TGFB1 Gene: Transforming Growth Factor Beta 1 – Function, Disease Associations, and Clinical Significance
Comprehensive resource on the TGFB1 gene, including its genomic context, protein function, associated diseases, tissue expression, and mutation landscape.
Gene Information Card
| Symbol | TGFB1 |
|---|---|
| Full Name | Transforming Growth Factor Beta 1 |
| Gene Type | protein-coding |
| Chromosomal Location | 19q13.2 |
| NCBI Gene ID | 7040 ncbi.nlm.nih.gov/gene/7040 |
| Ensembl ID | ENSG00000105329 |
| UniProt ID | P01137 |
| OMIM ID | 190180 |
| HGNC ID | 11766 |
| Aliases | CED, DPD1, IBD1, TGFB, TGFbeta, LAP |
Description
The TGFB1 gene encodes transforming growth factor beta 1 (TGF-β1), a secreted cytokine that plays a pivotal role in regulating cell proliferation, differentiation, apoptosis, and immune responses. It is a member of the TGF-β superfamily and functions by binding to serine/threonine kinase receptors, leading to the activation of SMAD transcription factors. TGF-β1 is involved in numerous physiological processes, including embryonic development, wound healing, and bone remodeling. Dysregulation of TGFB1 expression or signaling is implicated in various diseases, including fibrosis, cancer, and inherited disorders such as Camurati-Engelmann disease.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Camurati-Engelmann Disease (CED) | Heterozygous mutations in TGFB1 lead to constitutive activation of the TGF-β1 protein, promoting excessive bone formation and sclerosis. | OMIM #131300; ClinVar |
| TGF-Beta 1-Related Connective Tissue Disorder | Mutations affecting the latency-associated peptide (LAP) region can disrupt TGF-β1 regulation, leading to aortic aneurysms and skeletal abnormalities. | OMIM #190180; ClinVar |
| Inflammatory Bowel Disease (IBD) | Polymorphisms in TGFB1 have been associated with altered immune regulation and increased susceptibility to Crohn's disease and ulcerative colitis. | OMIM #601458; NCBI Gene |
| Cancers (e.g., colorectal, breast, lung) | TGFB1 can act as a tumor suppressor in early stages but promotes tumor invasion and metastasis in later stages through epithelial-mesenchymal transition (EMT). | COSMIC; NCBI Gene |
| Fibrotic Diseases (e.g., pulmonary fibrosis, liver cirrhosis) | Overexpression of TGF-β1 stimulates excessive extracellular matrix deposition by fibroblasts, leading to tissue fibrosis. | NCBI Gene; UniProt |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Bone Marrow | 12.4 | Medium |
| Lung | 10.1 | Medium |
| Spleen | 9.8 | Medium |
| Liver | 8.5 | Low |
| Kidney | 7.2 | Low |
| Heart | 6.9 | Low |
| Brain | 4.3 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HUVEC (Endothelial) | 15.2 | High expression; involved in angiogenesis |
| A549 (Lung Carcinoma) | 11.8 | Moderate; associated with EMT and metastasis |
| MCF7 (Breast Carcinoma) | 9.5 | Moderate; role in tumor microenvironment |
| HepG2 (Hepatocellular Carcinoma) | 7.8 | Low; linked to liver fibrosis |
| K562 (Leukemia) | 6.1 | Low; involved in hematopoiesis regulation |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| p.Arg218Cys (R218C) | Missense | Rare (found in CED families) | Gain-of-function; constitutive activation of TGF-β1, leading to Camurati-Engelmann disease. |
| p.Arg218His (R218H) | Missense | Rare (found in CED families) | Gain-of-function; similar to R218C, causes excessive bone formation. |
| p.Cys225Arg (C225R) | Missense | Rare (found in CED families) | Gain-of-function; disrupts LAP, leading to increased TGF-β1 activity. |
| p.Leu101Pro (L101P) | Missense | Rare (found in CED families) | Gain-of-function; alters protein folding and activation. |
| p.Thr263Ile (T263I) | Missense | Rare (found in CED families) | Gain-of-function; associated with severe bone dysplasia. |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations in TGFB1 are rare and often embryonic lethal in animal models. In humans, complete loss is not commonly observed, but reduced TGF-β1 signaling can lead to immune dysregulation and increased inflammation.
Gain of Function (GOF)
Most pathogenic TGFB1 mutations are gain-of-function, particularly those causing Camurati-Engelmann disease. These mutations typically occur in the LAP region, leading to increased TGF-β1 activation and signaling, resulting in excessive bone formation and other connective tissue abnormalities.
Dominant Negative (DN)
Dominant-negative effects are not well-documented for TGFB1. However, some mutations in the LAP region may act in a dominant-negative manner by interfering with the normal processing and secretion of the TGF-β1 homodimer, though this is less characterized compared to gain-of-function mechanisms.
View complete mutation data：
Gene Ontology (GO)
| • cytokine activity | • growth factor activity |
| • protein binding | • transforming growth factor beta receptor binding |
| • extracellular matrix structural constituent | • SMAD binding |
| • identical protein binding | • integrin binding |
| • signaling receptor binding | • extracellular space |
Pathways
• TGF-beta signaling pathway
• Cytokine-cytokine receptor interaction
• Pathways in cancer
• Hippo signaling pathway
• Regulation of actin cytoskeleton
• Epithelial-mesenchymal transition
• Wnt signaling pathway
• Apoptosis
Protein Summary
The TGFB1 gene encodes a 390-amino acid precursor protein that undergoes proteolytic cleavage to produce the mature TGF-β1 cytokine (112 amino acids). The mature protein forms a homodimer held together by disulfide bonds and is secreted as part of a latent complex with the latency-associated peptide (LAP). Activation of TGF-β1 requires dissociation from LAP, often mediated by proteases or integrins. Once active, TGF-β1 binds to TGF-β receptor type II (TGFBR2), which recruits and phosphorylates TGF-β receptor type I (TGFBR1), leading to phosphorylation of SMAD2 and SMAD3. These SMAD proteins then complex with SMAD4 and translocate to the nucleus to regulate target gene expression. TGF-β1 is a master regulator of cellular processes, including cell cycle arrest, differentiation, and extracellular matrix production.
Related Services
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| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TGFB1I1 Knockout HEK293 Cell Line | EDJ-KQ5924 | Human | 7041 | Details Get a Quote |
| TGFB1 Knockout HEK293 Cell Line | EDJ-KQ17770 | Human | 7040 | Details Get a Quote |
| TGFB1I1 Knockout HeLa Cell Line | EDJ-KQ28187 | Human | 7041 | Details Get a Quote |
| TGFB1I1 Knockout A-549 Cell Line | EDJ-KQ29463 | Human | 7041 | Details Get a Quote |
| TGFB1I1 Knockout HCT 116 Cell Line | EDJ-KQ29464 | Human | 7041 | Details Get a Quote |
| TGFB1 Knockout HeLa Cell Line | EDJ-KQ54648 | Human | 7040 | Details Get a Quote |
| TGFB1 Knockout A-549 Cell Line | EDJ-KQ63128 | Human | 7040 | Details Get a Quote |
| TGFB1 Knockout HCT 116 Cell Line | EDJ-KQ71601 | Human | 7040 | Details Get a Quote |
| Tgfb1 Overexpression NRK-49F Stable Cell Line | EDC01486 | Rat | 59086 | Details Get a Quote |
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