# TGFBR2

Source: https://onco.cc/targets/tgfbr2/  
OnCo record `tgfbr2` (Target). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

TGFBR2 (TGF-beta receptor type-2) is a protein kinase, an enzyme that switches other proteins on by adding phosphate groups. The public catalogues list it as an oncogene driver and a tumour suppressor, and it is called a cancer driver by mutation analysis of patient cohorts. Tied to Colorectal cancer, Oesophageal cancer, Pancreatic ductal adenocarcinoma and 5 more.

## Summary

Transmembrane serine/threonine kinase forming with the TGF-beta type I serine/threonine kinase receptor, TGFBR1, the non-promiscuous receptor for the TGF-beta cytokines TGFB1, TGFB2 and TGFB3. Transduces the TGFB1, TGFB2 and TGFB3 signal from the cell surface to the cytoplasm and thus regulates a plethora of physiological and pathological processes including cell cycle arrest in epithelial and haematopoietic cells, control of mesenchymal cell proliferation and differentiation, wound healing, extracellular matrix production, immunosuppression and carcinogenesis. The formation of the receptor complex composed of 2 TGFBR1 and 2 TGFBR2 molecules symmetrically bound to the cytokine dimer results in the phosphorylation and activation of TGFBR1 by the constitutively active TGFBR2.

Open Targets scores its association with cancer at 0.87 (direct and indirect evidence; datatypes genetic literature 0.61, affected pathway 0.87, literature 0.99, genetic association 0.85, somatic mutation 0.95, animal model 0.43). IntOGen calls it a driver in 14 cohorts (3 activating, 11 loss-of-function), covering Renal Clear Cell Carcinoma, Cervical Adenocarcinoma, Cervical Squamous Cell Carcinoma, Colorectal Adenocarcinoma, Oesophageal Adenocarcinoma, Head and Neck Squamous Cell Carcinoma and others.

## Fields

- Kind: Target
- Last checked: 2026-09-23
- Also known as: transforming growth factor beta receptor 2; TGF-beta receptor type-2; TBRII; TBR-ii; MFS2
- Tags: cancer-genes-wave
- Symbol: TGFBR2
- Class: kinase
- Biology: Transmembrane serine/threonine kinase forming with the TGF-beta type I serine/threonine kinase receptor, TGFBR1, the non-promiscuous receptor for the TGF-beta cytokines TGFB1, TGFB2 and TGFB3. Transduces the TGFB1, TGFB2 and TGFB3 signal from the cell surface to the cytoplasm and thus regulates a plethora of physiological and pathological processes including cell cycle arrest in epithelial and haematopoietic cells, control of mesenchymal cell proliferation and differentiation, wound healing, extracellular matrix production, immunosuppression and carcinogenesis. The formation of the receptor complex composed of 2 TGFBR1 and 2 TGFBR2 molecules symmetrically bound to the cytokine dimer results in the phosphorylation and activation of TGFBR1 by the constitutively active TGFBR2. Activated TGFBR1 phosphorylates SMAD2 which dissociates from the receptor and interacts with SMAD4. The SMAD2-SMAD4 complex is subsequently translocated to the nucleus where it modulates the transcription of the TGF-beta-regulated genes. This constitutes the canonical SMAD-dependent TGF-beta signalling cascade. Location: Cell membrane; Membrane raft; Secreted (UniProt). Locus 3p24.1 (HGNC).
- Where found: Colorectal cancer: Open Targets association 0.72 with colorectal cancer (MONDO_0005575); IntOGen driver in 1 cohort (COADREAD); Oesophageal cancer: Open Targets association 0.68 with oesophageal cancer (MONDO_0007576); IntOGen driver in 1 cohort (ESCA); Pancreatic ductal adenocarcinoma: IntOGen driver in 6 cohorts (PAAD, PANCREAS); Head and neck squamous cell carcinoma: Open Targets association 0.51 with head and neck squamous cell carcinoma (MONDO_0010150); IntOGen driver in 2 cohorts (HNSC); Cervical cancer: IntOGen driver in 2 cohorts (CEAD, CESC); Breast cancer: Open Targets association 0.58 with breast cancer (MONDO_0007254); Colorectal cancer: frameshift of the polyadenine coding microsatellite 3-10%

## 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 an activating (Act) driver in 3 cohorts; IntOGen calls it a loss-of-function (LoF) driver in 11 cohorts. Evidence tier "cohort-driver" is the strongest of those signals.
- Prevalence not recorded: none of the sources gives a positivity rate.
- Pancreatic ductal adenocarcinoma: mutated in about 4 to 5% (cBioPortal), part of the TGF-beta pathway with SMAD4, TGFBR1, ACVR1B and ACVR2A that Bailey's ten-pathway analysis names (Bailey 2016); SMAD4 and TGFBR2 mutations are frequently restricted to the invasive carcinoma in cyst progression (Noe 2020).
- Colorectal cancer: the archetypal coding-microsatellite target. A polyadenine tract in the gene slips when mismatch repair fails, so TGFBR2 is broken in 38.6% of MSI-high against 1.8% of microsatellite-stable samples in crc_msk_2026; it was the first such gene identified, in 8 of the earliest MSI colon cancer lines, with no surface receptor left (Markowitz 1995).

## Sources

- HGNC HGNC:11773: https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:11773
- UniProt P37173: https://www.uniprot.org/uniprotkb/P37173/entry
- NCBI Gene 7048: https://www.ncbi.nlm.nih.gov/gene/7048
- Ensembl ENSG00000163513: https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000163513

## Connected records

- collections: [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/), [Cervical cancer](https://onco.cc/cancers/cervical/), [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/), [Renal cell carcinoma](https://onco.cc/cancers/rcc/)
- pathways: [Mismatch repair & microsatellite instability](https://onco.cc/pathways/mismatch-repair-msi/), [TGF-β signalling](https://onco.cc/pathways/tgf-beta/)
- key papers: [Genomic characterization of malignant progression in neoplastic pancreatic cysts](https://onco.cc/key-papers/paper-noe-cyst-malignant-progression-genomics-nat-commun-2020/), [Inactivation of the type II TGF-beta receptor in colon cancer cells with microsatellite instability](https://onco.cc/key-papers/paper-markowitz-tgfbr2-inactivation-msi-colon-science-1995/), [Integrated genomic characterization of pancreatic ductal adenocarcinoma](https://onco.cc/key-papers/paper-tcga-pancreatic-integrated-characterisation-cancer-cell-2017/), [Pancreatic cancer genomes reveal aberrations in axon guidance pathway genes](https://onco.cc/key-papers/paper-biankin-pancreatic-exomes-axon-guidance-nature-2012/), [Stromal gene expression defines poor-prognosis subtypes in colorectal cancer](https://onco.cc/key-papers/paper-calon-stromal-gene-expression-poor-prognosis-colorectal-nat-genet-2015/)

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