TGFBR1 (TGF-beta receptor type-1) variants and mutations

TGFBR1 (also known as TGF-beta receptor type-1) is a human protein-coding gene encoding a TGF-beta receptor type-1 protein. After activation by the ligand-bound receptor complex, it phosphorylates SMAD2 and SMAD3 to propagate TGF-beta signals. Germline pathogenic variants cause Loeys-Dietz syndrome type 1 with arterial aneurysm and dissection and variable craniofacial or skeletal features. This analysis covers 1,511 TGFBR1 variants and mutations. Of these, 53% have computational variant effect predictions. Disease context includes Loeys-Dietz syndrome 1, Loeys-Dietz syndrome, and multiple self-healing squamous epithelioma. Example TGFBR1 variants include M1?, M1T, and E2*.

Variant analysis overview

Gene: TGFBR1
Protein: TGF-beta receptor type-1
UniProt accession: P36897
Organism: Homo sapiens
Variants analyzed: 1511
Variant scope: all variants
Completed: 2026-08-18

Variant and mutation evidence

Variant composition: 1,250 unspecified-consequence records; 133 missense variants; 11 in-frame deletions; 14 frameshift variants; 90 synonymous variants; 4 in-frame insertions; 5 splice-region variants; 2 stop-gained variants; 1 substitution
Prediction scores: 808 variants have prediction scores (53% of the analyzed set).

Clinical, disease, and population context

Disease context: 25 disease associations are represented. Top associations: Loeys-Dietz syndrome 1, Loeys-Dietz syndrome, multiple self-healing squamous epithelioma, familial thoracic aortic aneurysm and aortic dissection, cancer, Rare disease with thoracic aortic aneurysm and aortic dissection, Alzheimer disease, Parkinson disease, multiple sclerosis, neurodegenerative disease, lysosomal storage disease, Marfan syndrome.

Protein structure and variant hotspots

Protein features: 1 transmembrane segments; 2 domains; 2 binding sites; 7 post-translational modification sites.
Structural context: 890 variants have structural context.
PTM context: 10 variants overlap post-translational modification sites.

Data sources

Evidence in this analysis draws on EBI Proteins Variation, UniProt, gnomAD v4, EuropePMC, 3D Hotspot Analysis, Interaction Network Analysis, Protein Data Bank, AlphaFold DB, gnomAD constraint, Open Targets, ClinGen, MaveDB, LitVar.

Notable TGFBR1 variants

Examples include M1?, M1T, E2*, E2G, E2Q, E2K, E2A, E2V. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.

TGFBR1 analysis run — TGFBR1 (1,511 variants) — completed 2026-08-18