BAG3: BAG Cochaperone 3
A key regulator of autophagy, apoptosis, and cytoskeletal integrity, implicated in cardiomyopathy and cancer.
Gene Information Card
| Symbol | BAG3 |
|---|---|
| Full Name | BAG cochaperone 3 |
| Gene Type | Protein coding |
| Chromosomal Location | 10q26.11 |
| NCBI Gene ID | 9531 ncbi.nlm.nih.gov/gene/9531 |
| Ensembl ID | ENSG00000151929 |
| UniProt ID | O95817 |
| OMIM ID | 603883 |
| HGNC ID | HGNC:939 |
| Aliases | BAG-3, BIS, CAIR-1, DKFZp686C01235, MGC104327 |
Description
The BAG3 gene encodes a co-chaperone protein that interacts with heat shock protein 70 (HSP70) and Bcl-2, regulating protein quality control, autophagy, and apoptosis. It is essential for maintaining cardiac and skeletal muscle integrity and is implicated in various cancers and neurodegenerative diseases.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Dilated cardiomyopathy 1HH (CMD1HH) | Loss-of-function mutations in BAG3 impair protein quality control and autophagy, leading to myofibrillar disarray and cardiomyocyte death. | OMIM #613881; ClinVar |
| Myofibrillar myopathy 6 (MFM6) | Dominant mutations disrupt Z-disc integrity and protein turnover, causing progressive muscle weakness. | OMIM #612954; ClinVar |
| Charcot-Marie-Tooth disease type 2 (CMT2) | BAG3 mutations cause axonal degeneration through impaired chaperone-assisted autophagy. | OMIM #603883; ClinVar |
| Breast cancer | Overexpression of BAG3 inhibits apoptosis and promotes chemoresistance via Bcl-2 binding. | COSMIC; PubMed studies |
| Pancreatic cancer | BAG3 upregulation supports tumor cell survival under stress by enhancing autophagy. | COSMIC; PubMed studies |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Heart | 48.2 | High |
| Skeletal muscle | 35.1 | High |
| Brain | 12.4 | Medium |
| Liver | 8.7 | Medium |
| Lung | 6.3 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 22.5 | Cervical cancer cell line |
| K562 | 18.3 | Leukemia cell line |
| MCF7 | 15.7 | Breast cancer cell line |
| HepG2 | 11.2 | Liver cancer cell line |
| A549 | 9.8 | Lung cancer cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.872C>T (p.Pro291Leu) | Missense | Rare | Dominant negative; disrupts HSP70 binding, leading to myopathy. |
| c.991C>T (p.Arg331Trp) | Missense | Rare | Associated with dilated cardiomyopathy; impairs autophagy. |
| c.1132C>T (p.Arg378Cys) | Missense | Rare | Causes Charcot-Marie-Tooth disease type 2; reduces protein stability. |
| c.1385_1386del (p.Glu462Glyfs*5) | Frameshift | Very rare | Loss-of-function; linked to severe early-onset cardiomyopathy. |
Mutation functional classification
Loss of Function (LOF)
Frameshift and nonsense mutations (e.g., p.Glu462Glyfs*5) lead to truncated protein and haploinsufficiency, causing dilated cardiomyopathy.
Gain of Function (GOF)
Not well established; some missense mutations may enhance anti-apoptotic activity in cancer.
Dominant Negative (DN)
Missense mutations like p.Pro291Leu and p.Arg331Trp interfere with wild-type BAG3 function, disrupting chaperone activity and autophagy.
View complete mutation data：
Gene Ontology (GO)
| • apoptotic process (GO:0006915) | • autophagy (GO:0006914) |
| • unfolded protein binding (GO:0051082) | • ubiquitin protein ligase binding (GO:0031625) |
| • cytoplasm (GO:0005737) | • Z disc (GO:0030018) |
| • cytosol (GO:0005829) |
Pathways
• Autophagy - animal
• Apoptosis
• Protein processing in endoplasmic reticulum
• Chaperone-mediated autophagy
Protein Summary
BAG3 is a 575-amino acid co-chaperone protein containing a BAG domain that binds HSP70, a WW domain, and two IPV (Ile-Pro-Val) motifs. It plays a critical role in protein quality control by targeting misfolded proteins for autophagy and inhibiting apoptosis through Bcl-2 interaction. BAG3 is highly expressed in cardiac and skeletal muscle, where it maintains sarcomere integrity. Mutations cause dilated cardiomyopathy, myofibrillar myopathy, and neuropathy, while overexpression in cancers promotes cell survival and chemoresistance.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| BAG3 Knockout HEK293 Cell Line | EDJ-KQ6624 | Human | 9531 | Details Get a Quote |
| BAG3 Knockout A-549 Cell Line | EDJ-KQ30867 | Human | 9531 | Details Get a Quote |
| BAG3 Knockout HCT 116 Cell Line | EDJ-KQ30868 | Human | 9531 | Details Get a Quote |
| BAG3 Knockout HeLa Cell Line | EDJ-KQ30869 | Human | 9531 | Details Get a Quote |
