TGFBR2 Gene: Transforming Growth Factor Beta Receptor 2
Key regulator of TGF-β signaling, implicated in Marfan syndrome, Loeys-Dietz syndrome, and colorectal cancer
Gene Information Card
| Symbol | TGFBR2 |
|---|---|
| Full Name | Transforming Growth Factor Beta Receptor 2 |
| Gene Type | Protein coding |
| Chromosomal Location | 3p24.1 |
| NCBI Gene ID | 7048 ncbi.nlm.nih.gov/gene/7048 |
| Ensembl ID | ENSG00000163513 |
| UniProt ID | P37173 |
| OMIM ID | 190182 |
| HGNC ID | 11773 |
| Aliases | MFS2, LDS1B, HNPCC6, AAT3, FAA3, LDS2B, TAAD2 |
Description
The TGFBR2 gene encodes the transforming growth factor beta receptor 2, a transmembrane serine/threonine kinase that binds TGF-β ligands and forms a heteromeric complex with TGFBR1 to activate downstream SMAD signaling. This pathway regulates cell proliferation, differentiation, apoptosis, and extracellular matrix production. Germline mutations in TGFBR2 cause hereditary connective tissue disorders such as Loeys-Dietz syndrome and Marfan syndrome, while somatic mutations are associated with colorectal cancer and other malignancies.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Loeys-Dietz syndrome type 1B | Loss-of-function mutations impair TGF-β signaling, leading to aortic aneurysm and skeletal abnormalities | OMIM #610168 |
| Marfan syndrome type 2 | Dominant-negative mutations disrupt receptor function, causing aortic root dilation and lens dislocation | OMIM #154700 |
| Hereditary nonpolyposis colorectal cancer type 6 (HNPCC6) | Microsatellite instability leads to frameshift mutations in a polyadenine tract, inactivating the receptor | OMIM #614331 |
| Thoracic aortic aneurysm and aortic dissection | Missense mutations reduce kinase activity, weakening aortic wall integrity | OMIM #132900 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Heart | 12.5 | Medium |
| Lung | 10.2 | Medium |
| Colon | 8.7 | Medium |
| Breast | 7.3 | Low |
| Skin | 6.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 15.4 | Embryonic kidney, high expression |
| HCT 116 | 9.8 | Colorectal carcinoma, moderate |
| MCF7 | 5.2 | Breast cancer, low |
| A549 | 7.6 | Lung carcinoma, moderate |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.922-1G>A | Splice site | <0.1% | Loss of function, Loeys-Dietz syndrome |
| p.Arg460Cys | Missense | <0.1% | Dominant negative, Marfan syndrome |
| c.1308_1309delAA | Frameshift | 0.5% in MSI-H colorectal cancer | Loss of function, HNPCC6 |
| p.Ala355Val | Missense | <0.1% | Reduced kinase activity, aortic aneurysm |
Mutation functional classification
Loss of Function (LOF)
Frameshift and nonsense mutations in the polyadenine tract (e.g., c.1308_1309delAA) cause premature truncation and loss of receptor function, commonly seen in microsatellite-unstable colorectal cancers.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported in TGFBR2; most pathogenic variants are loss-of-function or dominant-negative.
Dominant Negative (DN)
Missense mutations in the kinase domain (e.g., p.Arg460Cys) produce a receptor that dimerizes with wild-type TGFBR2 but fails to signal, leading to Marfan syndrome type 2.
View complete mutation data：
Gene Ontology (GO)
| • GO:0004675 – transmembrane receptor protein serine/threonine kinase activity | • GO:0005024 – transforming growth factor beta receptor activity |
| • GO:0007179 – transforming growth factor beta receptor signaling pathway | • GO:0016301 – kinase activity |
| • GO:0046332 – SMAD binding | • GO:0005886 – plasma membrane |
Pathways
• TGF-beta signaling pathway (KEGG hsa04350)
• SMAD signaling pathway (Reactome R-HSA-2173789)
• Signaling by TGF-beta family members (Reactome R-HSA-9006936)
• TGFBR2 is a 567-amino acid transmembrane serine/threonine kinase receptor. The extracellular domain binds TGF-β ligands
• while the intracellular kinase domain phosphorylates TGFBR1 upon ligand binding
• initiating SMAD2/3 phosphorylation and nuclear translocation. The protein is essential for growth inhibition
• immune regulation
• and extracellular matrix homeostasis. Mutations that impair its kinase activity or receptor stability lead to connective tissue disorders and cancer.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TGFBR2 Knockout HEK293 Cell Line | EDC07591 | Human | 7048 | Details Get a Quote |
| TGFBR2 Knockout A-549 Cell Line | EDJ-KQ19443 | Human | 7048 | Details Get a Quote |
| TGFBR2 Knockout HCT 116 Cell Line | EDJ-KQ19444 | Human | 7048 | Details Get a Quote |
| TGFBR2 Knockout HeLa Cell Line | EDJ-KQ19445 | Human | 7048 | Details Get a Quote |
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