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GeneE
50 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
TGFBR2
transforming growth factor beta receptor 2
Chromosome 3 Β· 3p24.1
NCBI Gene: 7048Ensembl: ENSG00000163513.20HGNC: HGNC:11773UniProt: A0AAQ5BI06
617PubMed Papers
23Diseases
0Drugs
130Pathogenic Variants
FUNCTIONAL ROLE
ApoptosisHub GeneKinaseReceptor
RESEARCH IMPACT
Highly StudiedTrendingVariant-Rich
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
external side of plasma membranetype I transforming growth factor beta receptor bindingaortic valve morphogenesiscaveolaLoeys-Dietz syndromeLoeys-Dietz syndrome 2familial thoracic aortic aneurysm and aortic dissectionMarfan syndrome type 2
✦AI Summary

TGFBR2 is a transmembrane serine/threonine kinase receptor that binds transforming growth factor beta ligands (TGFB1, TGFB2, TGFB3) with picomolar affinity and mediates TGF-Ξ² signaling through SMAD2/3 phosphorylation 1. The receptor regulates diverse cellular processes including epithelial-mesenchymal transition, stem cell differentiation, and immune cell function. Mechanistically, TGFBR2 heterodimerizes with TGFBR1 upon ligand binding to activate downstream SMAD signaling and modulate reactive oxygen species metabolism 1. The receptor undergoes endocytosis and autophagy-mediated degradation, processes regulated by PIEZO1-dependent mechanisms 2. Clinical significance is substantial: heterozygous TGFBR2 mutations cause Loeys-Dietz syndrome type I, characterized by aggressive aortic aneurysms, arterial tortuosity, hypertelorism, and craniofacial abnormalities, with mean age at death of 22.6 years 3. Despite loss-of-function mutations, affected tissues paradoxically show increased TGF-Ξ² signaling 4, suggesting dominant-negative effects. TGFBR2 mutations also associate with Marfan syndrome-related aneurysm development 5. Therapeutically, TGFBR2 knockout or inhibition in CAR T and NK cells enhances anti-tumor immunity against solid tumors, glioblastoma, and hepatocellular carcinoma by preventing TGF-Ξ²-mediated immune suppression 678.

Sources cited
1
TGFBR2 mutations cause altered cardiovascular, craniofacial, neurocognitive and skeletal development; TGF-Ξ² signaling involvement in craniosynostosis, cleft palate, arterial aneurysms
PMID: 15731757
2
TGFBR2 mutations cause Loeys-Dietz syndrome with arterial aneurysms, mean age at death 22.6 years (type I)
PMID: 16928994
3
TGFBR2 mutations in Loeys-Dietz syndrome show paradoxical increased TGF-Ξ² signaling despite loss-of-function mutations
PMID: 24443023
4
TGFBR2 associated with Marfan syndrome and aneurysm development through TGF-Ξ² signaling pathway perturbation
PMID: 34220303
5
TGFBR2 knockout in CAR T cells improves tumor elimination efficacy against solid tumors by preventing Treg conversion and CAR T cell exhaustion
PMID: 31999649
6
TGFBR2 gene editing in NK cells prevents TGF-Ξ²-mediated NK cell dysfunction against glioblastoma stem cells
PMID: 34138753
7
TGFBR2 knockout or dominant negative expression required for effective iPSC-NK cell anti-HCC activity
PMID: 38986609
8
PIEZO1 regulates TGFBR2 endocytosis and autophagy; TGFBR2 inhibition prevents Marfan syndrome aneurysm development
PMID: 39585648
Disease Associationsβ“˜23
Loeys-Dietz syndromeOpen Targets
0.84Strong
Loeys-Dietz syndrome 2Open Targets
0.79Strong
familial thoracic aortic aneurysm and aortic dissectionOpen Targets
0.67Moderate
Marfan syndrome type 2Open Targets
0.67Moderate
esophageal cancerOpen Targets
0.66Moderate
neurodegenerative diseaseOpen Targets
0.57Moderate
Rare disease with thoracic aortic aneurysm and aortic dissectionOpen Targets
0.57Moderate
colorectal cancer, hereditary nonpolyposis, type 6Open Targets
0.56Moderate
cancerOpen Targets
0.54Moderate
Abnormality of the cardiovascular systemOpen Targets
0.52Moderate
breast carcinomaOpen Targets
0.52Moderate
pancreatic adenocarcinomaOpen Targets
0.52Moderate
Parkinson diseaseOpen Targets
0.51Moderate
Alzheimer diseaseOpen Targets
0.48Moderate
head and neck squamous cell carcinomaOpen Targets
0.47Moderate
multiple sclerosisOpen Targets
0.46Moderate
lysosomal storage diseaseOpen Targets
0.46Moderate
Marfan syndromeOpen Targets
0.46Moderate
Loeys-Dietz syndrome 1Open Targets
0.43Moderate
migraine disorderOpen Targets
0.43Moderate
Esophageal cancerUniProt
Hereditary non-polyposis colorectal cancer 6UniProt
Loeys-Dietz syndrome 2UniProt
Pathogenic Variants130
NM_003242.6(TGFBR2):c.1273A>G (p.Met425Val)Pathogenic
Loeys-Dietz syndrome 2|Familial thoracic aortic aneurysm and aortic dissection
β˜…β˜…β˜†β˜†2025β†’ Residue 425
NM_003242.6(TGFBR2):c.1483C>T (p.Arg495Ter)Pathogenic
Loeys-Dietz syndrome 2|Loeys-Dietz syndrome|not provided|Familial thoracic aortic aneurysm and aortic dissection|Malignant tumor of esophagus;Colorectal cancer, hereditary nonpolyposis, type 6;Loeys-Dietz syndrome 2|Cardiovascular phenotype
β˜…β˜…β˜†β˜†2025β†’ Residue 495
NM_003242.6(TGFBR2):c.761G>A (p.Arg254His)Pathogenic
Familial thoracic aortic aneurysm and aortic dissection|Loeys-Dietz syndrome 2
β˜…β˜…β˜†β˜†2025β†’ Residue 254
NM_003242.6(TGFBR2):c.1609C>T (p.Arg537Cys)Pathogenic
Loeys-Dietz syndrome 2|not provided|Familial thoracic aortic aneurysm and aortic dissection
β˜…β˜…β˜†β˜†2025β†’ Residue 537
NM_003242.6(TGFBR2):c.1379G>A (p.Arg460His)Pathogenic
Loeys-Dietz syndrome 2|not provided|Familial thoracic aortic aneurysm and aortic dissection
β˜…β˜…β˜†β˜†2025β†’ Residue 460
NM_003242.6(TGFBR2):c.1489C>T (p.Arg497Ter)Pathogenic
not provided|Familial thoracic aortic aneurysm and aortic dissection|Loeys-Dietz syndrome 2|Connective tissue disorder|Loeys-Dietz syndrome
β˜…β˜…β˜†β˜†2025β†’ Residue 497
NM_003242.6(TGFBR2):c.1378C>T (p.Arg460Cys)Pathogenic
Loeys-Dietz syndrome 2|not provided|Cardiovascular phenotype|Familial thoracic aortic aneurysm and aortic dissection
β˜…β˜…β˜†β˜†2025β†’ Residue 460
NM_003242.6(TGFBR2):c.1378C>G (p.Arg460Gly)Pathogenic
Familial thoracic aortic aneurysm and aortic dissection|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 460
NM_003242.6(TGFBR2):c.1582C>T (p.Arg528Cys)Pathogenic
Loeys-Dietz syndrome 2|not provided|Familial thoracic aortic aneurysm and aortic dissection|Loeys-Dietz syndrome|TGFBR2-related disorder|Neoplasm|Cardiovascular phenotype
β˜…β˜…β˜†β˜†2025β†’ Residue 528
NM_003242.6(TGFBR2):c.1261A>G (p.Thr421Ala)Pathogenic
Cardiovascular phenotype|Familial thoracic aortic aneurysm and aortic dissection
β˜…β˜…β˜†β˜†2025β†’ Residue 421
NM_003242.6(TGFBR2):c.1583G>A (p.Arg528His)Pathogenic
Colorectal cancer, hereditary nonpolyposis, type 6|Loeys-Dietz syndrome 2|not provided|Loeys-Dietz syndrome|Familial thoracic aortic aneurysm and aortic dissection|Adenocarcinoma of the large intestine
β˜…β˜…β˜†β˜†2025β†’ Residue 528
NM_003242.6(TGFBR2):c.1580C>T (p.Ala527Val)Pathogenic
not specified|Loeys-Dietz syndrome|Familial thoracic aortic aneurysm and aortic dissection|not provided|Loeys-Dietz syndrome 2
β˜…β˜…β˜†β˜†2025β†’ Residue 527
NM_003242.6(TGFBR2):c.1177T>C (p.Cys393Arg)Likely pathogenic
Loeys-Dietz syndrome 2|Familial thoracic aortic aneurysm and aortic dissection
β˜…β˜…β˜†β˜†2025β†’ Residue 393
NM_003242.6(TGFBR2):c.1379G>T (p.Arg460Leu)Pathogenic
Familial thoracic aortic aneurysm and aortic dissection|not provided|Loeys-Dietz syndrome 2
β˜…β˜…β˜†β˜†2025β†’ Residue 460
NM_003242.6(TGFBR2):c.1570G>A (p.Asp524Asn)Pathogenic
Loeys-Dietz syndrome|not provided|Loeys-Dietz syndrome 2|Marfan syndrome|Familial thoracic aortic aneurysm and aortic dissection
β˜…β˜…β˜†β˜†2024β†’ Residue 524
NM_003242.6(TGFBR2):c.1070G>A (p.Gly357Glu)Pathogenic
not provided|Loeys-Dietz syndrome 2
β˜…β˜…β˜†β˜†2024β†’ Residue 357
NM_003242.6(TGFBR2):c.1511G>A (p.Trp504Ter)Pathogenic
Familial thoracic aortic aneurysm and aortic dissection
β˜…β˜…β˜†β˜†2024β†’ Residue 504
NM_003242.6(TGFBR2):c.1301T>A (p.Met434Lys)Pathogenic
Loeys-Dietz syndrome|Loeys-Dietz syndrome 2
β˜…β˜…β˜†β˜†2024β†’ Residue 434
NM_003242.6(TGFBR2):c.1259G>T (p.Gly420Val)Likely pathogenic
Familial thoracic aortic aneurysm and aortic dissection|Loeys-Dietz syndrome 2
β˜…β˜…β˜†β˜†2024β†’ Residue 420
NM_003242.6(TGFBR2):c.914T>A (p.Leu305His)Pathogenic
Familial thoracic aortic aneurysm and aortic dissection|not provided
β˜…β˜…β˜†β˜†2024β†’ Residue 305
View on ClinVar β†—
Related Genes
ACVR2BProtein interaction100%ACVRL1Protein interaction100%ALKProtein interaction100%COL3A1Protein interaction100%CCN2Protein interaction100%FBN1Protein interaction100%
Tissue Expression6 tissues
Heart
100%
Lung
97%
Bone Marrow
20%
Liver
19%
Ovary
16%
Brain
8%
Gene Interaction Network
Click a node to explore
TGFBR2ACVR2BACVRL1ALKCOL3A1CCN2FBN1
PROTEIN STRUCTURE
Preparing viewer…
PDB1M9Z Β· 1.05 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.53Moderately Constrained
pLIβ“˜
0.91Intolerant
Observed/Expected LoF0.36 [0.25–0.53]
RankingsWhere TGFBR2 stands among ~20K protein-coding genes
  • #375of 20,598
    Most Researched617 Β· top 5%
  • #596of 5,498
    Most Pathogenic Variants130 Β· top quartile
  • #3,324of 17,882
    Most Constrained (LOEUF)0.53 Β· top quartile
Genes detectedTGFBR2
Sources retrieved50 papers
Response timeβ€”
πŸ“„ Sources
50β–Ό
1
The Molecular Genetics of Marfan Syndrome.
PMID: 34220303
Int J Med Sci Β· 2021
1.00
2
Aneurysm syndromes caused by mutations in the TGF-beta receptor.
PMID: 16928994
N Engl J Med Β· 2006
0.90
3
Armored bicistronic CAR TΒ cells with dominant-negative TGF-Ξ² receptor II to overcome resistance in glioblastoma.
PMID: 39086131
Mol Ther Β· 2024
0.84
4
A platform of functional studies of ESCC-associated gene mutations identifies the roles of TGFBR2 in ESCC progression and metastasis.
PMID: 39527477
Cell Rep Β· 2024
0.80
5
A syndrome of altered cardiovascular, craniofacial, neurocognitive and skeletal development caused by mutations in TGFBR1 or TGFBR2.
PMID: 15731757
Nat Genet Β· 2005
0.80