# SMAD4

Source: https://onco.cc/targets/smad4/  
OnCo record `smad4` (Target). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Summary

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.

CIViC holds 31 clinical evidence items and 0 assertions across 20 variants, naming Cetuximab, Trametinib, Bevacizumab and Panitumumab and others. Open Targets scores its association with cancer at 0.87 (direct and indirect evidence; datatypes genetic literature 0.56, affected pathway 0.61, literature 0.99, genetic association 0.89, somatic mutation 0.97, animal model 0.85). IntOGen calls it a driver in 37 cohorts (10 activating, 27 loss-of-function), covering Invasive Breast Carcinoma, Cervical Squamous Cell Carcinoma, Cholangiocarcinoma, Colon Adenocarcinoma, Colorectal Adenocarcinoma, Oesophageal Adenocarcinoma and others.

## Fields

- Kind: Target
- Last checked: 2026-09-23
- Also known as: SMAD family member 4; DPC4; MADH4
- Tags: cancer-genes-wave
- Symbol: SMAD4
- Class: transcription
- 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).
- Where found: Colorectal cancer: Open Targets association 0.79 with colorectal cancer (MONDO_0005575); CIViC evidence names this disease; Gastric & gastro-oesophageal junction cancer: Open Targets association 0.62 with gastric cancer (MONDO_0001056); IntOGen driver in 5 cohorts (STAD, STOMACH); Oesophageal cancer: Open Targets association 0.65 with oesophageal cancer (MONDO_0007576); IntOGen driver in 5 cohorts (ESCA, ESCC); Pancreatic ductal adenocarcinoma: CIViC evidence names this disease; IntOGen driver in 8 cohorts (PAAD, PANCREAS); Biliary tract cancer: Open Targets association 0.63 with biliary tract cancer (MONDO_0003060); Prostate cancer: CIViC evidence names this disease; IntOGen driver in 2 cohorts (PRAD, PROSTATE)

## 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: CIViC lists 11 therapies; IntOGen calls it an activating (Act) driver in 10 cohorts; IntOGen calls it a loss-of-function (LoF) driver in 27 cohorts; CIViC holds 31 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.
- Diseases the sources name that have no OnCo cancer page yet, so they are not linked: Juvenile Polyposis Syndrome.

## Sources

- HGNC HGNC:6770: https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:6770
- UniProt Q13485: https://www.uniprot.org/uniprotkb/Q13485/entry
- NCBI Gene 4089: https://www.ncbi.nlm.nih.gov/gene/4089
- Ensembl ENSG00000141646: https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000141646

## Connected records

- collections: [CIViC](https://onco.cc/collections/civic/), [IntOGen](https://onco.cc/collections/intogen/), [Open Targets Platform](https://onco.cc/collections/open-targets/)
- cancers: [Biliary tract cancer (all types)](https://onco.cc/cancers/biliary-tract-cancer/), [Breast cancer (all types)](https://onco.cc/cancers/breast-cancer/), [Colorectal cancer](https://onco.cc/cancers/colorectal/), [Gastric & gastro-oesophageal junction cancer](https://onco.cc/cancers/gastric/), [Head and neck squamous cell carcinoma](https://onco.cc/cancers/head-and-neck/), [Oesophageal cancer](https://onco.cc/cancers/esophageal/), [Pancreatic ductal adenocarcinoma](https://onco.cc/cancers/pancreatic/), [Prostate cancer](https://onco.cc/cancers/prostate/)
- pathways: [Colorectal cancer (KEGG map)](https://onco.cc/pathways/colorectal-cancer-signalling/), [Pancreatic cancer (KEGG map)](https://onco.cc/pathways/pancreatic-cancer-signalling/), [TGF-β signalling](https://onco.cc/pathways/tgf-beta/)

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JSON: https://onco.cc/api/v1/entities/smad4.json