BAG3
Chr 10ADBAG cochaperone 3
Also known as: BAG-3, BIS, CAIR-1, CMD1HH, CMT2JJ, HMND15, MFM6
BAG proteins compete with Hip for binding to the Hsc70/Hsp70 ATPase domain and promote substrate release. All the BAG proteins have an approximately 45-amino acid BAG domain near the C terminus but differ markedly in their N-terminal regions. The protein encoded by this gene contains a WW domain in the N-terminal region and a BAG domain in the C-terminal region. The BAG domains of BAG1, BAG2, and BAG3 interact specifically with the Hsc70 ATPase domain in vitro and in mammalian cells. All 3 proteins bind with high affinity to the ATPase domain of Hsc70 and inhibit its chaperone activity in a Hip-repressible manner. [provided by RefSeq, Jul 2008]
Definitive — sufficient evidence for diagnostic panels
2 total gene-disease associations curated
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
Tolerant to missense variation
This gene — mechanism propensity
This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to loss-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
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.
References
ClinVar Variant Classifications
1397 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 | 94 | 6 | 8 | 0 | 108 |
Likely Pathogenic | 50 | 2 | 0 | 0 | 52 |
VUS | 22 | 685 | 41 | 2 | 750 |
Likely Benign | 0 | 18 | 45 | 291 | 354 |
Benign | 0 | 1 | 24 | 2 | 27 |
Conflicting | — | 100 | |||
| Total | 166 | 712 | 118 | 295 | 1,391 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →33 pathogenic / likely-pathogenic (of 41) ClinVar copy-number / structural variants overlap BAG3 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →
Protein Context — Lollipop Plot
BAG3 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
A Phase 1 AAV Gene Therapy Trial Evaluating Safety and Preliminary Efficacy of RP-A701 in Subjects With BAG3 Dilated Cardiomyopathy
RECRUITINGALXN2350 in Adult Participants With BAG3-Associated Dilated Cardiomyopathy
RECRUITINGA Study About the Natural History in Adults With BAG3 Dilated Cardiomyopathy (a Type of Heart Disease) (BAG3 DCM)
ACTIVE NOT RECRUITINGAn AAV Gene Therapy Trial of AFTX-201 in Adults With BAG3-Associated Dilated Cardiomyopathy (DCM)
RECRUITINGTissue and Metabolic Characterization of Arrhythmogenic Cardiomyopathies by Hybrid PET-MRI Imaging, Impact of the Observed Profiles on the Phenotype and on the Evolution of Cardiomyopathy
RECRUITINGObservational Study of Natural History of BAG3 Gene Mutation-Associated Dilated Cardiomyopathy in Chinese Adults
NOT YET RECRUITINGExternal Resources
Links to major genomics databases and tools