- 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)
Notes
top- 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.
Latest papers
topQuery for this target: (TITLE:"SMAD3" OR ABSTRACT:"SMAD3" OR TITLE:"SMAD family member 3" OR ABSTRACT:"SMAD family member 3" OR TITLE:"JV15-2" OR ABSTRACT:"JV15-2" OR TITLE:"HsT17436" OR ABSTRACT:"HsT17436" OR TITLE:"MADH3" OR ABSTRACT:"MADH3") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about SMAD3, not a curated reading list.
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