# SMAD2

Source: https://onco.cc/targets/smad2/  
OnCo record `smad2` (Target). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

SMAD2 (SMAD family member 2) 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 an approved or late-stage drug is recorded against it. Tied to Colorectal cancer, Skin cancer, Gastric & gastro-oesophageal junction cancer and 1 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 SMAD2/SMAD4 complex, activates transcription. Promotes TGFB1-mediated transcription of odontoblastic differentiation genes in dental papilla cells.

CIViC holds 1 clinical evidence item and 0 assertions across 1 variant. Open Targets scores its association with cancer at 0.80 (direct and indirect evidence; datatypes literature 0.98, affected pathway 0.76, genetic association 0.59, somatic mutation 0.94). IntOGen calls it a driver in 5 cohorts (2 activating, 3 loss-of-function), covering Colon Adenocarcinoma, Colorectal Adenocarcinoma. In OnCo, 1 product record names it (Luspatercept).

## Fields

- Kind: Target
- Last checked: 2026-09-23
- Also known as: SMAD family member 2; MADR2; JV18-1; MADH2
- Tags: cancer-genes-wave
- Symbol: SMAD2
- Class: transcription
- 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 SMAD2/SMAD4 complex, activates transcription. Promotes TGFB1-mediated transcription of odontoblastic differentiation genes in dental papilla cells. Positively regulates PDPK1 kinase activity by stimulating its dissociation from the 14-3-3 protein YWHAQ which acts as a negative regulator. May act as a tumour suppressor in colorectal carcinoma. Location: Cytoplasm; Nucleus (UniProt). Locus 18q21.1 (HGNC).
- Where found: Colorectal cancer: Open Targets association 0.67 with colorectal cancer (MONDO_0005575); IntOGen driver in 5 cohorts (COAD, COADREAD); Skin cancer: Open Targets association 0.54 with skin cancer (MONDO_0002898); Gastric & gastro-oesophageal junction cancer: Open Targets association 0.52 with gastric cancer (MONDO_0001056); Melanoma: Open Targets association 0.55 with melanoma (MONDO_0005105)

## 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: 1 OnCo product record names it; IntOGen calls it an activating (Act) driver in 2 cohorts; IntOGen calls it a loss-of-function (LoF) driver in 3 cohorts; CIViC holds 1 clinical evidence items on its variants. Evidence tier "approved-drug" is the strongest of those signals.
- Prevalence not recorded: none of the sources gives a positivity rate.

## Sources

- HGNC HGNC:6768: https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:6768
- UniProt Q15796: https://www.uniprot.org/uniprotkb/Q15796/entry
- NCBI Gene 4087: https://www.ncbi.nlm.nih.gov/gene/4087
- Ensembl ENSG00000175387: https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000175387

## 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: [Colorectal cancer](https://onco.cc/cancers/colorectal/), [Gastric & gastro-oesophageal junction cancer](https://onco.cc/cancers/gastric/), [Melanoma](https://onco.cc/cancers/melanoma/), [Skin cancer (all types)](https://onco.cc/cancers/skin-cancer/)
- drugs: [Luspatercept](https://onco.cc/drugs/luspatercept/)
- pathways: [TGF-β signalling](https://onco.cc/pathways/tgf-beta/)

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JSON: https://onco.cc/api/v1/entities/smad2.json