# SMAD3

Source: https://onco.cc/targets/smad3/  
OnCo record `smad3` (Target). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

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.

## Fields

- Kind: Target
- Last checked: 2026-09-23
- Also known as: SMAD family member 3; JV15-2; HsT17436; MADH3
- Tags: cancer-genes-wave
- Symbol: SMAD3
- Class: tumor-suppressor
- 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).
- Where found: 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

- 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.

## Sources

- HGNC HGNC:6769: https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:6769
- UniProt P84022: https://www.uniprot.org/uniprotkb/P84022/entry
- NCBI Gene 4088: https://www.ncbi.nlm.nih.gov/gene/4088
- Ensembl ENSG00000166949: https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000166949

## 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: [Breast cancer (all types)](https://onco.cc/cancers/breast-cancer/), [Colorectal cancer](https://onco.cc/cancers/colorectal/), [Lung cancer (all types)](https://onco.cc/cancers/lung-cancer/), [Melanoma](https://onco.cc/cancers/melanoma/), [Pancreatic ductal adenocarcinoma](https://onco.cc/cancers/pancreatic/), [Skin cancer (all types)](https://onco.cc/cancers/skin-cancer/), [Thyroid cancer](https://onco.cc/cancers/thyroid/)

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JSON: https://onco.cc/api/v1/entities/smad3.json