TGFBR2
Chr 3ADtransforming growth factor beta receptor 2
Also known as: AAT3, FAA3, LDS1B, LDS2, LDS2B, MFS2, RIIC, TAAD2
The transmembrane serine/threonine kinase receptor forms complexes with TGF-beta cytokines and TGFBR1 to regulate cell proliferation, differentiation, wound healing, and immune responses through SMAD-dependent signaling pathways. Mutations cause Loeys-Dietz syndrome 2, a connective tissue disorder affecting the cardiovascular system, and hereditary nonpolyposis colorectal cancer type 6, both following autosomal dominant inheritance. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.52), reflecting its essential role in multiple developmental and physiological processes.
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
Moderately missense-constrained (top ~2.5%)
This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function, dominant-negative and loss-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
495 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 11 | 4 | 0 | 15 |
Likely Pathogenic | 2 | 19 | 0 | 0 | 21 |
VUS | 20 | 253 | 20 | 0 | 293 |
Likely Benign | 1 | 2 | 43 | 104 | 150 |
Benign | 0 | 1 | 2 | 0 | 3 |
Conflicting | — | 6 | |||
| Total | 23 | 286 | 69 | 104 | 488 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
TGFBR2 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools