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SMAD4 (SMAD family member 4) 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 clinical evidence ties its variants to diagnosis, prognosis or drug response. Tied to Colorectal cancer, Gastric & gastro-oesophageal junction cancer, Oesophageal cancer and 5 more. This dossier gathers the 0 products (0 approved), 0 trials, 0 pathways and 0 resistance routes in the corpus that involve it, with external identifiers so it can be joined to UniProt, ChEMBL, Open Targets and the rest of biology.
In muscle physiology, plays a central role in the balance between atrophy and hypertrophy. When recruited by MSTN, promotes atrophy response via phosphorylated SMAD2/4. MSTN decrease causes SMAD4 release and subsequent recruitment by the BMP pathway to promote hypertrophy via phosphorylated SMAD1/5/8. Acts synergistically with SMAD1 and YY1 in bone morphogenetic protein (BMP)-mediated cardiac-specific gene expression. Binds to SMAD binding elements (SBEs) (5'-GTCT/AGAC-3') within BMP response element (BMPRE) of cardiac activating regions. Common SMAD (co-SMAD) is the coactivator and mediator of signal transduction by TGF-beta (transforming growth factor). Location: Cytoplasm; Nucleus (UniProt). Locus 18q21.2 (HGNC).
| Cancer | Prevalence | Measure | Note | Source |
|---|---|---|---|---|
| Gallbladder cancer | 21-38% | Mutation or deletion | 38% in Chile, 36% in Japan and 27% in the United States among 81 patients, with worse survival (10 versus 25 months; Narayan 2019); mutation in 52 of 244 samples, 21.3%, and deep deletion in 11 of 244, 4.5%, in cBioPortal gbc_mskcc_2022; 26.2% of 103 in gbc_msk_2018; 7% of 376 Indian patients (Suryavanshi 2025); independently associated with reduced survival in metastatic disease (Giraldo 2022) and with inferior outcomes in ERBB2-driven tumours (Cowzer 2026). | doi.org |
| Pancreatic ductal adenocarcinoma | 17-33% | Mutation or deep deletion | cBioPortal: mutation in 512 of 2,336, 21.9%, and deep deletion in 102, 4.4%, in pdac_msk_2024 (R361H 30, R361C 26, R445* 15); 86 of 383, 22.5%, in paad_qcmg_uq_2016; mutation 37 of 179, 20.7%, and deep deletion 23 of 183, 12.6%, in paad_tcga_pan_can_atlas_2018; mutation 21 and deep deletion 32 of 109 in paad_utsw_2015; 68 of 395, 17.2%, plus 10 deletions in pancreas_msk_2024; 24 of 140, 17.1%, in paad_cptac_2021. TGFBR2 mutation in 91 of 2,336, 3.9%, and 18 of 383, 4.7%; TGFBR1 64 of 2,336; ACVR1B 11 of 383 (cBioPortal). SMAD4 and TGFBR2 mutations were largely restricted to the invasive carcinoma in cyst progression (Noe 2020). | cBioPortal (TCGA) |
| Colorectal cancer | 12-16% | Mutation or deep deletion (18q loss) | cBioPortal: mutation in 1,078 of 7,237, 14.9%, plus deep deletion in 205, in crc_msk_2026; 173 of 1,134, 15.3%, plus 42 deletions, in crc_msk_2017; 238 of 1,516, 15.7%, plus 46 deletions, in crc_eo_2020; 68 of 534, 12.7%, plus 28 deletions of 592, in coadread_tcga_pan_can_atlas_2018; 73 of 619, 11.8%, in coadread_dfci_2016. SMAD2 and SMAD3 are deleted alongside it (74 and 49 deep deletions in crc_msk_2026). A specific region of chromosome 18 was lost in 73% of carcinomas and 47% of advanced adenomas but only 11 to 13% of early adenomas, which is how 18q entered the model (Vogelstein 1988). | cBioPortal (TCGA) |
Approximate, population-level figures; the measure column says what was counted. Ranges show the midpoint as a bar.
No product in the corpus is aimed at this target yet.
No trial in the corpus names this target or one of its products.
No recorded escape route names this target.
No pathway diagram carries this target as a node.
No companion diagnostic in the registry measures this target.
No model entry for this target yet; check the cancer entries on the models page.
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Query for this target: (TITLE:"SMAD4" OR ABSTRACT:"SMAD4" OR TITLE:"SMAD family member 4" OR ABSTRACT:"SMAD family member 4" OR TITLE:"DPC4" OR ABSTRACT:"DPC4" OR TITLE:"MADH4" OR ABSTRACT:"MADH4") 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 SMAD4, not a curated reading list.
The dossier as machine-readable JSON, at /api/v1/dossiers/smad4.json: identifiers from HGNC, Ensembl, UniProt and ChEMBL, products with status, trials, pathways, hotspots, open questions and assays. The full entity record is in the open API at /api/v1/entities/smad4.json. Licence CC BY-NC 4.0.