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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.
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.
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.
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.
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.
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).
Tumour-specific alteration: the catalogues call it a tumour suppressor (IntOGen finds it knocked out more often than chance); 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 SMAD3: RNA low tissue specificity; high antibody staining in 27 normal tissues; highest cancer staining renal cancer (12 of 12 high). Distribution: 6 cancer families in the corpus carry a prevalence row, label threshold or catalogue link for it (Colorectal cancer, Pancreatic ductal adenocarcinoma, Skin cancer (all types), Breast cancer (all types), Thyroid cancer, Lung cancer (all types)); Open Targets associates it with 1 specific cancer type at or above 0.5 (thyroid gland carcinoma). (Rule 6 of scripts/fetch-target-specificity.ts.)
Sources: UniProt P84022; CIViC gene SMAD3; IntOGen SMAD3; Human Protein Atlas SMAD3 tissue; Open Targets ENSG00000166949 associations
First described 1996. Earliest sequence paper UniProt cites for the protein: Zhang et al, Nature, 1996, "Receptor-associated Mad homologues synergize as effectors of the TGF-beta response". Source.
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)
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).
RNA: low tissue specificity, detected in all normal tissues.
Medium: Epididymis, Heart muscle, Hippocampus, Kidney, Prostate, Salivary gland, Skeletal muscle, Thyroid gland.
Medium only: colorectal cancer, prostate cancer, thyroid cancer.
Human Protein Atlas version 25.1, antibody staining at reliability approved, enhanced or supported; used under CC BY-SA 3.0. Staining counts are patients per level in the atlas cohort, not population prevalence.
Query 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.
Shares Thyroid cancer, Skin cancer (all types), IntOGen, Lung cancer (all types).
Shares Thyroid cancer, Skin cancer (all types), CIViC, IntOGen.
Shares Thyroid cancer, Skin cancer (all types), IntOGen, Lung cancer (all types).
Shares Thyroid cancer, CIViC, IntOGen, Lung cancer (all types).
Shares Thyroid cancer, CIViC, Open Targets Platform, Colorectal cancer.
Shares Thyroid cancer, Skin cancer (all types), IntOGen, Lung cancer (all types).
Shares Thyroid cancer, Skin cancer (all types), CIViC, IntOGen.
Shares Thyroid cancer, IntOGen, Breast cancer (all types), Melanoma.