BAG3

Chr 10AD

BAG cochaperone 3

Also known as: BAG-3, BIS, CAIR-1, CMD1HH, CMT2JJ, HMND15, MFM6

NCBI Gene: 9531 ENSG00000151929 UniProt: O95817 OMIM: 603883

BAG3 encodes a co-chaperone protein that binds to the Hsc70 ATPase domain and inhibits its chaperone activity by promoting substrate release. Autosomal dominant mutations cause a spectrum of neuromuscular disorders including distal hereditary motor neuropathy, axonal Charcot-Marie-Tooth disease, myofibrillar myopathy, and dilated cardiomyopathy. The pathogenic mechanism involves disruption of protein quality control through impaired chaperone-mediated protein folding and degradation.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

?Neuronopathy, distal hereditary motor, autosomal dominant 15MIM #621094

Cardiomyopathy, dilated, 1HHMIM #613881

Charcot-Marie-Tooth disease, axonal, type 2JJMIM #621095

Myopathy, myofibrillar, 6MIM #612954

Clinical highlights

Gene-disease validity (ClinGen)

myofibrillar myopathy · ADDefinitivesufficient evidence for diagnostic panels2 gene-disease associations curated in total

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

144

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.45

LOEUF

Multiple*

Mechanism· predicted

📖

GeneReview available — BAG3

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.45LOEUF

pLI 0.617

Z-score 3.37

OE 0.20 (0.10–0.45)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

-0.74Z-score

OE missense 1.11 (1.02–1.21)

376 obs / 337.9 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.20 (0.10–0.45)

0≤0.351.4

Missense OE?1.11 (1.02–1.21)

0≤0.61.4

Synonymous OE?1.01

0≤1.21.6

LoF obs/exp: 4 / 20.5Missense obs/exp: 376 / 337.9Syn Z: -0.13

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

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

Franklin by Genoox

AI-powered variant curation and clinical analysis

DECIPHER

Genomic variants and phenotypes in rare disease patients

📖

GeneReview available — BAG3

Authoritative clinical overview · NCBI Bookshelf · Recommended first read

Open GeneReview ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

BAG3 Mutation Associated Dilated Cardiomyopathy

ALXN2350 in Adult Participants With BAG3-Associated Dilated Cardiomyopathy

RECRUITING

NCT07218887Phase PHASE1, PHASE2Alexion Pharmaceuticals, Inc.Started 2025-10-24

ALXN2350

Dilated Cardiomyopathy

Observational Study of Natural History of BAG3 Gene Mutation-Associated Dilated Cardiomyopathy in Chinese Adults

NOT YET RECRUITING

NCT07646600AstraZenecaStarted 2026-06-29

Observational, None intervention

Arrhythmogenic Cardiomyopathies

Tissue 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

RECRUITING

NCT05450783Nantes University HospitalStarted 2022-09-01

Biocollection

Dilated Cardiomyopathy (DCM)

A Phase 1 AAV Gene Therapy Trial Evaluating Safety and Preliminary Efficacy of RP-A701 in Subjects With BAG3 Dilated Cardiomyopathy

RECRUITING

NCT07137338Phase PHASE1Rocket Pharmaceuticals Inc.Started 2026-06

RP-A701 is a recombinant viral vector composed of an AAV serotype rh.74 (AAVrh.74) capsid encapsulating the transgene, BCL2-associated Athanogene 3 (BAG3)

Cardiomyopathy, DilatedBcl-2 Anathogene-3 (BAG3) Dilated Cardiomyopathy (DCM)

A Study About the Natural History in Adults With BAG3 Dilated Cardiomyopathy (a Type of Heart Disease) (BAG3 DCM)

ACTIVE NOT RECRUITING

NCT05981092Alexion Pharmaceuticals, Inc.Started 2022-10-14